Download Aunt Cathy`s Guide to Nutrition

Sanford Medical Center
Aunt Cathy’s Guide to Nutrition
Some Ideas for Trying to
Eat More of Those Terrific
Antioxidant Phytochemicals
. . . and Liking It.
Cathy Breedon PhD, RD, CSP, FADA
Clinical Nutrition Specialist
Sanford Medical Center, Fargo, ND
and UND School of Medicine
Recipe : Cranberry-Raspberry-Orange-Gelatin Thing
This one is originally out of the Better Homes and Gardens cookbook . . . probably an older one (1950s
- the red and white plaid one) or one that was a re-issue. It is called something like "Cranberry
Raspberry Ring" or something close. It is in the salad section.
Here's my version:
1. Cut up an orange and remove the seeds and stem area. Put it into a food processor (rind and all) with
a little orange juice (a splash or so) to blenderize it into mass of orange pulp.
2. Take a fresh or frozen bag of cranberries and pick out any bad ones (there are usually a few - they
often float up if you put them into some water to wash them off.) Pour the rest of the bag into the food
processor and blend it up with the orange. You can process it to bigger chunks of cranberry or down
to tiny, as you prefer. As a rule, frozen ones mush up faster than fresh but the fresh ones are the best
tasting if they are available.
3. Boil some water and pour 1-1/2 cups boiling water into a large bowl that can take changes in heat and
cold. Stir in a packet of Jello (or any brand) lemon gelatin and a packet of raspberry gelatin. Stir
while sprinkling it in so it dissolves well without globbing up into gelatinous strangely chewy
masses. You can use regular or sugar free. I use sugar free because I don't need the calories and one of
my Thanksgiving guests has diabetes. Using sugar free means she gets to have a lot more of it.
4. Stir in the cranberry/orange mixture. Pour in a bag of frozen raspberries (the kind that are frozen
without any added sugar.) The cold berries will gel it up pretty quickly. At this point, I just stick the
bowl into the fridge with some saran wrap on top and it is ready to eat in literally just a few minutes.
Just scoop some out and put it in a bowl or on a plate. Replace saran wrap on the remainder. (I have
also tried mixing the gelatin powder right into the cranberry mixture instead of dissolving it in the hot
water, and then just adding the hot water to that. That worked well … no globs.  )
The original recipe has two additional steps:
5. After it is partially gelled, gently stir in 6 oz of a diet or regular lemon-lime soda. (Chug the rest . . .
you have to stay hydrated while slaving over a hot stove.) The soda idea is to trap the carbonation,
which gives it a little fizzy kick. I usually don't bother with that part. I forgot once and barely noticed,
and since it was so much more work . . .
6. They have you put it into a ring mold or bundt pan so you can serve it in an attractive way, flipped
over and very “home-ec” looking. I have done this but it is pretty messy and really only looks nice for
about 3.5 minutes, or until people start taking some. If it gets a bit warm in the room it can experience
some melting. What a mess!
So, I just keep it in the mixing bowl itself in the fridge for normal use, or pour it all into a nice serving
bowl and put it into the fridge so it can go to the table later. You can also put it into individual
servings that people can take and enjoy all by itself. Yogurt containers work well. . .
Bottom line: It tastes great. Calories are low: cranberries are very low kcal, the sugar free version adds
no additional calories. So really, it is just the berries, and they are not high. However, both cranberries
and raspberries are full of those terrific red/blue anthocyanin antioxidant pigments. It also keeps a person
regular if consumed in large volumes daily. My mother likes it a little sweeter so she sprinkles some
Splenda or Nutrasweet on hers and mixes it in. I like it with a bit more bite. It is a nice healthy and
yummy snack. My mother also puts it on ice cream. Mothers are very wise.
Variation: My husband likes it even better if I use a bag of the frozen triple berry mixture (frozen
raspberries, blueberries and blackberries or boysenberries) instead of raspberries alone. He loves
blueberries and since all those berries are great antioxidant phytochemicals, we try different combos.
Recipe 2: Spinach and Raspberry Salad.
+
Get a bag of ready-to-use spinach and put some on a plate.
Get a bag of frozen raspberries (the same kind as above, frozen separately initially and without syrup)
and pour some onto the spinach. You can pour a little or a lot. I pour a lot. Fresh ones are great too, but
not always available or affordable. The frozen ones can be sitting there in your freezer for whenever you
need them. (But even the frozen ones can be pricey … so purple grapes in season sliced in half can be a
good substitute if there can be some smashed ones so they are juicy besides pretty.)
You can also use the sweetened kind of frozen raspberries … I just prefer the plain ones and I don’t need
the calories. The spinach and unsweetened berries are essentially a freebie in the calorie department!
Put it into the fridge ahead of time and the berries will melt a bit and some juices will be on the spinach
leaves. You can also have the berries already thawed, or whatever.
The juices of the raspberries (from a bit of smashing) is all I use as a dressing. My husband likes to put on
a bit of raspberry vinaigrette dressing.
For special deluxe salads (that is . . . for company) we sprinkle it with other goodies like slivered
almonds, strawberries, fresh sliced pears or apples, and pine-nuts. The apples and pears should be added
just before serving so they don't get brown, or use some fruit fresh. The raspberries usually go on top of
the pears, and then the nuts on top of it all. Really yummy and industrial strength phytochemicals and
magnesium!
I once fed this to my niece’s third grade class along with several other brightly colored fruits and
vegetables that were likely to be regarded as new and exotic (and therefore perceived to be icky.) If the
kids tasted everything they were rewarded (bribed) with cool glitter pens.
Afterward they voted and in general they liked a lot of the foods, but the spinach raspberry salad was the
food they elected as the clear favorite. (SPINACH??!!) My niece asked me if I would make this for
her for her birthday. I said yes.
Recipe 3: Pretty Darn Good Broccoli
I learned about this in a Russian restaurant in St. Paul. They served what looked like just a ton of plain
steamed broccoli as a side dish and I was preparing to be brave and eat it because a bunch of nutrition
people were there with me that I did not know. I remember thinking "Ratz! I'm going to have to eat
that!" 
I love broccoli if there is enough hollandaise
sauce, but plain can taste kind of bitter to me,
especially raw broccoli. But when I tasted it I
discovered that it was really good! (Not just
“I can eat this” good . . . it was “I WANT to eat
this” good.)
I asked them what the secret was. Just before the chef served it, he just sprinkled it with a little warm
water into which a small amount of honey had been dissolved. Plain sugar would likely work well,
too, or even certain artificial sweeteners if preferred. The point is that for many people who can taste
some bitter substances in vegetables like broccoli or kale (like a lot of little kids and immature people like
me,) a touch of sweet can cut the bitterness quite a lot.
But since foods like broccoli and kale are real nutrition giants (tons of nutrients and friendly
phytochemicals, fiber and extremely low calories . . . as in, practically none,) if the little bit of
sugar/honey used makes them palatable enough for the "I-hate-broccoli" set to eat them and enjoy them,
it is a very good trade-off
I remember thinking …
“Do you know any children personally?"
The same is true for using dips for
veggie-eating. The goal is to get them to try the
veggies and then to like the veggies … it is not
to make sure they eat bitter-tasting things plain.
What I DID say was that learning to eat them
plain was a noble goal but not the only goal. It is
reasonable to continue to offer them in whatever
form is preferred while working on expanding
their taste for “plain” veggies.
I was talking about this at a conference for
dietitians once and a lady disagreed with the
idea of using dips or sweeteners or anything else
because she felt that children should only be
offered vegetables plain because “they just have
to learn to eat them.”
These goals are NOT mutually exclusive … and
remember that their eating behavior is just one
goal. A goal I care much more about is actually
getting really nutritious foods INTO the little
guys … or big guys. Maybe when I grow up I
will begin to seek out raw broccoli as a treat.
Or not.
Recipe 4: Stealth Vegetables
Take any kind of left-over fruits or vegetables from a meal and put them into a freezer bag and pop
them into the freezer (using appropriately safe food handling techniques, etc., of course.) Do this for
several days, weeks or months. When the volume of these little freezer treats reaches critical mass,
put all of them into a food processor and blend the heck out of them.
Put the pureed veggie/fruit/whatever combo into an ice cube tray and freeze it. When frozen, pop
out the cubes and put them into a freezer bag. Keep them handy there in the freezer section where
they are visible, easy to grab and easy to remember that you have them. If they are out of sight or you
have to dig for them… well, you know …
Anyway, whenever you make something with a lot of flavor (chili, spaghetti sauce, soups, curry,
meatloaf, smoothies, etc.) toss a cube or two or six into the mix.
Now, here’s an important thing to remember: At least initially, you must be sure to blenderize
the stuff sufficiently and maybe even strain it so there are no recognizable chunks of actual
vegetable carcass remaining. That’s the stealth part. If they recognize the vegetable bits they will
be onto your scheme and it will be ALL OVER!
Depending what you put in the freezer bags, you can add a dollop of a nice variety of beneficial
phytochemicals, vitamins and minerals and hardly any calories. (And, yes, you can still try to teach them
to eat vegetables plain while you are quietly sneaking them into their other foods. You can do BOTH!)
Recipe 5: Sunshine Salad … so good I even eat it for dessert!
Here’s a really simple and yummy dish that even little kids can make for the whole family to enjoy.
1. Grated carrots (I just buy a bag of pre-grated fresh carrots because of laziness, time constraints and
general lack of skill, but you could certainly grate your own … it’s cheaper.)
2. Put a handful of the grated carrots into a small bowl, sprinkle on some golden raisins, and add plain
old orange juice as the dressing. (The picture shows dark raisins, which are just fine … I just like the
golden ones better myself and I'm usually the one making it! )You can do it ahead and put some cling
wrap on the individual dishes and keep them in the fridge until time for dinner. Zero fat, low in
calories, high nutrient density (the amount of goodies in any food compared to the number of calories
it contains,) great fiber, vitamins, minerals and … yes … a bunch of terrific phytochemical
antioxidants!
3. Variation: You can do something similar with the grated carrots and canned pinapple (or any
combination of fruits or veggies) in some lemon or orange gelatin … sugar-free or regular. It is really
easy for kids to eat. Although the carrot-raisin-orange juice salad described above works fine with a
spoon, at the end you may need to tip up the bowl and drink the rest of the juice … assuming that this
is acceptable behavior at your house. (It totally is in mine!)
But the gelatin version comes dangerously close to actually cooking something, so the orange-juice
type is much easier to prepare in no time flat. The picture above of a gelatin salad like this also shows
two unnecessary limitations: 1) they went to the trouble to do the whole “messy-gelatin-mold-forspecial-occasions” thing, and then 2) they put something green and (probably) kind of bitter on top.
Great color, and terrific nutritional value to include if the kiddies like it. But when using it as an
introductory food to win kids over to eating vegies, my best advice is to ditch the parsley garnish … at
least for now. Hey – you can always sneak it into something else later, right?
5. Making things fun:
Eat the Rainbow!
Many health and nutrition groups have had success with children using approaches like “Eat the
Rainbow!” I use that a lot. And there are lots of traditional great ideas like “eating trees” made of broccoli
or cutting fruits and veggies to make faces, or whatever. There are whole books out there on fruit and
vegetable art. The web is great for that kind of thing so I won’t say much more about it.
What I DO want to add here is my OWN
experience from childhood. We had a very
limited budget and ate baked potatoes very
often. But once in a while … and ONLY once in
a while … my clever mother would bake the
potatoes on a cookie sheet with toothpicks
joining them together to make a “Potato Man.”
We kids would get to pick if we wanted a leg or
an arm, etc., and it was a big deal to get to
choose. I remember being very excited about a
supper with a potato man. (I have always been
pretty easy to amuse.) But there was no
difference at all except for the novelty.
Creativity does not have to cost a lot.
Potato Man
Enjoy! Cathy B.
Sanford Health
Aunt Cathy’s Guide to:
Free Radicals and
Antioxidants Cartoons
(Antique Art from C. Breedon, 1990:
“Study Guide to Accompany J.E. Brown’s
The Science of Human Nutrition”)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical and Metabolic Nutrition Specialist
Sanford Health (formerly MeritCare)
and UND School of Medicine
Fargo, North Dakota
Newer Stuff:
When this book was written (1990?!) these four were pretty much the only antioxidants
that were in our radar. Now we know that there are other antioxidant substances that are even more
potent at quenching free radicals and protecting against oxidative damage than these four guys.
“Phytochemicals”
The term phytochemical just means “chemicals in plants” so it takes in a lot of territory
besides antioxidant activity. Some phytochemicals are not beneficial (… cocaine and poison sumac
come right to mind.) But it turns out that all of the plant pigments (the actual coloring agents in the
plants) have impressive beneficial antioxidant potential.
One of the first ones identified and studied was lycopene … the red color in tomatoes, red
grapefruit and watermelon. Its antioxidant potential is estimated to be about 200 times as potent
as vitamin E. That discovery rapidly led to the recognition of many other phytochemical pigments
with tremendous ability to protect cells from oxidative damage.
Many of these are in the same chemical family as beta-Carotene, which is the orange pigment
in carrots. Because beta-Carotene was one of the first to be identified, these plant pigments are
collectively called “carotenoids” … which means “carotene-like.”
There are over 500 known carotenoids with potential health benefits, which is why you need
to get started eating a big bunch of brightly colored fruits and vegetables. Many have been found to
have a potentially protective role against a variety of common health problems such as cancer, heart
disease, diabetes, MS, birth defects, and macular degeneration (a form of blindness.) Some of them act as
protective “antioxidants,” but they have many other benefits as well.
Eat the Rainbow!
Beta-carotene is also in green plants, but the green color chlorophyll hides the presence of yellow and
orange pigments. That’s one reason why green colored fruits and vegetables are such good foods …
they are rich in several antioxidant substances.
A good example of yellow and orange color hidden under green is the turning of leaves from green to
orange and red and gold. Those colors were always there, but they only can be seen when
chlorophyll leaves town in the fall.
Here is a quick list of just a handful of the many phytochemical
pigments studied that need to be in your lunchbox:
Phytochemical
pigments
Anthocyanin
Beta-carotene
Lutein and
Chlorophyll
Flavones
Lycopene
Zeaxanthin
Color
Some food examples
Reddish-blue
Orange
Green
White
Red
Yellow
(and also hidden
in all the green
plants)
(FYI: There are many other potent antioxidant substances that are not plant pigments.
Here are a few of those: Alpha lipoic acid, CoQ10 (Ubiquinone), and Carnitine)
Best Advice: Eat all the brightly colored fruits
and vegetable you can get your hands on!
Hot Topics in Nutrition: Back to Basics / Up to Speed
An All-Day Conference for Nutrition Professionals
2014
Cathy Breedon PhD, RD, CSP, FADA
Today’s workshop is designed to bring health professionals up to date on the newest
research about the role of nutrients and overall nutrition in health and disease. Because much has
changed in our understanding of these issues, we are sometimes caught between the information
we learned before and new research information that contradicts some of our earlier assumptions.
This is true whether we graduated long ago or more recently. People making a career change and
working with a population with a different nutrition focus may also feel a bit rusty about both the
basics and the specifics of the most helpful nutrition practices.
The goal is to provide nutrition practitioners with a sound and updated nutrition
foundation, new skills, and renewed confidence in making recommendations. It will address
critical new knowledge in basic nutrition in health and in common health problems, including an
update on the role of key nutrition issues in normal and disturbed metabolism, and new
knowledge about certain vitamin and mineral functions. It will also identify some changes in
nutrition requirements brought about by various health problems.
Content Overview:
1. Several nutrients have been shown to be commonly inadequate in the diets of many Americans
but the inadequacy is often unrecognized. At the same time, there have been many changes in
our understanding of the functions of these nutrients and changes in our assumptions about what
is an adequate intake and at what point toxicity concerns arise. All of these nutrients have
important new applications in health maintenance and in the treatment of health problems. These
include: Vitamins: D, K, B12 and Biotin and Minerals: Magnesium, Iodine and Zinc
2. Additionally, there is new research about the roles and uses of other nutrition-related
substances with importance for maintenance of health that have also now been shown to have
applications in the prevention and/or treatment of a variety of health problems. These include
Alpha-Lipoic Acid, Carnitine, Choline, CoQ10, various forms of Omega-6 and Omega-3
Fatty Acids, Phytochemical Antioxidants, and potential new uses for the Ketogenic Diet in
a wide variety of health conditions.
Note: Only some of the material will be able to be included in any particular presentation
depending on the length of time allowed by the conference planners, and the questions of
participants that will affect the amount of time devoted to each topic. The presentation length
allowed may be only 1 hour or up to three day-long programs. However, all the objectives will
be addressed in the accompanying very thorough handouts, and all handouts are accessible for
free on line.]
Objectives: After attending the workshop and studying the accompanying
thorough handouts, participants will be able to answer the following questions for
each of the vitamins, minerals and other nutrition-related substances below:
Vitamins: D, K, B12 and Biotin
Minerals: Magnesium, Iodine and Zinc,
Alpha-Lipoic Acid, Carnitine, Choline, CoQ10,
Various forms of Omega-6 and Omega-3 Fatty Acids,
Phytochemical Antioxidants, and
Potential new uses for the Ketogenic Diet in a wide variety of health conditions.
1. Describe significant changes in our understanding of this nutrient/substance.
2. Identify geographic and social factors that affect adequacy.
3. Describe age- or developmental-related factors that affect adequacy.
4. Describe common health problems that can be avoided or helped by adjustments in intake of
this nutrient/substance..
5. Identify drug/nutrient interaction of concern.
6. Identify simple, safe and inexpensive interventions to improve this picture.
Other Workshops Available with a Specific Health Focus
Also available is a set of workshops addressing critical new knowledge in
nutrition for a particular population (such as Breastfeeding, Infancy, Pregnancy, the WIC
Population, the Aging Population, and Men’s or Women’s Health Issues.) Workshops
are also available with a focus on specific health problems, both common and rare.
All include an update on the role of key nutrition issues in normal and disturbed
metabolism, including new knowledge about vitamin and mineral functions, our evolving
understanding of carbohydrate, lipids and protein metabolism, the role of certain
phytochemicals and other nutrition-related substances, and the changes in nutrition
requirements brought about by various health problems including drug interactions.
The depth of discussion and specific applications of the information provided can
be designed to focus on issues of most interest to particular groups. Below are some
examples of half-day, full-day, or 2-3 day workshops that have been done recently:
Focus on a particular health issue:
Anemias
Arthritis
Autoimmune Diseases Overview
(Shared nutrition issues important all)
Cancer
Inborn Errors of Nutrient Metabolism
Fuel metabolism issues (beta-oxidation
disorders, relative carnitine insufficiency
and other mitochondrial disorders,
Glycogen Storage Disease); Protein
metabolism Issues: aminoacidopathies
(PKU) and urea cycle disorders; Errors
of mineral metabolism (Wilson’s disease
and hemochromatosis.)
Cardiovascular Disease (general)
Inflammatory Bowel Disease
Cardiovascular Disease Specific (e.g.
focus on Congestive Heart Failure)
Lactation / Breast-Feeding
Celiac Disease
Mental Health
Cystic Fibrosis
Multiple Sclerosis
Diabetes
Myelodysplasia
Down Syndrome (Trisomy 21)
Osteoporosis
Drug/Nutrition Interactions
Parkinsonism
Epidermolysis Bullosa
Prader Willi Syndrome
Eye Health
Pregnancy
Fetal Alcohol Syndrome
Renal Disease
Focus on Nutrition Issues for Particular Populations:
Maternal/Child (Infant and Prenatal
Nutrition and/or WIC focus)
Growth Assessment in Children
The Aging Population
Children with Chronic Conditions and
Special Health Care Needs
Long Term Care
2013
Sanford Medical Center and
Roger Maris Cancer Center
Aunt Cathy’s
Guide to Nutrition:
(This is the shorter little-or no-references version;
a version with more references cited is also available)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center, Fargo, ND,
UND School of Medicine Dept. of Pediatrics
and Breast Cancer Survivor
(Roger Maris Cancer Center Class of ‟98)
This is a quick summary of some things in the nutrition news related to breast
cancer. Although very few references are provided in this brief version, all the
suggestions are based on reports in the legitimate scientific literature and the references
are available on my more thorough papers that are also on MeritCare Medical Center‟s
website. My recommendations are not based on goofy things found on the Internet.
When “researching” a topic on the internet, it is important to consider the
reliability of the source. After all, there is no law against fiction in America! People can
pretty much print anything. For example, websites that end in .edu (colleges and
universities) tend to be more reliable than sites designed primarily to sell you something.
We are learning a lot of new things every day, so the information here is subject
to change at any moment!  (That‟s why there is always a date on my papers.) And of
course, none of the following suggestions are intended to take the place of the advice of
your health care provider.
Outline:
page
1. A Plant-Based Diet
2
2. Soybeans … a Special Kind of Plant
6
3. Bundles of Joy: “Baby Plants” (Nuts, Seeds, Beans and the Germ of Grains)
8
4. Amounts and Types of Fats
9
5. Vitamin and Mineral Antioxidants
12
6. Intake of Other Vitamins and Minerals
14
7. Other Plant Chemicals
19
8. “Conditionally Essential” Nutrients
20
9. Miscellaneous
21
10. Quick Summary of My Best Guess for Reducing Risk of Breast Cancer
22
1. A PLANT-BASED DIET
Increasing the proportion of fruits, vegetables and whole grains in the diet
reduces risk of many cancers. They provide an amazing assortment of cancer-fighters,
including vitamins and certain “phytochemicals” (plant chemicals), some of which are
potent protective substances called “antioxidants.”
Although the word phytochemicals just means chemicals found in plants, and the
term does not indicate whether certain ones are good, bad or neutral, there is another
clear benefit of a primarily plant-based diet: it also decreases meat intake, a source of
saturated fat. Additionally, it has been found that curing or grilling meats or cooking meat
to a “well done” state can produce some substances that can increase risk of cancer,
including cancer of the breast. [Note: Under-cooking meat is not safe either because of
the risk of bacterial food-borne illness, so that won‟t help.]
Research reports can be very confusing with different conclusions reached based on
different study designs. Additionally, the studies brought to our attention via media soundbytes tend to be those perceived to be newsworthy because they are in disagreement with a
lot of other studies. [As a rule of thumb, one study reporting a contradictory finding does
not negate the findings of hundreds of other studies showing the opposite … it just makes
for better headlines.]
One thing that makes things so confusing is that in nature nothing occurs in a
vacuum. But research studies often try to study an issue by looking to see what happens
when everything is kept constant except for one particular variable, like, say, “hot dog
consumption.” But since these food qualities can interact with other circumstances, the
results may be only applicable under certain specific conditions. For example, a generous
antioxidant intake like eating brightly colored fruits and vegetables with the hot dog (or
even putting ketchup on it) decreases some of the negative effects of some components of
cured meats.
An example of one of these potentially cancer-causing substances is called “sodium
nitrite” which is used in curing meats to protect against certain bacteria and to preserve
the red/pink quality of the meat. In the stomach nitrites can be converted to nitrosamines
… which are the substances that appear to increase risk of cancer. However, eating foods
at the same time that provide generous antioxidants can prevent the formation of
nitrosamines. Some cured meats actually have some vitamin C (an antioxidant vitamin)
added to prevent nitrosamine production.
In any case, we Americans tend to eat quite a lot of meat … some estimates are that
we on average eat 3 times the suggested amount. And processed meats are usually very
high in sodium. So simply filling up on more veggies and fruits can help cut back on the
sheer volume of meats consumed. The fruits and veggies are the source of some of the
most potent beneficial antioxidant phytochemicals.
Many of the beneficial plant chemical substances happen to be the brightly
colored pigments that give fruits and vegetables their color. These pigments are very
promising as agents of reducing risk of cancers and many other threats to health (such as
the complications of diabetes or blindness due to macular degeneration.) As an example
of how powerful these pigments are, consider that lycopene, the red color in tomatoes,
ketchup and tomato sauce, has 200 times the protective antioxidant capacity of the
same amount of vitamin E, a well-known antioxidant vitamin.
The research questions now are about figuring out
HOW, WHEN and WHY
various plant substances appear to be protective,
not IF there is a role for any of them.
So, a good rule-of-thumb is to eat all the
brightly colored fruits and vegetables
you can get your hands on!
They are low in fat and calories, and they have lots of other important
substances like vitamins, minerals and fiber. Foods like these that have lots of
goodies relative to calories are called “nutrient dense” foods, which is the opposite of
much less desirable “empty calorie” foods, which have lots of calories but few
nutrients or other health benefits.
Here are a few of the specific substances in the news
that have been studied the most and which
(in addition to their vitamin and mineral content)
clearly have something special to offer in decreasing risk of cancer:
“Cruciferous” vegetables like cauliflower, Brussels sprouts, cabbage, and broccoli
contain many anti-cancer substances, including one called sulforaphane.
Dark green plants have lutein that is a potent antioxidant that also has a special role in
eye health.
Green plants like broccoli, spinach and asparagus also often have hidden orange
pigment like the beta carotene that can be seen in orange-colored plant foods
like carrots, peaches, cantaloupe and yams.
Green and black tea have polyphenols.
Limes have limonene
Blue/red colored fruits and vegetables like red grapes, blueberries, strawberries, beets,
egg plant, cherries, raspberries, pomegranates, and cranberries have anthocyanins.
Yellow corn and squash have zeaxanthin, which also appears to be especially important
in eye health.
Tomatoes and watermelon have lycopene, one of the phytochemical pig,ents that has
been studied the most so far.
Tea, apples, onion, grapes, and green vegetables have a beneficial “flavonoid” called
Quercetin.
Garlic has Allicin and SAC; they do not give it color but they certainly give it a smell.
(I have also heard that it repels vampires. )
Wine has several polyphenols and a very interesting substance called resveratrol.
The best thing about these phytochemicals is that they are being found to be
beneficial in a broad range of health conditions, so eating these fruits and vegetables
decreases our risk of much more than cancer. Many of these plant substances are not
destroyed by heat, so fresh, frozen and canned fruits and vegetables all have something to
offer. There are MANY others … literally thousands more in plant foods. Most have
not even been studied yet.
So although claims are sometimes made for taking certain ones of these
substances as supplements to reduce risk of cancer, (especially by people selling them)
it is clear that it would be naïve to think that the few we have researched so far are
“The Ones,” or that supplementing large amounts of one or a few of them would likely
substantially decrease risk of cancer for an individual.
Supplements of lutein and lycopene are common, and they have not been shown
to be injurious. They may or may not be helpful, but they are fairly expensive and each
provides only that one useful substance, so they are not as likely to be as beneficial
as eating a wide variety of actual fruits and vegetables that provides so many more. This
is in part because many of these substances are known to act most effectively together.
Fruits, vegetables and whole grains are also much less expensive than exotic
supplements. They provide lots of other important nutrients, they more filling and they
taste good, too! What‟s not to like?
If you don‟t like certain ones there are bound to be plenty of others that you
WILL like. Preparing them in many different ways can help too. You can even make
what I call “stealth vegetables” to sneak some into your family‟s meals.
[See my handout on line called “Some Ideas for Trying to Eat More
of Those Terrific Antioxidant Phytochemicals . . . and Liking It.”]
The complex composition of fruits and vegetables make it hard to tease out the
substances of special importance. In addition, it is not just what one eats, but the
relative balance of many diet elements. For example, one could follow a completely
“vegetarian” diet but still eat way too much nutrient-poor (empty calorie) food. After all,
french fries, soda, candy and beer are “vegetarian.” In America, in fact, the french
fry is THE most commonly eaten vegetable! 
The ratio of vegetables-to-meat consumption and the ratio of the amount of
calories-from-vegetables to calories-from-animal-products have been used
successfully to evaluate dietary patterns related to cancer risk. Research into these
beneficial “phytochemicals” is absolutely spilling over with new exciting findings.
2. Soybeans … a Special Kind of Plant
Soybeans are in a class of plantfoods called “legumes” that includes dried beans
(like kidney beans, black beans, navy beans, etc.,) peanuts, lentils and peas. Foods made
from soybeans, like soy milks, soy nuts, tofu and soy sauce, provide a number of
phytochemicals called isoflavones including one called genestein that may lower risk of
many cancers. They have other health benefits as well. These substances are often
described as “plant estrogens” and they are chemically and functionally similar to human
hormones. One definition of a hormone is that it is a substance that causes your body to
DO something, so hormones in general (plant or animal-based) are more likely to cause
problems if they are not in balance than other food substances are.
Think about all the things your very own estrogen can give you: acne, cramps,
babies, etc.  Pretty important stuff. And it is well known that hormones have a lot of
importance in breast cancer in particular, although the details are far from clear. However,
is it reasonable to assume that a plant-based estrogen supplement in a generous dose is
desirable or even safe? Recent studies have not found consistent relationships in the use
of these products relative to breast cancer. Much of the data comes from animal research
that tends to look at just the effect of varying one diet component at a time, which is not as
easy to generalize to real people eating a varied diet. Large human studies are underway,
and some have also reported conflicting results.
For example, it appears that there are certain personal genetic factors that affect
whether soy intake has a role in various cancers. It was first found to be of potential
benefit several years ago when it was noted that the incidence of breast and prostate
cancer is about six times lower in some parts of the world where soy is a regular part
of the diet. However, there are a great many other differences in the diets and lifestyles
and genetic patterns of those population groups besides just the average soy intake.
That kind of large epidemiologic (population-wide) study is useful to stimulate
questions and to guide further research, but it can never show that when two things are
often found together, one of the things is the cause of another. For example, it is true that,
overall, taller children have more math skills than short ones. Is that because being tall
makes you smart? No … it‟s actually because older children in higher grades at school
have been taught more math … and they happen to also be taller than younger children.
(But that doesn‟t keep me from trying to get taller to help me do better at math! )
“Soy nuts” provide the most soy isoflavones found naturally in a small serving of
food in the US. However, many other substances besides isoflavones in soybeans appear
to be important as well, including fiber, protein, vitamins, and minerals. One of the most
recently identified players on this team is the mineral magnesium. Large national studies
indicate that the majority of Americans take in at less than 2/3 of the recommended
amount of magnesium. Recently published studies of over 35,000 women in Iowa suggest
that there is an inverse association of dietary magnesium intake with incidence of
colorectal cancer. That is, the highest intakes of magnesium were associated with the
lowest incidence of colon cancer.
Colon cancer risk factors have often been found to be risk factors for breast
cancer and prostate cancer as well. So, paying attention to research in those areas
also helps us learn how we might decrease risk of breast cancer. And, hey – we all
have a colon, so reducing both kinds of cancer risk at once sounds like a smart idea!
It is recognized that soy foods are fine, certainly nutritious, and possibly helpful in
decreasing risk of cancer. But it is not clear that taking concentrated isoflavone
supplements (instead of just eating soy foods) is safe. In fact, some research suggests that
taking one type of concentrated soy isoflavone (daidzein) may enhance the cancerpreventive properties of the drug tamoxifen, but another (genestein) may actually interfere
with the protective effects of tamoxifen. Oh, fine!
It is interesting that people seem to perceive concentrated soy isoflavone products
as being “natural” and therefore automatically safe and more effective. However, high
concentrations of isolated plant chemicals (natural or not) put into pills and then taken out
of a little bottle is a long way from nature. And of course, just because something is a
plant, it is natural, and God made it does not mean it is safe or that it works to solve a
particular problem. There are a million examples of this … poison ivy, cocaine and
foxglove come right to mind. God may have made them all, but He does not want you to
eat them.
At this time the best advice is to include soy FOODS as desired, but to avoid
supplements that feature concentrated isoflavones until these issues are sorted out.
2. Bundles of Joy: “Baby Plants”
Nuts, Seeds, Legumes/Beans and the Germ of Grains
Because improving magnesium intake has the potential to improve cardiovascular
health, diabetes incidence and management, and neurologic health, and it has many more
benefits, there is clearly no reason NOT to be sure that you get the recommended amount.
The very best sources include the parts of the plants that will turn into the baby
plant. That is … seeds, nuts, beans and the “germ” of grains. Those are by far the best
sources of magnesium and quite a lot of other critical nutrients.
“Refined” grains like “enriched white flour” are missing the highly nutritious
germ part of the grain, and most of the lost nutrients are not added back when the flour
is “enriched.”
That process only adds back three B
vitamins (thiamin, riboflavin and niacin) and
iron. That is why there is so much interest
now in helping people choose “whole grain”
products instead of refined grains. Any whole
grains will do … it does not have to be
wheat.
To have a good amount of whole
grains, the first or second ingredient on the
list should have the word “whole” in it.
Just calling a product “wheat bread”
does not mean that it is WHOLE wheat
bread. Similarly, “12-Grain” bread has
12 different grains in it, but the name doesn‟t
tell you if any of them are WHOLE grains.
If the word “whole” comes much later on the list than the first or second ingredient, it
essentially means: “a whole grain walked by when we were making this.”
To give you an example of the amount of some “baby plant” foods one might eat to
obtain some benefit, consider that in large studies, for several health conditions measured,
differences were shown between a pattern of eating about an ounce of nuts or peanuts four
times a week or more, or never or rarely eating these foods. The measurably better health
outcomes were associated with eating those foods four or more times a week, and the
worst health outcomes were associated with the pattern of rarely eating them.
If you are allergic to a lot of these “baby plant” foods or simply do not like to eat
them, you should check into supplementing magnesium. These really are the richest
sources of magnesium (and several other minerals,) and most multivitamins with minerals
provide only about 10-25% of the recommended amount of magnesium. That may be
enough if your diet is just a bit low, but some folks will definitely benefit from an
additional supplement. But before you cross ALL these baby plant foods off your list,
remember that cocoa powder comes from cocoa beans --- another baby plant!--- (see
picture below) … and that means that chocolate covered peanuts might be considered a
“health food” in certain circumstances. 
[Please see my Magnesium handout for all the details and specific
recommendations about suggested forms and amounts.]
3. AMOUNTS AND TYPES OF FATS
Reducing total dietary fat is less important than previously believed, but lowering
the proportion of omega-6 fats and increasing the proportion of omega-3 fats and
monounsaturated fats appears to decrease risk of breast cancer.
Omega-6 fats are predominant in cornoil, safflower oil and many other cooking oils.
Omega-3 fats are most generous in flaxseed, canola oil, walnuts, fish and fish oils.
Monounsaturated fats are in nuts and legumes and in peanut oil and olive oil.
That‟s another benefit of eating nuts and peanuts: the fat tends to be “happy fat.” That
is, it has the same calories of other fat, but it does not increase your risk of heart disease
or cancer. I like to think of them as “dangerous to your butt, but not to your heart!”
The fish-oil omega-3 fats (EPA and DHA) have important anti-cancer
properties that are not available from the vegetable sources, especially among people
who have been found to be less able to convert the plant-forms to these longer forms. The
finding that some folks are more dependent on a ready-to-go source of EPA and DHA is
a fairly new discovery and it is often unrecognized at present. Inability to produce your
own EPA and DHA from plant oils is a serious (and not uncommon) problem.
This is why flax oil and fish oil are not equally helpful to all people. Although
both are omega-3 fats, some folks cannot convert the oil (linolenic acid) in flax and other
plants to EPA and DHA, the omega-3 fats so important in humans and other animals.
However, the flax seeds themselves have some substances besides the omega-3rich oil that may be useful in decreasing risk of cancer. First, because they are seeds
(baby plants) they are very nutrient dense and good sources of magnesium. Second, they
contain substances called “lignins” that may specifically reduce risk of breast cancer.
This combination makes the flax seeds, but not flax oil capsules, a particularly good food
to incorporate into the diet. Be creative … add ground flax to your meatloaf!
[Also, flax is a North Dakota product, so be sure to buy a lot! ]
Both EPA and DHA appear to be beneficial, and they also have benefits in a wide
variety of health concerns from heart disease to MS, diabetes, arthritis, depression and
dementia, so this seems like a prudent direction to go. [EPA stands for the molecular
description of this fat (EicosaPentaenoic Acid), but I always think of it as standing for
“Environmental Protection Agency” because it helps protect our internal environment!]
Fish oil is the source of both EPA and DHA, and the American Heart Association and
others encourage most people to take 1000 mg fish oil capsule daily, in part because we
can‟t readily tell who the individuals are who cannot make their own.
Omega-3 fatty acids also may increase the effectiveness of certain cancer
treatments. Certain types of chemotherapy seem to work better when additional omega-3
fatty acids are provided in the diet.
Increasing the ratio of omega-3 fatty acids relative to omega-6 fatty acids in
the diet has additional benefit in dealing with cardiovascular disease, diabetes and in
autoimmune disorders like MS and arthritis. Most Americans eat a diet that provides 10
or more grams of omega-6 fat for every gram of omega-3 fat --- that is, a 10-to-1 ratio.
For most people it is recommended that we try to change the ratio to be closer to
4-to-1, which is the ratio typically found in the “Mediterranean Diet” … a pattern
associated with decreased risk of cancer and heart disease.
If a person has an inflammatory disease like multiple sclerosis, diabetes or
arthritis, a ratio of 2-to-1 might be even better. [Please see my handout on line for more
detail about oils and fats and omega-6:omega-3 ratios, and also my papers on nutrition
for people with diabetes or MS for more information on this topic, including many
references.]
“Monounsaturated” fats are a type of fat
that also seems to be protective against cancer.
They are mostly found in olive oil, peanut oil, nuts
and avocados. Some of the protection is related to
beneficial phytochemicals found in those foods.
For example, olive oil is recognized as a source
Of additional cancer-fighting phytochemicals.
That is not a surprise, since these oils are also made
from foods that are “baby plants!”
Using monounsaturated fats also can displace
some of the less desirable omega-6 fats (like corn oil),
saturated fats or trans fat in our diet.
Trans Fats
It appears to be beneficial to decrease intake of certain types of saturated fat (animal
fat, coconut oil) and especially trans-fats (found in many types of shortening, margarine and
commercial baked goods.) Trans fats are accidentally formed by the traditional process used to
make vegetable oils into soft spreadable solids. The process is called “partial hydrogenation.”
It turns out that trans fats are particularly not healthy to eat. Trans fats in foods are
beginning to be banned in some places, such as in all New York City restaurants. Manufacturers
are developing ways to get it out of our food supply, but for now we still need to check labels.
Since 2006, trans-fats in foods
have to be listed on the food labels, but
looking for the words “partially
hydrogenated” in the ingredient list is
the best indication of whether a food
actually contains any trans fat.
This is useful because by law
amounts under 1 gram “per serving”
(like a teaspoon of margarine) can be
reported as “zero trans fat” on the label.
Their idea of what constitutes a
“serving” and those of consumers are
often quite different.
Many foods now being advertised that they are “trans free” and they actually are
because they have not used the partial-hydrogenation process to solidify them into a
spreadable texture.
Although most nutrition advice suggests limiting intake of animal fat in
general, it may be that dairy fat may be less cancer-promoting than some other
animal fats. This is possibly because it contains a special form of fat called conjugated
linoleic acid. High-fat dairy food and conjugated linoleic acid intakes were found to be
associated with a lower incidence of colorectal cancer in Swedish men and women. As
noted earlier, often the cancer risk factors associated with colon cancer and prostate
cancer in particular are very similar to those in breast cancer.
Conjugated linoleic acid is currently receiving a lot of attention as a possible
anti-cancer substance but no conclusions are available yet. As always, the factors
associated with the “dairy fat” piece, like the calcium intake piece and the vitamin D
piece, are very hard to separate in studies with humans. But it appears that all three of
these substances may contribute to decreased risk. (More on vitamin D later.)
5. Vitamin and Mineral Antioxidants
In general, generous amounts of antioxidants automatically accompany a diet rich in fruits
and vegetables. That diet pattern also has been shown to have benefits in decreasing breast cancer
risk. As discussed earlier, the antioxidant strength of the phytochemical pigments far exceeds that
of the antioxidant vitamins and minerals. However, most vitamins and minerals have many other
important roles to play in metabolism.
As discussed earlier, it appears that many dietary antioxidants work in conjunction with
each other, so studies that examine the effects of a substance in isolation are less likely to
demonstrate any effect that might potentially be present. Effects observed of vitamins C and E
and selenium are likely related in part to their antioxidant properties. A very low-fat diet may
actually provide inadequate vitamin E because the major natural food source is polyunsaturated
oil. (Saturated fats like fat in meat or milk are not very good sources of vitamin E.) Other minerals
like zinc and copper are involved in antioxidant activity as one of many important functions.
The mineral selenium has several roles in the body as an antioxidant and in the function
of energy metabolism and in the immune system. Inadequacy causes serious health problems.
Selenium inadequacy is more common in America than vitamin C or E deficiency, so it will get a
closer look here. There is a large amount of promising research into the role of assuring selenium
adequacy in several types of cancer. There is also data that suggests that assuring selenium
adequacy may help in the effectiveness of certain chemotherapy medications.
Some recommendations for decreasing cancer risk suggest aiming for at least 200 iu
vitamin E, about 500 mg vitamin C and 60 mcg selenium daily as safe and appropriate intake
levels, along with a diet rich in fruits, vegetables and whole grains. For comparison, the
RDA-type recommendations for most healthy people sets the level of vitamin E at 30 iu, vitamin C
at 90 mg and selenium at 60 mcg. Notice that the suggested levels here for vitamins E and C are
more generous than the usual recommended amount, but the selenium level is at the usually
recommended amount. This is because assuring normal adequacy of selenium is likely important
in protecting against the development of several cancers, but taking more provides no additional
benefit, and high doses can be unsafe.
The toxic level of selenium has been shown to be about 800 mcg/day over a long period of
time, and experts have suggested an upper limit of safety to be 600 mcg/day. The selenium content
of foods varies with where the food was grown, so it is hard to assess the amount in a particular
person‟s diet. However, a supplemental amount of 50-70 mcg is safe. Even if a person lives in a
“high selenium” region, that amount is unlikely to contribute significantly to toxicity problems.
The amount in supplements varies from none to about 200 mcg, so check the label. Your State
Extension Service Agent can tell you about the selenium level in the soil where you live.
Recently some confusion about the role of selenium in cancer risk was raised by a
large study called the Selenium and Vitamin E Cancer Prevention Trial [SELECT] that
involved 35,533 “healthy” men. They gave some of the men 200 mcg/day of selenium
and/or 400 iu of vitamin E and after five-seven years they found no difference in the
incidence of prostate cancer in the group given extra selenium compared with the men who
received no extra selenium (the “placebo” treatment.)
The fact that this regimen did not have an effect on the incidence of developing
cancer, however, was very likely due to the fact that none of the men in the study were ever
selenium deficient. Other research studies showing benefit from providing additional
selenium have involved correcting deficiency and assuring adequacy. In other words, if
one‟s selenium intake is fine, throwing more into the mix does not provide further
protection. But this study tells us nothing at all about whether correcting selenium
inadequacy might have decreased the incidence of developing cancer.
Besides questions about the role of antioxidants in terms of decreasing risk of
developing cancer, there is also the issue to comment on is the use of the antioxidants
vitamins E and C in minimizing certain side-effects of chemotherapy treatment or of
interfering with the effects of chemotherapy. Generally, the “benefits” have outweighed
the negatives.
One other area of emerging information about vitamin E is that some forms we
commonly use (like alpha-tocopherol) alone may be less protective against cancer and
other cell problems than some cousins of this substance, such as gamma-tocopherol, and
gamma- and delta-tocotrienols. That means new specific recommendations about various
substances of the vitamin E family are likely to be appearing soon.
Cancer preventive effects of vitamin E. Curr Pharm Biotechnol. 2012 Jan;13(1):156-64. Effect of vitamins C and E on
antioxidant status of breast-cancer patients undergoing chemotherapy. J Clin Pharm Ther. 2011 Jan 4.
Inadequacy of any nutrient can cause all kinds of problems,
so it is always wise to assure an adequate intake of all of them.
6. INTAKE OF OTHER VITAMINS AND MINERALS
The body's defenses against cancer depend on adequacy of all the tools needed by
the immune system. That is just what many vitamins and minerals are … the tools you need
to run your body. Many nutrients have been shown to be important for fighting cancer in
particular. For example, as described earlier, assuring adequacy of the mineral magnesium
has been found to reduce risk of colon cancer. Several B-vitamins are looking like they are
important as well.
For example, in one report, older women with the lowest vitamin B-12
levels were at greatest risk of breast cancer. Many people become less able to
absorb vitamin B12 from food as they age. When vitamin B12 status has been most
carefully assessed, it has been shown that about 1/3 of the elderly are actually vitamin
B12 deficient. Taking acid-blocking medications for gastro-esophageal reflux (heartburn)
can also cause this problem regardless of age. In both situations, the form of vitamin B-12
found in vitamin pills can bypass the problem and prevent deficiency.
Vitamin B-12 is also important for nerve health, and prevention of anemia and
hearing loss. There are some genetic conditions that result in vitamin B12 deficiency for
other reasons that require other methods to correct. [Please see my “Vitamin B12” paper on
MeritCare‟s website for more information about this issue.]
Adequacy of vitamin B6 and folic acid has long been found to be important
in lowering the risk of breast and/or colon cancer, especially among women who drink
alcohol regularly. Interestingly, regular alcohol use or chronic antibiotic use specifically
impairs absorption of folic acid in the intestine. A collection of genetic patterns and health
conditions also affect absorption or utilization of folates at the tissue level. That makes for a
lot of unaccounted-for variability in trying to see large over-riding patterns about intake and
breast cancer risk.
For a look at the complexity involved with trying to figure out the role of
any nutritional factor in health, cancer prevention and treatments,
lets look a bit closer just at the folic acid research:
Some studies show that inadequacy of folic acid increases risk of breast cancer.
Some suggest that high intakes might increase the rate of breast cancer.
At the same time, others are showing that generous folic acid or folate may increase
protection agains breast cancer and some other cancers. [e.g. High Intake of Folate from
Food Sources Is Associated with Reduced Risk of Esophageal Cancer in an Australian Population. J
Nutr. 2011 Feb;141(2): 274-283.]
Then there are others noting that the effects of folate in foods or folic acid as a
supplement or additive may affect people‟s risk of breast cancer differently
depending on several well-recognized genetic differences in folate metabolism, and
things like hormone status, age and status relative to menopause. An example of this
is the well-recognized MTHFR gene most commonly seen in some people of Irish
heritage … and there are quite a lot of us Irish (or part-Irish) people out there. Other
ethnic groups have also been found to have similar genetic problems with folic acid.
[This gene pattern affects one‟s ability to utilize certain food forms of folates,
and the problem is invisible without special testing. Luckily, the answer is not to
get yourself tested for possible Irish gene patterns … simply taking a standard
multivitamin will solve the problem whether you have that genetic pattern or
not. The form in the multivitamin is able to bypass the whole difficulty
with the food forms of folate.]
In nature, folic acid often works together with vitamin B12. That means that the
consistent finding of poor vitamin B12 status in many people can affect the outcome
of studies exploring folate intake in cancer prevention or treatment. However, in
most studies, the vitamin B12 status of the people being studied is not evaluated.
Food folates are also associated closely with consumption of certain vegetables and
fruits. [That‟s where the word “folate” comes from … the Latin name for “foliage.”]
So, how can we tell whether it is the folate or the other things in the food like other
nutrients, phytochemicals or even pesticides that are related to cancer risk?
Then, we know that some food forms of folate are just naturally much less available
to be absorbed than others by everyone, so it matters a lot which ones were actually
used by the people in the studies. But of course, that is generally not actually
evaluated in any of these studies.
There is also a raft of information looking at applications of folates (from foods or
supplements) in various forms as adjuncts (helpers) to make chemotherapy more
effective or to decrease certain bad side effects of the treatments. In some cases, it
has been shown to make it possible for a patient to tolerate a higher dose of
chemotherapy and to increase effectiveness of treatment. This was something my
oncologist and I utilized in my own cancer treatments over ten years ago with great
success. But these effects are very specific to the particular chemotherapy regimen,
so there is no universal one-size-fits-all recommendation in this area. I wish there
were.
Bottom line on Folic Acid / Folate and Breast Cancer: This research is much too
complicated to come up with a definitive statement that addresses all these issues.
However, with the usual caveat that the information provided here is not intended
to take the place of the advice of your heath care professional nor is it intended to
provide personal specific nutrition guidance for any particular individual, here’s
my current best guess about folic acid and breast cancer (subject to change at any
moment. ):
Eat lots of fruits and vegetables, some of which will contain absorbable folates
(along with a lot of good other stuff.) Interestingly, in some studies that
questioned a slightly increased risk of breast cancer in postmenopausal women
only, the increased risk was only related to food folate intake, but not to
supplemental folates or to total folates, and no “dose-response” was observed.
That means that there was no pattern apparent among the people in each group
related to how much folate they took in. Hmmm … that makes it kind of hard to
assume that it‟s the folate causing whatever effect they found. [Am J Clin Nutr. 2009
Feb;89(2):624-33. Folate and one-carbon metabolism nutrients from supplements and diet in relation to
breast cancer risk.]
Eat plenty of whole grains that are less “processed/refined” for many
reasons. Of the processed grains you eat, folic acid has been added in a wellabsorbed form since 1998, but that is not the reason for using more whole grains
and less refined grains. … it‟s the other good stuff in the germ of the grains.
Many studies show no effect on increased rates of various cancers since
fortification began, but since 1998 the folic acid fortification of grain products in
the US has hugely decreased birth defects and certain types of stroke. [An example of
the kind of reports out there: J Clin Pharmacol. 2010 May 10. Pediatric Cancer Rates After Universal Folic
Acid Flour Fortification in Ontario. “…These data may also provide some reassurance that universal flour
fortification does not heighten the risk of pediatric cancer.”]
Taking a multivitamin supplement that includes folic acid (e.g. 400 mcg, the
RDA) is not scary, and it can also improve intake of absorbable vitamin B12,
vitamin D and some magnesium … plus other good things. It also helps you
out if you are secretly part Irish. [Am J Clin Nutr. 2010 Apr 21. Folate and other one-
carbon metabolism-related nutrients and risk of postmenopausal breast cancer in the Cancer
Prevention Study II Nutrition Cohort. “CONCLUSIONS: Our study of predominantly supplement
users suggests that high intakes of folate averaged over 10 y do not increase breast cancer risk, but
may be protective, particularly against ER- breast cancers.”]
If you are being treated for cancer, ask your health care provider before
using any supplements. In terms of eating lots of good nutritious FOOD, I
am willing to bet that he/she will think that is a fine idea.
Vitamin D
Vitamin D adequacy is known to reduce the risk of breast cancer, colon cancer,
prostate cancer, pancreatic cancer and more recently lung cancer, cervical cancer, stomach
cancer, and ovarian cancer. New research is published very regularly now associating vitamin D
adequacy with lower risk of cancer in yet another body part. It is now quite reasonable (and very
important) to urge people to assure adequacy and not to simply assume it. This strategy is not
scary … what is scary about “assuring adequacy?” What is scary is inadequacy!
The World Health Organization estimates that 40-50% of the world‟s population is vitamin
D deficient (based on results of many studies in which vitamin D status is actually assessed.)
Traditionally, it rarely has been evaluated. Leading medical journals have described the situation
as an unrecognized epidemic of deficiency in the north especially but truly an epidemic / pandemic
all over the world because of variable sun exposure due to clothing, skin color, sun screen use, fear
of melanoma and the lure of air conditioning. Factors like aging skin also result in significantly
reduced production of vitamin D even with generous sun exposure.
Some people are covered up always because of modesty or religious beliefs, some because
they live in the desert and only long robes will protect from the heat. I am just covered up as a
public service.  The point is … lots of people are now known to be deficient regardless of where
they live because now we are beginning to actually check. Vitamin D is the number one assay
requested in America at present, but most people are still not having their deficiency recognized
and corrected. The consequences are severe in terms of a multitude of health problems, including
cancer, heart disease, osteoporosis, diabetes, MS and a variety of autoimmune diseases, falls,
frailty and depression. Nobody needs vitamin D deficiency but lots of folks have it.
Vitamin D has also been shown to be helpful as an adjunct to chemotherapy. In its role as
an “antiproliferative” agent, vitamin D helps to control inappropriate cell growth and it makes
some treatments work better. Additionally, it has been shown to be a factor in managing the side
effects of discomfort, pain and weakness associated with various chemotherapy treatments.
For example, a recent study was reported of women taking an aromatase inhibitor as
part of their breast cancer treatment. They were asked to rate the discomfort/pain they were
experiencing. Afterward, vitamin D levels were checked and those who had described the most
pain were found to be the ones who also had the lowest vitamin D levels. Low vitamin D levels
were then corrected in the deficient women and when they rated their pain again they described it
as much less severe. At the time of the study, neither the women nor the researchers were aware of
any particular woman‟s vitamin D level, her reported pain level, nor whether a vitamin D
correction was made.
In most cases, assuring adequacy has been found to require an intake significantly higher
than the RDA level, which was long ago set at 400 iu daily. Most recent research is showing that
the maintenance (not therapeutic) intake level for many people is 2000-5000 iu/day. This is a level
that is impossible to get just from food. Supplementation is required to provide that much.
Luckily, vitamin D supplements in that range (1000-5000 iu/day) are safe, inexpensive,
easily available, tiny and easy to swallow. The treatment dose to correct deficiency varies but it is
often 50,000 iu vitamin D per week for eight weeks. [Note that that amount is PER WEEK – NOT
PER DAY.]
Many oncologists will check a person‟s vitamin D level at the beginning of treatment to
determine whether a corrective dose of vitamin D is needed or if just a maintenance level of
2000 iu or so will keep them in the optimal range of around 40-50 mg/dL. The earlier level of
25 mg/dLthat was thought to be “normal” is now recognized as not being an adequateblood level to
promote optimal health. Around the country, some laboratory print-outs still have the old “25”
level shown as normal, so it is a good idea to ask what the actual number is and not just rely on a
report of “normal.”
Vitamin K
As always, assuring adequacy of all essential nutrients supports our ability to prevent
or fight cancer. We learn more about this every day. For example, recent research found that
vitamin K inadequacy increased risk of colon cancer and liver cancer, along with many other
serious health problems like heart disease, osteoporosis and kidney problems. It was also found
that, as has been the case with vitamin D, we very rarely check it and just assume that it is fine.
However, it has now been shown that inadequacy of vitamin K is fairly common. It is also
easy, cheap and safe to fix.
The best food sources are dark green leafy vegetables. Interestingly, no upper level of
safety has ever been established for vitamin K because overdose has never been seen. I know this
is a big relief to all you fans of the dark-leafy-green veggies out there. Nobody has ever overdosed
on spinach!
[Only people taking a particular medication called Coumadin need to be sure to eat a
consistent amount of vitamin K daily to regulate the effectiveness of the drug. Nobody benefits
from vitamin K deficiency … including people on this medication. Vitamin K inadequacy
actually makes the drug more dangerous to use. If you use this medication please see my separate
handout on line about vitamin K before making any changes to your vitamin K intake. Your health
care provider will want to see the new research on this before making any changes.]
At this time, many multivitamins do not even contain vitamin K --- until recently no
one knew it was a problem! This omission is in the slow process of being fixed, but one can take
vitamin K separately if there is a reason why those terrific leafy green vegetables are not an option.
The details about vitamin D and vitamin K (lots of „em!) are in my “Top Five
Recommendations” handout and in the separate “Vitamin K” handout, which (like all the others)
you can get for free by Googling “Cathy Breedon Handouts” or typing my name in the search box
at www.sanfordhealth.org. Please feel free to share any of my papers you find there with others.
Health care providers can also contact me for a special paper addressing the specific issues of
vitamin K nutrition for patients using the drug Coumadin.
7. WHAT ABOUT OTHER PHYTOCHEMICALS?
Besides all the phytochemical research with the pigment antioxidants and soy
products described earlier, there is a great deal of interest in literally thousands of other
plant substances in the prevention and treatment of cancer of all types. Some of these
substances have anti-cancer properties, and some appear to be able to minimize side
effects of chemotherapy or help it work better. On the other hand, some are not safe to
take in amounts beyond what one would get from eating the plants that contain them
for dinner. And some are not safe at all … remember poison ivy and cocaine? Actually,
most of our current pharmaceutical products are derived from phytochemicals.
Most of this kind of phytochemical research is just in the discovery and
initial confirmation phase, where many current well-established medications once
started out. Most of these substances have not yet been studied in the large carefully
controlled clinical trials needed to show that they are both effective and safe, even though
they may be described as having been used somewhere in the world for some purpose for
many years. Some have only been shown to be potentially useful in test tubes and labs
and they have not yet been tested in animals or people. Some have turned out to help with
cancer but cause some other type of serious problem. An example of the opposite
problem is the use of chaparral tea, a beverage traditionally used as a relaxing agent. It is
now banned because it was discovered to also be a potent cause of liver cancer. [Herbal
interactions with anticancer drugs: mechanistic and clinical considerations. Curr Med Chem.
2010;17(16):1635-78]
So it is much too premature to recommend that people should seek to take in
abnormally high amounts of these plant substances in an effort to prevent or treat cancer.
When we isolate and concentrate a plant chemical because it has some particular
chemical activity, we move out of the world of nutrition and into the world of
pharmacy. In other words, a much better description of the use of concentrated herbal
substances would be “herbal pharmacy” and not “herbal nutrition.”
The reason that the terms “herbal nutrition” or “food supplement” are used is not
because the substance is actually a nutrient or a food. It is because there is a loop-hole in
the FDA‟s laws governing the sale of drugs. The law does not require safety testing or
even testing to show effectiveness of a product if the manufacturer simply labels it as a
food or nutritional supplement. If the same substance were marketed as a pharmaceutical
product or drug, such (expensive and time-consuming) testing would be required. In other
words, we are essentially not at all protected from scams nor from harm when we use
these products.
Although this labeling seems confusing, usually one can quickly tell the difference
between what is an actual nutrition function and what is truly a pharmacy function. Just
ask yourself whether the substance under discussion is being taken in a concentrated
amount to cause some chemical effect on body functions, or if it is just your dinner. An
example is shown below:
Sorting it out: Is it a food/nutrient or is it a pharmaceutical product?
Some examples:
Food
Slice of cinnamon toast
Pharmacy
1000 mg powdered cinnamon in a capsule
Piece of licorice candy
1000 mg of the isolated plant flavonoid
“isoliquiritigenin” found in licorice.
Bowl of vegetable curry
flavored with the common
curry spice tumeric
1000 mg isolated curcumin, a phytochemical
found in the common curry
spice turmeric.
There are WAY too many reports of this type to cite here, and the whole herbal
pharmacy issue is outside of my area of expertise … I only know about nutrition. But
interested health care professionals … or anyone at all … can find them easily on line at
www.pubmed.gov (Free Public Medline from the National Library of Medicine,
National Institute of Health.) Just type the words cancer and herb in the search box …
or you can limit your search by specifying a particular substance … like the spice
curcumin … or a particular form of cancer … like breast cancer. This is also how I keep
up with the nutrition and cancer research. (Ain‟t technology wonderful?!)
However, it is encouraging to note that there are so many potentially helpful
substances waiting to be discovered and developed in a wide variety of plant foods. And
while we wait for the definitive research on concentrated plant chemicals in the battle
against cancer, it is certainly reasonable to eat lots of fruits, vegetables and whole grains,
and to cook with a variety of commonly used interesting spices that appear to have health
benefits.
8. “Conditionally Essential” Nutrients
Conditionally essential means that usually one makes enough of a necessary
substance, but sometimes we can‟t make enough of it. When that happens, that nutrient
becomes “essential” to take in from outside the body, just like well-recognized essential
vitamins and minerals. Three of these substances of interest in breast cancer are CoQ10,
alpha-lipoic acid and carnitine.
Coenzyme Q (CoQ10 – also called ubiquinone) and alpha lipoic acid (also
called thioctic acid) are both potent antioxidant substances that one can normally make
enough of, but in certain medical conditions patients benefit from being provided with a
supplemental amount. They are “conditionally essential.” Both are very safe, but as
supplements they can be pricey. Some applications of alpha lipoic acid (e.g. in diabetic
neuropathy) showed benefit when the dosage was 600 mg/day or more.
In the cancer applications, both substances look to be helpful in helping people
physically cope with side effects of chemotherapy and other treatments for cancer that
can result in neuropathy and heart damage. They both have several other roles in normal
metabolism, especially in energy production.
Carnitine is a tiny molecule normally made in the liver, kidney and brain. It is important
for making energy for muscles to work, and that includes the heart muscle. Carnitine also
has a role as an antioxidant. Some people are normally less able to make carnitine as well
as others can. Some medications and treatments also result in inadequate production of
carnitine. This results in considerable fatigue and even heart damage. Some “cancer
fatigue” studies have shown benefit from 4000 mg carnitine daily.
There is evidence that some people fighting cancer may benefit significantly from
receiving supplemental carnitine, CoQ10 and alpha-lipoic acid with their cancer treatments.
All three are very safe and they are available over the counter and also by prescription.
Prescriptions are more likely to be covered by insurance. The only apparent down side is the
cost. As always, be sure to discuss the use of any of these substances with your health care
provider. I have a paper just on carnitine on Sanford‟s website because it has many other
important health applications. Additionally, all three of these supplements are discussed in
more detail in my paper on nutrition for people with diabetes which is also on the website.
9. Miscellaneous
There is plenty of evidence that exercising, not smoking, maintaining a healthy
weight and breast-feeding one‟s infants are also players on the team to decrease the risk of
breast cancer. I‟m going to go out on a limb here and advocate that we all try to do these
things too. 
Also, remember to laugh a lot.
I think finding something to laugh about went a long way toward helping me cope with
cancer and its treatment. In fact, as the memories of the tough times recede, it‟s the funny
stuff that hangs around … like shaving my head with duct tape after chemotherapy, or
having a contest at work to help me find the right look when picking out a wig
Here‟s the picture that won by a landslide: it‟s
my husband Dan and I wearing the 1970s
“Sonny and Cher” look. What do you think?
I have other great memories from my
experience of having a stem-cell transplant to
treat my breast cancer. While I sure don‟t
want to go through all that again, there are
terrific memories that I will always treasure
from that period.
For example: The high dose chemotherapy
made it extremely hard to eat anything at all. I
stayed in a “medical apartment” beside the
hospital for about 6 weeks. My mother moved
in with me there and took care of me … sort
of like 1950 all over again!
I couldn‟t eat much at all, so she made all kinds of things that I was able to eat at least a
little of and every day took me to the hospital for an IV. We got to spend a lot of “quality
time” together in spite of the whole cancer business and I think it has helped us maintain the
special bond we have.
Another example: Every day my husband called me and he drove for hours every weekend
to stay with me. This was all while he was working full time and had additional
responsibilities at work that year. That was terrific. Also, during that time I was a puffy, red
and wrinkly bald girl, so as a result of that experience I have great confidence in the idea
that he did not just marry me for my looks. [Actually, it was always pretty unlikely that he
married me for my looks, but it‟s still very comforting to have proof. ]
Don’t let worries about nutrition suck the joy out of life.
At our house we have battled cancer, and we eat lots of wonderfully healthy foods
and dutifully take our appropriate nutrition supplements. But my husband and I also like
having a regular ten-o‟clock date in the kitchen with the local news on TV and a some
brownies or some other treat. And anyway … most of the time my brownies:
Have lots of walnuts (baby plants!)
Are made with olive oil (monounsaturated fat!)
And they usually even have some of those “stealth vegetables” in there
(like powdered spinach or kale … sounds icky but it isn‟t.)
That means that these brownies may actually be “health foods” … kind of like
chocolate-covered peanuts. Consider the terrific nutrient density … the ratio of good-foryou stuff to calories. They just happen to taste good and to impart a certain party
atmosphere to the end of the day! But even if a food has very minimal nutrition value,
whatever you choose to enjoy and share with family and friends can be a “health food” …
especially for mental health. Bon appetite!
10. Quick Summary: My Best Guesses for Breast Cancer Risk Reduction:
Eat lots and lots of fruits, vegetables and “baby plants” and aim for most of your overall diet to
be “plant-based,” with less meat than Americans usually eat.
If you do eat cured meats or grilled meats, be sure to eat lots of fruits or vegetables with them,
and avoid charring the outside … or the inside, for that matter.
Take a standard multivitamin with minerals for many reasons. I use a store brand – it does
NOT have to be expensive. Take it whenever it is convenient for you; I have a bad memory
(from a gigantic dose of chemotherapy that saved my life) so I know I won‟t remember to take
things through the day. So, I just take everything in the morning and let it fight it out in there!
It doesn‟t have to be perfect. [I have a magnet on my fridge that says: “Happiness is good
health and a bad memory!” … I‟ve got both so that makes me pretty darned happy.
Have your vitamin D level checked. Lot‟s of folks are deficient and completely unaware of the
problem. If your level OK simply take a daily 2000 iu vitamin D capsule to maintain a good level.
If your level is found to be deficient, (your doctor can help you correct it with a temporary
higher "treatment" dosage followd by 2000-5000 iu capsule daily vitamin D maintainance amount.
Check to see if your multivitamin contains vitamin K if you do not regularly eat a good amount
of dark leafy greens. If you usually don‟t eat those dark leafy greens, either switch to a
multivitamin with about 100 mcg of vitamin K, or add a separate vitamin K supplement.
It is a good idea for your multivitamin or some combination of supplements to provide 50-60
mcg of selenium (the advisable intake.) Vitamins C and E can be taken at the advisable intake
of 90 mg C and 30 iu of E, but in general they can be safely taken at 5-10 times that amount.
Remember, the usual amount recommended (as RDAs or RDIs or AIs or whatever is used
currently) is set at a level that is assumed to “meet the needs of most healthy people.” People
with cancer or any other serious condition are simply not members of that group. Their actual
requirements can be far different from the needs of “healthy” people. Additionally, look for
emerging research on some vitamin E products that contain some of the “cousins” of alphatocopherol, such as gamma-tocopherol and gamma- and delta-tocotrienols.
Increase your ratio of omega-3 to omega-6 fats by replacing omega-6 fats (e.g. corn oil) with
monounsaturated oils (olive and peanut). Eat some flax seed or use flax oil if you like it. Take
at least one 1000 mg fish oil capsule daily (one that says EPA and DHA) if you do not eat fatty
fish like salmon or mackerel at least twice a week. Take the fish oil even if you also east flax
… there are some big differences that makes it reasonable to do both, (And, no, deep-fried
breaded fish does not count … wrong kind of “fatty” fish! Darn!).
If you do not eat much in the way of baby plants, consider both a magnesium and chromium
supplement to provide the amount recommended for most folks, and be sure you are getting a
good amount of dietary fiber in some form (from foods or fiber supplements.) If you do eat a
good amount of baby plants fairly often, the amount of magnesium and chromium in a standard
multivitamin with minerals may be enough. That is because most have about 10-25% of the
recommended amount of magnesium. If you don‟t eat the baby plants, though, you would
benefit a separate product that provides additional amounts to reach the desirable range..
Enjoy every day, every friendship, and every meal!
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
Calcium Odds and Ends:
Food sources, supplements,
and some factors that affect how
well it is absorbed and utilized.
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist & Perinatal/Pediatric
Nutrition Specialist
Sanford Medical Center, Fargo, ND
and UND School of Medicine
A table of the amount of calcium in various foods is provided on page 7. The focus of the
following pages is the use of calcium supplements. If supplemental calcium is needed to get the right
amount (a goal may be as high as 1000-1500 mg/day, depending on age and health factors,) the
following information will help you pick a product to use.
Most general vitamin/mineral tablets contain very little calcium (usually less than 250 mg,)
so if you need to rely on supple-ments, you will probably need to use an additional calcium
supplement. There are many calcium supplements on the market. A physician or Registered
Dietitian (RD) can help you pick the right kind and the amount to use. Here is an overview of the
issues to consider:
Absorption:
Form:
Not all supplements are equally well absorbed into the body, and if they are poorly
absorbed the calcium cannot be used. As a rule, chewable or liquid products are well
absorbed, as is the calcium citrate that is added to some brands of orange juice. Absorption from
tablets is variable. You can test the absorbability of a product by placing the tablet in some
vinegar. If it has not dissolved in a half hour or so, it is unlikely to be well absorbed in the
intestines. However, a more important factor than the form of calcium in calcium absorption
is adequacy of vitamin D, which will be described later.
Timing:
Generally, taking smaller doses of calcium supplements several times a day results in
better absorption than taking just one great big dose daily. For example, taking one calcium
carbonate antacid tablet per meal (200 mg each X 3 meals) would result in better absorption
than taking a tablet that provided all 600 mg at once. However, if unable, unwilling or unlikely
to take a supplement more than once a day, the higher calcium product would be a better choice.
1
For most calcium supplements, absorption is best when taken with a meal, except with
very high fiber foods such as bran cereal. Ideally, they should also be taken at a different time
from other mineral supplements, because some compete for absorption. For example, if taking
iron supplements or a multi-vitamin/mineral supplement at one meal, take the calcium
supplement with a different meal for best absorption.
However, although this kind of recommendation is often heard, the absorption
differences they are describing are aimed at achieving “ideal absorption” of a supplement. In
reality, this issue is much less of a real problem than not taking a supplement if you need one.
For example, if one product claims that it is 5% better absorbed than another, it is only important if
those people‟s needs are not met and they were truly relying on that 10 mg of calcium to save their
lives or bones. One could always just take a little more from food or pill sources to account for the
slight difference in absorption.
Remember that the ads you see recommending particular products are designed to convince
you that one product is clearly much better than another. It is about market share and not necessarily
about science. In one of the ads a lady tells us that “My doctor said only this product can be taken
with or without food” with the implication that one can barely squeeze any calcium out of food and
supplements with any other brand. As noted above, in general this kind of small mathematical
difference in absorption is not very important unless you are living on the edge with no options.
Here‟s a question: Who the heck is HER doctor and why should we do what she says that he
said? The implication is that this one anonymous doctor has the inside track on these issues. Do
physician specialist organizations recommend that particular calcium product (calcium citrate) over
others based on research demonstrating great absorption differences between the products? Well, no.
And if that kind of claim COULD be made, you can be sure that it would be shouted to the rafters if
the manufacturer had that kind of backing for their claims. Instead we are urged to rely on hearsay
that some lady‟s doctor told her.
By the way … there is nothing at all wrong with that product. The calcium in calcium citrate
is at least as well absorbed than other calcium forms … and better than some to a small degree. I
recommend it for people who experience some constipation problems with calcium carbonate. For
those that have this problem, calcium citrate can be a better choice. However, in general calcium
citrate is also a bit more expensive.
Similarly, a competing company says that “more doctors have recommended our product than
any other!” That is absolutely true, but primarily because until about 10 years ago their calcium
carbonate product was the only one on the market. If you were to count up all the doctors, living and
dead, who ever made a calcium supplement recommendation over the last century, I am very sure
that it would add up to more doctors recommending calcium carbonate (specifically calcium
carbonate from oyster shells) than the number of doctors recommending other products which have
only been available for a relatively short time. So, it‟s a true statement, but not a good reason to pick
a particular supplement product.
2
If worrying about when and how to take a supplement gets in your way of actually taking it, it
is clearly best to just take it when it is convenient or likely to be remembered at all.
Personally, I simply do not remember to take things throughout the day. So, I follow Mark Twain‟s
advice and just take everything all at once in the morning and then let „em fight it out in there! It‟s
WAY better than not taking them at all just because you can‟t take them perfectly.
The Biggest Factor in Calcium Absorption: Vitamin D Adequacy
As mentioned earlier, by far the biggest factor in whether calcium in any form is
absorbed is the adequacy of a person’s vitamin D status as measured by the amount of 25hydroxy vitamin D circulating in their blood. If the level of vitamin D in one’s blood is at least
30 mg/dL all these tiny form-of-calcium absorption differences simply go away. Note that 30 mg/dL
is the bottom edge of normal and not really one‟s target goal. Levels in the 40s and 50s are clearly
safe and achieving levels in that range appear to be some additional benefit in a variety of health
conditions.
Also, note that it is not whether or not the vitamin D is IN the calcium product that
matters, but whether the amount in one’s blood is adequate. The vitamin D in the pill does not
affect absorption of the calcium it contains … it is the vitamin D already circulating around in the
blood (from what was taken in earlier) that can be activated to enhance calcium absorption in the
intestine.
That means that calcium supplements can have vitamin D in them, or one can take a
supplement without vitamin D and just be sure to take whatever amount is needed from a separate
capsule. Tiny vitamin D capsules containing 2000 to 5000 iu are readily available over the counter
and they are safe and inexpensive. Most combination products contain only 400-800 iu of vitamin
D, which is insufficient for many people to maintain vitamin D blood levels at or above 30.
How much may be needed depends on what one‟s blood vitamin D level is. Checking the
blood level is really the only way to be sure vitamin D is adequate. Inadequacy is very common and
very harmful but often unrecognized because it does not make you look funny, so no one sees the
problem. However, the World Health Organization (WHO) estimates that about 50% of the
world’s population obtains inadequate vitamin D, and this has health consequences far beyond
the calcium absorption/ bone issues.
3
Safety of Calcium Supplements:
Certain products are still being sold that are not recommended because they have lead or
other undesirable and dangerous substances in them. Examples are bone meal and dolomite
calcium supplements; these are not recommended, especially for children or during pregnancy.
There is also some concern as well about calcium from any "natural" source (such as oyster
shell) because pollutants in the environment might be incorporated into the shell. For this
reason, it may be safest to use purified forms of calcium carbonate, calcium citrate, etc.
While some surveys of selected "natural" calcium supplements have not detected a
problem level of lead or other heavy metals in the samples tested, other studies have shown that
there is cause for concern. And as described above, some makers of oyster shell calcium
supplements suggest that these products are known to be safe because they have been “used in more
studies” or “recommended by more physicians.”
Again, it sounds impressive until you realize that until quite recently they were the only
products on the market! These statements do not address the safety issues, or even absorbability
issues. Until the safety issue is fully resolved, it would be safest to use purified forms instead of
oyster shell, bone meal or dolomite calcium products.
Cost:
There is a great difference in cost among the various supplements. Some products are
quite expensive but not appreciably better than less costly products. Some products require a
person to take many tablets a day to obtain the right amount of calcium. If the number of
tablets needed to provide the prescribed amount of calcium is great, the likelihood is higher that a
person would be unable or unwilling to take the prescribed amount.
It is helpful to evaluate cost per day's supply rather than as cost per tablet. If you have to
take four times as many tablets per day to get the prescribed amount of calcium, a product may
not be a bargain even if the cost per 100 tablets is less.
Generally, "calcium gluconate" and "calcium lactate" require a person to take many more
tablets to get the same amount of calcium as "calcium carbonate", "calcium phosphate" or "calcium
citrate" tablets. They are very good supplements … they are just pricey and they require taking a lot
more pills. Often a generic or store brand will be substantially cheaper than a "brand name"
product.
4
Other Nutrition Interactions with Calcium Supplements:
Magnesium
Magnesium is critical for formation of flexible, less brittle bone, and there are safety
concerns (such as a possible increased risk of stroke) when a person takes a large amount of
supplemental calcium if magnesium is not adequate. Magnesium in the supplement does not
interfere with calcium absorption, so it will often be found in combination supplements.
The RDA levels provide a ratio of about 4-to-1 (4 mg calcium to 1 mg magnesium.)
Maintaining that ratio if/when higher calcium amounts are supplemented seems to be a
reasonable adjustment. The Center for Disease Control has reported that magnesium is often found
to be inadequate in the diets of the majority of Americans.
As magnesium is critical for over 300 functions in the body, there are many good
reasons to assure adequacy. Inadequacy is associated with problems like leg cramps,
insulin resistance (Type 2 Diabetes), high blood pressure and more brittle bones.
Magnesium inadequacy is often unrecognized because blood tests of magnesium levels
reflect kidney function and generally they do not reflect intake adequacy. Additionally, health
care professionals rarely try to evaluate the likelihood that a person’s magnesium intake might be
poor because many of us were not taught that it was a problem nutrient. Well, it IS.
Happily, it is very easy to identify the very best sources of dietary magnesium. It is
in very few foods except for the parts of plants that will turn into a baby plant: nuts and
peanuts, seeds, the germ of grains, nuts, and legumes (dried beans, peas, and lentils.) This
simple rule of thumb makes it easy to ask a few questions and get the picture:
Question: “Do you eat nuts and peanuts very often? How about whole grains and chili beans
or soy beans or baked beans or refried beans?”
Answer 1: “Oh, I LOVE those foods and eat a lot of them!”
Interpretation: magnesium intake is likely just fine.
Answer 2: “Well, nuts and peanuts are high in fat and I am watching my calories. Beans all
give me gas so I rarely eat them. I only like white bread and enriched pasta”.
Interpretation: magnesium intake is quite UNlikely to be just fine.
For the person with a “likely-to-be-not-so-hot” magnesium intake from food, it is very
reasonable to provide a magnesium supplement either in combination with a calcium supplement
or separately. They do not need to be taken together. Most multivitamins have only 10-25% of
the RDA for magnesium … and often none … so check the label.
(See “Aunt Cathy’s Guide to Nutrition: Magnesium” for more information.)
5
Vitamin K
Adequacy of vitamin K is needed for activating a hormone (calcitonin, now called
osteocalcin) that is important for moving the calcium into the bones. Without it, all the work
to obtain and absorb calcium for bone-building is wasted and the calcium you worked so hard to
absorb will just be excreted in the urine or deposited in the kidneys and arteries. Not good. There
is a diagram of this interaction of calcium, and vitamins D and K in bone-making on the last page.
There is often misunderstanding about taking vitamin K in foods or supplements for
people taking a medication to decrease blood clotting to help prevent strokes. The medication is
called Coumadin or warfarin. When taking this medication, it is very important to take in a
consistent amount of vitamin K everyday, but it is very harmful to bone health if a person is
deficient in vitamin K. Many people actually obtain far too little vitamin K when using the
medication and it can be very harmful. Check with your physician to assure that everything is in
balance.
Also note that OTHER medications to prevent blood clots do not operate by interacting with
vitamin K, so there is no reason to try to maintain a very consistent vitamin K intake. It is also
interesting to note that a food and nutrition supplement plan that assures a consistent and adequate
vitamin K intake can be matched by your physician.
Vitamin K inadequacy benefits no one, and it is responsible for the relationship found
between Coumadin/warfarin use and higher incidence of osteoporosis. It turned out that it
wasn‟t the drug that caused the bone problems – it was the vitamin K deficient diet that caused the
problem. Vitamin K is highest in dark green leafy vegetables. So, a diet low in vitamin K would
also be low in lutein. Lutein is a pigment (color) that is a potent antioxidant in leafy greens with a
role in (among other things) protecting against blindness due to macular degeneration.
Some vitamin K can be produced by bacteria in the intestine. However, recent research
has shown that it is not well utilized, and so we are much more dependent on taking in
vitamin K from diet or supplements than was previously believed. The standard assumption
was that about half of the vitamin K people require was provided by intestinal bacteria, and intake
recommendations from foods was set with that idea in mind.. As a result, the current official
recommendations appear to be set too low to support optimal health..
As a result, vitamin K intake is often quite low and its inadequacy is rarely
recognized. It is rarely tested or even asked about, and the most common way health professionals
try to assess vitamin K adequacy by checking the time it takes for blood to clot in people using
anticoagulants. However, impaired ability to clot blood is a very LATE-APPEARING
symptom of vitamin K inadequacy. Other important vitamin-k-dependent functions are
impaired long before changes in blood-clotting rate are seen.
6
Several new discoveries about vitamin K have changed
our understanding of it a lot in the past few years.
Here are five:
1. For anyone NOT on Couadin/warferin (that is, MOST people) vitamin K is
extremely safe. There is not even an upper intake of safety established for this vitamin
because no one has EVER overdosed on it, either from food or supplements. Most of us were
taught that it is potentially toxic because it dissolved in fat. Wrong.
2. Vitamin K produced by bacteria in our intestines was thought to contribute about half of what
we need. The only people thought to be at risk of vitamin K inadequacy were those taking
chronic antibiotics, because those drugs also kill the “friendly” vitamin-K-making bugs.
However, it has now been found that the bugs do produce it, but we do not get much of it.
As a result, we are all more reliant on an outside source of vitamin K than
we thought.
3. Many vitamin supplements contain no vitamin K at all because of assumptions
that people‟s intakes were adequate because of the contribution of the bacteria.
4. The recommendations (like the RDA) have recently been found to be
insufficient to assure adequacy in people‟s blood because they were set based on the
assumption that we also got a lot from intestinal bacteria, which it turns out we don‟t.
5. People using Coumadin/warfarin are at high risk of vitamin K deficiency
because of misunderstandings on the part of both patients and health
professionals about vitamin K safety issues. Vitamin K inadequacy and
inconsistency actually makes the use of this medication MORE dangerous
to use because of increased volatility of blood clotting, and increased
calcification of blood vessels.
For more information on the role of vitamin K in calcium metabolism, including prevention
of osteoporosis, kidney damage and artery damage leading to cardiovascular disease, please see my
other handouts: “Vitamin K --New Issues in Cardiovascular Health, Renal Health, Osteoporosis,
Liver & Colon Cancer, Diabetes, Pregnancy & Varicose Veins” and one for health care
professionals about the issues with one of the common anti-clotting medications: “Vitamin K -Focus on the Vitamin K and Warfarin/Coumadin Anticoagulant Drugs Issues”
7
Weight-Bearing Activity
Our bones are always breaking themselves down and rebuilding themselves. This is
called remodeling. The breaking-down activity goes on 24 hours a day. However, the bone
building activity has to be stimulated by weight-bearing activity.
Weight-bearing activity includes activities like walking, running, dancing, playing ball,
doing weight training, and other activities. Inactivity decreases our weight bearing activity, and so
it allows the bone breakdown to occur faster than bones can be rebuilt. That is why being
“sedentary” --- sitting or lying down much of the time --- can be so bad for bone health.
Being in bed a lot due to illness, or working in a “sit-down” job both can contribute to
serious bone loss, but we often have little choice in these matters. However, finding ways to
add in weight-bearing activity can really add up for bone health…like taking the stairs, parking
farther away from work, and taking walks during breaks. Even if one is in a wheelchair or in bed
much of the time, occupational and physical therapists can help design some safe activities,
which may involve adaptive weight training or exercise.
Some forms of exercise, like swimming or water aerobics, are less “weight-bearing”
because the water does some of the work of holding you up. So they are less helpful in terms of
bone building, but they are still excellent forms of exercise for other health benefits. For
example, they can be very helpful if a person has joint pain … having the water support one’s
weight can make exercise even possible for some people.
The “builder” cells of bone are called osteoblasts and the “crushers” of bone are called
osteoclasts. Some anti-osteoporosis medications work by holding the activity of the crushers down,
with the idea that the builders could catch up. To optimize this and enhance the safety of the drugs,
it is still extremely important to do weight-bearing exercise (to to wake up the builders and get them
going) and to assure adequacy of all the nutrients needed to make bones.
Illustrations and a table:
I drew some cartoons on this topic for a study guide for a nutrition textbook in 1990. In
those days there were no computer-generated art options available. Typing was done on the first
Mac computer available to the public. The pictures on the next page I actually had to draw by hand
and paste them (with glue!) on the page. The drawings were intended to illustrate some concepts
about calcium metabolism, and although they may qualify as ancient art, they are still pertinemt.
After that page there is a table of the calcium content of food from the Department of
Agriculture, to which I added a few comments added. (I can’t help it!) On the last page I made a
diagram to help sort out some newly recognized interactions of calcium, vitamin D and vitamin K in
bone metabolism.
I always learn better with cartoons … if they don’t help you … hey! … Don’t look at them! 
8
Sanford Medical Center
After All These Years, It All Keeps Coming
Back to These Two Ideas.
Aunt Cathy’s Guide to Nutrition:
Two Really Good
Rules-of-Thumb about
Absolutely Everything to
Do with Nutrition
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center, Fargo, ND
and UND School of Medicine
1. “We need everything to do everything.”
Missing any key component interferes with the whole process … which is why (in this case)
just “taking calcium” is unlikely to be as effective as it might be if there is an absence of
adequate vitamin K, vitamin D and weight-bearing exercise.
Without all these factors in place, calcium consumed simply does not go where you want it
to go. Besides not helping your bones, a lot of other damage can result.
2. “Assure nutrient adequacy
instead of just Assuming it.”
I always assume that anyone could easily have some nutrition problem that has been
shown to be quite common, generally not visible, potentially very important to health (see
#1 above), and I further assume that there is likely something to be done to safely,
inexpensively and easily help to correct it.
This does not solve all their problems, but it does give them a level playing field to achieve
a health goal, and it also makes the ministrations of other health providers just a bit more
likely to be effective. It is totally “win-win.”
This does not usually require labs, but it does require knowing and asking the right
questions. Finding time to ask anything is difficult, but there are many ways to streamline
the process and to do some significant good. As I hope this paper illustrates, failing to
assure adequacy will make us much more likely to fail to avoid and/or solve serious and
expensive health problems.
…
9
10
Food Sources of Calcium
Dairy
Serving Size
mg
Mustard greens (cooked) **
Onions (cooked)
Parsnips (cooked)
Raisins
Rhubarb (cooked)
Spinach (cooked) **
Squash, summer or winter
Turnip greens (cooked) **
Calcium-fortified orange juice*
(Dairy calcium is a well-absorbed form in general, but
like all sources of calcium, vitamin D adequacy is
necessary for it to be truly well-absorbed. The foods
fortified with vitamin D are marked with a star*, and an
explanatory note follows at the end.)
American cheese, processed
Blue cheese
Cheddar cheese
Cottage cheese
Cream cheese
Ice cream
Milk* (whole, 2%, fat-free/
skim, and chocolate )
Calcium/Protein fortified milk*
Parmesan cheese
Swiss cheese
Yogurt (very few products*)
1 oz
1 oz
1 oz
1/2 cup
1 oz
1 cup
175
150
200
80
25
175
3 oz
1/2 cup
3 oz
3 oz
3 oz
Nuts, Dry Beans and Seeds
Almonds
Beans (cooked)
Brazil nuts
Hazelnuts
Sesame seeds (whole dried)
Soybeans, roasted “nuts”
1/2 cup
150
1/2 cup 45-100
1 oz
50
1/2 cup
120
1 Tblsp
90
1/2 cup 120-230
*
For many years, only milk has been fortified with
vitamin D . . . it was not added to cheese, yogurt, ice
cream or other dairy foods. In milk the amount
supplemented is 100 iu vitamin D per cup. Therefore, the
recommended 2-3 dairy servings from suggested eating
patterns such as the Food Guide Pyramid would provide
no vitamin D unless the only food chosen was milk with
vitamin D added, and then it would be too little.
Re: Vitamin D in food.
Recently, SOME other dairy products are being
fortified with vitamin D. But this is not yet commonly
done for all dairy foods, so remember to look closely at
your total vitamin D intake. The amount provided in a
typical multivitamin is 400 iu, and the amount in 1 cup of
fortified milk or yogurt is usually about 100 iu. Although
officially 400 iu is still the RDA amount, there is a huge
amount of research and professional opinion from vitamin
D researchers that this is simply too low to assure a
healthy blood level for a very large number of people.
Most recommendations now are for a daily intake of at
least 2000 iu, with certain groups and individuals
needing significantly more (e.g. 2000-5000 iu/day).
60
110
165
370
100
---------------------------------------------------Fruits and Vegetables Serving Size mg
This is the result of checking people‟s vitamin D
blood levels instead of simply assuming that they are fine.
It suggests that a separate vitamin D capsule is a very
good idea. After all, 2000 iu would be achieved by
drinking 20 cups of fortified milk daily. That is a very
unrealistic approach to assuring vitamin D adequacy. The
only naturally good food sources are salmon (3 oz = 340
iu) tuna (3 oz = 150 iu) and shrimp (3 oz = 127 iu.) Next
highest is 3 oz of liver with 42 iu and an egg yolk has 27
iu.
(calcium absorption is mixed; oxalates decrease the
absorption of double-starred ** items.)
Apricots, dried
Asparagus
Beans, green **
Beet greens (cooked)
Broccoli
Cabbage (cooked)
Cabbage, bok choy (cooked)
Carrots
Celery
Collard greens, (cooked) **
Dates
Kale (cooked)
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
95
25
35
25
100
85
55
125
150
-------------------------------------------------------
1 cup
300
500
1 cup
1 oz
390
1 oz
275
1 cup 275-350
Seafood
Clams, raw
Oysters, raw
Salmon, canned with bones*
Sardines, canned with bones*
Shrimp
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
1/2 cup
45
15
30
75
70
35
125
25
25
180
50
100
For more information, please see “My Current
Top Five Easy Ways to Improve Your Family‟s
Nutrition” and “Vitamin D: A Quick Review of Forms,
Labs and Other Things People Have Asked Me about
Recently.”
Lettuce, iceberg
11
1/4 head 25
(dried kern
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
Cathy Breedon PhD, RD, CSP, FADA
Clinical & Metabolic Nutrition Specialist
Sanford Medical Center, Fargo, ND
and UND School of Medicine
Calcium Odds and Ends:
Absorption and Where it Ends Up
Role of Vitamins D and K
12
13
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
By Request:
A SHORT CARNITINE
DISCUSSION THAT
MIGHT BE HELPFUL
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
and Clinical Associate Professor of Pediatrics
UND School of Medicine, Fargo, ND
The role of supplemental carnitine in conditions characterized by excessive
obesity, hunger, lethargy, hypotonia, and poor exercise endurance
Carnitine is a substance normally made in the liver and kidney, and it is also available in
meats. It consists of a molecule of methionine and a molecule of lysine — two essential amino
acids. It plays a critical role in the ability to burn fat for fuel because it is part of the enzyme
system "carnitine palmitoyl transferase" which transfers fat molecules into the mitochondria
to produce ATP. Because muscle (including and especially heart muscle) is very dependent on
fat fuels for aerobic energy production, anything that compromises carnitine's operation can
result in a variety of problems. For example, for people with inborn errors of mitochondria
metabolism, providing additional carnitine can help to prevent extremely serious consequences.
An example is the not uncommon beta-oxidation disorder MCADD (Medium-Chain AcylCoA
Dehydrogenase Deficiency.)
Some drugs impair the production of carnitine so that one is more dependent on an
exogenous source than normal. Valproic acid is an example of this, and relative carnitine
insufficiency can often be a big contributor to the lethargy and certain other side effects reported
with the use of this medication. Additionally, inadequate carnitine also compromises the efficacy
of the valproic acid itself, resulting in break-through seizures and increased risk of liver toxicity.
With this medication, carnitine supplementation appears to decrease liver toxicity
significantly. Valproic acid is the seizure medication most studied in relation to carnitine, but
other seizure medications appear to affect carnitine requirements as well. Certainly if the child is
symptomatic a trial on carnitine is very reasonable.
People on ketogenic diets for seizure control also need extra carnitine because they are
burning fat as almost their only fuel - - they need much more carnitine than they could be relied
upon to make on their own. Additionally, many people on these special diets do continue to need
seizure medications, which may further increase the need for an outside source of carnitine.
People with various liver and kidney conditions are sometimes supplemented with
carnitine because production can be compromised. We also use it with premature infants on
TPN in the NICU because their ability to produce carnitine is compromised by the immaturity of
the liver and kidney.
Carnitine-related problems contribute to difficulty burning
fat for fuel resulting in symptoms that may include:
________________________________________________________________________
1. excessive fat storage
2. low muscle tone
3. excessive appetite due to failure to make the needed amount of ATP
(usable energy) from food consumed
4. very poor tolerance of aerobic activity and endurance-type of exercise
5. abnormally high sense of fatigue or excessive sleeping
6. muscle pain with exertion
7. cardiomyopathy
8. episodes of dangerously low blood sugars that can result in brain damage,
or even death … sometimes labeled a SIDS event.
9. unusual difficulty with control of blood sugar in people with insulindependent diabetes … we should be especially suspicious of carnitine
inadequacy among those with blood sugar volatility who are carefully
following their nutrition plans and medications.
These are among the symptoms that have been corrected by carnitine supplementation in at
least 25 people (not counting premies) that I have worked with personally who turned out to have
had unrecognized metabolic abnormalities. [This also does not count the patients for whom we
automatically initiated carnitine therapy in anticipation of need, thereby preventing the problems
described.] If someone way out here in Fargo, ND has found that many patients with what turned
out to be (previously unrecognized) carnitine-related health problems, the likelihood is good
that there are lots of folks out there whose carnitine problems are simply not being looked
for and therefore not recognized.
There are clearly many people who have some of the symptoms described above for
whom carnitine adequacy/inadequacy is completely unrelated. To determine if carnitine is a
problem, a trial on carnitine will often result in noticeable changes within few weeks …
2
sometimes days. If it is not a factor, supplemental carnitine could be discontinued after a trial of
about a couple months. We would normally continue the trial at least that long before writing it
off because some conditions result in a degree of carnitine depletion so pervasive that it takes a
while to get enough cells operating well enough to see a benefit. [Please see the note on the last
page regarding special carnitine issues to consider for people who are candidates for bariatric
surgery.]
Carnitine used as described is very safe. The only problem with the stuff is that it is
pricey. Insurance will usually cover it (ordered as "Carnitor, or the generic equivalent,") but the
amount of coverage varies. For this reason, we do not do this kind of trial casually. However, as I
mentioned earlier, the metabolic abnormalities in symptomatic patients that I have seen who
benefitted markedly from carnitine supplementation were undetected at the time the trial
was initiated. As you know, what we often think is extremely rare can sometimes be fairly
common but just rarely recognized. The only way to know for sure is a trial on carnitine. I
much prefer a prescription form of carnitine for the trial, as some OTC carnitine products
may not provide the amount of carnitine on the label. [I do not want to miss a potential effect
because the product used in the trial provided the wrong amount. People can use OTC carnitine
after the trial if they wish, but insurance will usually not pay for that form.]
Blood levels can reflect inadequacy when they are low or if the total:free carnitine ratio is
disturbed. However, the blood level apparently does not necessarily reflect the muscle tissue
level, including the level available to the heart muscle. So if a person is symptomatic but labs
are normal, one would still do the trial and watch for changes in symptoms. In other words, there
is probably little reason to get labs except for curiosity or research. Certainly, when labs do
indicate deficiency, we would supplement. But when labs do not reflect a deficiency state, we
would still do a trial of supplemental carnitine in a symptomatic patient. So, the labs are really
not of great use in this situation. As the health effects of carnitine inadequacy (for whatever
reason) are not benign, my prejudice is to do a rule-out trial with symptomatic patients.
So, that is the story in a nutshell. If you decide to do a trial, the usual trial in adults is
about 1 gram three times a day (i.e. 3000 mg/day.) The pills are in a 330 mg size, so 3000 mg can
be adequately approximated by three pills 3 times a day. The pills are spread out (any way that is
comfy for the patient) to avoid an osmotic diarrhea that can result from giving the whole lot of tiny
particles all at once. The pediatric dose (PDR info) is 50-100 mg/kg/day divided into 3 doses, with
a 3000 mg/day the usual upper level. The therapeutic/maintenance amount may be much less than
this, but the higher end of the usual range is often best in a test situation, since the person may be
starting out with a significant deficiency. If we under-shoot with a low dose, there may not be
enough carnitine to see changes during the trial period. I don't want to miss something if it is there.
I have had some very large patients whose symptoms (hypotonia, excessive hunger,
lethargy, excessive weight gain and poor endurance, etc.) have responded very well, but an
amount above the theoretical 3000 mg “top” was sometimes needed to bring the positive changes
about. One very heavy and fatigued adolescent responded beautifully but he required 6000
mg/day to bring about the changes we were looking for. [Happy aside: He is now normal weight
and going to college.] As is usually the case, when one is very far outside the “normal” rage for
body weight, a standard per/kg intake level may no longer directly apply.
3
A number of patients with “familial hypotonia of unknown etiology” have responded
amazingly well to this therapeutic intervention even though as yet no one has identified their
actual metabolic problem. All we know is that something about their genetic pattern causes
problems, some of which may be ameliorated by providing supplemental carnitine.
This picture (hypotonia, excessive hunger, lethargy, excessive weight gain and poor
endurance) is intriguingly like some of the typical symptoms observed in Prader-Willi
Syndrome. The #15 chromosome is missing all or part of a leg, but exactly what disturbance in
metabolism results from the deletion is not well understood, nor is it the same in all people with
PWS. However, as these individuals suffer greatly from their condition, it is reasonable to do a
trial as described above. It will either help or it won’t in any individual, but I do have four
patients with PWS for whom supplementation appears to significantly help control the
symptoms, making their lives and those of their families much better.
The children also have more energy to learn and to engage in play. They also learn better
because they are not as obsessed with accessing food. Prader-Willi Syndrome is currently treated
with growth hormone in some children, so one cannot ascribe all of any observed benefit to
carnitine in children treated with both. However, it is reasonable to do both, as the efficacy of
growth hormone treatment could certainly be compromised if energy metabolism was limited by
a relative problem with carnitine adequacy. Certainly a trial would be in order if the symptoms
described above continue to be observed after growth hormone therapy has been initiated.
When a patient demonstrates that supplemental carnitine is helpful, the level that seems
to be effective needs to progress with growth (i.e. mg/kg body weight). I have seen some
situations in which a child out-grew his prescription because this aspect of his care was not being
monitored and the treatment became less effective the more he grew. With math-competent
parents (and the doctor’s permission, of course) I teach the parents how to increase the dosage as
the child attains certain weights. Other families call me each month with the baby’s weight and I
calculate the level for them,
When initiating treatment, the carnitine dose is generous in an attempt to correct a
possible inadequacy … that is, the bucket may be empty so we need to fill it up as part of our
test. However, once the bucket is appropriately full, the therapeutic level is no longer needed
and a maintenance level should be identified. This will be quite individual. As a marker for
having reached the point of having a “full bucket” I tell parents that an indication of this will be
that the child may “start to smell a bit like a little fish” (reflecting getting rid of unneeded
carnitine.) One mother called me and left this message: “At last! We have achieved fishiness!”
At that point we back off and set about to find the maintenance level for that particular child.
Other conditions can be characterized by the same symptoms (lethargy, weight gain,
hypotonia, etc.) Some of my patients with Down Syndrome or Phenylketonuria have struggled
with the same set of energy-related problems, and in several cases, the carnitine supplementation
has helped tremendously. It has been life-altering. For others, the carnitine was not shown to
alter the situation at all. The only way to know which person with these symptoms will respond
to carnitine supplementation is to do a trial.
4
There are many other applications of supplemental carnitine being studied in
addition to the scenario discussed above. These include (among others): hypertriglyceridemia,
mitochondrial diseases, retinal health and macular degeneration, cardiovascular disease,
metabolic syndrome, diabetes, renal disease, parkinsonism, chemotherapy adjunct to minimize
neurologic damage and fatigue, various chronic conditions characterized by fatigue, prevention
of liver toxicity due to use of certain medications, age-related cognitive impairment and
osteoporosis. (See my Diabetes hand-out, Eye Health hand-out and Prental Nutrition hand-out
for more information about those specific carnitine issues.)
SOME THOUGHTS ABOUT BARIATRIC SURGERY
IN INDIVIDUALS WHO HAVE A
CARNITINE-RELATED WEIGHT PROBLEM
___________________________________________________________________________
I think it would be very reasonable to do a trial on generous carnitine
in severely obese individuals prior to moving to bariatric surgery.
One reason is that people who do respond to carnitine can likely avoid the costs,
pain and complication risks of bariatric surgery. Carnitine use does not interfere with an
individual’s ability to absorb micronutrients the way the surgery does, which avoids the
documented problems of clinically significant vitamin and mineral deficiencies like copper,
vitamin B12, thiamin (vitamin B1) and many others months or years after surgery. These three
nutrients are mentioned specifically because neurologic injury (sometimes irreversible injury)
from deficiency is documented in spite of generous oral intake in some bariatric surgery patients.
Long term follow-up of these micronutrient issues is absent in many bariatric
surgery programs, and often the only outcome of professional interest has been whether or not
weight loss occurred, and whether there were improvements in dyslipidemias or diabetes
management. Failure to establish long-term nutrient adequacy is particularly problematic
because many women of childbearing age do become pregnant after bariatric surgery. That
increases risk of birth defects and other types of poor pregnancy outcome. And now some places
have begun to do bariatric surgery on pediatric patients. They do lose weight post-surgically …
but they are likely to lose much more than weight unless overall nutrition is carefully monitored.
One other reason for doing a trial on carnitine before moving on to surgery is that if
patients do have a carnitine-related weight problem they will continue to have it. The
surgery does not correct the problem. That means they will continue to be unable to burn fat
efficiently, and they will continue to experience significant hunger that may drive them to
overeat in spite of surgery. This may be a factor especially in the number of individuals who
regain their weight after surgery or who undergo a second bariatric surgery. Therefore, a trial on
carnitine would help to identify the people who might fail to do well in terms of maintaining
weight loss after surgery unless carnitine supplementation was a continued part of their regimen.
For those bariatric surgery patients who do need supplemental carnitine, continuing to
provide it can play a role in successfully keeping the weight off.
5
Carnitine: Content of Foods
and Quick Fact Sheet
Foods providing about 100 mg of carnitine
Beef steak
100 g
95 mg
Ground beef
100 g
94 mg
Foods providing 10-30 mg of carnitine
Pork
100 g
28 mg
Bacon
100 g
23 mg
Tempeh
100 g
20 mg
Promote
100 ml
12 mg
Foods providing 1 to 6 mg of carnitine
Cod fish
100 g
5.6 mg
Chicken breast
100 g
3.9 mg
American cheese
100 g
3.7 mg
Ice cream
100 ml
3.7 mg
Whole milk
100 ml
3.3 mg
Avocado
one medium
2.0 mg
PediaSure
100 ml
1.7 mg
Cottage cheese
100 g
1.1 mg
Foods providing less than 1 mg of carnitine
Whole-wheat bread
100 g
0.36 mg
Asparagus
100 g
0.20 mg
White bread
100 g
0.15 mg
Macaroni
100 g
0.13 mg
Foods providing less than 1/10th of a mg of
carnitine
Peanut butter
100 g
0.08 mg
Rice (cooked)
100 g
0.04 mg
Eggs
100 g
0.01 mg
Orange juice
100 ml
0.002 mg
Ensure
100 ml
0 mg
Typical intake from food:
Generally, 20 to 200 mg are ingested per day by those
on an omnivorous diet, while a strict vegetarian diet
may provide only 1 mg/day.
The word carnitine comes from the Latin word for meat
but the amount varies with type of meat.
Also note the high variability in carnitine in commercial
“complete nutrition” products.
Production:
In animals, carnitine is biosynthesized primarily in
the liver kidneysDQGWKHEUDLQ from the amino acids
O\VLQHDQGmethionine. Vitamin C (ascorbic acid) is
essential to the synthesis of carnitine.
During growth, pregnancy or wound healing
requirements for carnitine can exceed its natural
production. That is, it is conditionally essential
during periods of anabolism, and also in a variety of
other metabolic conditions.
People with liver or kidney problems may have
difficulty producing it. Renal patients may also be
eating a low meat diet, which can result in a diet
low in pre-formed carnitine. It is also lost in
dialysate, so needs of dialyzed patients are greater
than they would otherwise be.
Other Applications:
The seizure medication valproic acid impairs
production of carnitine, but needs it to work.
Inadequate carnitine reduces effectiveness and
increases potential for liver toxicity of the drug,
and it accounts for some of the reported side
effects such as lethargy and weight gain.
Supplemental carnitine has a role in low muscle
tone, managing diabetes, exercise tolerance,
macular degeneration, obesity, heart failure, cancerrelated and HIV-related fatigue, male infertility,
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6
2013
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
Why Supplementation of
Carnitine is Important
when on the Ketogenic
Diet for Seizure Control
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center, and UND School
of Medicine, Dept. of Pediatrics, Fargo, ND
Introduction:
It is not uncommon to have to convince insurance companies that they should cover the
cost of supplemental carnitine for patients following a ketogenic diet for seizure control. I have
written explanations many times for patients and their physicians, so I decided to finally get
smart and write it up in this form to make it easily available to other folks working on this issue.
(It also helps me a bit because I type with one finger! )
I recommend that people give the information I have written below to the patient’s health
care provider and have that person submit the request. This is because the insurance company
will often only look at things coming from an MD and not from a PhD. But do include the
credential part shown above by the picture so the doctor might more comfortably believe me that
this is really a big deal, along with giving him/her some ammunition to include in the letter
requesting coverage.
As always, nothing I say here takes the place of the advice of your physician or other
health care provider. Also, please note that: I have no relationship with manufacturers or sellers
of carnitine. All my observations are based on the legitimate scientific literature and my own 30
years of experience as a pediatric nutrition specialist. In other words, the following is just a wellintentioned collection of thoughts on the issue.
Good luck! Cathy B.
Carnitine supplementation (a carbohydrate-free form) is a key
part of managing the ketogenic diet because:
1. One normally makes carnitine in the liver, kidney and brain, which allows fat to be used
for fuel to do things like have a heartbeat, diaphragm function and all movement. It has
other important uses as well, but these functions are clearly critical for health.
2. The distorted fuel mix that controls her seizures on the ketogenic diet (WAY more fat
and WAY less CHO than the usual dietary mix) means that the amount of carnitine a
person might ordinarily make will simply be no longer adequate to meet her needs
because much more is needed to process the high fat content.
The situation is somewhat analogous to the fact that everyone needs to produce insulin to
utilize CHO fuels. Children who develop Type I diabetes cannot produce enough of the
insulin they need, with potentially injurious and even lethal consequences. Providing
insulin to these children is always covered by insurance. It would never be denied.
3. Failure to provide carnitine to children on the ketogenic diet and/or certain seizure
medications that impair carnitine production is analogous to telling children with Type-I
diabetes to just get busy and make their own insulin, since other people can easily do it.
They simply can’t, and it is clear that the situation is not at all benign.
4. Failure to provide adequate carnitine to efficiently use fat for fuel will result in seriously
dangerous low blood sugar. It can cause brain damage and/or death from hypoglycemia.
This is because the body’s first need is for energy and it will need to burn glucose it
cannot afford to burn if it can’t burn fat because of inadequate carnitine. This decreases
the blood glucose that is available to fuel the brain.
5. Some seizure medications (valproic acid / Depekene, and likely some others that have not
been as closely studied) will actually cause people to stop making their own carnitine.
Because the medication itself REQUIRES carnitine to work, the loss of carnitine results
in break-through seizures and the need to continually increase the amount and types of
seizure meds required to control seizures. This causes problems like excessive sleepiness
and lethargy, etc., and it also results in risk of very dangerous liver toxicity.
6. Assuring adequacy of carnitine is known to prevent the very serious complication of liver
toxicity. The emergency treatment for children hospitalized with this kind of liver
toxicity includes intravenous carnitine.
7. Failure to provide it and the resultant toxic liver situation has been the cause of
admissions to our pediatric intensive care unit which have been very lengthy (several
months) and very expensive, and from which the children experienced further
(preventable) neurologic injury. It also resulted in their requiring more therapies post
discharge, and they often experienced the loss of important skills.
For example, one very memorable child lost her ability to smile, which was especially
devastating to her family and to all of us who cared for her. These events were tragedies
that were totally preventable by simply assuring adequate carnitine supplementation.
8. When the ketogenic diet is shown to be helpful to a particular patient in terms of seizure
control, its use results in significantly reduced overall costs. These include lower cost
due to less total medication needed, the commonly found ability to discontinue the use of
certain medications altogether, reducing side effects, and improving quality of life.
9. Please my short overview paper on carnitine issues that provides more detail;
6DQIRUG Medical Center
Aunt Cathy’s Guide to:
Thinking About
OTHER
Nutrition Issues
in Celiac Disease
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
University of North Dakota School of Medicine
1. General Nutrition Adequacy Issues
It is important for individuals avoiding gluten to take a close look at the nutritional
adequacy of the foods remaining in the diet. This may mean getting some help from a Registered
Dietitian, as not all the threats to complete nutrition are obvious. Any diet that eliminates a number
of common foods has the potential to leave some gaps in nutrient intake.
In addition to general nutritional adequacy, there are diet/nutrition factors besides gluten
control that can provide additional benefit to people with celiac disease. Many chronic health
conditions have an inflammatory component. CD, MS, diabetes, rheumatoid arthritis,
inflammatory bowel disease and lupus, for example, all have the potential to result in increased
inflammation. It is now recognized that inflammation is an important contributor to heart disease
as well, so the recommendations included here to decrease inflammation and to protect tissues from
the negative effects of inflammation are of great potential benefit.
2. Omega-3 and Omega-6 Fats in the Diet and the Problem of Inflammation.
One of the most important issues in controlling inflammation is the ratio of two different
families of certain polyunsaturated oils in our diets. The two families are called omega-3 and omega-6
fats, and in America we tend to eat far more omega-6 fats than omega-3 fats - - in fact we eat them in a
ratio of 10-to-1! There is a clear benefit for all of us in moving toward a ratio of 4-to-1 (as in the heart
healthy “Mediterranean Diet.”)
Some researchers believe that for people with inflammatory conditions, a ratio of 2-to-1
may be even more beneficial. This is because certain inflammatory substances (prostaglandins) are
made out of these fats, and the ones made out of omega-6 fats are much more inflammatory than
the ones made out of omega-3 fats. That means that by altering the ratio of these fats in our diet,
we can decrease the degree of inflammation experienced. In brief here is how to change the
ratio:
1
A. Replace corn oil (high in omega-6 and very low in omega-3) in cooking and baking with olive
oil (neutral, so it displaces the high omega-6 oils) or canola oil (an oil with a better ratio of
omega-3 and omega-6 fat.)
B. Incorporate ground flax seed and fatty fish like salmon in the diet. These are terrific sources of
omega-3 fat. Flax oil is a good source of omega-3 fat, but the rest of the flax seed is very nutrient
dense as well, including nutrients that are often low in the diets of Americans, like magnesium
and chromium. Additionally, it has some substances (lignans) that appear to decrease risk of
breast cancer. For that reason, the ground flax has a better benefit-to-cost ratio that buying
flax oil or flax oil capsules.
C. If eating fish is not attractive (or if you are worried about mercury), you should consider taking
fish oil or krill oil capsules. These are labeled “EPA and DHA” and a Consumer Reports
survey showed that all the brands in the US were safe and equal in quality, with price being the
only difference. The price ranged from 6 cents each to 60 cents each, so check out a local
warehouse-type or discount store for the best buy. The fish oil capsules tend to be a bit large
for some folks to easily swallow. Because the benefits of taking fish oil (for nearly everyone,)
are being recognized, more and more products are becoming available. Many new forms are
already available, including smaller capsules, liquids and pastes that are citrus flavored and not
fishy-tasting. You can find many products on line just by Googling fish oil or omega 3.
Although flax is rich in a certain omega-3 fat (linolenic acid --- a vegetable oil,) there is a
special benefit to taking in at least some of the omega-3 fat in the forms found in fish (EPA
and DHA.) Think of EPA as standing for “Environmental Protection Agency” – protecting
your internal environment! Even the American Heart Association (a very conservative
organization) recommends that most people take 1000 mg of fish oil daily. Fish oil is also being
used to decrease risk of cancer and as an adjunct to chemotherapy. The form of fat that is DHA
in fish is also particularly important in brain / neurologic health. Some people have been found to
be unable to make enough EPA and DHA out of the vegetable oil linolenic acid (the one in flax
and canola) so taking some in a ready-to-go form is a wise idea.
3. Fiber Issues.
Unless carefully planned, the gluten-free diet can also be low in dietary fiber, including the
kind that “moves things along” (like cellulose in wheat bran), and the kind that helps to lower
cholesterol. That type is called “water soluble fiber”, and it includes Guar gum, Legumes, Oat bran
and Pectin – which can be remembered by the acronym “GLOP.” Some of the cholesterol eaten and
some that enters the intestinal tract in the form of bile from the liver can be thought of as “getting
stuck in the GLOP” and excreted instead of being absorbed into the body.
People with celiac disease obviously cannot have wheat bran, and the oat bran can be iffy
because of cross contamination, so they need to work a little harder to obtain the many benefits of
foods that contain both kinds of dietary fiber. Legumes are one option … dried beans and peas (like
chili beans, navy beans, pinto beans, split peas, etc.) are great sources of fiber and additionally they
are very nutritious. This is because any plant part that is actually what turns into a baby plant is full
of all the nutrients needed by the new plant. In grains it is the “germ.” The rest of any grain is
2
primarily starch and the fibrous coating. Other foods that are high in both fiber and nutrients like
this are nuts and seeds (like the flaxseed discussed earlier.)
4. Increased “Free Radical” Production and Protection by Antioxidants:
Just running your body produces a certain type of waste product called “free radicals.”
They can cause injury to cells, but normally they are kept from causing injury by substances that
we eat or make collectively called “antioxidants.” They include certain vitamins (like vitamins C
and E), and a substance made with the mineral selenium (glutathione peroxidase.) There is some
new evidence that assuring adequacy of selenium may be a therapeutic tools to prevent both tissue
damage and complication of CD such as autoimmune thyroid diseases (AITD.)
A number of substances in plants (certain phytochemicals) are now known to be terrific
antioxidants, and there is a lot of interest in these plant substances for promoting good health in
general. The plant pigments (coloring agents) especially, such as “lutein” in leafy greens,
“lycopene” in tomatoes and “anthocyanins” in blueberries are examples of some very promising
protective substances. Eating plenty of brightly colored vegetables and fruits is a very good
idea for many reasons for everyone.
Inflammatory conditions result in a much greater production of free radicals than is
usual. For this reason, people with inflammatory conditions like CD and diabetes should aim
for a much more generous intake of antioxidants than usual to minimize the increased risk of
cell damage. In this situation, a reasonable and safe daily amount of vitamin E is 400 iu, vitamin C
500-1000 mg, and selenium 100-200 mcg, plus lots of brightly colored fruits and vegetables. The
vitamin C, E and selenium amounts shown above are higher than the usual Recommended Dietary
Allowance (RDA) amount, because the RDA is designed to meet the needs of folks without a
chronic inflammatory disease. Do not take more than this (especially of selenium) without
consulting your health care provider.
Even more potent antioxidants are the phytochemicals that are pigments (coloring agents)
naturally occurring in plants. For example, lycopene, the red color in tomatoes, is 200 times more
potent as an antioxidant than vitamin E, and it has been shown to help minimize the oxidation
damage from excess free radicals related to CD.
[Neurologic impairment due to vitamin E and copper deficiencies in celiac disease. Neurology 2009 Sept 9; 71(11):860-1. Selenium
deficiency in celiac disease: risk of autoimmune thyroid diseases. Minerva Med. 2008 Dec;99(6):643-53. Lycopene, quercetin and
tyrosol prevent macrophage activation induced by gliadin and IFN-gamma. Eur J Pharmacol. 2007;566(1-3):192-9.]
5. Vitamin K Inadequacy: A Newly Recognized National Problem Needing
Special Attention in Celiac Disease
Eating leafy green vegetables has an additional benefit because it is now recognized that vitamin
K is often inadequate in Americans. Dark leafy greens are broccoli are the very best natural sources.
At the moment, vitamin K is not included in most multivitamins because the serious inadequacy
3
problem is only newly recognized. It has now been discovered that inadequate vitamin K contributes
to osteoporosis, arterial calcinosis (an independent risk factor for cardiovascular disease,) kidney
calcinosis and liver cancer as well as pregnancy problems and bleeding problems, so eating these
foods is very important for everyone. Additionally poorly controlled CD greatly increases the risk of
vitamin K deficiency. For more on this, including issues for people using the blood-thinning
medication Coumadin, please see my handout just on vitamin K.
[Celiac disease with diffuse cutaneous vitamin K-deficiency bleeding. Adv Ther. 2007 Nov-Dec;24(6):1286-9. Coagulopathy due to
celiac disease presenting as intramuscular hemorrhage. J Gen Intern Med. 2007 Nov;22(11):1608-12.]
6. Re-emergence of Iodine Insufficiency in the USA
Another new problem on the horizon for everyone is a re-emergence of iodine deficiency
disease in the United States and the world. In short, the problems are these: Certain regions are
known to have inadequate iodine in the soil and this results in IDD (Iodine Deficiency Disease) if
iodine is not provided in some other way. Iodizing salt has been the traditional approach, but that
intervention was initiated before we advised people to cut way back on salt consumption to help
control high blood pressure. [see iodine map on the last page.]
Additionally, there is a popular fad of using exotic “gourmet” salts from around the world, most of
which are not iodized. “Sea salt” is usually not iodized, but some brands are. Even the common salt
at the grocery store looks pretty similar … iodized vs non-iodized … and folks are no longer being
reminded to pick the iodized version. Most vitamins, (including many prenatal vitamins) contain no
iodine because of the assumption that the iodization of salt program “took care of” the widespread
public health problem of iodine deficiency.
Recently the World Health Organization increased the iodine recommendation for pregnant
women, in part because they found that even in regions where salt was regularly iodized, the amount
was insufficient for the best pregnancy outcome. (Iodine deficiency is actually the number one cause
of preventable mental retardation in the world.) Thyroid function is very reliant on adequacy of both
iodine and selenium. So, in addition to issues in brain development of infants, iodine deficiency can
rob people of energy because of hypothyroidism.
What is the connection to celiac disease? Well, people with celiac disease are not protected from
this deficiency, nor is the issue likely to be in the radar of most health care professionals yet, so I am
bringing it up here. It is not unreasonable to suppose that any person with nutrient absorption
problems would have an increased risk of poor iodine status beyond that of the general public.
Additionally, as described above, there is the suggestion of a possible connection to autoimmune
thyroid disease for selenium deficiency. Selenium and iodine work together for the thyroid to
function. I have not seen any specific celiac/iodine connection in the scientific literature, but the
whole issue is very new. In general, in the US most men tend to get an adequate amount of iodine,
but many women do not … this is probably just a reflection of how much total food one typically eats.
[Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr.
2009 Feb;89(2):668S-72S. Iodine Content of prenatal multivitamins in the United States. NEJM. 2009;360:939-940. Iodine status
of the U.S. population, National Health and Nutrition Examination Survey 2003-2004. Thyroid. 2008 Nov;18(11):1207-14.]
4
7. “Eat Right” AND take a Multivitamin with Minerals
AND take extra vitamin D!
It is now well recognized throughout the scientific community that most people would
benefit from taking a standard multivitamin with minerals. The old advice to “just eat right” has
been found to be extremely unlikely to assure optimal health in most people. The new advice is
“Eat right … and take a multivitamin with minerals … and take additional vitamin D”
References for these audacious claims are in the handouts in great number.
There are many reasons for the recommendation that everyone should take a multivitamin
with minerals even if one does “eat right,” including significant individual variability in absorbing
certain vitamins in the forms found in foods. For example, folic acid and vitamin B-12 are
actually more reliably absorbed in the pill form than in the forms found in foods. There are 1)
genetic reasons, 2) aging-related reasons, 3) drug interaction reasons, and 4) intestinal injury (e.g.
CD) reasons that make it hard for some people to absorb adequate amounts of these vitamins from
the usual food sources. It is wise to simply assure an intake at (at least) the RDA level of these two
vitamins in the form found in vitamin pills because this form bypasses the problem in all of the
above situations except for intestinal injury from poorly controlled CD.
Both of these vitamins have been shown to be critical to cardiovascular health because they
prevent the build-up of a substance called “homocysteine” and other problems that the high
homocysteine level reflects. It is prudent to simply prevent the problem. Inadequate folic acid is a
known risk factor for cancer of the breast, colon and prostate, and for depression and birth defects.
Vitamin B-12 is critical for neurologic health. Assuring adequacy of these vitamins in an easy-toabsorb form has broad benefits. If your CD is not in good control, a much more generous intake is
certainly needed. These nutrients are commonly inadequate in newly diagnosed individuals with
CD … poor control would mimic that situation.
[Effect of B vitamin supplementation on plasma homocysteine levels in celiac disease. World J Gastroenterol. 2009 Feb
28;15(8):955-60. Celiac disease and ischemic stroke. Rev Neurol(Paris);2009 Jan 12. Vit A Celiac Disease Presenting as
Xeropthalmic Fundus. Retina;2008 Mar 28(3):525-5. Undiagnosed coeliac disease and nutritional deficiencies in adults screened in
primary health care. Scand J Gastroenterol. 2007 Jan;42(1):60-5; Celiac sprue, hyperhomocysteinemia, and MTHFR gene variants. J
Clin Gastroenterol. 2006 Aug;40(7):596-601; Prevalence of hyperhomocysteinemia in adult gluten-sensitive enteropathy at
diagnosis: role of B12, folate, and genetics. Clin Gastroenterol Hepatol. 2005 Jun;3(6):574-80.]
Additionally, inadequate vitamin D intake is now recognized as a serious underdiagnosed and widespread problem with a great many serious health consequences. These
include congestive heart failure, heart attack, MS, diabetes, osteoporosis, muscle/nerve pain,
muscle weakness, rheumatoid arthritis and cancer of the breast, prostate, colon and pancreas,
to name a few. Note the many “autoimmune” conditions listed. It appears that vitamin D
deficiency can be a trigger for the development of many of these conditions in genetically
susceptible people, just as certain viruses can trigger them.
Over 200 tissues in your body have receptors looking for vitamin D in order to operate
correctly. The current RDA is 200-400 iu of vitamin D, and it is now known that in the northern
third of the US especially, this amount is inadequate to maintain appropriate blood levels of
the vitamin. [see map]
5
This is also true in people who are elderly, or have dark skin, or who are covered up or out
of the sun. In these situations, 1000-2000 iu/day has been shown to be needed in several recent
studies. Some individuals have been shown to require 5000-6000 iu/day to maintain appropriate
blood levels of vitamin D … and people with celiac disease are sometimes members of this group.
In fact, while getting a vitamin D level for some other health problem for a patient, I have seen
many levels that are extremely low. In some of these cases, the low vitamin D level turned out to
be the clue that caused celiac disease to be identified.
It is now known that the upper level of safety for vitamin D is actually over 10,000 iu daily
chronically, so the amount above is nowhere near a dangerous amount, particularly when it is
shown to be needed by a particular person just to maintain normal levels. What is a real and
present danger now all around the world is inadequacy. The World Health Organization
(WHO) estimates that half of the world’s population has inadequate vitamin D levels for a
wide variety of reasons … even in the sunny equatorial regions.
There are few foods that are naturally good sources of vitamin D—liver and salmon are the
only one that one might actually eat, so the 400 iu provided by a vitamin pill is a good place to
start. Milk is fortified with vitamin D (it doesn’t have it naturally) and only a few other foods are
fortified, such as some orange juice and some yogurt. So, while milk is one of the “very best”
dietary sources in the US, one cup has only 100 iu of vitamin D added to it. Note that milk
“straight from the cow” does not contain any vitamin D, so some of our farm families get none and
are quite unaware if it.
It is clear that relying on milk to provide the target amount of vitamin D described is
unrealistic without additional vitamin supplements on the team. If you are in an at-risk group
(e.g. dark skin, living up north, etc.) it is necessary to take an additional vitamin D supplement even
if you drink a lot of milk and take a multivitamin. And now that we know that people all over the
world are living with vitamin D inadequacy, that whole “at risk” concept is not very useful. We
should consider ourselves to be “at risk” unless we have some evidence to the contrary.
For people who are eliminating wheat, rye, barley and often oats from their diet, and
often dairy foods as well for other reasons, there is great potential for failing to obtain the
best health-promoting level of a number of nutrients. Not all of these will be corrected with the
multivitamin with minerals, but it is certainly a good start. You do not need to buy an expensive
product – the best-known discount and warehouse stores have very good ones that are well
absorbed (contrary to the information provided by people selling more expensive products.)
An important CD note regarding vitamin D is that the recommended amounts
described are not taking any malabsorption into account. If your CD is in good control, those
levels (1000-2000 iu) could be fine. If your CD is NOT in good control, you could easily have a
seriously inadequate intake. However, having intestinal symptoms of celiac disease is not necessary
for it to result in severe vitamin D deficiency. In some cases the only symptom of celiac a person
had was the pain and bone damage from vitamin D deficiency. Additionally, there was no
difference in some studies of nutrient status between people with partial villous atrophy compared
with those who had severe villous atrophy. So although avoiding gluten is clearly the most
6
important factor in CD, it appears that generous supplementation of vitamins is a very reasonable
adjunct factor in making CD hurt people less even if they have the gluten–free diet well in place.
Interference with absorption of bone-related nutrients (vitamins A,D, K and the minerals
calcium, phosphorus and magnesium in particular) are all seen commonly in celiac disease. For
example, poor bone density was found in 75% of newly diagnosed children, but it was still very
common (40%) among those who were not newly diagnosed and who were said to be following the
gluten restricted diet.
Assessment 0f bone mineral density in children with celiac disease. Pol Merku Kekarski. 2008 Mar 24(141);219-26.
Severe primary hypothyroidism masked by asymptomatic celiac disease. Endocr. Pract. 2008 Apr 14(3);347-50. Adult celiac
disease with severe or partial villous atrophy: a comparison study. Gastroenterol Clin Biol. 2008 Mar;32(3):236-42. A correlation of
symptoms with vitamin D deficiency and system response to cholecalciferol treatment: a randomized controlled trial. Endocr Pract.
2009 May-Jun;15(3):203-12. Resistance to vitamin D treatment as an indication of celiac disease in a patient with primary
hypoparathyroidism. Clinics(Sao Paulo)2009 Jan;64(3):259-61. Disabling osteomalacia and myopathy as the only presenting feature
of celiac disease: a case report. Cases J 2009 Jan 7;2(1)20. Osteoporosis in celiac disease and in endocrine and reproductive
disorders. World J Gastroenterol. 2008 Jan 28;14(4):498-505;Bone in celiac disease. Osteoporos Int. 2008 Apr 17. Osteomalacic
myopathy associated with coexisting celiac disease and primary biliary cirrhosis. Med Princ Pract 2008; 17(5):428-8.
Because a low vitamin D level is so dangerous and it is very common, it is a VERY
good idea to ask your health care provider to check your blood vitamin D level at least
annually in the winter. Ask him/her to order a “25-hydroxy cholecalciferol level” --- the form of
vitamin D that tells if you have enough on board.
Please share this handout with him/her as well so that it is clear how important this is.
Interestingly, it is looking like EVERYONE should probably have vitamin D levels checked annually
– not just folks with CD -- because they are finding what has been described as “an unrecognized
epidemic of vitamin D deficiency” in the US and around the world. Because the symptoms are nearly
always invisible, and the problem is very common and very dangerous, the only way to be sure that
any individual is “OK” is to check the blood level. Until fairly recently this has rarely been done.
8. New investigations into milk intolerance in CD: Casein and/or Lactose
Many people with CD experience some difficulty drinking milk at all, let alone drinking 10
cups a day. For them, it is useful to remember that there is no reason why one must take their
vitamin D supplement in a form that involves drinking milk. The form in milk is just a supplement
of vitamin D – it is not naturally there. All that is required is that one make sure to get the nutrients
one would expect to get from milk -- i.e. calcium, phosphorus, potassium, vitamins D and B12 and
B2 (riboflavin) – from some other sources. A Registered Dietitian can help figure out lots of ways
to reach a nutrition goal.
The milk-intolerance itself has often been attributed to lactose intolerance – trouble
digesting milk sugar because of intestinal injury. This causes cramps, gas and diarrhea. Certainly
some individuals may be lactose intolerant for reasons unrelated to CD, but that would likely be a
minority of them. So, it has been hard to explain the continued gastro-intestinal distress when the
individual has been controlling the CD diet very well and there is no expectation of intestinal injury
that would lead to lactose intolerance. Now there is a new clue:
7
It appears that for many people with CD, there is an actual intolerance of the cow’s
milk protein that is similar in many respects to the intolerance of gliadin protein in gluten.
In that situation, it would be especially inappropriate to try to meet one’s vitamin D requirement in the
form of dairy foods. It appears that it is the casein part of the protein that is the problem … that is, the
curds rather than the whey. (The whey part is primarily a protein called lactoglobulin.) That means
that foods made from milk that happen to be very low in lactose could still be a problem for
some people with CD. For example, cheese is very low in lactose, but the protein is almost all casein.
I have included some highlights of a study that looked at this recently:
Mucosal reactivity to cow's milk protein in coeliac disease. Clin Exp Immunol. 2007
Mar;147(3):449-55. Patients with coeliac disease (CD) on a gluten-free diet may still have gastrointestinal
symptoms. On clinical grounds cow's milk (CM) protein sensitivity may be suspected. Here, using rectal protein
challenge, we investigated the local inflammatory reaction to gluten and CM protein in adult patients with CD in
remission. … Casein, in contrast to alpha-lactalbumin, induced an inflammatory response similar to that produced
by Cow’s milk. A mucosal inflammatory response similar to that elicited by gluten was produced by CM
protein in about 50% of the patients with coeliac disease. Casein, in particular, seems to be involved in this
reaction.
One practical suggestion that comes from this research is that people who continue to have
celiac symptoms in spite of careful avoidance of gluten should do a trial of strictly avoiding casein
for a few weeks to see if symptoms improve. If it doesn’t help, then that is not the problem so
dairy foods can be re-introduced. But if it does result in improvement, consider removal of milk
protein from the diet and replacing of the nutrients usually contributed by milk in the American diet
as described earlier. And as emphasized earlier, it is NOT SAFE to simply remove this kind of
food and then not replace the nutrients.
9. A Mineral of Special Note: Magnesium
Magnesium is critical for over 300 processes in the body. And yet, according to a large
national survey by the CDC (the NHANES Report), this important mineral is low in the diets of
the majority of Americans. Inadequacy contributes to diabetes, obesity, migraine, muscle spasms,
poor pregnancy outcome, and many other problems, but it is often unrecognized. Because one of
the most important dietary sources is the “germ” part of whole grains, there is a greater likelihood
of poor intake among people avoiding gluten. Other good sources include nuts and legumes, but
many people do not eat much of these foods for a variety of reasons. Most multivitamins with
minerals contain very little magnesium -- often only 10-25% of the recommended amount for
healthy people. For these reasons, some folks will need an additional magnesium supplement of
200-300 mg/day in the form of magnesium oxide or magnesium chloride. Others can do well with
just some diet tinkering. Check out the Magnesium handout on the website for the particulars and
specific recommendations.
8
10. Iron, Copper and Zinc
These three minerals have all been found to be problematic in celiac disease, especially when
The diet is poorly managed and intestinal damage is present. It is well known that the first recognized
symptom of celiac disease is often anemia. Iron deficiency because of intestinal injury can be a
cause of this. However, newly recognized as a factor in this picture is copper deficiency, which
can result in inability to transport iron well and therefore looks like iron-deficiency anemia. This is
one reason why treatment with supplemental iron alone can often be ineffective. Another is that
chronic inflammation alone can result in an anemic state in spite of iron status.
Additionally, there are many factors that affect both iron and zinc absorption …
enhancing it or impairing it. Both are affected by the same factors, but often only iron status is
measured in the form of hemoglobin or hematocrit measures. A good rule of thumb is to assume
unrecognized zinc inadequacy when one is known to be iron deficient. As zinc is a factor in over
200 enzyme systems in the body, including the immune system, making DNA, growth, and wound
healing (including intestinal injury repair), inadequacy can be globally damaging. If one supplements
zinc, however, it is important to also supplement copper, because supplementation of zinc alone can
interfere with copper absorption.
New reports also suggest that there may be an increased urinary loss of copper in the urine of
women with celiac disease … a factor separate from the question of impaired absorption. And in
addition to the anemia issue, unrecognized copper deficiency can also result in irreversible
muscle/nerve damage.
I have additional information available on line with lots of information about factors that affect
absorption of these nutrients that can be used to help improve the situation: “Nutrition Support of
Iron Deficiency” is on line with other handouts of potential interest as described at the end of this
paper.
[Copper deficiency in celiac disease. J Clin Gastroenterol. 2009 Feb;43(2):162-4. Serum zinc in small children with celiac disease. Acta
Paedoiatr 2009 Feb 98(2); 343-5. Anemia of chronic disease and defective erythropoietin production in patients with celiac disease.
Haematologica. 2008 Dec;93(12):1785-91.Neurologic disorders in adults with celiac disease. Can J Gastroenterol 2008 Nov
22(11);909-11, .Serum copper, ceruloplasmin and 24-h urine copper evaluations in celiac patients. Dig Dis Sci. 2008 Jun;53(6):156472. Copper Deficiency in Celiac Disease: A Report of 5 Cases and a Review of the Literature. J Clin Gastroenterol. 2008 May 15.
Anemia of chronic disease. Haematologia 2008:dec 93(12);1785-91. Neurologic impairment due to vitamin E and copper deficiencies in
celiac disease. Neurology 2008 Sept 9; 71(11):860-1. The soluble transferrin receptor (sTfR)-ferritin index is a potential predictor of
celiac disease in children with refractory iron deficiency anemia. Clin Chem Lab Med. 2005;43(1):38-42.Hematologic manifestation of
childhood celiac disease. Acta Haematol. 2004;111(4):211-4.Refractory iron deficiency anemia as the primary clinical manifestation of
celiac disease. J Pediatr Hematol Oncol. 2003 Feb;25(2):169-72. Efficacy of gluten-free diet alone on recovery from iron deficiency
anemia in adult celiac patients. Am J Gastroenterol. 2001 Jan;96(1):132-7.]
11. A Newer Topic: Carnitine and Celiac Disease
Carnitine (also called L-carnitine) is a substance one produces in the liver and kidneys, but
which is also found in meats. It is important for getting fuel into your muscles, so having an
inadequate amount contributes substantially to fatigue and even to heart muscle problems
(cardiomyopathy.) Normally we hear little about it because most folks take in or produce all they
9
need. However, in a number of health conditions, adequacy may require an additional supplemental
intake. For several years there has been interest in evaluating the possibility of a relative carnitine
deficiency in people with CD.
[Encephalopathy due to carnitine deficiency in an adult patient with gluten enteropathy. Clin Neurol Neurosurg. 2006
Dec;108(8):794-7. Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet.
World J Gastroenterol. 2005 Nov 14;11(42):6671-5. Carnitine deficiency in patients with coeliac disease and idiopathic
dilated cardiomyopathy. Nutr Metab Cardiovasc Dis. 2005 Aug;15(4):279-83. Intestinal permeability in long-term follow-up
of patients with celiac disease on a gluten-free diet. Dig Dis Sci. 2005 Apr;50(4):785-90. Serum carnitine and selenium levels
in children with celiac disease. Indian J Gastroenterol. 2004 May-Jun;23(3):87-8. Plasma L-carnitine levels in children with
celiac disease. Minerva Pediatr. 1992 Sep;44(9):401-5 Serum carnitine and selenium levels in children with celiac disease.
Indian J Gastroenterol. 2004 May-Jun;23(3):87-8.]
A recent prospective investigation looking specifically at carnitine supplementation in
CD patients with fatigue found that they benefitted from supplementation. I have included the
complete abstract of the research study below so that you can share this information with your
health care provider. This benefit in fatigue-reduction is consistent with applications in many other
conditions in which fatigue is a common problem. I listed a few examples of those after the
abstract below.
L-Carnitine in the treatment of fatigue in adult celiac disease patients: a pilot study. Dig
Liver Dis. 2007 Oct;39(10):922-8. BACKGROUND: Fatigue is common in celiac disease. LCarnitine blood levels are low in untreated celiac disease. L-Carnitine therapy was shown to
improve muscular fatigue in several diseases. AIM: To evaluate the effect of L-carnitine
treatment in fatigue in adult celiac patients. METHODS: Randomised double-blind versus
placebo parallel study. Thirty celiac disease patients received 2 g daily, 180 days (L-carnitine
group) and 30 were assigned to the placebo group (P group). The patients underwent clinical
investigation and questionnaires (Scott-Huskisson Visual Analogue Scale for Asthenia, Verbal
Scale for Asthenia, Zung Depression Scale, SF-36 Health Status Survey, EuroQoL). OCTN2
levels, the specific carnitine transporter, were detected in intestinal tissue. RESULTS: Fatigue
measured by Scott-Huskisson Visual Analogue Scale for Asthenia was significantly reduced
in the L-carnitine group compared with the placebo group (p=0.0021). OCTN2 was decreased
in celiac patients when compared to normal subjects (-134.67% in jejunum), and increased
after diet in both celiac disease treatments. The other scales used did not show any significant
difference between the two celiac disease treatment groups. CONCLUSION: L-Carnitine
therapy is safe and effective in ameliorating fatigue in celiac disease. Since L-carnitine is
involved in muscle energy production its decreased absorption due to OCTN2 reduction
might explain muscular symptoms in celiac disease patients. The diet-induced OCTN2
increase, improving carnitine absorption, might explain the L-carnitine treatment
efficacy.
A few examples of related elated applications of carnitine in the treatment of fatigue:
Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related
quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition. 2006.
Levocarnitine administration in elderly subjects with rapid muscle fatigue: effect on body
composition, lipid profile and fatigue. Drugs Aging. 2003. Safety, tolerability and symptom
outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and
10
carnitine deficiency: a phase I/II study. J Pain Symptom Manage. 2006. Double-blind, multicenter
trial comparing acetyl l-carnitine with placebo in the treatment of fibromyalgia patients. Clin Exp
Rheumatol. 2007. L-carnitine decreases severity and type of fatigue induced by interferon-alpha in
the treatment of patients with hepatitis C. Neuropsychobiology. 2003.
12. Effects of Gluten Exposure on Absorption of Nutrients in the Intestine
As a recap, poor control of gluten intake results in poor absorption of essentially all
nutrients, whether in food or taken as supplements. Several examples of this were described
earlier, but the poor absorption would affect all nutrients, so your body would not have a “level
playingfield” to do all the things it needs to do. This includes brain function as well. So, as always,
gluten avoidance remains the cornerstone of nutrition for Celiac Disease. All the other issues
described above are just the icing on the (gluten-free) cake.
[Metabolic and nutritional features in adult celiac patients. Dig Dis. 2008;26(2):128-33.Affective and psychiatric disorders in celiac
disease. Dig Dis. 2008;26(2):140-8.]
11
MAPS of INTEREST: VITAMIN D and IODINE
VITAMIN D:
https://www.health.harvard.edu/newsweek/images/latitude-vitaminD.jpg
Except during the summer months, the skin makes little if any vitamin D from the sun at latitudes
above 37 degrees north (in the United States, the shaded region in the map) or below 37 degrees
south of the equator. People who live in these areas are at relatively greater risk for vitamin D
deficiency.
(Actually, that’s where I live … but you can see why it’s a really big deal Up North!”)
IODINE: Map showing spatial correlation between the former "Goiter Belt" in the northern U.S. and
areas where the iodine content of drinking water is naturally low.
www.uwsp.edu/gEo/faculty/ozsvath/images/goiter_belt.htm
12
Sanford Medical Center
Aunt Cathy’s Guide to
Nutrition:
Carbohydrate Mnemonics
(Monosaccharides, Disaccharides
and Polysaccharides)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center
Clinical Associate Professor
UND School of Medicine, Fargo, ND
Aunt Cathy’s “PMS” System for
Decision-Making:
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Whole, 2% or Skim Milk for Ages 1-2.
Sorting out the formulas or questions about when to use whole milk or skim milk can be
complicated by issues unrelated to the science of nutrition. For example, a formula may not be
usable in a situation for which it might be helpful because of costs, contracts with other formula
companies, or confusion because of the way a product is promoted.
Health professionals serving large infant-feeding programs like WIC (“Special
Supplemental Food Program for Women, Infants and Children” of the Dept. of Agriculture) often
find this sort of confusion to be very costly in terms of time, money and frustration. In response
to hearing these concerns raised by many state WIC programs, I devised a way of thinking about a
formula and milk choice issue that attempts to sort out the important aspects from those that are
irrelevant or changeable. The following example examines the question of the need to use whole
milk after the first birthday until a child is two (which remains the current AAP recommendation):
The “Whole Milk Dilemma”
Many health professionals expressed concern that insisting on the use of whole milk for
all of this age group of children may be inappropriate for those with lower than average ability to
expend calories (e.g. children with spina bifida) and those who are already in the overweight /
obese categories. However, they felt obligated to follow the official AAP recommendation.
In some states WIC programs did not allow clients to use whole milk without getting a
physician’s prescription. Much time and money was invested in obtaining documentation that
the child needed a lower-calorie product. Policies and flow-charts had to be established to assure
that these issues were handled correctly. Here’s a great example:
“Proposed Policy Regarding the Use of 2% or Skim Milk by Children under Age Two
Participating in the _____ State WIC Program.
1. For children observed to have three rolls of fat on the thigh, the Nutritionist may call the child’s
physician to request a prescription for skim or 2% milk to be used in place of whole milk.
2. Children under age two who have two or fewer rolls of fat on the thigh are to receive whole milk.
Their fat stores will be monitored at clinic visits. Should they develop a third roll of fat, a
prescription will be requested as described above.”
It sounds pretty silly and unhelpful, but it was real.
This is especially irritating to the client and the MD when have both agreed that the child
is doing very well on 2% or skim milk. So, lets look at the “PMS” of this issue:
1
P = Policy
M = Marketing
S = Science
Policy: “Only whole milk will only be allowed from the end of the first year of life until age two.”
Marketing is not really an issue/problem with this issue (but it sometimes certainly IS.)
Science:
1. The only difference between whole, 2% and skim milk is in the amount of fat and calories per
ounce. Other nutrients are provided in the same amounts.
2. The form of fat in the milk is a very poor source of essential fatty acids, it can be somewhat
constipating, and there is no special property of cow’s milk fat (or goat’s milk fat) that promotes
brain development … babies just need calories for that. None of the formulas contain milk fat so a
formula-fed infant got none in the important first year. Neither did the breastfed
baby because Mother’s milk does not contain cow’s milk fat either. So why would it be so important that
children between ages 1 and 2 be fed a large percentage of their calories in the form of cow’s milk fat, and
why would we insist on it? Answer: I can’t think of one.
3. Babies need adequate calories to grow and to myelinate their brains. Before the WIC Program was
established many poor babies did not get enough calories because skim milk was a few cents cheaper than
whole milk. The reason for the AAofP recommending whole milk was to try to at least provide
enough calories for the baby’s growth and development, and whole milk has twice the calories of
skim. Once the WIC Program was established, no infant should be at risk of obtaining inadequate calories
for growth and development because of poverty. The original reason for the recommendation is gone.
4. Insisting on using high fat milk in this situation may result in excess caloric intake, and if so it
could contribute to obesity, the more common problem these days. However, usually it does
NOT result in over consumption of calories, because the baby self –regulates caloric intake. But
in that case it would certainly decrease the content of vitamins, minerals and protein in the
children’s diets because satiety induced by all those fat calories would cause them to eat less of
other foods.
5. However, in the extreme, such as when a child has very low caloric requirements because of
being able to move very little, this can cause lots of trouble. Similarly, it can cause real problems
if (for example) the child is tube-fed and therefore unable to regulate his/her caloric intake.
Additionally, policies that require waiting until a child is demonstrably overweight or obese
before allowing a lower fat milk to be used are clearly not in children’s best interests. (See my handout
on nutrition for children with special needs for more information.)
Conclusions: In this scenario, it appears that the Science evaluation did not argue against using skim
or 2% milk in children ages 1-2. What remains then is to determine if there is a good reason for continuing
a Policy of requiring WIC nutritionists to provide only whole milk for children of this age group. If so, this
also totally undermines the idea that professional WIC nutritionists are able to evaluate the appropriateness
of a child’s nutrition and to act on it. If no good reasons can be proposed for requiring whole milk at
this age, then CHANGE THE POLICY to use the form of milk or milk substitute judged to be best
by the WIC health care professional who is considering the needs of the individual child in his/her
care.
2
Sanford Medical Center
I received this excellent question in the
mail, and I think it’s a discussion worth
sharing:
“At our WIC program, we are able to provide
several different formulas if an infant does not
tolerate our contract formulas. Typically, at
the age of 5-6 months we will ask parents to
reintroduce a contract product. We do this on
the basis that as an infant gets older, he or she
may tolerate the formula better than before
(mainly due to the fact that the infant is
tolerating solid foods at this point). This has
been in practice long before my time here and
I’m now looking for evidence/research to back
this up.”
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Regarding “A Trial Back on . . .”
A WIC Nutritionist Question
Reply: The practice of re-trying a baby who did not tolerate a formula back on the original
product was originally based on three things:
1)
For many years, doctors and nutrition people perceived that soy-based products were
inherently significantly lower quality than milk-based products. My formula handout discusses
where we are with that. Basically, unlike some years ago, there is no big nutritional advantage
to switching back to milk-based formulas for non-premature babies or those who are otherwise
healthy.
If the baby's initial intolerance problem was in fact allergy-related (i.e. involving
immunoglobulin E and not just a lactose intolerance type of issue,) such a trial would not be a
great idea because allergy to cow's milk CAN "go away" but not usually in the first year. If it
were a true allergy I would be very hesitant to just switch them back at 6 months (or whenever)
without specific orders for safety reasons. If the baby were to have a severe anaphylactic
reaction, for example, there could be very serious consequences.
An additional feature to consider here is the issue of trust between the nutritionist and the
client. Many parents perceive the insistence on a re-trial of the formerly-problematic formula
as being dangerous and foolhardy. We say, "well, if he still has the problem we can always
switch back." However, the "if he still has the problem" part suggests that we pretty casually
put their baby in what may be jeopardy.
Now, if it were very important to switch back, that is one thing. But if not? Why would
we put them through this kind of anxiety-inducing experience? This is especially a problem
when the parents feel very strongly about staying on the present product. We have the power to
make them switch ("take it or leave it,") but to do it when there is no pressing reason (like a
relative non-issue such as the perceived nutritional value of milk-based vs soy-based) it does
have the potential to harm to our relationships with them.
1
2.
A lot of the "switch back to the old formula" has roots in the use of more pricey
hypoallergenic formulas in place of standard or soy products. In this situation, if the problem is
not of a true allergy nature (rendering the hydrolyzation of the protein unnecessary) then the
family or the WIC program can save some money by moving toward an intact-protein formula.
However, if it is a true allergy, the same caveats apply as above. Example: hypoallergenic
formula might be used for a colicky baby for whom it seemed to be helpful in the first months
of life; however, most babies are not colicky after 6 months and they would likely do fine on
standard or soy formula, saving big bucks. But colic is not an “allergy” and a recurrence is not
potentially life-threatening the way an allergic response can be.
3.
WIC costs have also been players in this drama, as the more costly hypoallergenic
formulas have sometimes not been on a state's rebate formula list. In that case, the WIC people
may be very eager to get back onto any of the “contract” formulas for budgetary reasons.
However, again, in that case the primary urge is financial and not baby health, so we really
have to be cautious about the circumstances in which we “make” the baby switch back.
So, the bottom line is that it is sort of a relic of the past to insist on switching back from
soy-based back to milk-based. In regard to trials of intact protein in place of a hypoallergenic
formula, it would depend on whether or not the reason for the switch initially was because of a
true allergy. If it is an allergy I wouldn't see any big (non-financial) reason to switch back.
Risks to baby health trump thriftiness every time in this situation.
Hope this helps! Cathy B.
2
Sanford Medical Center
Aunt Cathy’s Guide to:
Choosing
Appropriate
Infant Milks and
Formulas
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
and Clinical Associate Professor of Pediatrics
UND School of Medicine, Fargo, ND
Part 4: Thinking about When to Recommend Whole Milk,
Low Fat (2%) Milk or Skim Milk before Age Two
A. What percent of calories is provided by fat in each type of milk?
At a time when many American infants were often being fed skim milk, Fomon et al,
(1974) showed that young infants fed skim milk as their major food drank about 1.5 times the
amount normally taken, in an effort to get adequate calories. This was a concern for several
reasons:
1. The amount of protein would be very high because skim milk provides 40% of calories as
protein. This is much more than in whole milk (20%) or human milk (7%.) Because so much of
the baby's energy would be derived from protein, there would be a large amount of nitrogenous
waste produced that must be excreted via the kidney (i.e., it would contribute to a high "Renal
Solute Load").
In the first months of life, this can result in dehydration because of the obligatory loss of
water to excrete the waste products; sometimes the loss of fluid can be more than the baby can
afford. In very young infants or in those with special health problems, including those with
growth failure, diarrhea, or fluid limits, a high "Renal Solute Load" can be dangerous. It becomes
much less of an issue in an older baby or child who is growing normally.
2. The volume of milk required to achieve a particular caloric intake is about twice as much for
skim milk compared with whole milk or human milk. Some children, as noted above, simply
could not take in enough volume to maintain appropriate fat stores and to grow. I call that
problem “Tiny Tummy Syndrome.” However, they will try hard to take in the calories they need
and so they do increase the volume of milk, resulting in an even higher net protein intake provided
in inadequate calories.
1
3. The essential fatty acid content of cow’s milk was discussed earlier in the infany feeding
section and there is a chart there of EFA levels indifferent types of cow’s milk. The same applies
here. The major point is that NONE of these milks (skim, 2% or whole) have much in the
way of essential fatty acids, so it is not a reason to insist on whole milk for a child.
What About after One Year?
Whole?
2%?
Skim?
After one year, whole cow's milk has been recommended for most children until age two.
This recommendation is being seriously reconsidered at this time. Lower fat milks can also be
appropriate based on a particular child’s caloric requirements and the presence of other sources
of fat in the diet. A complete review of this topic is beyond the scope of this paper, but it is useful
to note that the global “whole-milk-to-age-two” concept is a public health guideline, and it is not
intended to tie the hands of qualified health care professionals who determine that an individual
child would be better served by using 2% or even skim milk. As shown later, there are no magic
qualities of cow’s milk fat that make it an essential component of a child’s diet.
Consider that the breast-fed baby receives no cow’s milk fat at all, nor does the formula-fed
baby because the fat is replaced by vegetable oils. So why, at age one, would a child suddenly
“need” milk fat? And unlike human milk, infant formulas provide no cholesterol (the precursor to
myelin) at all. Interestingly, the milk fat is not the baby’s primary source of cholesterol, so skim
milk is not very different in regard to pre-formed cholesterol content than whole milk. (See chart on
the next page.)
As noted earlier, cow’s milk fat is a poor source of essential fatty acids, including those
leading to production of DHA, a major fat involved in brain development. It is no more beneficial
to the myelinization of a child’s brain than any other source of acetate (the 2-carbon unit that is the
substance from which cholesterol and then myelin are produced.) Acetate can be made from any
calorie source … carbohydrate, protein or fat. Interestingly, the reason I am given most often
by health professionals for insisting on whole milk for a toddler is because “he needs it for
brain development.” Unfortunately, all that milk fat only provides a lot of calories and not
the truly and directly brain-building components DHA or cholesterol.
It is useful to consider that children have a growth schedule to keep, and if for some reason
calories are inadequate, the child will burn fat stores to continue to grow in length and continue
brain-building operations. If calories remain inadequate, linear growth will next be compromised
and available energy will be preferentially used for brain-building. What this means is a child
with inadequate calories will not have to make a judgment like “Gosh! I just can’t decide! Should
I make a brain or a fat bottom?”
Anyway, it means that one could conclude that a child of appropriate/normal weight and
apparent fat stores would have adequate calories for brain-building. When I see a little “Three-Roller”
toddler (related to the number of rolls of fat on thighs) in my office, I do not worry that he would be
at risk of getting inadequate calories “for his brain” if I switch him to skim milk from whole.
2
Consideration of these issues can allow for safe and intelligent departures from the
“whole milk until two” recommendations, even as we wait for official changes to come from
professional associations.
This is especially true when insisting on feeding a high fat milk is contrary to the
child’s best interests, as is often the case with children with handicaps that decrease mobility,
or overweight children whose caloric intake is clearly already generous.
The negative effect of whole milk on the overall nutritional quality of the diet
Many American toddlers are already consuming a generous amount of calories as fat from
other food sources. The use of whole milk also actually decreases the amount of other foods
that a child with a normal appetite would consume. If our model is that healthy infants will
control their intake of calories to match their caloric requirements (and it is,) then feeding a diet
that is higher in calorie-to-nutrient ratio would certainly decrease the over-all nutrient content.
Here is a simple example:
The calories in 4 oz whole milk is equal to the calories in
4 oz skim milk + 4 oz strained carrots.
They provide the same calories. Which provides more nutrients?
Insisting on using a high fat milk with a chubby toddler is generally not in his/her best
interest. One consideration might be whether this would encourage excessive caloric intake, but
the more likely response of an otherwise healthy child is that he/she will simply eat less food in
general to obtain the appropriate (lower) number of calories, so the nutrient:calorie ratio of the
diet will decline.
This is especially non-helpful if the parent tells you that the child’s usual diet features
foods already high in fat like macaroni and cheese, french fries, potato chips, butter, gravy, peanut
butter and hot dogs [I know … there is a choking issue with these last two especially that is very
real. But the fact is, in real life many babies and toddlers are commonly fed these foods: “I give it
to him because he really likes it.”]
3
If the rest of the child’s diet is described as above, it is already a very generous source
of fat. It w ould be hard to come up w ith a logical reason w hy one w ould want to increase it
further by insisting that the baby use whole milk simply because he/she is “not yet two.”
Is there a risk of essential fatty acid deficiency ifZHgive skim milk before age
two instead of whole milk?
No, for these reasons:
1. There is the same risk of EFA deficiency whether one uses whole, 2% or skim milk
because, as shown earlier, none of these milks is a good source of essential fatty acids.
2.
For “normal, healthy children” who were either breastfed or fed commercial
formulas for the first year, both feeding products provided generous EFAs and the
child’s fat stores would therefore contain generous amounts. This assumes that the
child has reasonably appropriate “normal healthy” fat stores upon visual inspection; an
emaciated child would of course be at greater risk of EFA deficiency … but that child
is not a member of the “normal, health\ children” group and a lot of rules will beGLIIHUHQW
3. Ironically, an example of the primary exception to the assumption of good EFA
stores in a child with reasonable fat stores would be one who was switched to milk
(whole, 2% or skim) at age 6 months or so of age. That child will have had 6 months
of EFA-free milk, so his/her fat stores are less trustworthy in this regard. In terms of
stored EFA fat at least, we ARE what we eat!
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4
B
The protein and micronutrient content of skim, 2% and whole milk is quite
comparable. Vitamins A and D are equally fortified in all three. The only real difference is
the calorie content:
Per 8 fluid oz
Protein Calories Cholesterol Calcium
(g)
(Kcals) (mg)
(mg)
(mg)
Phosphorus
Vit. D Vit. A Vit. B2 Potassium
(iu) (iu)
(mg)
(mg)
Skim milk
8.4
86
4
300
300
100 500 0.3
406
2% Low Fat milk 8.1
121
18
297
232
100 500 0.2
399
Whole milk
159
33
291
228
100 500 0.4
370
8.2
(data from Pennington, J. Bowes & Church’s Food Values of Portions Commonly Used 16th Ed. )
Interpretation of the chart above:
The difference in the cholesterol content is not a very significant, especially as we know that
infants fed formula instead of mother’s milk receive no pre-formed cholesterol at all for the first
year. This means that infants apparently can make their own cholesterol to myelinate their brains
called Smith-Lemli-Opitz Syndrome which interferes with the ability to make cholesterol. &KLOGUHQ
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The protein and micronutrient differences are also not significant.
The difference in calories ,6 significant:
A teaspoon pat of butter has about 36 kcals.
The difference between skim and 2% milk is 35 kcals.
The difference between 2% and whole milk is 38 kcals.
So, one could picture their relative caloric and fat value as follows:
Skim milk = 8 oz Skim Milk
2% milk = 8 oz skim milk with a pat of butter floating in it. Whole milk = 8 oz skim milk with 2 pats of butter floating in it.
5
Comparison of Skim Milk, 2% Low Fat Milk and Whole Milk
Today in the USA, the situation is quite different from the situation in the early 1970s
described above. Because of programs like WIC, more babies are being breastfed, and no nonbreastfed baby has to use skim milk instead of formula to save a few pennies and in the process
receive only half the calories per oz.
It is also interesting to note that there is a priority system among the body’s tissues, and
a child’s calories will be preferentially used for brain development at the potential cost to other
tissues. Therefore, if a child has normal-to-generous fat stores on board one can assume that
calories, at least, are sufficient for brain development. [Think of it this way: A toddler who takes
in too few calories to meet all of his/her needs will NOT choose to have “thunder thighs”(also
called “two-rollers”) instead of a well-made brain.] The misunderstanding of this situation often
leads to inappropriate use of high fat milk out of concern “for his brain.”
See
“Aunt Cathy’s PMS System of Baby Formula Decision-Making” on the next page
for a quick example of problem solving that uses the “Whole-2%-or-Skim” issue as an example.
6
Sanford Medical Center
Aunt Cathy’s Guide to:
Choosing
Appropriate
Infant Milks and
Formulas
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
and Clinical Associate Professor of Pediatrics
UND School of Medicine, Fargo, ND
Part 3: Cow’s/Goat’s Milk and Evaporated Milk Formulas as the
Primary Feeding Product for Infants.
Cow’s milk and goat’s milk are inappropriate for use as the primary feeding product in
place of human milk or commercial formula. They fall outside of the "desirable range" of
carbohydrate, protein and fat, and can present problems for some infants.
This is especially true for very young babies or for those who have special health
problems. In addition, 2% (low fat) and skim milk provide inadequate calories (about 15 and 11
calories per ounce, respectively), so babies tend to drink even more of these products than they
would whole milk, formula or human milk, which all provide about 20 calories per ounce.
Percent of calories from:
CHO PRO
FAT
__________________________________________________________________________
Desirable range:
35 - 65
7 - 16
30 - 55
______________________________________________________________________
Cow's milk: Whole:
30
20
50
2% :
38
26
36
Skim :
57
40
3
Goat's milk:
27
19
54
Are there any other problems?
At a time when many American infants were being fed skim milk, Fomon et al, (1974)
showed that young infants fed skim milk as their major food drank about 1.5 times the amount
normally taken, in an effort to get adequate calories. As you can see on the chart above, the amount
of protein would be very high, and since so much of the baby's energy would be derived from protein,
1
there would be a large amount of nitrogenous waste produced that must be excreted via the kidney
(i.e., a high "Renal Solute Load.")
This has the potential to result in dehydration because of the obligatory loss of water to
excrete the waste products. Sometimes the loss of fluid can be more than the baby can afford. In
very young infants or in those with special health problems, including those with growth failure,
diarrhea, or fluid limits, a high "Renal Solute Load" can be dangerous.
These milks are also less than ideal because they contain up to 8 times as much sodium as is
in human milk and formula. If skim milk is used as described above, that can mean a sodium intake
of 12 times the amount in human milk, since the baby will drink so much more of it.
In addition, these milks do not provide complete nutrition, because they are poor
sources or iron, vitamins C and B-6, copper, zinc and essential fatty acids. Vitamins A and D are also
low unless they are added in processing.
Most commercial milk has vitamin D added, but milk obtained directly from a dairy farm or
the family barnyard often has none. As a result, severe vitamin D deficiency is not uncommon
among many “farm” children, especially in the north [Rickets in the Dairy State. Wisconsin Medical Journal.
2004;103:84-87. 7.]
In addition to these problems, goat's milk (but not cow’s milk) is also naturally too low
in folic acid (a B-vitamin especially important during periods of rapid growth because of its role in
DNA production), and offers no special advantage over cow's milk. Many commercially canned
goat's milks do have folic acid added. Babies who are allergic to cow's milk protein are often allergic
to goat's milk, too.
I was involved in the care of an infant whose exclusive (“natural”) diet of raw goat’s milk
landed him in the hospital at age 4 months, very near death, with overt scurvy, anemia and neurologic
problems from deficiency of folic acid, vitamins C, B6, D, iron, zinc and several other nutrients.
Fortunately, emergency treatment saved this baby’s life, but there is no way to determine if there will
be any long-term consequences of such severe malnutrition of multiple nutrients during infancy.
These are serious issues.
Unpasteurized milks are not recommended due to the risk of bacterial contamination.
This includes conditions like listeria, brucellosis and salmonella, to mention just a few. Heat
treatment also improves the digestibility of the milk, but the milk fat remains much harder for babies
to digest than the fat in human milk or commercial formulas, and it is a poor source of linoleic and
alpha-linolenic acid, the essential fatty acids.
Some babies appear to have a sensitivity to unheated cow's milk (but usually not to formula)
that causes bleeding from the intestine. The amount of blood loss is often so small as to be
unnoticeable in the stool, but it can result in a serious loss of iron. This blood loss, along with the
poor iron content of cow's milk and its impairment or iron absorption from other sources, can
contribute to the development of anemia.
2
I have seen young children with this kind of “cow’s milk anemia” related to these factors
plus a diet pattern that provided too much of the child’s calories in the form of milk/yogurt/cheese,
etc., and very little other foods. Interestingly, several children had been identified as anemic, but the
solution recommended was just to give a supplement of inorganic iron (e.g. ferrous sulfate.) This is
particularly unlikely to be very helpful because:
1)
milk impairs absorption of inorganic iron and
2)
the basic problem of dietary imbalance is not addressed so multiple other critical (but less likely
to be tested for) nutritional inadequacies remain uncorrected. For example, this dietary pattern
would also lead to relative inadequacy of zinc and copper, both of which can be very serious
inadequacies.
Essential Fatty Acid Deficiency
Of the linoleic acid found in butterfat (the fat in cow’s milk,) it appears that only 50-80% of
the total amount is in the form of linoleic acid that is biologically active (Fomon 93), so the values
shown on the chart on the next page overestimate the actual amount of linoleic acid available for
metabolic uses. This is another clear indication why cow’s milk or goat’s milk should only be used
as a part of a child’s diet and certainly not as the main source of calories.
Other forms of fat need to be included in an infant’s diet, as cow’s milk fat alone can actually
result in essential fatty acid deficiency. I once observed this situation in a child admitted to the
intensive care unit in our hospital with a variety of unusual symptoms. A careful diet assessment
revealed that nearly all of his fat intake was in the form of dairy fat. A laboratory measurement of
the triene:tetraene ratio then confirmed the suspected EFA deficiency.
Note that the table on the next page addressing the relative inadequacy of linoleic acid (the
omega-6 essential fatty acid.) It does not address the additional inadequacy of linolenic acid (the
omega-3 essential fatty acid) discussed earlier as being so important for making subsances such as
EPA and DHA. Further, most vegetable oils are not well-balanced in the ratio of omega-6 to
omega-3 fatty acids. The essential fatty acids in corn oil, for example, are almost all omega-6.
[For additional information on this issue please see
“All Those Lipids: Recommendations for Using Different Types of Vegetable Oils
(Omega-3, Omega-6 and Monounsaturated Oils.)”]
3
Essential Fatty Acids
_________________________________________________________________________________________
Suggested Intake: (FAO/WHO) and regulation level for formulas is 1.2 % of energy as Linoleic Acid.
Goal is to provide 500 mg/day (Foman 93)
________________________________________________________________________________________
Linoleic Acid as a
Total PUFAs
Total PUFAs as a
Linoleic Acid per 100 kcals &
mg/oz
Percent of Total Fat
intake per 18 or 24 oz milk/day Percent of Total Fat
(Pennington: Bowes & Church 94)
(Fomon 93)
(Worthington Roberts 96)
_____________________________________________________________________________________
Cow 's milk:
Whole: 1.12 mg/100 kcals
1%
37
4
18 oz = 4.1 mg
24 oz = 5.4 mg
_____________________________________________________________________________________
2% : 0.92 mg/100 kcals
1%
25
4
18 oz = 2.5 mg
24 oz =3.3 mg
_____________________________________________________________________________________
Skim : 0.02mg/100 kcals
1%
18 oz = 0.04 mg
24 oz =0.05 mg
______________________________________________________________________________________
Human milk:
5%
200
14.3
So why do people want to use cow's milk for infants?
Some people have the mistaken notion that unpasteurized cow's milk or goat's milk is
somehow more nutritious or "natural" . . . which it is for baby cows and goats. For human infants it
is significantly less appropriate than human milk or formula, and as already described, it is potentially
dangerous. The major reasons for switching from commercial formula to cow's milk (pasteurized or
not) during the first year are cost and convenience factors.
For young infants or those with health problems, this practice should not be encouraged.
However, if the infant is at least six months old, is a healthy baby, and is eating the equivalent
volume of 2-1/2 to 3 jars of baby food daily, some of the problems with whole cow's milk can be
tempered.
For example, by adding three 4-oz servings of cereal, fruit, or vegetables daily, the
carbohydrate portion of the diet moves into the acceptable range, and the protein percentage
decreases down to the acceptable range. By filling up on other foods, the baby will probably also
drink less milk, which will also decrease the protein and sodium intake. If one selects the other foods
carefully (including meats and a wide variety of other nutrient-dense foods), some of the other
nutritional shortcomings can be remedied as well, such as decreasing the high sodium content and
improving the vitamin /mineral content of the diet.
4
Because of the observations about inadequacy noted above, a few years back (about 30,
actually) when I was first working for the (brand new) WIC Program, the American Academy of
Pediatrics decided that switching from human milk or formula to whole milk would be acceptable
after age six months “for babies who were eating a variety of foods.”
However, studies were done that showed that although it is possible to achieve a balanced diet
this way, most babies who had been put onto whole milk, in fact did not receive a balanced and
appropriate diet. So the recommendation of human milk or formula for the first year of life was reinstituted. The more recent questions about the safety of pasteurized cow's milk products during
infancy (e.g. yogurt, cottage cheese and ice cream) as adjunct foods do not represent a major policy
change. [Interestingly, during the AAP’s “6-months-is-ok” period, WIC held its ground and
continued to provide only iron-fortified formula to non-breastfeeding infants for the entire first year
of life. Way to go, WIC!]
One further caution before switching to cow’s milk or goat’s milk is to be sure that the baby
regularly eats table foods that contain some (especially omega-3 rich) vegetable oils in order to obtain
appropriate levels of essential fatty acids. Most baby foods are extremely low in fat, as are many of
the “starter” table foods like fruit, crackers and cereals. Other dairy foods like cheese, butter or
yogurt provide only the same limited amount as milk does, even when the total fat content is high.
So, especially when the baby is eating commercial baby foods as a major part of the diet and
has switched to milk, extra care must be taken to provide sufficient essential fatty acids. Fortunately,
this can be done quite easily when one is aware that it is an issue. Hydrogenated oils like margarine
and shortening should not be considered as sources of essential fatty acids because the
hydrogenation process significantly decreases the essential fatty acid content of the product.
This is in addition to the well-known concerns about partially hydrogenated oils forming trans fat.
What about evaporated milk formula?
Many people have been raised on home-made evaporated milk formula, although it is rarely
used today. Its major advantage is its lower cost than commercially made formulas, while being
better suited to infants than regular cow's milk. Because it is canned, it has been sterilized and the
heat treatment makes the protein more digestible.
Corn syrup or sugar has traditionally been added to adjust the proportion of carbohydrate, protein
and fat, as shown below. Water is added to adjust the calories to 20 calories per oz, (the same calories
as in human milk, formulas and whole milk). (See the chart on below)
______________________________________________________________________________________
Percent of calories from:
CHO
PRO
FAT
____________________________________________________________________________________________________
Desirable range:
35 - 65
7 - 16
30 - 5
Evaporated Milk Formula made with Corn Syrup:
45
15
40
______________________________________________________________________________________
5
Digestion and absorption are still not as good as is seen with human milk and formula,
because the form of fat is more difficult for babies to digest in addition to being a poor source of
essential fatty acids. Milk fat can be quite constipating for some children, but the corn syrup
usually has an osmotic laxative effect to counter it. (Somehow that arrangement does not sound
optimal!)
In the 1980s a concern was raised about the safety of corn syrup for small infants (J. Food
Protect. 1989:45,1028.) Some samples were found to contain heat-resistant spores of Clostridia
botulinum, a type of bacteria that has been associated with a form of SIDS (Sudden Infant Death
Syndrome). It was estimated that about 5% of SIDS cases at that time may have been due to "infant
botulism" linked to the use of corn syrup or honey in young infants.
For this reason it was suggested that when this type of formula is used, the corn syrup or honey
should be replaced by table sugar. Since then, manufacturing techniques have improved and corn
syrup no longer is regarded as a risk factor for developing infant botulism (J Food Protect. 1991),
although honey should continue to be avoided in the first year of life. [Note: Honey baked into foods
like graham crackers is safe because the high temperature of preparation kills the spores. This
question still comes up often.]
Human milk or commercial infant formulas are still preferred over evaporated milk
formula because of their more complete nutrition and better digestibility. As with any cow's
milk product, evaporated milk formula is naturally low in iron, copper, selenium, zinc, essential fatty
acids, and vitamins C and B-6. Vitamins A and D are usually added, but might not be. This product
should be of historical interest only. It belongs to what I call the “This is white … just feed it to ‘em
School of Nutrition”
Because of the great potential for nutrient inadequacy, a registered dietitian or physician who
is knowledgeable about these issues should look carefully at a baby's whole feeding plan to assess its
adequacy. A supplement should be recommended if other foods are not providing these missing
nutrients. However, my experience has been that nobody looks at this issue at all, so careful
nutrient supplementation in this situation is theoretically possible but practically non-existent.
And, as the babies do not “look funny” their deficiency state usually remains unrecognized.
And finally, I found on the internet a blog from a woman who has discovered the joys of
making one’s own evaporated milk infant formula. The main benefit she cited was that it was
much cheaper than regular formula. [But not as cheap as breastfeeding! ☺] The best part: she is quite
comfortable about using it for her baby because she has “talked to some people over fifty and they
seem to be OK.”
As it happens, I was fed evaporated milk formula with corn syrup in 1950 and I lived to tell
about it. But in those days we were not fed that product exclusively … we were also fed ironfortified cereal practically before we left the hospital, and right away we were regularly fed egg
yolks and liver as well. The yolks were also given “for iron,” since then (as now) that was about the
only nutrient ever evaluated so anemia was actually sometimes recognized as a problem. But it turns
out that the iron was not wonderfully absorbable from either the cereal or the yolks.
6
In retrospect, the yolks turned out to have lots of other good things we didn’t even know
existed, like choline. Choline is looking like a very important nutrient for brain function (as in the
neurotransmitter “acetylcholine”) and providing some ready-made choline to babies looks like a very
good idea.
Pre- and Postnatal Health: Evidence of Increased Choline Needs. JADA August 2010)
And thank heaven for that liver, which provided actually absorbable iron and zinc, plus lots of
choline and vitamins A and D and many other nutrients!
Using the classical (translation: “old”) evaporated milk formula with today’s typical feeding
patterns (e.g. waiting to introduce other foods until 4-6 months) has the potential to do significant
harm to that baby.
And even if some of us over-fifty people are actually “OK,” it is really quite foolish to trust
that precious baby’s health and development to our scientific knowledge base of 60 years ago. We
old folks didn’t have seat belts either and we’re still here. Well … at least, SOME of us are!
7
Sanford Medical Center
Aunt Cathy’s Guide to:
Choosing
Appropriate
Infant Milks and
Formulas
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
and Clinical Associate Professor of Pediatrics
UND School of Medicine, Fargo, ND
Part 1: Nutrition Issues in Breastfeeding.
The ideal food for most babies is human milk. Even for this nearly Universal Truth
however, there are exceptions (e.g. infants with the rare inborn metabolic error "galactosemia" may
not have human milk.) Formulas are attempts to provide similar nutrition for healthy babies who
are not breast-fed, or to meet the nutritional requirements of infants with special health problems.
The American Academy of Pediatrics recommends human milk for at least the first year of life.
Although it is less common in America than in other nations, nursing through the second
year (or even longer) is also beneficial and the practice is increasing. [However, it is important to
note that, for reasons described later, it is not recommended to breastfeed the baby exclusively
without the addition of selected other foods after six months, and without vitamin D
supplementation throughout breastfeeding.]
This part of the paper will focus primarily on some evolving issues regarding the
assurance of macronutrient and micronutrient adequacy in human milk. Commercial
formulas and cow’s/goat’s milk issues in infant feeding will follow.
[For a more complete discussion of the many benefits of human milk and a review of the data now
available that demonstrates its clear superiority to any formula for most babies, please see my
separate paper entitled “Some Issues in Breastfeeding.”]
Macronutrients: Protein, Carbohydrate and Lipids
The best infant diets are those which provide adequate but not excessive amounts of
calories, protein, vitamins, minerals and fluid, with a distribution of calories from carbohydrate,
protein and fat in the "desirable range". This is the range within which babies have been seen to
grow well without excessive metabolic stress (Fomon, 1974.) It appears that most babies are fairly
flexible little people and tend to do well within a fairly broad range of feeding practices.
1
Percent of calories from:
CHO
PRO
FAT
_________________________________________________________________________
Desirable range:
35 - 65
7 - 16
30 - 55
_____________________________________________________________
Human milk:
38
7
55
_________________________________________________________________________
Protein
Why is human milk at the lower end of the range in protein?
Human milk has a protein content on the lower end of the range and a fat content on the
upper end. This is acceptable because the forms of protein and fat are so perfectly suited to baby's
immature digestive and metabolic systems that absorption and utilization of these nutrients is
optimal. The protein content of human milk will continue to stay in the appropriate range even
when mothers are protein deficient. This is because protein goes into the milk at mother’s
expense if there is an inadequacy.
No other food has protein that is so well absorbed or well utilized, so it is best to avoid the
extremes of the “desirable range” if something other than human milk is fed. In other words, a
diet that provides only 7% of calories as protein from formula or any other source could be
inadequate for optima growth.
As discussed in a later section, commercial formulas do provide a more generous
percentage of calories as protein for that reason (milk-based formulas provide ~9-11 % of calories
as protein, and soy products provide 11-13%. But both human milk and formula protein
adequacy can be compromised by practices such as adding lots of additional carbohydrate or fat
calories for babies with higher calorie needs, or giving a substantial amount of cereals, fruits or
juices to the diet.
Neither the protein nor calcium content of human milk is greatly affected by current
maternal diet, but that does mean that maternal dietary inadequacies will be compensated for by a
loss from the mother’s stores or tissues. For that reason, a poor intake is certainly not optimal for
mother’s health. Mother and baby should not be in competition for nutrients. There are also
specific examples of the many benefits associated with assuring the adequacy and absorbability of
maternal calcium intake during both pregnancy and breastfeeding.
For example, the adequacy of current calcium intake and absorption has been shown to
decrease the developing baby’s exposure to harmful substances that may be stored in the mother’s
bones. This includes heavy metals like lead. If the mother has to mobilize her bone calcium to
replace blood calcium lost to the fetus or the milk, any lead present in her bones would be freed
and enter the bloodstream along with the calcium. It would therefore reach both mother and baby.
2
Carbohydrate
The carbohydrate of human milk is lactose …a combination of glucose and another
simple sugar (a monosaccharide) called galactose. The lactose is broken apart by lactase enzyme
and the two monosaccharides are then small enough to be absorbed. Failure to break it apart
means the lactose will not be absorbed. If the problem is severe enough this can result in wasted
calories, diarrhea and intestinal gassiness … the classical picture of “lactose intolerance.”
So how common is lactose intolerance in infants? Actually, babies all around the
world are rarely truly “lactose intolerant” even in populations who become less able to digest
lactose as they get older. Babies can be temporarily lactose intolerant due to intestinal damage
due to malnutrition, infection, or certain diseases like unrecognized celiac disease (after gluten
has been introduced.) But even then, the benefits of continuing to provide human milk far
outweigh any potential problem with lactose in most instances.
The popular conception that lactose intolerance is a big problem with infants is very
overblown, and it is primarily a marketing opportunity. As discussed later, many formulas that are
advertised as lactose free also have other changes in their construction that can contribute to baby’s
tolerance.
Lipids: Fats and Sterols
Cholesterol One of the components of human milk that is not in any formula is readymade cholesterol. Cholesterol is actually a very important structural sterol, being a key
component of all cell membranes and the myelin around nerves. Babies need to grow rapidly so
they need to make lots of new cell membranes, and they need to myelinate their nervous system
in utero and in the first two years after delivery. Several hormones and bile are also made out of
cholesterol.
We have always assumed that babies could simply make their own cholesterol from the
other substances in formula. However, if a baby had difficulty making the optimal amount of
cholesterol, no commercial formulas would help him/her out. But human milk would provide
that extra boost.
[There is a rare genetic condition of severe inability to produce cholesterol called SmithLemli-Opitz Syndrome. Impairment of cholesterol production is so severe that even the human
milk pre-formed cholesterol content is insufficient to solve the problems for several reasons.
However, babies having difficulty producing optimal cholesterol temporarily for reasons of
serious illness or prematurity might truly benefit from having some delivered “ready-made.”]
Essential fatty acids The fatty acid distribution depends on the mother’s diet, and in
most instances in America, people take in generous total fat (or other calorie sources,) and
sufficient amounts of linoleic and alpha-linolenic acids from plant oils (the “essential” fatty
acids.) It is not difficult to assure caloric adequacy and adequate amounts of these two essential
fatty acids for the fetus and for human milk.
3
However, it now appears that some other fatty acids may also be “essential” because
the ability of some people to make enough of them on their own is insufficient. Pregnancy
and lactation in particular appear to be periods where some people fail to make an optimal
amount from the two 18-carbon essential vegetable oils.
One example of a potentially essential form of fat is the 22-carbon omega-3 fat called
DHA (DocosaHexaenoic Acid). DHA is critical to brain and retinal development. Our
assumptions have been that this fat can be readily made from alpha-linolenic acid by way of an
intermediate 20-carbon fat called EPA (Eicosapentaenoic Acid.). Now it appears that the
omega-3 fats EPA and DHA, and the 20 carbon omega-6 fat ARA (Arachidonic Acid) are
“conditionally essential.” In other words, some people can make enough on their own and some
people cannot, and they are especially unable to do it during pregnancy and lactation when
providing DHA is so important for brain development.
Milk DHA levels can be quite variable depending on the mother’s current intake and
stores, and worldwide the DHA content of human milk has been found to be decreasing. This is
now seen to be a serious issue during pregnancy as well. Bottom line: It is now recognized
that the ability of most humans to produce DHA from the essential plant fatty acid
linolenic acid via EicosaPentaenoic Acid (EPA) is much less than was presumed.
Long-Chain Omega 3 Fats in Mother’s Milk:
Fetal and Infant Development Issues:
The discussion of omega-3 fats in particular is included here because it is unrelated to the
macronutrient (calorie) function of fat discussed later. Oils rich in omega-3 fatty acids perform
many specific important metabolic functions. They have important implications in pregnancy
and infant nutrition in particular. As described, DHA is a major fat of the brain, and research is
growing that providing some pre-formed DHA is advantageous. Other health benefits continue to
be identified, including the (so far) a possibility of decreased risk of preterm delivery and
decreased risk of allergies.
[There are many additional health benefits identified for other age groups as well, including
maintaining cognition as we age, and issues related to attention and mood. These are described in
some detail in my paper “All Those Lipids: Recommendations for Using Different Types of Fats
and Oils (Omega-3, Omega-6 and Monounsaturated Oils)” That paper also explains the
relationship of the different fatty acids more clearly … and it has pictures!]
Food sources of EPA and DHA: Fish and fish oil provide ready-made EPA and DHA.
Taken during pregnancy they improve the DHA content of the fetal brain, and during lactation it
increases the amount of pre-formed DHA provided to the infant.
The “pre-formed” part is important: it is now recognized that there is considerable
variation in the ability of different individuals to efficiently operate the pathways that make
alpha-linolenic acid into EPA and then into DHA. Alpha-linolenic acid is the form of omega-3
4
fat found in plants. Flax, canola and walnut oil are the most generous sources. Many --- perhaps
even most ---people can use it to make the DHA as needed. But for many people there is a clear
benefit from getting at least some EPA and DHA “ready-made” in fish and fish oil supplements.
This appears to be particularly true during pregnancy and lactation.
That means that many people must rely on an outside source of EPA and DHA to assure
adequacy for their own needs and for the baby. In essence, this means that for some people,
these fats are also “essential” because that term means that a person cannot make enough on
their own.
This discovery of impaired ability to make adequate EPA and DHA from linolenic acid is
well demonstrated now. For example, it is one of the reasons behind the recommendation of the
American Heart Association that people eat fatty fish twice a week or take supplemental fish oil
because that is the ready-made source of both EPA and DHA. So, clearly, we need to look
closer at the adequacy of the mother’s diet and nutritional status in general.
Many health professionals erroneously assume that mother’s milk will have all the
nutrients needed by the baby regardless of mother’s nutrient intake. As noted earlier, it is
the same concept as the old “perfect parasite” theory of a generation or two ago that presumed
that babies simply took whatever they needed from the mother’s body during pregnancy. That
view has been disproved and discarded long ago, but the same old idea continues to be
erroneously applied to the concept of nutritional adequacy in both pregnancy and lactation.
DHA made from an algae source is also available as a supplement, and it is the kind
used in some supplements designed for pregnant women and in some children’s gummi DHA
supplements. This is the same form used to provide pre-formed DHA in infant formulas. It can
be a reasonable source of DHA depending on the dosage or amount of DHA per-gummi. And
comparison shopping shows that gummi-type DHA supplements for often children provide very
little DHA per gummi and they can be quite costly. Additionally, the algae-based products do
NOT contain any EPA … the omega-3 fat between linolenic acid and DHA.
EPA has many metabolic roles in the body involving inflammation, blood clotting,
the immune system and other functions, and a person with an inability to produce DHA will
likely have a difficulty making EPA as well. For that reason, fish oil as a supplement for
pregnant and nursing women has advantages over the products that only provide DHA. Fish oil
supplements are easily available now that are free of mercury and other substances that
would be of concern when eating fish to get these special oils.
Do breast-fed babies need anything else?
A Look at Micronutrients: Vitamins and Minerals
5
Maternal diet/stores CAN be a factor in the amount of several vitamins and
minerals in mother’s milk as well. These include iodine, zinc, selenium, all the B-vitamins
and vitamin C, so attention must be paid to the adequacy of her intake. The fat soluble vitamins
(A, D, E and K) are now being re-evaluated in this regard as well.
This is a surprise to many health professionals because earlier models of prenatal and
infant nutrition were based on assumptions that the fetus was a “perfect parasite” taking
everything it needed, even at mother’s expense. The same assumption carried over to
assumptions about the nutritional content of human milk.
This was all in the absence of being able to confirm things scientifically. However, now
that these issues have been able to be evaluated, it is clear that the presumption of nutritional
adequacy provided to the fetus or breastfed infant needs to be replaced with careful
attention to a number of nutrients in the mother’s diet.
Micronutrient Issues: Vitamins
Vitamin D
An epidemic of vitamin D inadequacy in people of all ages has been the focus of
literally hundreds of recent reports in the scientific literature. For years, vitamin D inadequacy
has been assumed to be a non-issue because most of the time, deficiency lacks the only symptom
that has traditionally led physicians to even look for it: that is, overt bone deformity in children.
It has long been (erroneously) assumed that everybody easily produces generous amounts
of vitamin D from the action of sunlight on skin. Additionally, as vitamin D is found naturally in
very few foods, it has been added to milk and a few other foods more recently in the US.
However, the amount currently added is insufficient to maintain appropriate blood vitamin D
levels in most cases. Vitamin D deficiency is now recognized as very common,
very dangerous, very often unevaluated and rarely corrected. The health
consequences are very serious, but the entire situation is very easy to fix once
the issue is recognized.
Maternal/child vitamin D deficiency issues deserve a close look here.
[The following is an excerpt on specific vitamin D deficiency issues in lactation from my paper “Aunt
Cathy’s Guide: My Current Top Five Ways to Improve Your Family’s Nutrition.”
There is much more on multiple vitamin D issues in that publication, including recommendations for
action. A version is also available with many references from reports in the scientific literature.]
----------------
6
Vitamin D Inadequacy in Breastfeeding Alert
Interestingly, mother’s milk is an amazingly nutritious food and breastfeeding is certainly
encouraged. However, the milk does not contain vitamin D. This is probably because when
people were invented nobody lived in Fargo. As an adaptation to live well up here, we need to
have a furnace, a coat, really good mittens and vitamin D. It is that simple. It is also a possibility
that the milk would provide adequate amounts if the mother herself were not vitamin D deficient.
This question is being studied, but in the meantime, for the health of both mother and baby, it is
best to assume that it provides too little unless it is actually checked.
Because of the finding of serious vitamin D deficiency in many breast-fed babies, in 2003
the American Academy of Pediatrics recommended that breastfed babies be given “at least 200
iu of vitamin D by two months of age.” In 2008 that recommendation was changed to
400 iu/day for ALL infants and they recommended starting it right away because many
babies were actually born with inadequate stores of vitamin D because their mothers were
deficient during pregnancy (in spite of taking prenatal vitamins.)
This recommended change also included formula-fed babies and not just breast-fed
babies because the standard formulas provided 400 iu only when about a quart (32 oz) a day is
consumed. Newborns usually take only about 20 oz, so formula-fed infants would also fail to
obtain 400 iu without supplementation.
This change brings US recommendations in line with those of their Canadian colleagues
who have recommended 400 iu for babies, and at least 800 iu for everyone else up there for
several years now. Here are some details of the kind of research that led to this change in
recommendation:
A recent study in Boston of 380 healthy infants and toddlers who were seen for a routine
health visit evaluated the prevalence of vitamin D inadequacy or overt deficiency. Forty four of
365 children,12%, had levels lower than 20 ng/mL (clearly deficient) and 146 children (40%)
had inadequate vitamin D status based on levels below an accepted optimal threshold (<30
ng/mL.*)
[Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers.
Arch Pediatr Adolesc Med. 2008;162(6):505-512.
Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of
deficiency. J Perinatol. 2007 Sep;27(9):568-71.]
The same Boston authors studied the therapeutic amounts of vitamin D supplementation
needed to correct the low vitamin D status of the children. They concluded that these two
approaches were effective for bringing low vitamin D levels into the range of >30 ng/mL*
within a 6 week treatment period: Daily 2000 IU vitamin D2 or D3, or Weekly 50,000 IU
vitamin D2.
[Treatment of Hypovitaminosis D in Infants and Toddlers.
J Clin Endocrinol Metab. 2008 Apr 15.]
7
*However, note that a report described earlier suggested that the healthiest ranges of serum
vitamin D may in fact be above this “optimal threshold” of >30 ng/mL, and that it might be in
the range of 36-48 ng/mL. [Optimal serum 25- hydroxyvitamin D levels for multiple health outcomes.
Adv Exp Med Biol. 2008;624:55-71.]
Many other approaches to therapeutic supplementation are being investigated as well.
There are concerns about inadequacy of vitamin D in breastmilk (or in any infant feeding
regimen) in MANY areas beyond its relationship to the pattern of overt bone deformity we call
rickets. Most are not visible.
Inadequacy of vitamin D is now known to be an independent risk
factor for an ever-widening range of negative health conditions:
“All-Cause Mortality”
Asthma Diabetes (both Type 1 & Type 2)
Cancer of the Breast, Colon, Prostate, Pancreas
and other types, with roles in both prevention and treatment.
Cardiovascular Disease
both heart attack and especially congestive heart failure
Depression and Dementia
Developmental Problems
End-Stage Renal Disease
Immune System Compromise
Lupus, Fibromyalgia and Scleroderma
Multiple Sclerosis
Osteoarthritis, Osteomalacia and Osteoporosis
Pain in Muscle, Nerve and Bone
Pre-eclampsia in Pregnancy
Rheumatoid Arthritis
Sarcopenia (muscle weakness) and Falls
8
Clearly, assuring the mother’s vitamin D adequacy is very
important to her health as well as the health of her infant, but this is
a topic outside the scope of the present article.
“The recommended adequate intakes for vitamin D are inadequate, and, in the
absence of exposure to sunlight, a minimum of 1000 IU vitamin D is required to
maintain a healthy concentration of 25(OH)D in the blood.”
Optimal serum 25- hydroxyvitamin D levels for multiple health outcomes.
Adv Exp Med Biol. 2008;624:55-71.
Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers Arch Pediatr Adolesc
Med. 2008;162(6):505-512. Treatment of Hypovitaminosis D in Infants and Toddlers. J Clin
Endocrinol Metab. 2008 Apr 15.] Prevalence of Vitamin D Deficiency Among Healthy Infants
and Toddlers Arch Pediatr Adolesc Med. 2008;162(6):505-512. Vitamin D Status: Measurement,
Interpretation, and Clinical Application. Ann Epidemiol. 2008 Mar 8. Sunlight, UV-radiation,
vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol. 2008;624:1-15.
Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008
Apr;87(4):1080S-6S. Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of
deficiency. J Perinatol. 2007 Sep;27(9):568-71.Am J Clin Nutr. 2004 Mar;79(3):362-71) ]
[See my “Top Five” handout for much more on vitamin D.]
This topic is absolutely mushrooming in the scientific literature and the issue is too big to
describe thoroughly. Note that the references cited above were from 2007 and 2008. Below
are just a few of the 2008-9 references out there I had in one of my other papers, and the 2010
literature has even more Every day another study pops out! I just don’t have time to organize
it all in time for this Feb. 2011 paper to get where it has to go.
However, anyone interested in looking further into this issue can easily go to
www.pubmed.org and enter the search term vitamin D. The response is overwhelming. You
can also limit your search, say, by entering the words vitamin D infant or lactation, or
whatever. “Pubmed” stands for “Public Medline.” It is a free service provided by the National
Library of Medicine at the National Institute of Health in Washington DC)
A Sample of Some of the Many 2007-2009
Vitamin D References in the Scientific Literature
2009
Modern concepts in the diagnosis and treatment ovitamin D deficiency and its clinical consequences. J Environ
Pathol Toxicol Oncol. 2009;28(1):1-4. Vitamin D and aging. J Steroid Biochem Mol Biol. 2009 Mar;114(1-2):7884. Vitamin D and type 2 diabetes Is there a link? Prim Care Diabetes. 2009 Apr 21. Behavioural and physical
characteristics associated with vitamin D status in women. Bone. 2009 Jun;44(6):1085-91 Hypovitaminosis D is
Associated with Greater Body Mass Index and Disease Activity in Pediatric Systemic Lupus Erythematosus. J
Pediatr. 2009 May 14. Association between 25-hydroxyvitamin D levels and cognitive performance in middle-aged
and older European men. J Neurol Neurosurg Psychiatry. 2009 Jul;80(7):722-9. Sex-specific association of serum
vitamin D levels with physical function in older adults.Osteoporos Int. 2009 May;20(5):751-60. Vitamin D status
and muscle function in post-menarchal adolescent girls. J Clin Endocrinol Metab. 2009 Feb;94(2):559-63. 25.
9
Vitamin D Supplementation and Reduced Risk of Preeclampsiain Nulliparous Women. Epidemiology. 2009 May
15. Association of 25-Hydroxyvitamin D With Blood Pressure in Predominantly 25-Hydroxyvitamin D Deficient
Hispanic and African Americans. Am J Hypertens. 2009 May 14. Effect of vitamin D supplementation in the
institutionalized elderly. J Bone Miner Metab. 2009 May 15. Association between serum 25-hydroxyvitamin D level
and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern
Med. 2009 Feb 23;169(4):384- 90. Nutrition and health: guidelines for dental practitioners.Oral Dis. 2009 May 15.
Circulating calcitriol concentrations and total mortality. Clin Chem. 2009 Jun;55(6):1163-70. Vitamin D and
cardiovascular disease.Pharmacotherapy. 2009 Jun;29(6):691-708.Serum vitamin D, parathyroid hormone levels,
and carotid atherosclerosis. Atherosclerosis. 2009 Jun 6. Prospective Study of Serum 25-Hydroxyvitamin D Level,
Cardiovascular Disease Mortality, and All-Cause Mortality in Older U.S. Adults. J Am Geriatr Soc. 2009 Jun 22
Increased Levels of 25 Hydroxyvitamin D and 1,25-Dihydroxyvitamin D After Rosuvastatin Treatment: A Novel
Pleiotropic Effect of Statins? [Crestor] Cardiovasc Drugs Ther. 2009 Jun 20.
2008
Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers Arch Pediatr Adolesc Med. 2008;162
(6):505-512. Treatment of Hypovitaminosis D in Infants and Toddlers. J Clin Endocrinol Metab. 2008 Apr 15.
Optimal serum 25- hydroxyvitamin D levels for multiple health outcomes. Adv Exp Med Biol. 2008;624:55-71.
Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need? Adv Exp Med Biol.
2008;624:1-15. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008
Apr;87(4):1080S-6S.] [Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother. 2008
Jan;9(1):107-118. Prevalence of vitamin D deficiency among healthy infants and toddlers. Arch Pediatr Adolesc
Med. 2008:162(6):505-512 Hypovitaminosis D among healthy children in the United States. .Arch Pediatr Adolesc
Med. 2008:162(6):513-519. ndependent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin
D levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008:168(12):1340-1349. Vitamin D and
cardiovascular disease risk. Curr Opin Clin Nutr Metab Care. 2008 Jan;11(1):7-12. Hypovitaminosis D in obese
children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. Metabolism. 2008
Feb;57(2):183-91. 25- Hydroxyvitamin D and Risk of Myocardial Infarction in Men A Prospective Study Arch
Intern Med. 2008;168(11): 1174-1180. Diagnosis and treatment of vitamin D deficiency. Expert Opin Pharmacother.
2008 Jan;9(1):107-118. Vitamin D in Health and Disease. Clin J Am Soc Nephrol. 2008 Jun 4. Monthly ambient
sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology. 2008;31(4):271-9,
2007
Neonatal vitamin D status at birth at latitude 32 degrees 72': evidence of deficiency. J Perinatol. 2007
Sep;27(9):568-71. Dose response to vitamin D supplementation among postmenopausal African American women.
Am J Clin Nutr. 2007 Dec;86(6):1657-62. The urgent need to recommend an intake of vitamin D that is effective.
Am J Clin Nutr. 2007 Mar;85(3):649-50. Vitamin D and prevention of breast cancer: pooled analysis. J Steroid
Biochem Mol Biol. 2007;103(3-5):708-11 Prevalence of Vitamin D Deficiency Among Healthy Infants and
Toddlers Arch Pediatr Adolesc Med. 2008;162(6):505-512. Neonatal vitamin D status at birth at latitude 32 degrees
72': evidence of deficiency. J Perinatol. 2007 Sep;27(9):568-71. Macro- and micronutrients in patients with
congestive heart failure, particularly African-Americans. Vasc Health Risk Manag. 2007;3(5):743-7. Vitamin D
supplementation & total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007
10;167:1730-7
Vitamin K
A new focus on a previously unrecognized inadequacy of vitamin K in many Americans
is showing that many people get far too little and that it contributes to serious health problems
such as osteoporosis, kidney damage, calcification of the arteries, pre-eclampsia, diabetes and
cancer of the liver and colon. This is in addition to the long recognized role of vitamin K as a
tool needed when one needs to clot blood.
10
Until fairly recently (starting in about 2005) the blood-clotting function was the only
known role of vitamin K. Another factor recently identified as contributing to inadequacy is our
assumption that generous amounts of vitamin K are provided by intestinal bacteria. Because of
this, little nutrition advice focused on this nutrient, it was not included in many multivitamin
products, and even the MyPyramid.gov website neglected to include it (or vitamin D) in the
sample two-week diet for nutritional adequacy evaluation.
However, it appears that we are all actually much more dependent on an outside source
(dietary or supplement) than was assumed. Vitamin K status was (and still is) rarely evaluated,
so it is still assumed that all is well. Recent research makes it clear that many people are in fact
getting far too little of this nutrient, and it is hurting them.
Concerns about “toxicity” of vitamin K based on the observation that it dissolves in oil
have also been shown to be incorrect. In fact, vitamin K is so non-toxic that there is not an upper
end of safety identified for its intake. No-one has ever demonstrated an overdose. One reason it
is not toxic is that it operatesna s a simple co-factor … a tool that must be present for certain
things to move forward. It does not MAKE you clot your blood … it LET’S you clot your blood
if your body is telling you to do it.
[Aside: People on the anti-coagulation drug Coumadin need to have a very consistent
amount because the drug works by interfering with vitamin K. Inadequacy is dangerous
for them too, however because it increases the volatility of coagulation. It also puts them
at risk for osteoporosis, cardiovascular disease and cancers like everyone else. No one
benefits from a vitamin deficiency situation. The Coumadin issue is a specific
drug/nutrient interaction … not a general nutrition issue. For people NOT on this drug,
vitamin K is not scary … although inadequacy of vitamin K IS scary.
Please see my paper “New Roles for Vitamin K” for all the details and references, and
another paper I have available for health professionals specifically on the Coumadin issue
and the new research that should significantly change how we manage it.]
Some of the new issues being identified have significant implications for pregnancy
and lactation. Women who have insufficient vitamin K are at risk of hemorrhage at
delivery and have an increased risk of pre-eclampsia. Their infants are at risk of
intrauterine hemmorhagic events.
Consider that in America it is common to give infants a vitamin K shot at birth, to
reduce the risk of hemorrhage in newborns who received inadequate vitamin K in utero.
That means that overt consequential deficiency in the newborn was a common enough
occurrence to make vitamin K administration at birth become a standard practice.
I think that means that we should look more closely at maternal vitamin K status (and
everyone’s for that matter.) For one thing, the vitamin K shot at birth does not protect against
hemorrhagic events in either mom or fetus. Studies of newborns have demonstrated that some
11
children are born with evidence of earlier hemorrhagic events that can contribute to
developmental delays.
Additionally, not all babies actually receive the vitamin K shot because of home delivery
options, parents’ right of refusal, etc. Teleologically, it would seem to be an inefficient plan to
design people in such a way that infants all around the world would be born vitamin deficient
and at great risk unless someone is on hand with a syringe full of vitamin K. This is an issue
requiring attention from both the obstetric and pediatric medical experts working together.
In the meantime, mother’s milk can easily be low in vitamin K if mother is low. And
many mothers have been shown to be low. If the baby received the vitamin K shot, the low
vitamin K status of her milk will not be an issue any more for the baby (Although it will still be a
problem for mother.)
But any breastfed baby to whom that shot was not administered really needs to have
vitamin K reliably provided. And again … at the moment it is not standardly in many vitamin
supplement products. Additionally, it would be a good idea to provide that extra vitamin K to a
formula-fed infant as well if the shot was not given … the amount provided in the formula does
not provide a generous enough amount to compensate for a combination of low stores at birth
and no vitamin K shot.
Vitamins B12 and B6
The B vitamins play many critical roles in metabolism and inadequacy can compromise
the growth and development of the baby. In America, serious deficiency of B vitamins is
presumed to be extremely rare, but it is now recognized that some of them need a much closer
look. Most health professionals are aware that alcohol abuse frequently results in dangerous
deficiency of thiamin and folic acid, and of course, perinatal alcohol abuse is even more
problematic. But there are other specific concerns about vitamins B12 and B6 that deserve
some special attention during both pregnancy and breastfeeding.
As described earlier, for some nutrients (e.g. calcium and protein,) a relatively deficient
mother will still provide a good amount to the fetus/baby even at her own body’s expense.
However, all of the water soluble vitamins (B vitamins and vitamin C) will fail to be
provided optimally to the baby if mother is deficient … maternal needs for these nutrients
must be met before she “shares.”
Vitamin B12
Recently, for example, it was found that babies of mothers who had an inadequate
intake of vitamin B12 have deficiency levels even if the mother’s labs show her own vitamin
B12 level to still be in the normal range. Deficiency is extremely injurious to the nervous
system of both mother and baby. The following are three circumstances that put people at special
risk.
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1. Because vitamin B12 is found naturally only in animal products, vegans are well known
to be at great risk unless they take a vitamin supplement containing vitamin B12. There
are MANY reports in the scientific literature about this problem and the damage to the
infants when it occurs during pregnancy or lactation. But simply assuring that the vegan
mother has been taking a supplement regularly for quite some time is all one needs to do.
But if she has not been taking one, or has only begun to take vitamin B12
during pregnancy, for example, her vitamin B12 status could easily still be too low
for the fetus/baby to receive the needed amount for optimal development. As vitamin
B12 is extremely non-toxic, ideally in this situation a physician or other provider should
consider giving her a therapeutic level to correct a suspected deficiency right away.
2. One of the less-well-recognized emerging risk factors for vitamin B12 deficiency is
among people who have GERD (gastro-esophageal reflux disease) and use PPI
(proton pump inhibitor) medications that prevent gastric acid production. Natural
sources of vitamin B12 require the presence of gastric acid before it can be absorbed.
[This is different from the role of Intrinsic Factor in vitamin B12 absorption.]
People who use these medications cannot absorb vitamin B12 from natural
sources, but they can easily get around this problem by taking a supplement that
contains vitamin B12 … just like vegans but for a different reason. In this case it is
because the crystalline B12 in supplements does not require the presence of acid in order
to become absorbable. But also just like vegans, if she has been taking the medication
for a long time and has only recently begun to take supplemental vitamin B12, there
may be a degree of deficiency sufficient to warrant giving a therapeutic amount.
3. It is becoming increasingly common for women of childbearing age to have undergone
bariatric surgery (gastric bypass for weight loss) prior to becoming pregnant. Longterm vitamin and mineral status in the women is rarely evaluated, but when it IS, there
are several nutrients commonly found to be seriously inadequate even with the use of
prescribed supplements.
Some of these, like copper deficiency (generally extremely rare in the general
public and therefore not monitored) are showing up as causes of serious neurologic
damage. The potential damage to a fetus or breast-fed infant is huge. Additionally,
months/years after the actual surgery many woman stop taking their prescribed
supplements for a variety of reasons. This is even more common among people with
less ability to afford them. Long term follow-up is rarely undertaken for anything
besides weight status and effect on cholesterol or diabetes. By the time micronutrient
inadequacies are recognized it is because they are severe enough to be visible … and
that is often past the point where prevention of injury is an option.
An additional important observation is that a study evaluating the nutritional status of
people considering bariatric surgery found that the majority had significant inadequacy
of a number of nutrients even before having the surgery. This may be because of a
likely history of trying various restrictive or unbalanced diets to lose weight. But it is also
13
a reflection of the fact that many people whose appearance suggests that they are very
“well-fed” are actually not “well-nourished” at all in terms of vitamins and minerals. In
fact, intake of several vitamins and minerals is recognized in large national studies to be
unsatisfactory in a large number of Americans.
[Please see my “Carnitine Explanations” paper for more information about another important
problem issue that may be present in some people undergoing bariatric surgery.]
Deficiency of vitamin B12 is just one of several problems that are of great concern in
the special pregnancy/lactation context. This mother may have several severe nutritional
problems that are very likely to have gone unrecognized. Unfortunately, the simple
multivitamin that solved vitamin B12 problems for vegans and PPI users is unlikely to be an
adequate intervention here. What should be done about it is outside the scope of this paper, but
vitamin B12 shots would likely be a needed. Heightening the awareness of healthcare
professionals about the existence of the problem is a good place to start.
[Please see my “Vitamin B12” handout for more information about problem issues with this nutrient.]
Vitamin B6
Adequacy of vitamin B6 in exclusively breast-fed infants has been found to rely often on
gestationally accumulated stores. For some infants, human milk alone without supplemental
foods may be insufficient to meet vitamin B6 needs after 6 months of age (Pediatr Gastroenterol Nutr
1996 23(1):38-44.) Earlier introduction of meats or the use of a multivitamin drop will correct this
situation. Most infant vitamin drops contain vitamin B6 and they often contain iron, but they do
not contain zinc. Meats are the richest sources of vitamin B6 and well-absorbed iron and zinc
… the three nutrients that have been observed to “drop out” of breastmilk after 6 months.
This argues for reversing our most recent traditional pattern of introduction of solids
by introducing meats by about age 6 months instead of introducing it after 10 months or
later. This problem can also be addressed by using a crushable-type multivitamin with minerals
instead of an infant vitamin drop; it contains all three of the micronutrients (zinc, iron and vitamin
B6) that decrease so precipitously in mother’s milk after 6 months. It can be crushed and added to
baby food.
Micronutrient Issues: Minerals
Iron
The iron in human milk is very well absorbed – the best of them all, with estimates
between 25% and 50% absorption. Compare this with the next best source of iron (meats, at
about 20%) and with the much less absorbable form in plants and pills (which are only about
14
0.25-2% absorbed.) But although iron in human milk is well absorbed, but there is not a great
deal of it.
Most term babies are presumed to have enough iron stored up so they do not "run out"
until about 4 months of age. Since this is the age at which many babies begin to have the
developmental skills to eat from a spoon, providing foods that are good iron sources plus the iron
in mother’s milk may be adequate.
On the other hand, one might argue for providing an additional source of iron (e.g. an
iron drop) to avoid emptying baby's iron reserves before he/she actually “runs out.” Premature
babies often have poorer iron stores because the iron (like zinc, calcium and other minerals) is
stored in the baby's body primarily in the third trimester of pregnancy. They simply get out of
line too soon.
The iron "cost" of growth is high, and inadequacy of iron stores can have serious
consequences. Anemia is associated with decreased ability to learn and to pay attention that can
remain a problem for months after the anemia itself is corrected by treatment. Additionally, the
“presumed iron stores” of the average term baby are just that … “presumed” … not “assessed.”
Historically this approach has not always served us well.
Iron-deficiency anemia has also been found to be associated with increased likelihood of
being identified as having mild or moderate developmental delay in school. This is likely
because iron has many important rolls in all of the cells of the body, including such tasks as
oxygen transport, energy production, protection against environmental toxins, and function of
brain neurotransmitters. For example, some iron-related brain-development functions in utero
are on such a strict time-table that inadequacy of iron during that period can cause irreparable
impairment.
As was the case with calcium, good iron status also decreases the absorption of lead from
the environment, a known agent of severe injury to brain, bone and kidneys, and a contributor to
hypertension. Iron deficiency results in an attempt to increase absorption of iron in the intestine,
and the process accidentally increases the absorption of lead as well.
Reliance on hemoglobin to screen for poor iron status is risky without also having
information about the adequacy of the person’s iron intake. This is because hemoglobin levels
can actually remain normal until iron stores are depleted. A low hemoglobin is a sign of trouble,
but a normal one tells very little about the status of iron stores. Measures of iron stores (like a
“ferritin” level) are rarely used at present in evaluating babies who appear to be healthy. But
asking specific questions about regular iron supplement use and/or meat consumption tells us a
lot about the likelihood of there being an unrecognized compromised iron status in a particular
woman or infant.
There is some concern that providing additional iron to a breast-fed baby may decrease the
effectiveness of one of the substances in human milk that helps to control bacterial growth.
Lactoferrin in human milk binds iron that E. coli bacteria in the gastro-intestinal tract need in
order to reproduce. Giving additional iron would make more free iron available to the bacteria
as well as to the baby.
15
It is not clear that this is a big problem, however, since there are many other bacteriafighting substances in human milk that are not affected by the presence of iron. Also, the fact
that most formula-fed infants thrive while regularly receiving generous dietary iron that is not
bound to lactoferrin suggests that is not a major problem. After all, these babies receive none of
the many other protective substances in breast milk either.
Complicating the picture is the finding that the iron in infant cereal that has traditionally
been used to provide iron in baby's diet may not be as well absorbed as had been believed. Its
ability to provide useable iron to the infant has been questioned, but so far no one has questioned
whether iron provided in the form of fortified cereal increases the risk of E coli infection in
breast-fed (or any) infants.
Two feeding practices can sometimes have an effect on the absorption of iron in infants:
1) Iron supplements given with a (non-human) milk or formula feeding are likely to be less
well absorbed compared with supplements fed with an acidic food or meat. Meat
contains “Meat Protein Factor” which enhances absorption of inorganic iron from other
foods fed with the meat.
2) Although in some cultures it is common to feed tea to infants, the tannins in it greatly
reduce inorganic iron absorption in both infants and adults. This does not appear to be a
problem for organic iron forms such as are found in breastmilk and meats, so feeding tea
to breastfed infants does not induce iron deficiency anemia the way it can in those not
breastfed.
Interestingly, in some world situations the traditional feeding of tea to infants has
actually been of great benefit in terms of child survival for the simple reason that the
water fed to baby has been boiled and germs have been destroyed. Together, protective
elements in mother’s milk and boiling any water fed to baby are a terrific combination
where bacteria and parasites make the water unsafe.
However, there is a risk of iron (and zinc) deficiency in a non-breastfed
infant who is regularly given tea, and people in many cultures do commonly give it.
One way to solve this potential problem (besides encouraging breastfeeding) would be to
advise them to introduce meats earlier, because the generous iron and zinc content is in
a form that is unaffected by the presence of tannins, plus the effects of Meat Protein
Factor can help avoid the problem.
Zinc
Iron often described as the micronutrient most likely to be deficient in Americans.
However, it is useful to remember that iron status is also the only non-electrolyte nutrient we
evaluate in many settings. Status of many other nutrients may be suboptimal, but one that is
particularly likely to be “iffy” in an individual with iron deficiency is zinc.
16
This is because in nature iron and zinc tend to be distributed similarly in foods and they
are also similarly affected by substances that impair or increase intestinal absorption. A person
who is iron deficient may also be zinc deficient, although we rarely evaluate it and therefore do
not recognize it. And if that person is iron deficient in spite of taking iron supplements and eating
iron-fortified foods (which are usually NOT also fortified with zinc,) the odds are even greater
that zinc adequacy may be compromised. The exception would be a person has relative iron
deficiency because of excessive blood loss.
This is not to make a case for checking zinc levels in people’s blood … the point is that
we can regard iron inadequacy as a marker/screening-tool for suspicion of unrecognized
inadequacy of zinc in particular, and many other nutrients as well. In general, people do not
consume a diet that gives them a terrific amount of all the nutrients needed except for just the
only one we check. Think of that low iron measure as the “canary in the coal mine” that tips you
off to an otherwise invisible threat in time to do something about it.
Why is zinc such an issue here?
Zinc is a co-factor in over two hundred metabolic pathways in the body, including making
DNA (the genetic center of every cell and hugely important for growth), making T-cells, and
metabolizing alcohol and other potentially dangerous substances. Inadequacy is known to impair
growth and the function of the immune system. However, zinc has been found to need some
attention in breast-fed infants. The same mineral storage patterns are seen for both iron and zinc,
with the third trimester being the major period of mineral accretion in the fetus. For this reason,
preterm infants are also especially likely to have poor zinc stores.
For term infants, the combination of a well-nourished mother who provided normal fetal
zinc stores and then provides human milk should meet growth needs until about age six months.
After that time, zinc and iron may be inadequate as described earlier. Of course, a history of poor
zinc nutrition of the mother complicates the picture further. Some studies have found that zinc
supplementation of exclusively breastfed infants in these circumstances improves growth or other
parameters of zinc adequacy [e.g. Lancet 2000 Jun 10;355(9220.)]
Supplementing a mother to maintain adequate zinc status does not correct this problem
because the zinc content of the milk begins to drop regardless of her zinc status. As described
earlier, a change in recommended “starter food” patterns has been suggested that includes an
earlier introduction of meats (the most abundant source of bioavailable forms of both iron and
zinc, and also a generous source of vitamin B6) in breast-fed infants [Acta Paediatr 1998;87(6); J
Mammary Gland Biol Neoplasia 1999;4(3)].
Again, note that infant vitamin drops do not provide zinc (or any minerals except iron
and sometimes fluoride) and they contain no folic acid. So if earlier introduction of meats is
undesirable, the best way to assure adequacy of zinc, iron and vitamin B6 would be to give a
crushed chewable children’s multivitamin with minerals.
Nutrient levels will not exceed safe ranges with this dosage, and this approach also
provides baby with the 400 iu of vitamin D recommended for all infants by the American
17
Academy of Pediatrics and the Canadian health groups as well. If texture is an issue, the pill can be
crushed to a fine powder using a small mortar and pestle. These are sold in kitchen stores and
discount stores (often for $10 or less) because they are used to crush fresh spices. The powder can
be mixed into any baby food.
More information about the zinc content and foods, zinc absorption
and some special zinc-related issues in fetal alcohol syndrome, are included in my handouts:
“Nutrition Support of Iron Deficiency” and “Thinking about Prenatal Nutrition and Fetal Alcohol Syndrome (FAS.)”
Iodine
Another nutrient problem that has recently been found to need more attention is
IODINE DEFICIENCY. In many parts of the world (including parts of the US) iodine
deficiency is common, and the traditional international approach to solving it has been to add
iodine to salt. However, it appears that the amount obtained from iodized salt is actually not
sufficient during pregnancy, and that even in areas that have been thought to have corrected
iodine deficiency many women obtain too little.
Iodine Deficiency Disease (IDD) is the number one cause of preventable mental
retardation in the world. The resurgence of the problem of iodine deficiency in the US has
great importance in pregnancy and lactation in particular because of the devastating effects on
the intellectual development of the child. Iodine deficiency can also result in deafness, and a
serious lack of energy in anyone affected because it impairs the function of the thyroid gland.
The World Health Organization is now increasing the recommendation for iodine intake by
25%, especially in pregnancy.
Here is an excerpt from a presentation by UNICEF Deputy Executive Director Kul
Gautam:
“… IDD is the single greatest cause of preventable mental retardation. Severe deficiencies cause
cretinism, stillbirth and miscarriage. But even mild deficiency can significantly affect the
learning ability of populations. Scientific evidence shows alarming effects of IDD. Even a
moderate deficiency, especially in pregnant women and infants, lowers their intelligence by 10 to
15 IQ points, with incalculable damage to social and economic development of nations and
communities. Today over 1 billion people in the world suffer from iodine deficiency, and 38
million babies born every year are not protected from brain damage due to IDD…”
UNICEF Deputy Executive Director Kul Gautam
This quotation comes from the website http://www.saltinstitute.org/Issues-in-focus/Food-salt-health/Iodized-saltother-additives. It has much more information about the problems of (and solutions for) IDD.
[For more detail on the most recent research on this topic in the scientific literature, please see my handout
“New Attention to an Old Problem: Iodine Deficiency in Pregnancy and Lactation”
18
The area of the United States that used to be designated the “goiter belt” because of low
iodine in the soil is shown on the map on the next page. The actual iodine content of foods
depends on where they were grown, and some protection has likely been provided to the lowiodine regions by the fact that at least some produce may have been grown in an iodine-sufficient
region.
This is a new issue to keep in mind as we promote growing one’s own food and buying
from local producers instead of transporting produce from far away. Local food production is
terrific for many reasons, but if one lives in an iodine-poor region, it is important to assure iodine
sufficiency via a demonstrably adequate intake from some form of iodine supplement.
Map showing spatial correlation between the former "Goiter Belt*"
in the northern U.S. and areas where
the iodine content of drinking water is naturally low.
www.uwsp.edu/gEo/faculty/ozsvath/images/goiter_belt.htm
[*Goiter is an abnormal enlargement of the thyroid gland, often due to iodine deficiency.]
Back home in America, many people under age 50 who live in iodine-poor regions of the
country are quite unaware that they should select “iodized salt.” The public health hoopla that
accompanied the iodizing of salt in the early 1950s (yes, I remember it … I was THERE!)
somehow faded away and the issue went off the radar. Many people of child-bearing age today
have no knowledge that this was once a widespread deficiency disease in the US of critical
19
importance to everyone’s health and especially dangerous to the development of infants
and children … and they don’t know it has come back
Even when one intends to buy the iodized salt, the packaging is often very similar and
they are side-by-side on the shelf at the store. Most specialty salts that are popular now, like sea
salt or exotic salts, are also not iodized. So generally, one should choose iodized salt if one uses
salt at home, and people who use little salt should be sure to find an iodine supplement,
especially if they live in the northern half of the country.
Additionally, we frequently are advised to cut back on salt for other health reasons,
which can further limit iodine intake. Recently some national health recommendations pushed
for an even lower daily sodium intake than before … instead of 3000 mg/day they recommended
1500 mg. I am not arguing against this recommendation … just pointing out the need to make
sure that people who follow this health advice are not accidentally injured by iodine deficiency.
Remember that the choice of salt as the way to supplement dietary iodine was made
well before ideas of sodium restriction were common for health reasons. Other factors have
made an inadequate intake much more likely today. For example, in the 1950s people made
most meals from scratch, so iodized salt would be added whenever salt was used in cooking.
Now most of our sodium intake comes in the form of processed foods, which are high in salt but
the salt is not iodized. Here is an excerpt from a website on this topic:
“…In the United States, from the outset, salt producers cooperated with public health authorities
and made both iodized and plain salt available to consumers at the same price. Even so, the Salt Institute
estimates that only about 70% of the table salt sold in the United States is iodized.
Salt used in processed foods is not iodized. Given that people are cooking less at home and
buying either restaurant or processed foods, iodine intakes in the U.S. have declined from about 250
μg/day to 157 micrograms/day. Public health authorities recommend 150 μg or more and the need is
particularly acute for expectant mothers. Daily Iodine intakes of 1,000 - 1,100 μg are safe for adults and
children over 4 years of age…”
http://www.saltinstitute.org/Uses-benefits/Salt-in-Food/Essential-nutrient/Iodized-salt
Also, because it has long been assumed that the iodine deficiency problem was “solved”
in the US by the iodizing program, at present many vitamin pills contain no iodine at all,
including many prenatal vitamins. So, this is one more nutrient that a person should check for
when they select a multivitamin.
20
The WIC Program recently added
use of a prenatal vitamin without iodine as a
nutrition risk factor for women enrolling in
the program. That means that some low
income women of childbearing age may
soon begin to have this addressed.
At least an awareness of the problem
is developing. However, MOST women
are NOT on the WIC Program so this
problem is unlikely to be readily
recognized. There is great potential for
harm.
There has been a resurgence of goiter development (a marker of iodine deficiency) in
America as well as around the world, and thought to be a problem. Additionally, data it is often
missed because it is no longer shows that average iodine intakes have decreased markedly in the
US. It is also reported that on average iodine intake is sufficient here [Iodine status of the U.S.
population, National Health and Nutrition Examination Survey 2003-2004. Thyroid. 2008 Nov;18(11):1207-14.]
However, when one stratifies the data it becomes clear that a great many women
here (and around the world) do NOT have a sufficient iodine intake even when men
generally do. The risk to fetal and maternal health is substantial, and easy to fix once the
problem is recognized.
Major Point: The problem of iodine deficiency needs
to be put back on our radar; this is a very newly recognized and
extremely important health problem that needs attention.
Please see my paper “Aunt Cathy’s Guide to Nutrition:
New Attention to an Old Problem:
Iodine Deficiency in Pregnancy and Lactation 2011”
for detail on this topic, including an annotated bibliography.
Some newer references are included here since this topic may be quite new to many
readers and I don’t want them to think I am making this stuff up! ☺
Iodine deficiency in infancy - a risk for cognitive development. Dtsch Med Wochenschr. 2010 Aug;135 (3132):1551-6.Parameters of thyroid function throughout and after pregnancy in an iodine-deficient population.
Thyroid. 2010 Sep;20(9):995-1001. Some subgroups of reproductive age women in the United States may be
at risk for iodine deficiency. J Nutr. 2010 Aug;140(8):1489-94. Iodine intake and maternal thyroid function
during pregnancy. Epidemiology. 2010 Jan;21(1):62-9.Georgian Med News. 2010 Jan; (178):65-8.Iodine
deficiency in the prenatal period may form learning ability deficiency in the postnatal period. Epidemiology of
iodine deficiency: Salt iodisation and iodine status. Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):111. Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development. 2010
Feb;24(1):29-38.Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the
offspring: a review. Am J Clin Nutr. 2009 Feb;89(2):668S-72S.
21
Fluoride
Fluoride is low in human milk and whether the mother's fluoride intake affects the amount
in milk is still subject to some debate. The recommendations for using fluoridated water, fluoride
drops, fluoride toothpaste and topical fluoride treatments have changed many, many times over the
years that I have been involved in pediatric nutrition. They are being changed again this year
regarding the recommended amount of fluoride to add to low-fluoride-containing water supplies.
The American Dental Association has a current list of very specific recommendations on
all aspects of the topic of fluoride as it relates to dental issues. It is available at this website:
http://www.ada.org/public/topics/fluoride/infantsformula.asp
22
6DQIRUG 0HGLFDO&HQWHU
Aunt Cathy’s
Guide to Nutrition:
CHROMIUM
(Short version without references.)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
6DQIRUGMedical Center Dept. of Pediatrics and
UND School of Medicine Dept. of Pediatrics
Chromium is an important nutrient that has been in the news recently. There have
been some unsubstantiated claims for chromium as a weight loss or muscle-building aid,
and careful studies have NOT found it to be helpful for these uses.
However, chromium adequacy IS important for controlling blood
sugar and fat metabolism (including triglyceride and cholesterol
metabolism), and the diet of many Americans contains considerably less
chromium than is recommended.
Current expert opinion is this:
1.
Inadequate chromium intake can certainly contribute to high
blood sugar (diabetes), to high blood triglycerides, and to cholesterol
problems.
A high triglyceride level in a person with diabetes is considered an important risk
factor for stroke. In a study of men and women with diabetes who had high
triglycerides, providing supplemental chromium just at the standard intake level of
200 mcg/day resulted in a significant improvement in triglyceride levels. (For those
who are interested: The study was randomly assigned placebo-controlled trial with a
crossover design)
The form of chromium used in that study was “chromium picolinate.” It appears
that not all forms of chromium supplements are equally well absorbed and utilized by the
body. The picolinate form has been shown to be one of the best absorbed sources.
Chromium chloride, the form used in many multivitamins is less well absorbed. There is
much interest now in studying the relative safety and the absorbability of the various
chromium–containing compounds now used as supplements. There are also several large
NIH studies underway exploring chromium supplementation in a variety of medical
conditions. Stay tuned . . .
1
2.
Many people in America eat a diet that does not provide enough
chromium because much of the grain products we use have been
“refined.”
The refining process removes many important vitamins and minerals in grain,
including chromium and magnesium in particular, ut many others as well. Most are not
added back when the product is “enriched. ” For example, only iron, and three B
vitamins (thiamin, riboflavin and niacin) are added back to original levels. [Since
1998, folic acid is now added to grain products in the US at a level above the original grain content.]
The “germ” of the grain is the nutrient-dense part … that’s the part that will
become the baby plant. The rest of the grain is starch for fuel for the baby plant, and a
fibrous protective bran coating. Guess which part we remove from the grain when we
refine it! If you guessed the bran and the germ, you’d be right. That means that we eat a
lot of processed grain foods that contain just the starch calories and the few added-back
nutrients mentioned above. That’s it. We don’t add back the many micronutrients
that are necessary to properly metabolize the starch, and we do not add back the
bran fiber and its many heath-related benefits. These include increasing the feeling of
satiety associated with eating it and (possibly) assisting in helping us limit our intake of
less satisfying sources of starch calories.
In spite of recommendations, most Americans eat few whole grains and
legumes. Interestingly, when people with diabetes are fed a diet that is rich in foods
that are “high in fiber”, their blood sugar control often improves. This is often
attributed to the effects of the fiber itself on absorption of carbohydrate in the intestine.
However, along with that effect there is the “accidental” great improvement in
chromium and magnesium intake with a diet that is high in fiber-rich foods, and
both of these nutrients have a role in blood sugar control and in many metabolic
pathways. In other words, there are many players on the team supporting healthy blood
sugars; it makes sense to assure that all are present in appropriate amounts.
Eating lots of foods with refined sugar and flour -- even “healthy” non-sugary
carbohydrate foods like rice or pasta -- increases the body's need for chromium. This is
because chromium is needed in order to use carbohydrate for energy, and these refined
foods are not good sources of it. If one cannot use the carbohydrate for energy, it is
converted to fat and stored for later.
The richest food sources of chromium are:
brewer's yeast, wheat germ, and oysters.
broccoli, cheese, prunes, peanuts, whole grain cereals,
mushrooms, asparagus and peas are also sources.
2
3.
If a supplement is used, how much is recommended?
For healthy people, there is no apparent advantage associated with taking more
than the recommended "adequate and safe" range of 50-200 mcg/day, although
studies suggest that levels up to twice this amount may be helpful for some people with
diabetes. This amount, even with a high fiber diet, is not dangerous.
An interesting question is: “Do people with diabetes actually need more
chromium than other people, or does people’s poor chromium status contribute to their
developing the diabetes?” That has not been evaluated yet. It may be that they do better
with a higher supplement level because their chromium stores are quite low and giving
just a regular maintenance dose may not get them up to speed. In any case, ASSURING
ADEQUACY instead of assuming adequacy is the way to go.
However, as with all minerals, excessive chromium can be toxic. Toxic
chromium levels are usually only seen with accidental food contamination, not from a
generous intake of chromium-containing foods. One would not overdose on chromium
from eating a big bunch of wheat germ. But it may be possible to cause chromium
poisoning from excessive use of chromium supplements, and it also appears that
excessive supplementation may interfere with absorption of other important nutrients. So
the safest course is to avoid supplementation above the recommended 200 mcg upper
level unless advised to do so by a physician.
3
Aunt Cathy’s Guide to Nutrition:
Sanford Medical Center
A Poem to Help Remember the
Highest Copper
Food Sources
Cathy Breedon PhD, RD, CSP, FADA
Clinical & Metabolic Nutrition Specialist
Sanford Medical Center, Fargo, ND
and UND School of Medicine
And some thoughts about
Managing Wilson’s Disease
The point of this little poem is that it is hard to memorize all the individual foods
that are high in copper, but the poem identifies some food groups to keep an eye on by
naming an example of each of those food groups. [I wrote this poem to solve my own
nutrient memorization problems in 1991, and … hey! I still remember it! ]
The poem can be helpful in identifying healthy and nutritious copper-rich food
groups to eat a good amount of (for most folks.)
It can also serve exactly the opposite function for people with Wilson’s Disease.
In this rare condition, people can absorb copper from food and beverages, but they cannot
get rid of it normally. Over time, the excess copper can build up and cause very serious
injury, especially to the liver and nervous system.
1
So, here’s how to interpret the poem:
Of meats, lamb tends to be the highest, and liver from all animals is generous in
copper. (And of these, lamb liver is really high. Luckily, it is pretty easy to avoid
lamb liver!)
Of seafood, the mollusks are highest (oysters, clams, etc.) They are much higher than
fin fish.
Nuts (e.g. almonds), beans (like pinto beans), seeds and the germ of grains have a
generous amount of copper. The way to think about them is that they are the
group of foods (or parts of foods) that would ordinarily be able to turn into
“Baby Plants.”
These are very healthy foods for most people, but not for people with Wilson’s
Disease. However, leaving them out can reduces our intake of magnesium and
chromium and some other nutrients, so people with Wilson’s DFisease will want
to work with a dietitian/nutritionist who can guide you toward other foods to
provide these critical nutrients and/or assist with identifying appropriate
supplementation.
Cooking with copper pans or other implements and running water through copper
pipes can add copper to your food. It’s easy to pick non-copper cookware, but
copper pipes are very commonly around, and for most people (i.e. people without
Wilson’s Disease) they are more healthy than many other pipe materials. [And of
course, lead pipes aren’t good for ANYBODY!]
One way that may help to lower exposure from pipes is to let the tap run for a
while to try to remove some of the water that has been sitting there in contact with
the pipe. This is not necessary for water that will not be taken into the body as
beverages or through cooking. (If you are concerned about wasting water, you
can collect it to water plants, wash socks or put it in the doggie dish.)
Another more effective solution is a “Reverse Osmosis” water treatment system
for the drinking and cooking water. However, not all types of water treatment
products or systems remove significant copper, so you need to ask about this
detail.
They can also be fairly expensive. You could ask your insurance company if the
water system could be covered as medically necessary if your physician orders it.
The “change her name to Penny” line is so that after getting through the whole
poem I could still remember what nutrient I was looking at. Pennies are copper
colored.
2
Some Additional Issues for People with Wilson’s Disease:
Limiting dietary copper will not be sufficient to protect you from copper
build-up. It is just one of the necessary tools. Your doctors will have other tools to
use as well, such as medications to do “chelation therapy” … a treatment to remove
excess copper from your body. Triethylenetetramine or D-penicillamine are medications
of this kind. Providing generous supplemental oral zinc can also be useful, as it
competes with dietary copper for absorption. For some people liver transplant is
necessary.
Another nutrition issue that appears to be helpful for people with Wilson’s Disese
is providing generous antioxidants. These include vitamins E and C, and the colorful
pigments in fruits and vegetables (a class of plant chemicals … “phytochemicals” … that
can provide even greater antioxidant protection than vitamins E and C.) Recent research
suggests that the need for generous antioxidant protection is higher in people with
Wilson’s Disease, as it is demonstrated to be in people with many types of metabolism
problems, like diabetes or hemochromatosis.
Some investigation with certain B vitamins, like vitamin B1 (thiamin) are being
evaluated as possibly of use in decreasing the increased risk of liver cancer sometimes
seen in Wilson’s Disease. Some particular lipid metabolism issues are also emerging
involving “HDL” (High Density Lipoproteins) --- the so-called “Good Kind” of cholesterol.
However, even though excess copper is dangerous for you, copper is still an
essential nutrient. Allowing copper DEFICIENCY to develop is also very injurious.
Your health care professionals will need to monitor your copper status to be sure that you
are safe from excessive copper, but not deficient in copper!
For everyone, assuring an adequate intake of ALL nutrients is very
important. For example, maintaining a blood vitamin D level of 40-50 mg/dL is
associated with decreased risk of cancer in general, and it is a factor in risk and treatment
of liver cancer, which is a particular risk in Wilson’s Disease. For more information on
the antioxidants, magnesium and chromium, omega -3 fats and vitamin D, please see:
“My Current Top Five Easy Ways to Improve Your Family’s Nutrition”
(subject to change at any moment! )
Your health care professionals will help you determine which approach(es) will
be best for you. [As always, my papers are NOT intended to take the place of careful
management of this dangerous and complex condition by your physicians. They are
just an attempt to help your care-givers sort through the nutrition end of this problem to
facilitate your overall control of the disease.]
3
Here are a few of the most recent references that I found in the scientific literature:
Diagnosis and care of Wilson disease with neurological revelation. Arch Pediatr. 2012 Jan 17.
Thiamine supplementation attenuated hepatocellular carcinoma in the Atp7b mouse model of
Wilson's disease. Anticancer Res. 2011 Oct;31(10):3395-9.
Long-term exclusive zinc monotherapy in symptomatic Wilson disease: experience in 17 patients.
Hepatology. 2009 Nov;50(5):1442-52.
Potential of vitamin E as an antioxidant adjunct in Wilson's disease. Med Hypotheses. 2009
Dec;73(6):1029-30.
Alterations of lipid metabolism in Wilson disease. Lipids Health Dis. 2011 May 19;10:83.
Excess copper chelating therapy for Wilson disease induces anemia and liver dysfunction. Intern Med.
2011;50(14):1461-4.
Inherited Copper Transport Disorders: Biochemical Mechanisms, Diagnosis, and Treatment.
Curr Drug Metab. 2011 Aug 12.
Wilson disease. A case report and review of the literature. Rev Med Inst Mex Seguro Soc. 2011 MayJun;49(3):331-4.
Fragmentation of mitochondrial cardiolipin by copper ions in the Atp7b-/- mouse model of Wilson's
disease. Chem Phys Lipids. 2011 Jul;164(5):393-400.
Wilson disease. Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):531-9.
A primer on Wilson disease for the general practitioner. Rev Med Suisse. 2011 Sep 7;7(307):1690-2,
1694-5.
Antioxidants as therapeutic agents for liver disease. Liver Int. 2011 Nov;31(10):1432-48. doi:
10.1111/j.1478-3231.2011.02604.x.
Repeated transplantation of hepatocytes prevents fulminant hepatitis in a rat model of Wilson's
disease. Liver Transpl. 2012 Feb;18(2):248-59. doi: 10.1002/lt.22466.
Acute Gallbladder Hydrops and Arthritis: unusual initial manifestations of Wilson's Disease (WD):
Case Report. Prilozi. 2011 Dec;32(2):207-15.
A clinical study of Wilson's disease: The experience of a single Egyptian Paediatric Hepatology Unit.
Arab J Gastroenterol. 2011 Sep;12(3):125-30.
4
Sanford Health
Aunt Cathy’s Guide to:
8-13
Thinking About
OTHER
Nutrition Issues
in Diabetes
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical and Metabolic Nutrition Specialist
Sanford Health (formerly MeritCare)
and UND School of Medicine
Fargo, North Dakota
Introduction:
Blood sugar control is the key focus of nutrition and diet planning for people with diabetes.
Historically the most attention has been paid to adjusting the intake of the types and amounts of
carbohydrate throughout the day, including the newer concepts of “carbohydrate counting” and the
“glycemic index.” Additional attention has been paid to total calories and total fat content, plus the
content of saturated fat and “trans” fat because of the importance of weight control in diabetes, and the
increased risk of cardiovascular disease. These remain the basis of diet and nutrition
interventions for diabetes.
However, information is becoming available about the special roles of certain vitamins,
minerals, phytochemicals, and some forms of dietary fat that appear to be useful in various ways in
fighting diabetes and its consequences. The nutrition tools described here do not “cure” diabetes – but
in many cases they have been shown to have the capacity to decrease the risk of diabetes developing.
Others have demonstrated that they can be useful for people who already have it by helping with
diabetic control, or by making diabetes hurt them less. This includes reduction in complications
like blindness, kidney failure, neuropathy, impaired circulation, and even birth defects.
Some have been shown to be helpful in at least one of seven ways:
1)
Enhancing insulin sensitivity.
2)
Using antioxidants to minimize secondary damage from poor diabetes control caused by
higher than normal production of free radicals.
3)
Reducing the severity of inflammation that has been shown to be associated with
diabetes in order to decrease risk of developing diabetes complications (including Type I,
Type II and gestational forms.)
4)
Helping stabilize/improve excessive fluctuations of blood sugar that can sometimes be a
problem in spite of following the diet very carefully (e.g. what some people used to refer
to as “brittle” diabetes.)
1
5)
Minimizing risk of developing other threats to health and well-being,
including conditions that are known to be exacerbated by diabetes.
6)
Minimizing the risk of developing diabetes.
7)
Discovering the emerging miscellaneous effects of a variety of phytochemicals
(plant substances) on the diabetic state.
Happily, all of the diet or nutrient ideas suggested here are also reported to be beneficial for
most folks in terms of decreasing risks associated with one or more of a variety of chronic illnesses,
including cardiovascular disease, cancer, MS, arthritis (both rheumatoid and osteo,) alzheimers,
parkinsonism, depression and osteoporosis.
In other words, the suggestions made here are all health-promoting for
the whole family, whether one has diabetes or not … they are just even more
important if you DO have diabetes.
It is also extremely important to note that all of the suggestions are based on research
reported in the legitimate peer-reviewed scientific literature. None are based on wild claims made
on the internet (or elsewhere.) There is no law against fiction in America, and therefore there are quite
a lot of false claims made for diet and nutrition in particular, often in the interest of selling products.
Many of the “dietary supplements” sold are in fact not related to nutrition at all. Many are
actually pharmaceutical products, but a loop-hole in the FDA laws allows the marketing of substances
in the “dietary supplement” category without having to show “safety and effectiveness” as they would
if marketed as pharmaceutical products.
Understandably, the existence of so much nutritional quackery in the world has made health
professionals hesitant to consider nutrition manipulations to be legitimate adjuncts to management of
complex diseases like diabetes. There is a tendency to just “throw the baby out with the bathwater.”
The purpose of this paper is simply to highlight areas of research that are identifying the real “babies”
to watch out for.
All the suggestions included here are generally regarded as safe at this time (I never
recommend anything that comes anywhere near to “scary,”) and they are often easy to do and
inexpensive. In two cases, the amount of the substance that has been shown to be beneficial is
somewhat impractical to attempt when using the currently available over-the-counter products. In
these cases, a prescription for the appropriate higher dosage product makes it much simpler.
Although these two products and one other are also among the more expensive interventions
discussed, the prescription form may be covered by insurance even though the over-the-counter form
is not.
2
As always, the information provided here is simply my best interpretation of the
research currently available. No claims are made that any of the large official health organizations
have approved this message. It is all subject to change, which is why my papers are marked with a date.
And as is always the case for everything in the world, “more research is ALWAYS needed,” but now
there is actually quite a lot of research out there, and certainly for some things there is clearly enough
evidence to initiate some safe and cheap changes. It’s at the “won’t hurt / really might help” level.
I am not selling anything – no supplements, no diet plan, no books. My only goal is to try to
do some good for people. However, also as always, not all the suggestions are appropriate for every
individual, so be sure to discuss things with your personal health care provider. Feel free to share
these materials with him/her.
References for the research cited in this paper through 2010 are included at the end, divided
into subtopics. There are LOTS more that has been published since 2010 in the same direction relative
to the recommendations below, but I haven’t yet had a chance to write up a nice big bibliography for
each topic. However, some of the most up-to-date references are included in the discussion and
suggestions in this paper, and they are also available on Public Medline www.pubmed.gov. This
website allows anyone to access the scientific reports available in the National Library of Science /
National Institute of Health.
On the www.pubmed.gov website, just type the word diabetes and another word of interest in
the search box (examples: “diabetes biotin” “diabetes carnitine”
“diabetes alpha-lipoic acid”)
and you will find the references (and abstracts) noted here and also those that have appeared on this
topic since 2010. The some data and conclusions from these newer reports have been incorporated
into the text of this paper. I just haven’t shined up the reference pages to reflect the post-2010
references. I plan to do this, of course, but just reading all this stuff on diabetes and nutrition (and
other nutrition topics in my other papers) and thinking about it and then tucking it in where it goes in to
make the latest version of the paper is pretty time consuming. It’s like writing term papers for school
every single day … not a pretty picture! 
Also, in the interests of brevity and saving trees, I will sometimes refer you to another of my
papers for more complete information about a particular topic. In addition, papers with more details on
this topic and others available for free on the Sanford Health website.
Part One:
Enhancing insulin sensitivity and
decreasing incidence of diabetes.
Magnesium and chromium are two minerals which have specific roles in carbohydrate
metabolism. Both are frequently suboptimal in the diets of the majority of Americans (based on
data from the National Health and Examination Survey – NHANES) for a variety of reasons and
3
assuring adequacy has been shown to be critical for insulin sensitivity. For more details, references,
and specific recommendations, please see “Aunt Cathy’s Guide to Nutrition: Magnesium” and “Aunt
Cathy’s Guide to Nutrition: Chromium.”
Chromium
Chromium is a component of “Glucose Tolerance Factor.” It has roles in the metabolism of
carbohydrate, protein and fat. Supplementation of chromium picolinate (a well-absorbed form) has
been shown to be helpful in blood sugar control and weight loss among people with Type II diabetes on
sulfonylurea medication. However, at least in the amounts studied, it may not show all the same
benefits among obese people on insulin whose type 2 diabetes is poorly controlled. But just
supplementing at the Advisable Intake levels has also been shown to have a role in managing
dyslipidemias like high triglycerides and high LDL cholesterol.
As expected, additional supplementation is unlikely to add further benefit if one’s needs
are already met. However, the assumption of chromium adequacy is clearly erroneous for most
Americans and standard care typically does not include asking questions about intake of
chromium-rich foods or chromium supplements. In fact, many folks, including many health
professionals, are not familiar with which foods are the richest sources. It has been generally “not in
our radar.” This continues to a be a problem when interpreting studies providing supplemental
chromium are conducted showing no apparent benefit with outcomes like “developing diabetes” or
changes in “insulin resistance,” but actual chromium status at the onset is not evaluated.
Chromium is not the only player on the team, but it is definitely one of them. It also has roles in
cholesterol and triglyceride metabolism, heart disease and possibly atypical depression. Improved
cognitive-cerebral function has been demonstrated in older adults with chromium supplementation.
Inadequacy is common and definitely not benign. References follow at the end of this paper.
For more information please see my handout: “Aunt Cathy’s Guide to Nutrition: Chromium.”
Magnesium
Magnesium has many roles in metabolizing carbohydrate, protein and fat, including being an
essential cofactor in the production of ATP via the TCA Cycle. [ATP is a major form of energy used by
the cells … we make by burning carbohydrate, fat or protein fuel.] In fact, magnesium is known to
play a role in over 300 chemical reactions in our bodies including nerve activity and managing
heartbeat, so it is not a surprise that it is a very important nutrient, and that inadequacy can be an issue
in a broad range of health conditions.
4
Magnesium is specifically important for the functioning of the insulin
receptors on cells, so magnesium inadequacy is a known contributor to insulin
resistance, a key feature of Type-2 diabetes.
In a very large prospective study from Harvard University it was found that women
with the poorest magnesium intake from food compared with the highest were 25%
less likely to have developed diabetes over a 16 year period.
Detail: They found that women who ate about an ounce of nuts or peanuts four times a week
or more were 25% less likely to have developed Type II diabetes in the 16 years of data
analyzed, compared with the women who ate these foods rarely.
They then re-evaluated the data looking at magnesium intake from ALL sources, and they
found the very same step-wise relationship: dividing magnesium intake into four groups, there
was a stepwise relationship found in the incidence of Type II diabetes.
The higher the magnesium intake group, the lower the incidence of developing diabetes.
Two more major studies with important contributions on this topic:
In a Framingham study, magnesium intake was associated with insulin
sensitivity in a threshold fashion, with a threshold seen at 325 mg
magnesium daily.
And, an important finding in the huge National Nutrition and Health
Examination Survey (NHANES) from the Center for Disease Control was
that the MAJORITY of Americans take in less than 2/3 of the normally
recommended amount of magnesium.
But in spite of that very eye-opening NHANES finding, still we (including health
professionals) assume that folks are just fine in the magnesium intake department. This is because
people who are deficient in magnesium do not “look funny” … at least not for that reason.  So, we
just conclude that the person “looks well-nourished.”
The problem is that when 300 metabolic pathways are compromised by inadequate
magnesium, the consequences are too general to easily pick them out. If there was just one system
down we have a chance of recognizing the problem. With so many systems down, the best
description I can come up with for the effect is a sort of “global crummy-ness” … very serious health
problems but too general to pin down to recognize all the causes.
5
But what the NHANES study DOES mean is that if I met you on the street and had to place a
bet on whether your magnesium intake was at the recommended level or not for healthy people, I
would win my bet far more often if I said that your intake failed to meet that amount.
For that reason, one of my key operating rules is to assume that magnesium intake is
fairly crummy unless I ask some specific simple questions and am assured that they are likely
doing just fine. I don’t assume adequacy, I assume INadequacy until proved otherwise.
Here’s how to do that simply and easily:
Magnesium Status Evaluation Rule of Thumb: “Baby Plants”
The terrific magnesium food sources are the parts of plants that will become
“baby plants” … nuts, seeds, legumes and the germ of grains.
That is, if it is a seed, it’s a good source. If it’s a nut it is a good source. If it is the germ of grain
it is a good source. If it is a legume (bean, pea, lentil, peanut, etc.) it is a good source. Are we seeing
a pattern here?
So, if they say they eat them often, the odds are good that they are in the generally OK
range for healthy people.
If they eat them rarely, the odds are good that they are not taking in optimal amounts of
magnesium even for healthy people. This is also WAY below the optimal intake for most folks
with diabetes.
One really nice thing about this rule is that you can easily get a picture of someone’s usual
magnesium intake just by asking specifically about eating these foods, and you also know what foods
to suggest they include more of if they have a poor magnesium intake! 
It also allows us to easily and intelligently answer specific questions that people ask. At a
conference recently somebody asked if chia seeds were good magnesium sources. Another asked
about sesame seeds. Without having to have the amounts memorized or having ever even looked them
up, I could easily answer … “Yep … they are SEEDS!” Being a baby plant means that the
magnesium content per weight or per calorie is good.
However, an additional comment of importance in this context would be “but those guys are
really tiny so you would have to eat a whole lot if you were counting on them to meet your magnesium
needs.”
The Baby Plant rule also helps me easily answer questions that I regularly get like this: “Which is
better for you: flax oil or flax seeds?” Answer: both have flax oil … a heart-healthy fat. But the flax
SEED has lots of other goodies in there that the oil alone cannot contribute. So nutritionally, the flax
seed is more “nutrient-dense” … but both are perfectly fine foods to use in one’s diet or as a
supplement.
6
Application … since doctors and others have no time to be asking this kind of thing (there are a lot
of other critical issues to cover in their 15-20 minutes of contact time), one way to incorporate this
approach is to have the receptionist give each patient checking in a bit of paper with screening
questions like this on it:
About how often do you eat nuts and peanuts?
___ More than 5 times a week ___A couple of times a week
___Once a week or less
About how often do you eat peas or beans (like chili beans, baked beans, lentils, soy, refried beans.)?
___ More than 5 times a week ___A couple of times a week ___Once a week or less
This quickly identifies for the doctor/nurse/pharmacist/dietitian who might need some
encouragement to eat more of these.
Then there could be a simple sheet given to all the patients that encourages intake of these
foods for everyone. Most folks appreciate being told that nuts and peanuts are actually great foods for
them … often they have been avoiding them because “they are high in calories” or “they have fat in
them.” The fat has the same calories as any other fat but they mostly monounsaturated and omega-3
fats. They don’t increase risk of cancer or heart disease as some other fats appear to do. Because of
this, I think of them as “Happy Fat: Dangerous to your butt, but not to your heart.” 
Note that if calories ARE a major issue for a patient, the legumes, beans and whole grains have
the magnesium and other goodies, but far less fat and fewer calories than nuts and peanuts have.
Also, note that if a person is actually allergic to these foods it is not appropriate to encourage
them to eat them anyway … do I really have to say this? This is a situation in which a supplemental
magnesium oxide or magnesium chloride is appropriate to provide adequate magnesium. Another
situation for which supplemental magnesium is reasonable is if they simply hate those foods and are
quite unlikely to eat them. You can still “encourage” them to eat these healthful foods, but don’t count
on them actually doing it. Get real!
Most “multivitamins with minerals” have between 10% and 25% of the RDA for
magnesium, and this can be helpful if one’s intake is just a little low, but it will not solve the problem if
the dietary intake of magnesium is quite low … especially if the person has diabetes. Taking that
multivitamin with minerals is still recommended for many reasons … but some additional magnesium
would be in order.
[Do not recommend magnesium citrate or sulfate … these have poorly absorbed magnesium and
they can cause loose stools. That’s why they are used as laxatives and to clean out the colon before
having a colonoscopy. They are a poor choice as nutritional supplements. ]
The magnesium RDA for women is 320 mg and 420 mg for men, and the RDAs are based on
the needs of people who do not have diabetes or other health problems. People with diabetes,
however, often need magnesium intake levels above the RDA for reasons explained later.
7
A low magnesium level in the blood (hypomagnesemia) is highly prevalent in outpatients with
diabetes. High plasma triglycerides, waist circumference and albuminuria (all of importance in
diabetes) are also independent correlates of hypomagnesemia.
The amount of magnesium in the blood is extremely important for heartbeat and other critical
functions so the body works very hard to keep the amount in the blood in the normal range. The blood
magnesium level is controlled by hormones and not by daily intake, so a low level of magnesium in the
blood can be a marker of serious problems. It also means that a normal blood magnesium level does
not assure adequate magnesium levels in other parts of the body or in the diet.
People with poorly controlled diabetes are at particular risk of actually losing
magnesium. That is because when blood sugars are high enough that sugar spills over into the
urine, it takes magnesium with it, resulting in an additional loss of magnesium.
This also occurs when one uses certain blood pressure medications like thiazide diuretics, like
furosemide (Lasix.) Any diuretics known to result in potassium loss will also result in a magnesium
loss, but often this is not recognized and corrected. More will be said about magnesium later, and I also
have a separate handout available on line with much more detail on this critical nutrient.
Magnesium Summary
Magnesium insufficiency in the general public is quite common
Magnesium insufficiency is even more common among people with diabetes.
In spite of the recognized problems of in adequate magnesium intake from foods or
supplements, intake is rarely evaluated by health professionals.
Laboratory assessment of serum magnesium levels does not reflect magnesium status in
the tissues. The amount in the blood is controlled by the kidney so it is not very useful for
assessing general adequacy. A low level is associated with serious health problems for a
variety of reasons, but a normal level tells us very little about magnesium status in the tissues.
It is not an indicator of excellent magnesium status.
Improving poor magnesium intake has the potential to help reduce the incidence of both
obesity and type 2 diabetes. It also has roles in preventing hypertension (high blood pressure)
and some neurologic problems such as leg cramps.
Improving poor magnesium intake has the potential to help decrease insulin resistance
among people who already have diabetes. (At least, it gives us a more level playing field.)
Identifying folks whose diet is likely suboptimal is actually pretty darned easy, and giving
them specific advice to improve it is also pretty darned easy using the “Baby Plants” rule
as described above.
For more information on magnesium, please see: “Aunt Cathy’s Guide to Nutrition: Magnesium” and
“Aunt Cathy’s Guide to Nutrition: My Current Top Five Easy Ways to Improve Your Family’s Nutrition”
8
Vitamin K
Vitamin K adequacy is now recognized as important in diabetes because it has a role in
both body fat and diabetes/glucose metabolism. Researchers have described a potential beneficial
role for phylloquinone (vitamin K in the form found in plants) in glucose homeostasis. Higher
phylloquinone intake was associated with greater insulin sensitivity and glycemic status.
(Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr.
2008 Jul;88(1):210-5.) Other forms of vitamin K (e.g. menaquinone and menatretenone) are also
being studied with success in correcting complications of deficiency.
As vitamin K inadequacy is now known to be much more common than was previously
believed, the role of vitamin K in diabetes and obesity will likely begin to be evaluated even more
closely in the scientific community.
Assuring vitamin K adequacy has also been found to be of great importance for prevention of
certain contributors to cardiovascular disease, such as calcification of the arteries, increased arterial
inflammation and high blood pressure. Calcification of the kidneys is another consequence of
vitamin K deficiency of particular importance in diabetes, as is osteoporosis, a condition known to be
more prevalent among people with diabetes. The role of vitamin K in these many conditions has
only been identified in the years since 2005, so it is not yet well known, but the research is
exploding on this topic.
Other general health problems related to vitamin K deficiency include pre-eclampsia, varicose
veins and cancer of the stomach and colon. Clearly assuring adequacy is a very good idea for
everyone, but it is especially important for people with diabetes.
Vitamin K is fat soluble and this gives some folks the impression that it is therefore potentially
quite toxic. However, vitamin K has been shown to be very safe. In fact, no upper
level of safety has been established for it because no one has ever been found to
be harmed by it.
A good way to think about its role in blood clotting is that it ALLOWS you to clot your blood
if you get a biochemical message that you need to do some clotting to avoid excessive blood loss.
Vitamin K does not MAKE you clot your blood, nor does it initiate the clotting of blood. It is not a
hormone causing things to happen … it is just a tool along an assembly line that is needed for making
clots when they are perceived to be needed because of injury and/or blood loss.
Re: Vitamin K interactions with the drug Coumadin/warfarin
The exception to the general non-toxicity of vitamin K is an interaction with a specific
medication. Coumadin is an anticoagulant that works by interacting with vitamin K. For this reason,
consistency and adequacy of vitamin K are very important for the safety of using the drug.
People can actually use the drug Coumadin more safely when an adequate blood level of vitamin K is
maintained because it prevents the extreme volatility that can be dangerous with this medication.
9
At present many people taking Coumadin are in fact deficient in vitamin K because of frequent
misunderstandings and also due to the fact that the recognition of the body’s many other roles for
vitamin K is quite new. Correcting the problem of actual vitamin K deficiency among users of
this medication must be managed by the patient’s health care provider.
Note that many other anticoagulants do not operate via interaction with vitamin K, so assuring
vitamin K adequacy is very easy and safe to achieve.
My paper for health care providers on this specific topic is available along with a more general
one just on vitamin K and all the new findings about its roles in the body, recommended intake levels
and sources.
For more information and details on the roles of vitamin K and ways to assure adequacy, please see my other
handouts on line: “Aunt Cathy’s Guide to Nutrition: Vitamin K -- New Issues in Cardiovascular Health,
Osteoporosis, Cancer of the Liver and Colon, Diabetes and Varicose Veins.” The other paper is called “Aunt
Cathy’s Guide to: Vitamin K -- Focus on the Vitamin K and Warfarin/Coumadin Anticoagulant Drugs Issue
Seven factors are contributing to the high prevalence of
unrecognized vitamin K inadequacy:
1. Vitamin K is not included in many vitamin supplements because it was assumed that we could rely
on intestinal bacteria to provide a substantial amount.
2. Our ability to rely on intestinal bacteria for vitamin K has been found to be overly optimistic, and
we are more reliant on an outside source than we thought.
3. The best sources are dark leafy green vegetables and many folks rarely eat them.
4. Vitamin K status is rarely evaluated because it has always been assumed to be just fine based on
the assumption that the intestinal bacteria made enough. At the moment, a blood test for
vitamin K adequacy is not included in any of the major blood-test “panels” commonly
obtained during a health evaluation. This situation may change as the problem of vitamin K
inadequacy becomes better recognized, but for now it is very unlikely to be measured in
anyone … even in people on the medication Coumadin, who are at great risk of vitamin K
deficiency because of misunderstandings about the need for consistent vitamin K intake …
not inadequate vitamin K intake. Inducing a vitamin deficiency is never in the best interests
of anyone.
5. Currently established RDA-type recommended levels of vitamin K intake have been shown to
be insufficient to maintain older individuals in the normal range of blood vitamin K. This has
not yet been evaluated in other age groups, but it is likely that a similar result will be found.
6. People often incorrectly believe that vitamin K is likely to be very toxic because it is “fat
soluble.” It is actually extremely safe and no upper end of a safe intake has ever been found.
10
7. People using the medication Coumadin are the only people for whom vitamin K must be provided
in a consistent and adequate) amount. Many of them are actually vitamin K deficient and the
deficiency interferes with the safe use of the drug. At this time, because these issues are so
new, the safe use of vitamin K with the drug Coumadin is very often poorly understood by the
public and by many health care professionals.
Vitamin D
Vitamin D inadequacy is now known to be very common throughout the USA and around the
world. The World Health Organization estimates that 40-50% of the world’s population is vitamin D
inadequate or insufficient. It is frequently unrecognized but it is now beginning to be checked much
more often, and today a vitamin D assay is actually the most requested laboratory value in clinics and
hospitals.
Over 200 tissues have receptors for vitamin D hormone, so inadequacy compromises a
number of functions and increases risk of many health problems, including cardiovascular
disease, cancer, autoimmune diseases and compromised immune function. New roles in diabetes
are also being identified. Here are some highlights:
Type I Diabetes:
There is a growing body of good evidence that inadequacy of vitamin D in early life may be
one of the triggers that brings on Type I diabetes among genetically susceptible children. For
example, in a study in Finland, children who had experienced vitamin D –deficiency rickets as infants
were four times more likely to develop Type I (insulin dependent) diabetes. The data is accumulating
all around the globe, and it is consistent with the well known observation that the northern tier of the
US (and places of similar latitude around the world) is known as the “Rickets Belt”, the “MS
Belt” and the “Type I Diabetes Belt.”
Latitude is the most obvious factor in vitamin D inadequacy, but many other people are at risk
because of skin color, clothing that covers a person up, diet, and several other important factors. For
many reasons, vitamin D inadequacy is a very large public health problem that has not yet
captured the attention of most health professionals. [I hope to be able to edit this last statement
out in the near future.]
In terms of Type I diabetes in particular, the current state of the art is to recognize that assuring
adequacy of vitamin D can be protective against Type I diabetes to at least some degree. There appear
to be several polymorphisms of vitamin D receptors that can affect the relationship, and a variety of
other factors. In any case, the documented high prevalence of vitamin D insufficiency in Americans
and others, and in children with Type I diabetes in particular make it very reasonable to monitor
vitamin D status in everyone and supplement if necessary to ASSURE adequacy instead of simply
assuming adequacy.
11
Here are just three examples of the many references on this topic found at the end of this paper:
Vitamin D and increasing incidence of type 1 diabetes-evidence for an association?
Diabetes Obes Metab. 2010 Sep;12(9):737-43.
Significant vitamin D deficiency in youth with type 1 diabetes mellitus.
J Pediatr. 2009 Jan;154(1):132-4.
Vitamin D in diabetes mellitus-a new field of knowledge poised for D-velopment.
Diabetes Metab Res Rev. 2009 Jul;25(5):417-9.
Type II Diabetes:
Other studies suggest that inadequacy of vitamin D may contribute to Type II Diabetes
as well as Type I, with additional roles in a wide variety of health problems. These include death
from all causes, heart failure, cardiac arrest, cancer of the colon, prostate, pancreas and breast, MS,
muscle/nerve pain that is often missed and diagnosed as fibromyalgia, rheumatoid arthritis and
osteoarthritis, muscle weakness and falling (sarcopenia), fractures, osteoporosis, poor prenatal
outcome, and much more.
In the spring of 2013 a meta-analysis of prospective studies was done by Harvard researchers
that demonstrated a strong inverse relationship between vitamin D blood levels and incidence of type 2
diabetes. This is a very important report so I have pasted the abstract below:
Blood 25-Hydroxy Vitamin D Levels and Incident Type 2 Diabetes: A
meta-analysis of prospective studies [Harvard] Diabetes Care May 2013 vol. 36 no. 5 1422-1428
OBJECTIVE To quantitatively assess the strength and shape of the association between blood 25-hydroxy vitamin
D [25(OH)D] levels and incident risk of type 2 diabetes. RESEARCH DESIGN AND METHODS A systematic
search of the MEDLINE and Embase databases and a hand search of references from original reports were
conducted up to 31 October 2012. Prospective observational studies that assessed the association between blood
levels of 25(OH)D and risk of incident type 2 diabetes were included for meta-analysis. DerSimonian and Laird’s
random-effects model was used. A quadratic spline regression analysis was used to examine the shape of the
association with a generalized least-squares trend test performed for the dose-response relation. RESULTS A total
of 21 prospective studies involving 76,220 participants and 4,996 incident type 2 diabetes cases were included for
meta-analysis. Comparing the highest to the lowest category of 25(OH)D levels, the summary relative risk for type 2
diabetes was 0.62 (95% CI 0.54–0.70). A spline regression model showed that higher 25(OH)D levels were
monotonically associated with a lower diabetes risk. This inverse association did not differ by sex, duration of
follow-up, study sample size, diabetes diagnostic criteria, or 25(OH)D assay method. A linear trend analysis
showed that each 10 nmol/L increment in 25(OH)D levels was associated with a 4% lower risk of type 2
diabetes (95% CI 3–6; P for linear trend < 0.0001). CONCLUSIONS Our meta-analysis showed
an
inverse and significant association between circulating 25(OH)D levels and risk of type 2
diabetes across a broad range of blood 25(OH)D levels in diverse populations.
Assuring adequacy is easy, cheap and crucial to good health, and it is now recognized that
vitamin D inadequacy is very widespread in the US and around the world. The World Health
Organization (WHO) estimates that 40-50% of the world’s population is at risk of inadequate vitamin
D for a variety of reasons.
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It is very clear that many people require levels of vitamin D intake well above the 200-400 iu
RDA-ish recommendations. As a rule-of-thumb, an intake of 2000 iu is a safe and reasonable
maintenance dose. Many people have been found in research studies to require that much to
maintain healthy blood levels of this critical vitamin. Additionally, some people have been shown
to actually require levels as high as 5000-6000 iu/day just to MAINTAIN healthy levels.
This illustrates the fact that people are not all the same and some people’s requirements
for particular nutrients are different from the presumed adequacy level. This is one important
reason why a follow-up serum vitamin D level is a good idea a few months after having achieved a
good blood level.
[Also note that 2000 iu presumed maintenance level is not a therapeutic dose for rapidly
correcting a very low blood level. That level is often 50,000 iu/wk for eight weeks (a little above 7000
iu/day.) [The “Top Five Recommendations” paper discusses these issues in greater detail.]
Because both diabetes and vitamin D deficiency independently increase
risk of cardiovascular disease, it would be prudent to take the extra step to
ASSURE that one’s vitamin D level is adequate by getting an annual check of
vitamin D stores especially during the winter.
Also as discussed in the “Top Five Recommendations” paper, the blood level associated with
the best health is 35-40 ng/dL or higher, and not the 25 ng/dL that had earlier thought to reflect a health
level. An important note: Some lab report print-outs do not yet reflect this changing interpretation of
“adequacy”; they still say that 25 is “normal.” So when your lab comes back, be sure to ask what your
actual number of ng/dL is, and not be satisfied with a description that says “normal.”
As discussed earlier, one’s intake of fruits and vegetables, intake of vitamin K, magnesium
and chromium, and one’s serum vitamin C level all also appear to be factors in the likelihood of
developing Type II diabetes. It makes sense that assuring adequacy of all of these (and not simply
assuming it) is a very reasonable goal.
Gestational Diabetes:
Gestational diabetes (“pregnancy diabetes”) develops in mid-pregnancy in some women.
It appears to develop less often among women with more vitamin D and vitamin C in their
blood. A recent study showed a positive correlation of 25(OH) vitamin D concentrations (the
measurement of vitamin D stores) with insulin sensitivity; they suggested that “vitamin D deficiency
could be a confirmative sign of insulin resistance.”
In another study maternal 25(OH)D concentrations were found to be inversely related to
fasting glucose. Women in another study identified in a clinic as having gestational diabetes may
actually have had unrecognized Type II diabetes all along. Additionally, people who are significantly
overweight need higher intakes than others to maintain a normal blood level of vitamin D.
13
A side note: with so many young women being overweight now, and because some will
actually have unrecognized Type II diabetes, it will be important to begin checking for diabetes much
earlier in pregnancy (preferably before conception) in order to minimize the birth defects that are
associated with poorly controlled diabetes in very early pregnancy.
For much more on this issue, please see
“Aunt Cathy‟s Guide to Nutrition: Top 10 Issues in
Nutrition for Pregnancy”
Adequacy of Iodine and Selenium
Iodine is important for normal metabolism. The mineral selenium also appears to assist with
moving glucose into the cells. Both selenium and iodine are centrally involved in the production
of the hormone thyroxine by the thyroid gland. Thyroxine is responsible for setting one’s basal
metabolic rate (BMR) … the amount of calories used to run one’s body in a resting state. Poor
production of thyroxine contributes to weight gain and fatigue.
Selenium is also a part of a very important antioxidant in the body called glutathione
peroxidase. More will be said about selenium later. Risk of selenium and/or iodine inadequacy
depends on the soil upon which one’s food was grown. Recently, a resurgence of inadequacy of
iodine has been documented in America and around the world because of changes in food
patterns. It is likely that the documented increase in iodine inadequacy is also contributing to
weight problems and fatigue that interferes with exercising.
A brief history:
Iodine deficiency remains the number one cause of mental
retardation in the world and unfortunately it is coming back
here in the USA.
We thought we took care of it in the 1950s by iodizing salt, but since then many things changed.
When iodizing salt was established in the US, our mommies stayed home all day and
made everything from scratch using iodized salt. The world is not like that now.
Then, we told people “Don’t Eat Salt!”
Then we have developed fads for using exotic sea salts (most are not iodized.)
We make (and applaud) well-intentioned decisions to “not have a salt shaker on the
table!” not realizing that that iodized salt might be the only iodine our family gets.
We do eat a lot of sodium … usually a whole lot more than we should … but most folks
are unaware that all that sodium in commercially made foods is not iodized. So they
think they get plenty of iodine and aren’t worried about it. Wrong!
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The newest factor to contribute to risk of inadequate iodizing is the (otherwise terrific)
movement to eat locally grown food. It supports the local economy, reduces diesel
fumes across America and the food is fresher. However, all across the northern tier
there is inadequate iodine in the soil, so plants that grow there simply don’t incorporate
it. And plants do not look or taste any different if they have iodine in them or not.
In this situation, people don’t get enough iodine if most of their foods were raised
locally. That is why the northern US used to be called “the Goiter belt.” (Goiter is an
enlargement of the thyroid gland… the gland gets bigger trying unsuccessfully to make
up for not producing enough thyroxine because of inadequate iodine. )
Many multivitamins (including prenatal vitamins) do not yet contain iodine because
we thought we got enough from the iodized salt alone. Check labels.
Some places in the world with the same problem, like Australia, are mandating
iodizing bread products instead of salt as a new way to get iodine into people. We are
not there yet, but our old 1950s “iodize-the-salt” solution is no longer working.
This big but largely unrecognized problem affects everyone, but I am discussing it
especially here because avoiding the weight gain/exercise-intolerance/fatigue/BMRlowering component of iodine deficiency is especially important for people with Type
II diabetes or trying to avoid it. The other very critical issue is the deleterious effects of
iodine deficiency on fetal development, so iodine status in pregnancy (whether
diabetes-related or not) requires an even closer look.
For more information on the return of iodine deficiency as a major public health problem, please see:
“Aunt Cathy’s Guide to Nutrition: My Current Top Five Easy Ways to Improve Your Family’s Nutrition” and
“Aunt Cathy’s Guide to Nutrition: New Attention to an Old Problem: Iodine Deficiency in Pregnancy and Lactation
Exercise
Exercise is not a nutrient, but it does play important roles in metabolism. Besides affecting
lean body mass (and so BMR,) and the calories burned from activity itself, it also has the capacity of
helping to move glucose into the cells, so it is a cornerstone of prevention and also of treatment of Type
II diabetes. Exploring this topic further is outside of the scope of this nutrient-focused paper, however.
[One other CB note: People are getting the impression from ads from folks selling things that pushing protein
intake way higher than what one would normally use will induce muscle development and reduce body fat. Sounds
good, and I get asked about this all the time. The answer, though, is that while adequacy of protein is very important,
any extra protein consumed beyond one’s requirements is not stored as muscle. It is converted to calories. (Yes …
calories.) The thing that induces muscle building is exercise … which explains why if I ate an entire meatloaf with ten
times my daily protein requirement and then napped all day on the couch, I would still not achieve that svelte,
lean-mean-fighting-machine physique. But I keep on trying … I mean, it has to be true if I saw it on TV or read about
it on the internet, right? Pass the meatloaf! ]
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Part Two:
Minimizing secondary damage from poor
diabetes control caused by higher than normal
production of free radicals
“Free radicals” are normal waste products of metabolism. They can injure cell membranes all
over the body if they are not “quenched.” “Antioxidants” are the substances that quench free radicals.
A much greater production of free radicals than usual is well known and documented among
people with diabetes. This is also true in many other diseases with disturbed metabolism, such as
inflammatory diseases like MS or arthritis, or conditions with irregular fuel metabolism, such as
obtaining a high proportion of calories from alcohol.
In diabetes, the greatest production of free radicals occurs in the people with the least
well-controlled blood sugar levels. Such excessive production of free radicals causes serious injury
to cells and tissues and it is an important contributor to the development of diabetes-related
complications like heart disease, blindness, poor wound healing, kidney injury and nerve damage.
The many references on this topic are at the end of the paper, but here is just one as a sample:
Dietary antioxidant capacity is inversely associated with diabetes biomarkers:
The ATTICA study. Nutr Metab Cardiovasc Dis. 2010 Feb 18.
“CONCLUSIONS: Although more prospective studies are required, the data
presented support the view that dietary modification towards higher
consumption of antioxidants should be implemented in public health
strategies, in order to better control glycemic markers in individuals, and
prevent the development of diabetes at the population level”
Here are some important points from a number of different studies:
There is evidence of significant slowing of the development of diabetes complications by
assuring a generous intake of antioxidants. “Generous” in this context usually means
substantially more than the usual RDA-type levels (i.e. RDA, RDI, AI, etc.). As noted
earlier, the RDA-type guidelines (by definition) are designed to meet the needs of the
“healthy” population, so also by definition, they have little to say about the specific needs of
people with serious metabolic diseases.
Vitamin and minerals with roles as antioxidants that have been studied quite a lot have
included vitamins C and E, and the minerals selenium (part of the important antioxidant
“glutathione peroxidase”) and zinc (as part of “Zn-Cu superoxide dismutase.”) Our old
friend vitamin E (alpha-tocopherol and its cousins like gamma-tocopherol, “mixed
tocopherols” and tocotrienols) are back in the news with new evidence of their safety, and a lot
16
of new research into its potential to protect against a variety of diabetes related complications
and other problems.
The ideal level of antioxidant vitamins is unlikely to be around the RDA-type levels.
As just one example, the author of a recent study concluded that: “The results suggest that
megadose vitamin C supplementation [1-3 grams/day] may have a beneficial effect in diabetes
mellitus patients on both glycemic control and antioxidant status. Thus dietary measures to
increase plasma vitamin C may be an important health strategy for reducing the complications
of diabetes for patients.” Also, many of these antioxidant substances like tocotrienols or
phytochemical pigments do not have RDA levels established at all because they are not
identified as essential substances like designated essential vitamins and minerals.
Higher vitamin C levels in the blood, and higher fruit and vegetable consumption were
recently reported to be related to decreased incidence of type II diabetes in a 12 year study
of over 20,000 people. They found a strong inverse association between plasma vitamin C
level and diabetes risk. The “odds ratio” of developing diabetes in the top quintile of plasma
vitamin C was 0.38 in a model adjusted for demographic, lifestyle, and anthropometric
variables. That means that they divided folks up into 5 groups based on their blood vitamin C
level, and the group with the highest level was less likely to have developed diabetes. For
every 100 who developed it in the group with the lowest vitamin C level, there were only
38 who developed diabetes in the highest vitamin C group.
In a similarly adjusted model, the odds ratio of diabetes in the top quintile of fruit and
vegetable consumption was 0.78. (That is, people in the top fourth of intake were found to be
about ¼ less likely to have developed diabetes.) They concluded that higher plasma vitamin
C level and, to a lesser degree, fruit and vegetable intake were associated with a substantially
decreased risk of diabetes.
It is also being shown that combinations of antioxidants may provide more benefit than a
generous intake of any one antioxidant alone. As an example, in a study with rats with diabetes,
the treatment with a combination of generous vitamins C and E had a significant positive effect
on decreasing diabetic damage to learning and memory.
Another unique antioxidant that has been studied extensively in diabetes is alpha lipoic acid,
(also called thioctic acid,) a B-vitamin-like substance made in the body from the essential
fatty acid linoleic acid. It also has a role in energy production, as it is required in two places in
the TCA cycle involved in making ATP energy out of fuel. It is very safe, and the level that is
generally agreed as being most likely to bring about positive effects in diabetes research
has been at least 600 mg/day. A randomized, double-blind, placebo-controlled, multi-center
trial showed that alpha lipoic acid at an oral dosage of 800 mg/day for 4 months significantly
improved cardiac autonomic neuropathy in patients with type 2 diabetes. (Treat Endocrinol.
2004;3(1):41-52. )
Since that time there has been considerable amount of research exploring alpha lipoic acid in
relation to several aspects of health for people with diabetes. Here is just a sampling from the
last few months (as of 4/13) describing the use of alpha-lipoic acid in neuropathic pain, kidney
and liver disease related to diabetes, converting fuel into energy (ATP), and protecting against
17
oxidative damage from excessive free radical production associated with diabetes:
The protective effects of α-lipoic acid on kidneys in Type 2 diabetic goto-kakisaki rats via reducing oxidative
stress. Int J Mol Sci. 2013 Mar 26;14(4):6746-56. Painful diabetic neuropathy management. Int J Evid Based
Healthc. 2013 Mar;11(1):77-9. Nutritional supplements and their effect on glucose control. Adv Exp Med
Biol. 2012;771: 381-95.Whither pathogenetic treatments for diabetic polyneuropathy? Diabetes Metab Res
Rev. 2013 Feb 5. Decreased O-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a
novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver. Br J Nutr. 2013 Jan
14:1-12Alpha-lipoic acid preserves the structural and functional integrity of red blood cells by adjusting the
redox disturbance and decreasing O-GlcNAc modifications of antioxidant enzymes and heat shock proteins in
diabetic rats. Eur J Nutr. 2012 Dec;51(8):975-86. The protective effect of α-Lipoic acid on mitochondria in
the kidney of diabetic rats. Int J Clin Exp Med. 2013;6(2):90-7. Alpha-lipoic acid upregulates antioxidant enzyme
gene expression and
enzymatic activity in diabetic rat kidneys through an O-GlcNAc-dependent mechanism. Eur J
Nutr. 2012 Oct 12.
This is one of the three supplement substances that were described earlier as being
more expensive, and it is sometimes available on line or over the counter in pills of 50 mg or
more. A prescription for a higher dose pill would facilitate things. One area in which alpha
lipoic acid has been most effective (and most studied) is in peripheral neuropathy (nerve pain)
research, but it now looks very promising in several areas of diabetes complication research.
Another potent antioxidant with other roles in energy metabolism is “ubiquinone”
– Coenzyme
Q-10. It is very safe and helpful in a number of applications, but it is also more expensive and a
prescription might be helpful for this reason. CoQ10 treatment significantly improved deranged
carbohydrate and lipid metabolism of experimental chemically induced diabetes in rats. The
mechanism of its beneficial effect appears to be its antioxidant property.
It has shown benefit in a variety of conditions involving altered metabolism (like diabetes but others as
well) and specifically useful in eye health and muscle health and in parkinsonism. It also appears to be
protective against some muscle side-effects of statin drugs.
There is evidence that using combinations of CoQ10 with carnitine and DHA (a particular omega-3
polyunsaturated fat discussed later,) or with alpha-lipoic acid, carnitine and biotin, for example, may
elicit more positive change than any one alone.
A combination of nutriments improves mitochondrial biogenesis and function in skeletal muscle of type 2 diabetic \
Goto-Kakizaki rats. PLoS One. 2008 Jun 4;3(6):e2328.
Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a
combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005
May-Jun;219(3):154-66.
In early 2013 there has been promising information popping up about apossible benefit of
supplemental CoQ10 in diabetic neuropathy. Here are three reports on that topic:
Diabetic Neuropathic Pain Development in Type 2 Diabetic Mouse Model and the Prophylactic andTherapeutic Effects
of Coenzyme Q10. Neurobiol Dis. 2013 May 16.
Prophylactic and antinociceptive effects of coenzyme Q10 on diabetic neuropathic pain in a mouse model of type 1
diabetes. Anesthesiology. 2013 Apr;118(4):945-54.
Coenzyme Q10 prevents peripheral neuropathy and attenuates neuron loss in the db-/db- mouse, a type 2 diabetes model.
Proc Natl Acad Sci U S A. 2013 Jan 8.
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A generous intake of a variety of plant pigments (natural coloring agents) like carotene
in carrots, lycopene in tomatoes, lutein in spinach, zeathanthin in corn, and anthocyanin,
the blue/red color in blueberries, are being shown to be hugely beneficial in decreasing
the complications rate in people who have diabetes. They have been found to be VERY
potent antioxidants – some (like Lycopene) have shown antioxidant protection at 200 times the
antioxidant potential of vitamin E! These fruits and vegetables also tend to be “nutrient dense”
foods ---lots of nutrients per calorie provided – and that is a definite benefit as well.
Research into the control of free radical production (or “quenching” them after they are
formed,) has shown antioxidants to have promising roles in kidney health, circulation to the eye,
lens and retinal health, circulation of blood to the extremities, wound healing, peripheral
neuropathy, erectile dysfunction, the development of gestational diabetes, and birth defects.
It’s time to seriously consider adding
antioxidant protection to our standard protocols
For a review and recommendations for these vitamins, minerals and the plant pigment antioxidants, please see “Aunt
Cathy’s Guide to Nutrition: Eye Health” and others noted earlier.
Part Three:
Reducing the severity of inflammation that has
been shown to be associated with diabetes
Inflammation is now being recognized as a significant contributor to heart disease and to
tissue damage in general. For example, inflammation inside the blood vessels is an important
reason why cholesterol sticks to the arteries and builds up to block circulation. Poor control of
diabetes especially results in an increase in inflammation.
Besides being a special problem in diabetes, this has been found to be true for many conditions
that have an inflammatory component, such as rheumatoid arthritis, MS and inflammatory bowel
disease. Inflammation is a normal part of the immune system, but excessive inflammation is injurious.
Sometimes inappropriate messages can be sent to cause tissues to be inflamed more than they should.
The inflammation results from any chronic disturbances in normal fuel metabolism, such as that seen
with diabetes, autoimmune diseases and excessive alcohol consumption.
Two particular families of fats (called the omega-3 family and the omega-6 family) are used to
make the inflammatory agents that are part of our immune system. The inflammatory agents are called
prostaglandins. When prostaglandins are made from an omega-6 fat they are way more inflammatory
than when they are made from an omega-3 fat.
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Altering the ratio of omega-6 to omega-3 polyunsaturated fats has been shown to be an
important step in achieving health for most Americans, and especially so in diabetes. Americans
tend to eat about 10 grams of omega-6 fat for every gram of omega-3 fat. That is, we have about a
10-to-1 ratio of “sixes-to-threes.”
The demonstrably heart-healthy “Mediterranean diet” provides about a 4-to-1 ratio,
and most healthy people would clearly benefit from change in this direction. For people with
diabetes, MS, and other hyper-inflammatory conditions, it has been suggested that a ratio of
two-to-one may provide additional benefit.
One reason why our intake of omega-6 fats is so high is because many vegetable oils that we
use a lot, like corn oil, are almost all omega-6. Soy oil has a little omega-3, canola has more, and flax
oil has even more. However, the majority of our foods are not made with canola oil, much less flax oil.
What vegetable oils do they use in the Mediterranean Region? They use a lot of olive oil
and peanut oil instead of other vegetable oils. Olive and peanut oils both are high in MONOunsaturated fat … a type that is neither omega-3 nor omega-6 and which is not involved in making
inflammatory prostaglandins. If we were to replace a significant amount of our usual omega-6
dietary fat (like corn oil) with monounsaturated olive or peanut oil, though, it would make a
very substantial change in the omega-6 to omega-3 ratio.
These “heart healthy” monounsaturated and omega-3 fats are well represented in nuts and
peanuts. This another good reason to eat these foods which are also such excellent sources of
magnesium and chromium. Nuts and peanuts are real winners for people with diabetes.
The omega-3 and omega-6 vegetable oils can usually be converted in our bodies to the
forms of fat used to make prostaglandins. These are the fats called EPA (the omega-3 one) and ARA
(the omega-6 one.) We have always thought that if people ate the vegetable forms they could easily
convert them to the EPA and ARA forms. However, another important new discovery is that
many people are unable to efficiently convert vegetable essential fats to these critical EPA and
ARA fats that are used to make a variety of important substances.
We can eat ARA omega-6 fat “ready-made” in meats, and “ready-made” EPA omega-3 fat in
fish. However, if people who are unable to efficiently make these fats from vegetable oils eat meat
and little fish, then ALL the fats they have available to make prostaglandins are the really
inflammatory omega-6 type.
Additionally, we are supposed to make an important fat called DHA out of EPA. DHA is a
primary fat of a healthy functional brain. Adequate DHA appears to be important in maintaining
cognition, in retina health in the eye, and in mood. (This was mentioned above in the antioxidants
–in-combination-with-stuff discussion.) This means that some folks are much more
dependent on their diet to assure adequacy of both of these key substances.
This defect in producing EPA, ARA and DHA fats from the forms in plants may be a significant
contributor to inappropriate hyper-inflammation and so it is very important in diabetes especially.
20
This discovery is behind recommendations that “ready-to-go” sources of these fats, like fish
or fish oil supplements have important health benefits for minimizing complications of diabetes, risk
of cancer and heart disease, and in promoting a healthy outcome of a pregnancy. The American Heart
Association recommends eating fatty fish twice a week or taking a 1000 mg daily of fish oil
(which contains ready-made EPA and DHA.) Some folks are advised to take more … for example
some people who have high triglycerides in their blood respond well to 2-4 times that amount. [Check
with your doctor before using the higher doses, especially if you are taking aspirin or a medication to
block blood clots.]
Omega-3 and Omega-6 Memory Tricks:
Here’s an easy way to remember which family of polyunsaturated fat is which in the ratios
of omega-6 and omega-3 fats, and also which family produces the most inflammatory
prostaglandins and also the strongest blood-clotting messengers (thromboxanes):
Just remember this “six is always bigger than three.”
The omega-6 fat family produces the more inflammatory prostaglandins than omega-3 fats do.
The omega-6 family also produces stronger clot-promoting thromboxanes than omega-3 fats do.
No matter whether the ratio of these fats in one’s diet is expressed (that is, whether it is described as
4-to-1 or 1-to-4, the bigger of the two numbers will always represent the omega 6 fat!
(Thank heaven for these memory tricks or I couldn’t keep this stuff straight!)
For more information and specific recommendations, please see:
“Aunt Cathy’s Guide to Nutrition: Omega-3 Fats and Other Lipids.”
Part Four: Helping to stabilize excessive fluctuations of blood sugar
Some individuals have a problem with widely fluctuating glucose levels in spite of following
the diet, exercise and medication program very carefully. This used to be called “brittle” diabetes. In
the past, these people were sometimes suspected of “cheating” on the diet, since health care
professionals could not explain the phenomenon. Unfortunately, this accusatory response is still
common in some settings.
21
Increasing knowledge of the effects of other differences in types of carbohydrates
consumed and factors affecting absorption have led to some changes in our globally
accepted recommendations. For example, the carbohydrate called sucrose (regular table sugar) is not
looking automatically bad, and the carbohydrate in the form of high fructose corn syrup is looking a bit
worse. The high-fructose corn syrup issue is a matter of considerable discussion just now and the jury is
still out.
But clearly, some of the issues are related to whether one is taking in these forms of
carbohydrate alone (as “empty calories” like in soft drinks) or whether they are eaten as a part of a meal
that provides key nutrients involved in metabolizing the carbohydrate taken in.
The popular movement toward whole grains/whole foods has improved the nutrientto-carbohydrate ratio, resulting in an improved magnesium and chromium intake, as described
above. Increasing the intake of soluble and insoluble fiber in foods has positive effects,
although we are quick to assume that it is the fiber in a “high fiber diet” that does all the good, when a
high fiber diet clearly alters many other nutrition parameters as well. (If it were just the fiber providing
the benefits, just taking some fiber supplements would do the job; but we only see the great results
when people eat nutrient-dense foods that are naturally high in fiber.)
In the not too distant past, the prescribed diet for diabetes was pretty strict about whether the
carbohydrate in a food was sucrose or glucose or lactose or fructose or starch, so people were advised
to eat very specific amounts of very specific food groups at each meal. Swapping foods between
different food groups was discouraged because it was thought that the carbohydrate would probably be
used very differently in the body.
However, because we can now easily check people’s blood sugar, we have learned that this
distinction of carbohydrate type is much less important. We now commonly use a system of
counting grams of carbohydrate in a meal or snack instead of the more rigid (and much
less effective) “exchange system” for meal planning. This has been shown to make managing diabetes
much simpler and people are much more successful using this approach than the older version.
Now we also no longer perceive apple juice and an intact apple to be nutritionally identical in
regard to the diet for diabetes, even if the number of grams of carbohydrate are identical and they are
both from the old “fruit group.” Other substances in the apple, like pectin (a type of fiber) for
example, make a difference in how it affects our blood sugar and also affects absorption of dietary
cholesterol to some degree.
The same is true of enriched white bread and whole grain bread. Whole grain offers many
important nutrients like magnesium, chromium, fiber and vitamin E that are not provided in white
bread. That means that compared with nutrient-dense whole grain bread, white bread is more of an
“empty calorie” food, and therefore less helpful in managing diabetes.
“Enriched” flour” means that the germ (the “baby plant”) and the bran (fiber) of grains
is removed and only four nutrients are replaced: vitamins 1, 2, and 3 and iron. That’s all.
They do not replace the magnesium, chromium, or other nutrients so it is clear that “whole grain” flour
22
is nutritionally very superior to “enriched.” This is confusing to many people because the word
“enriched suggests that this is the superior and more nutritious product. That’s why I teach my
patients to think of “enriched” as meaning “UNriched” … meaning that they took nutrients away and
did not add them back.
Improved understanding of the fate of specific carbohydrate-containing foods as described
above is lending some light to this puzzle, resulting in exploration of concepts such as genetic
differences in people’s metabolism, and the “glycemic index” of foods and meals. A quick
definition: The Glycemic Index is a comparison of the effect on blood sugar from eating 50 grams of
carbohydrate from a food compared with eating 50 grams of carbohydrate as plain glucose. (“Glyc- =
glucose or sugar; “-emic” = in the blood.)
A food that is described as having a “low glycemic index” is one that will cause a smaller rise
in blood sugar in response to eating it than would be produced by plain glucose. The lower blood
sugar response can help decrease injury to the circulatory system caused by frequent high peaks of
blood sugar. In general, and for several reasons, more complex “nutritionally-dense” foods will
usually have a lower glycemic index than “empty calorie” foods like regular soda. However, the
glycemic index is just one more tool to use to manage blood sugar in diabetes. A complete evaluation
of this research is too large to include here.
Carnitine:
A player in energy metabolism with particular importance in
diabetes (and also a potent antioxidant)
One other important piece of the puzzle of large fluctuations in blood sugar is less well
known among health professionals, so I will address it here in some detail. It has been found that
relative inadequacy of a substance called “carnitine” exists in some people with diabetes and in
others.
Additionally, there is increasing evidence that supplemental carnitine can be of significant help
in prevention or improvement of a number of complications of diabetes. For example, in a recent study
the average serum free-L-carnitine levels in patients with diabetes who had complications was
almost 25% lower than in the patients with no diabetes-related complications. On the basis of the
study results, the researchers suggested that “carnitine supplementation in diabetic patients, especially
in patients with diabetes complications, might be useful.”
Relative carnitine inadequacy has also been found to be a factor in a number of other
health conditions, with special importance in kidney disease, high triglycerides, obesity, poor
wound-healing and poor eye health … all of which are risk factors related to diabetes.
Normally, one makes an adequate amount of carnitine in the liver, the brain and the kidney
from methionine and lysine (two essential amino acids,) and additionally carnitine may be obtained
23
from meat. (That’s why it is called carnitine – it comes from “carne” which means meat in Latin and
Spanish. Memory device: think of “chili-con-carnitine.”) Individual differences in requirements,
diet, genetic carnitine production, and the use of certain medications (like valproic acid –
“Depekote”) for seizure control) can result in a relative inadequacy.
Carnitine is a key component of a cellular transporter called “carnitine
palmitoyl transferase” which allows fatty acids to cross the mitochondrial
membrane to be used as fuel to make ATP.
Because inadequate carnitine impairs one’s ability to move fatty acids into the mitochondrial
membrane to be used for fuel, symptoms can include lethargy, significant weight gain and obesity,
poor exercise endurance, poor muscle tone, heart muscle damage (cardiomyopathy,) greatly
fluctuating blood sugar, excessive appetite, elevated triglyceride levels in the blood, and if
applicable, “breakthrough seizures.” and increased risk of liver toxicity from use of certain
medications.
The key feature that affects blood sugar is the fact that there are times when we normally
switch to burning primarily fat as a fuel source in order to spare glucose for the brain – sort of like
having “dual heat” in your home: gas and wood. The brain does not burn long chains of fat like other
tissues can do. It can use only tiny bits of fuel like glucose molecules. But if fat is unable to be
burned by other tissues because of carnitine inadequacy, a person will have to burn glucose that
he/she really can’t afford to burn. [It is like living in North Dakota in the winter and running out of
fuel. You have to burn something to stay alive so you start burning the furniture!]
This unusual need to burn carbohydrate because fat cannot be used can result in an
extremely low blood sugar. This, in turn, can trigger release of glucose as glycogen from the liver,
causing blood sugar to rebound up high. At night when we are fasting, we usually switch over to
burning mostly fat. But poor carnitine status can make that effort fail. As a result, people can
experience a low blood sugar in the night and it may not even wake them up. While they sleep, a rush
of “rescue” glucose from the glycogen stores in the liver will result in people waking up with
surprisingly high blood sugars.
Even more seriously, if no glycogen is available to provide the glucose to correct it, the
low blood sugar can be injurious, and even life-threatening. This very serious kind of low blood
sugar is especially a problem in people who use insulin as part of their diabetes management.
People using insulin who experience unexpected low blood sugars or unstable blood
sugars should be sure to check out the possibility that inadequate carnitine is contributing to the
problem. In some studies people with Type-1 diabetes have been found to have low carnitine levels in
spite of our usual ability to simply make enough ourselves. It is a bit like insulin in that way … people
usually simply make enough ourselves and they do not need to take insulin. But as you are aware, some
folks DO need to take it even if others do not. It may be the same with carnitine.
And, it may also turn out to be similar in another way as well. Many autoimmune diseases
24
involve the decreased production of a key substance that one’s body used to make and then quits
making. In Type I diabetes, it is insulin. In pernicious anemia it is carnitine. In parkinsonism it is
dopamine. Failed production of thyroxine hormone by the thyroid gland is another. This is just my
speculation here, but it occurs to me that carnitine production may be similarly affected in genetically
susceptible people, and they simply begin to make less.
What started me to think about it was the following eye-opening 1989 report of 54
children with Type I diabetes who were screened for this and about 1/4 were found to be
carnitine deficient and about half had other evidence of carnitine inadequacy.
Now, how many children in any group would one expect to have inadequacy or deficiency of a
substance one easily makes oneself? The answer to that should be zero . But then why was this a
very common problem found in these children with diabetes? Maybe the ability to readily make
adequate carnitine is also something that can be lost as a consequence of autoimmune disease. Just
thinkin’ …. This has not been studied yet as far as I know. Here’s the abstract of the report … I am
including it here in its entirety because it is such an important finding but it has received amazingly
little attention in spite of my going on and on about this all the time.
Relative carnitine insufficiency in children with type I diabetes mellitus.
Winter SC, Simon M, Zorn EM. Am J Dis Child. 1989 Nov;143(11):1337-9.
Department of Pediatrics, University of California, San Francisco.
Recognizing the similarity of type I diabetes mellitus to inborn errors of metabolism that have
responded to carnitine therapy, we initiated a study of 54 children with type I diabetes mellitus.
Examining a fasting blood sample for levels of carnitine, glucose, and glycosylated hemoglobin
A1c, and a urine sample for levels of ketones and glucose, we found 13 children were deficient of
free carnitine (less than 20 mumol/L) and 30 had elevated acyl carnitine levels (greater than
11 mumol/L).
Statistical tests confirmed a significant difference between the diabetic population and normal
population for reduced free carnitine, elevated acyl carnitine, and an elevated ratio of acyl carnitine
to free carnitine.
Also, a significant correlation was found between the levels of urine glucose and ketones and the
level of acyl carnitine.
Our data indicate that carnitine deficiency and relative insufficiency may be an overlooked
component in the management of diabetes.
25
Interestingly, since we now know that carnitine lab values underestimate the number of people
with carnitine problems (because they do not reflect all the tissues likely to be affected,) the number of
children in the study above found to have inadequate or deficient carnitine likely is an underestimate of
the prevalence of this problem as well.
Since that report was published, I have worked with several children with Type I
diabetes whose blood sugar was very hard to manage in spite of the family doing everything
right in terms of insulin shots, carbohydrate consumption and exercise. They had frequent
episodes of very low glucose. A trial on carnitine worked amazingly well for doing away with
the troubling low blood sugar episodes in these children.
Bottom line: if a person experiences this kind of yo-yo blood sugar pattern with no
identifiable cause, a trial on carnitine would be a good idea. Getting a blood level is not as helpful
(even though they did it in the study), because if it is low, then one would prescribe some carnitine.
However, even if it is “normal,” the blood levels do not necessarily reflect adequacy in the other tissues
like the heart muscle. Carnitine deficiency is well known to result in severe cardiomyopathy. So, if
there are suggestive symptoms at all, one would want to do a trial anyway.
For health professionals who want to do a trial for a patient who has symptoms as described,
the usual dose in children is 50-100 mg/kg/day divided into 3 doses (just because of the potential GI
effects of high osmolality,) with a maximum usually 3000 mg/day. There is no reason not to start at
the 100 mg/kg level in this situation, as the working presumption of the trial is that tissues may be
depleted because the child has symptoms suggesting it.
Starting too low and stopping too soon may mask a true effect. When I do a trial, we monitor
selected symptoms for change, and usually the trial would be continued for at least a month even in the
absence of symptom relief, in order to be sure that any deficiency would have been corrected to the
point of detection of symptom change.
The other group of people with diabetes for whom a trial on carnitine is a
very reasonable step is those who are extremely obese.
They may also have very poor exercise tolerance and a variety of other symptoms, and we have
a tendency to assume that the “lazy couch-potato lifestyle” is a choice that causes their obesity. While
that is always a possibility and often quite contributory, remember that having inadequate carnitine
can cause one to be both very fat AND be a “couch potato” … which is one reason why simply
telling some folks that they should get off the couch and exercise more is not always helpful.
Some folks simply can’t fuel their leg muscles to do endurance-type exercise if they can’t get
the preferred fuel of muscles (fat) into the mitochondria to burn it. I have had many patients who fit
this description. Rather than blame them for being lazy and obese, a bit of compassion is in order …
and a trial on carnitine to see if it helps. I have had MANY patients for whom it did amazing things to
allow them to burn fat for fuel, exercise longer, feel stronger, lose weight and not feel starved all the
time. Life changing in many cases. No effect at all in others.
26
Carnitine is the other supplemental substance that could requires a prescription for a
trial and which can sometimes be expensive. Expense is quite variable, however. Insurance will
sometimes pay for the prescription kind but not pay for over-the-counter products. Both prescription
and over-the-counter products are available, and more carnitine supplements are becoming available
over-the-counter for lower prices, especially on-line.
When considering the cost of a trial on carnitine, it is useful to consider the cost of carnitine
supplementation against the cost of failing to identify and correct a carnitine insufficiency problem:
Consider the risk to your patient in damage from blood sugar vacillation, impairment of energy
production, compromised endurance, heart muscle injury, hypertriglyceridemia, excessive drive to eat,
the cost and consequences of bariatric surgery that might have been avoidable, and the social
consequences of being obese in America.
I am especially suspicious of a carnitine metabolism problem when a person has had bariatric
surgery but who somehow manages to gain the weight back and may even undergo a second surgery.
These folks often suffer considerable derision (“You’d think she would have more self respect than to
let herself gain all that weight back again!”) I think we should be less quick to be insulting and more
quick to explore the very real possibility of a carnitine-related metabolic problem. Just sayin’.
Please see my more detailed paper on this topic:
“Aunt Cathy’s Guide to Nutrition: A Short Carnitine Discussion That Might Be Helpful.”
Part Five: Minimizing risk of developing other threats to health and
well-being, including some conditions that are known to be exacerbated by
diabetes.
There are a number of conditions for which people with diabetes are at increased risk. These
include elevated homocysteine levels, depression, cardiovascular disease (including stroke), leg
cramps, and general neuropathy.
Some are related to medications, such as the effect of metformin (Glucophage) on vitamin
B12 level. Other common problems that can cause trouble for people with diabetes (or anyone) are
these: Proton pump inhibitors for GERD may also contribute to poor absorption of vitamin B12 from
food, and seriously obese people with diabetes may have had (or plan to have) gastric bypass
(bariatric) surgery, which can also compromise vitamin B12 absorption and absorption of many
nutrients. Old age alone can also impair absorption of vitamin B12 from food sources because of a
common loss of stomach acid with aging. These situations will need a closer look than usual among
people with diabetes.
At present, follow-up of micronutrient status in people who have had bariatric surgery
27
has not been consistent or studied adequately. Often the only outcomes evaluated are losing weight
and keeping it off, and any benefits seen in terms of cholesterol, blood pressure and diabetes. While
positive changes in these health conditions are extremely welcome, the important potential problem
of relative micronutrient inadequacy will not show up until a few years after the surgery. Some
are surprising and quite severe, such as permanent neurologic damage from copper deficiency … a
condition rarely seen but now showing up among some of the post-bariatric surgery populations.
For many patients, risks associated with potential multiple micronutrient deficiencies are not
assessed or followed at all. Some programs just note in the chart that the patient was told to take a
multivitamin with minerals. There is huge variability among these products in terms of actual content
(from clearly inadequate products with very minimal numbers of micronutrients to more balanced
products, but none is truly “complete” even for the healthy population.) The forms and the cost are
other variables. But my observation is that one of the most common mistakes in failing to prevent
micronutrient deficiencies in this context is the simple assumption that “normal” RDA/RDI/AI levels
of nutrients are at all likely to be sufficient for this population. There are so many reasons why they
will not do the job.
An additional concern is a lack of long term monitoring of these issues for bariatric surgery
patients. Interestingly, many people discontinue whatever supplementation regimen they were
prescribed after a few months or years, and apparently this is rarely recognized prior to discovering a
serious problem.
Overweight people anticipating bariatric surgery are often presumed by the public and also by
health professionals as being “well nourished.” However, their size is really only a reliable indication
of generous amounts of calories stored, not micronutrient or even protein adequacy. Many studies
have shown that the population undergoing bariatric surgery are often in very poor
micronutrient status even before the surgery is performed, so impaired absorption of nutrients
after surgery is even more serious. Recovery from the surgery itself can also be compromised.
High triglycerides are known to be a risk factor for stroke in people with diabetes especially.
Three of the nutrition factors described earlier are associated with correcting high triglycerides:
assuring an adequate intake of chromium as chromium picolinate, maintaining a ratio of omega-6 to
omega-3 fatty acids in the neighborhood of 4:1, and correcting relative carnitine inadequacy. All
are potentially quite beneficial. High triglycerides are often seen in renal failure as well … another
diabetes-related problem. This may also have a carnitine connection, as the kidney is one of the three
places in the body where we do make carnitine.
Inadequate vitamin B6 and magnesium appear to be involved in diabetic neuropathy, and
also in heart disease and leg cramps. Vitamins B1,B6, B12 and folic acid are critical for
preventing elevated homocysteine, a major contributor to stroke (or at least a marker for increased
risk of stroke,) and possibly to alzheimers. Folic acid inadequacy is associated with cancer of the
breast, prostate and colon. It is also a contributor to depression and inadequacy also makes
therapeutic interventions for depression (such as SSRIs) work much less well. Chronic antibiotic use
and alcohol abuse both impair folic acid absorption.
28
Certain groups of people have a genetic problem that requires special attention to folic acid.
For example, among some people of Irish heritage, the MTHFR gene has been discovered that
contributes to higher rates of certain birth defects, depression and alcoholism related to problems
associated with folic acid metabolism.
Happily this particular problem is significantly less of a concern since 1998 when folic acid in
a well-utilized form was added to grain products in America. In the five years after starting this
supplementation compared with the 5 years before supplementation, neural tube birth defects were cut
in half, and stroke occurrence was cut by 10% across the USA. Wow! This illustrates that there is
greater variety in the needs of individuals for nutrients in general than was assumed in the past, and it is
clear that the assumed “adequate” intake of a nutrient for public health estimates is not the same as an
individual’s optimal intake.
(Please see “Aunt Cathy’s Guide to Nutrition: Folic Acid” and “Aunt Cathy’s Guide to Nutrition: Vitamin
B12” for details, references and recommendations.)
Some studies with vitamin B6 have used levels of 50 to 100 mg to achieve a desired effect
in people with diabetic neuropathy. This is much higher than the RDA-type level of about 2 mg,
but not anywhere near a level that might be a problem. This is especially true if one is hypothesizing
that their vitamin B6 requirements are in fact higher than the requirements of other people. Vitamin
B6 (pyridoxine) is a cofactor with magnesium in a large number of metabolic pathways, including all
amino acid metabolism, all energy metabolism, and all nerve function. They work together so often
in nature that some attention is now being paid to evaluating the effectiveness of using either of these
nutrients in combination with each other to bring about a particular metabolic effect.
Niacin (vitamin B3), riboflavin (vitamin B2) and thiamine (vitamin B1) and biotin are all
being studied. Biotin is less familiar to most people but it is looking to be extremely interesting in a
variety of metabolic conditions including diabetes. For example, biotin has a key role in
gluconeogenesis … making new glucose out of amino acids.
Some examples of some newer reports exploring the role of biotin in
diabetes, including biotin combined with other nutrients in diabetes
research:
Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and
beta-cell proportion. J Nutr Biochem. 2013 Jan;24(1):169-77.
Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat and
streptozotocin. Br J Nutr. 2012 Dec 5:1-9.
Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis. J Nutr
Biochem. 2012 Apr;23(4):392-9.
Pharmacological concentrations of biotin reduce serum triglycerides and the expression of lipogenic genes. Eur
J Pharmacol. 2010 Oct 10;644(1-3):263-8. A combination of nutriments improves mitochondrial
29
biogenesis and function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. PLoS One. 2008
Jun 4;3(6):e2328. [CB note: They used biotin, alpha-lipoic acid, carnitine and nicotinamide (vitamin
B3)] Their conclusion: All of these effects of mitochondrial nutrients are comparable to that of
the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone,
did not cause body weight gain.
Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes
mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Am J Med Sci. 2007
Mar;333(3):145-53.
B vitamins are generally among the least toxic vitamins – B6 is the only one documented to
cause problems with high amounts, and that was only in the most sensitive people, and never at levels
below 200 mg/day. Most people who experienced any tingling in the forearms (the symptom in
question) were taking over 500 mg chronically. Some people find it safe, cheaper and convenient to
take a “B-100 Complex” tablet along with their general multivitamin with minerals, instead of trying to
tinker with a lot of individual B vitamins.
As always, check with your physician about applying any of these ideas to your own
health circumstances. But it may be helpful to share this handout with him/her with the section
marked that you are asking about. Providing it before your visit to discuss it will give your physician
a chance to review the research studies I have listed.
Much of this is quite new, and there is a lot of research out there to try to keep up with.
They have a boatload of other diabetes-related research to study … I keep up just on some
nutrition issues. Additionally, there is a lot of wacky stuff out there that health professionals
are aware of. It can be overwhelming, so there can be a tendency to “Throw the Baby out with
the Bathwater.” The purpose of this review is to help sort out the real “babies” in that
bathwater that are very safe and that can be very helpful for improving the health of patients.
It has recently been found that serious chronic conditions like celiac disease,
hemochromatosis and certain thyroid problems are much more prevalent in the general
population than has been previously thought. Health professionals would do well to keep these
conditions in mind especially among their patients with diabetes. There are some links between
hemochromatosis and diabetes, between hemochromatosis and celiac disease, and between
diabetes and celiac disease. For example, according to a recent report, “higher iron stores (reflected
by a significantly elevated ferritin concentration and a lower ratio of transferrin receptors to ferritin)
are associated with an increased risk of type 2 diabetes in healthy women independent of known
diabetes risk factors.”
Thyroid health problems may be related to diabetes, but as described earlier, there is also a
newly recognized recurrence of iodine deficiency in the US resulting in goiter (enlarged thyroid),
weight gain and loss of energy. Additionally, the American Medical Association recommends that all
women over 40 have their thyroid function checked annually. There are age-related changes that
can make women’s (especially) thyroid hormone gradually become inadequate.
Celiac disease, an autoimmune disease that is triggered by exposure to gluten in wheat,
rye and barley is genetically more common among people with Type I diabetes. At our clinic, we
30
screen children with Type I diabetes for hidden celiac disease with a “Tissue Transglutaminase” blood
test. We also check children with Down syndrome, as they have an increased risk of both celiac
disease and Type I diabetes. They have also been found to produce way more free radicals than other
people so they need more antioxidants than usual. They also sometimes benefit from carnitine
supplementation, which can be helpful in particular with low muscle tone.
In addition to the gastrointestinal problems that are the most commonly recognized symptoms
of celiac disease (which can certainly affect absorption of many nutrients,) it is now recognized that
there are other less well recognized neurologic and dermatologic manifestations of celiac disease, and
they could be complicating the recognition and treatment of neurologic and skin disorders thought to
be primarily related to diabetes. Celiac is also by nature inflammatory and it also contributes to
increased production of free radicals. Crohn’s disease (Inflammatory Bowel Disease / IBD) now
appears to be another inflammatory autoimmune “cousin” to watch out for.
The increased risk of developing “pernicious anemia” (an auto-immune type of very
injurious kind of anemia) is also a threat in people with Type I diabetes. It may not be recognized
because the neurologic symptoms of B-12 deficiency are often mistakenly attributed to diabetesrelated neurologic complications. The development of pernicious anemia was recognized in an adult
friend who has Type I diabetes, and she suffered terrible neurologic pain, some of which continues to
be a problem even after the vitamin B12 deficiency was resolved by administering it as a shot.
This is a big deal because it is so harmful if unrecognized and uncorrected, so I am going
to re-cap this here a bit. As noted earlier, in addition to developing the autoimmune diseases called
pernicious anemia that blocks intestinal absorption of vitamin B12, there are other factors that can
interfere with vitamin B12 deficiency as well with serious consequences unless adjustments are
made. These include:
* certain gastrointestinal diseases or intestinal surgery (e.g. gastrectomy, bariatric surgery,
inflammatory bowel disease)
* age-related loss of stomach acid,
* the use of medications that block acid production called PPIs – “proton pump inhibitors”
for GERD (Gastro-Esophageal Reflux) and
* the use of the diabetes drug metformin (Glucophage.)
For more information, please see “Aunt Cathy’s Guide to Nutrition: Hemochromatosis” “Aunt Cathy’s Guide to
Nutrition: Vitamin B12 ” and “Aunt Cathy’s Guide to Nutrition: Other Nutrition Issues in Celiac Disease.”
7. Discovering the emerging miscellaneous effects of a variety of
phytochemicals on the diabetic state.
31
Around the world and in the US quite a number of plants and their various “phyto-chemicals”
(“plant chemicals”) are being investigated for their ability to influence health in diabetes and in
general. The phytochemical pigmanets (naturally occurring coloring agents in plants) were described
earlier as being very important as potent antioxidants that protect against free radical damage. These
are important for everyone’s health, but especially so for people with diabetes.
However, there are many other (non-pigment) plant chemicals that are being invesitigated as
being of possible benefit in diabetes in a variety of ways. This is a huge area of research and it is far
outside of the scope of this paper. In general, the properties being looked at are more of a
pharmaceutical nature than a nutrition nature, even though some of the plants have a food connection.
The food-related substances include certain herbs and spices like cinnamon, curcumin, ginger, ginseng
and other substances in fruits and vegetables like pomagrate, stevia, and many, many more. In most
cases the research is in early days in terms of drawing any conclusions about form, efficacy, and safety.
But if you would like to get a taste of the kinds of studies being undertaken, simply log on
to Public Medline (www.pubmed.gov) and pick the box at the right that says “for health
professionals.” Then check the “Medline” box. You will see a box at the top of the screen in which
you should enter search terms such as: “diabetes plant” or “diabetes herb” or “diabetes
phytochemical.”
You will find reports like this: “Coffee consumption and risk of type 2 diabetes mellitus: an
11-year prospective study of 28,812 postmenopausal women” in the journal Arch Intern Med. 2006
Jun 26;166(12): 1311-6. The conclusion of this study was that “Coffee intake, especially
decaffeinated coffee, was inversely associated with risk of type 2 diabetes mellitus in this cohort of
postmenopausal women.” That is, the coffee-drinkers had LOWER risk. More recent studies have
supported this finding. It is notable because assumptions have long been that something we like so
much has GOT to be really bad for you. Personally, I am not too surprised that coffee may have some
health benefits … Hey! It’s a BEAN! 
Some References (…these are just the ones from 2010 or earlier … there are lots more
that are newer, but I am leaving these here from when I wrote the very first versions of this paper so
you can see that there is a TON of research and it is piling up more and more every day … and that I
am not making this stuff up!)
References: Chromium
2010
Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2 diabetes mellitus.
Metabolism. 2010 Aug 31. Characterization of the metabolic and physiologic response to chromium supplementation in subjects with type 2
diabetes mellitus. Metabolism. 2010 May;59(5):755-62. Chromium Effects on Glucose Tolerance and Insulin Sensitivity in People at Risk for
Diabetes. Endocr Pract. 2010 Jul 14:1-21. Current concepts about chromium supplementation in type 2 diabetes and insulin resistance. Curr Diab
Rep. 2010 Apr;10(2):145-51.J Inorg Biochem. 2010 Jul;104(7):790-7. Urinary chromium loss associated with diabetes is offset by increases in
absorption. J Inorg Biochem. 2010 Jul;104(7):790-7. Chronic maternal dietary chromium restriction modulates visceral adiposity: probable
underlying mechanisms. Diabetes. 2010 Jan;59(1):98-104. Maternal dietary chromium restriction programs muscle development and function in
the rat offspring. Exp Biol Med (Maywood). 2010 Mar;235(3):349-55 The content of elements in rainwater and its relation to the frequency of
hospitalization for diabetes and obesity in Opole Voivodship, Poland, during 2000-2002. Biol Trace Elem Res. 2010 Aug;136(2):149-56.
Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood
32
vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats. Mol Nutr Food Res.
2010.Sep;54(9):1371-80. Improved glucose control associated with i.v. chromium administration in two patients receiving enteral nutrition. Am J
Health Syst Pharm. 2010 Apr 1;67(7):535-41. Oral Administration of the High-Chromium Yeast Improve Blood Plasma Variables and Pancreatic
Islet Tissue in Diabetic Mice. Biol Trace Elem Res. 2010 Mar 2. Improved cognitive-cerebral function in older adults with chromium
supplementation. Nutr Neurosci. 2010 Jun;13(3):116-22.Nutraceuticals in diabetes and metabolic syndrome. Cardiovasc Ther. 2010
Aug;28(4):216-26.
2009 and earlier Effect of chromium supplementation on the diabetes induced-oxidative stress in liver and brain of adult rats. Biometals. 2009
Aug 20Protective effects of combined micronutrients on islet beta-cells of streptozotocin-induced diabetic mice. Int J Vitam Nutr Res. 2009
Mar;79(2):104-16. Chromium picolinate inhibits resistin secretion in insulin-resistant 3T3-L1 adipocytes via activation of amp-activated protein
kinase. Clin Exp Pharmacol Physiol. 2009 Aug;36(8):843-9. Chromium picolinate does not improve key features of metabolic syndrome in obese
nondiabetic adults. Metab Syndr Relat Disord. 2009 Summer;7(2):143-50. Effect of microelements supplementation on beta-oxidation activity in
healthy and type 1 diabetic rats. Cent Eur J Public Health. 2008 Dec;16(4):205-8.Chromium: the forgotten mineral. Harv Mens Health Watch. 2007
Jan;11(6):6-7; Chromium treatment has no effect in Patients with Type 2 Diabetes Mellitus in a Western Population: A Randomized, Double-Blind,
Placebo-Controlled Trial. Diabetes Care. 2007 Feb 15; Limited evidence for effects of diet for type 2 diabetes from systematic reviews. Eur J Clin
Nutr. 2007 Jan 24; Synergistic effects of conjugated linoleic acid and chromium picolinate improve vascular function and renal pathophysiology in
the insulin-resistant JCR:LA-cp rat. Diabetes Obes Metab. 2007 Jan;9(1):87-95; In vitro study of elements in herbal remedies. Biol Trace Elem Res.
2006 Winter;114(1-3):143-50; Longitudinal hair chromium profiles of elderly subjects with normal glucose tolerance and type 2 diabetes mellitus.
Metabolism. 2007 Jan;56(1):94-104; Relative element levels in the paired samples of scalp hair and fingernails of patients from New Delhi. Sci
Total Environ. 2007 Jan 1;372(2-3):474-9; Chromium picolinate supplementation attenuates body weight gain and increases insulin sensitivity in
subjects with type 2 diabetes: response to Martin et al. Diabetes Care. 2006 Dec;29(12):2764; Chromium picolinate supplementation attenuates
body weight gain and increases insulin sensitivity in subjects with type 2 diabetes: response to mark. Diabetes Care. 2006 Dec;29(12):2764-5;
Clinical studies on chromium picolinate supplementation in diabetes mellitus--a review. Diabetes Technol Ther. 2006 Dec;8(6):677-87; The
effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a
placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006 Dec;8(6):636-43; Chromium picolinate intake and risk of type
2 diabetes: an evidence-based review by the United States Food and Drug Administration. Nutr Rev. 2006 Aug;64(8):357-63; Chromium(III)
complexes of D-glucosaminic acid and their effect on decreasing blood sugar in vivo. Arch Pharm (Weinheim). 2006 Sep;339(9):527-30;
Transcriptome of the subcutaneous adipose tissue in response to oral supplementation of type 2 Leprdb obese diabetic mice with niacin-bound
chromium. Physiol Genomics. 2006 Nov 27;27(3):370-9; Conjugated linoleic acid and chromium lower body weight and visceral fat mass in
high-fat-diet-fed mice. Lipids. 2006 May;41(5):437-44; Chromium picolinate supplementation attenuates body weight gain and increases insulin
sensitivity in subjects with type 2 diabetes. Diabetes Care. 2006 Aug;29(8):1826-32; Clinical studies on chromium picolinate supplementation in
diabetes mellitus--a review. Diabetes Technol Ther. 2006 Dec;8(6):677-87. The effect of chromium picolinate and biotin supplementation on
glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes
Technol Ther. 2006 Dec;8(6):636-43. The influence of chromium chloride-containing milk to glycemic control of patients with type 2 diabetes
mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism. 2006 Jul;55(7):923-7. Chromium picolinate supplementation
attenuates body weight gain and increases insulin sensitivity in subjects with type 2 diabetes. Diabetes Care. 2006 Aug;29(8):1826-32; Chromium
picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic
diabetic conditions. Mutat Res. 2006 Nov 7;610(1-2):93-100; The influence of chromium chloride-containing milk to glycemic control of patients
with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled trial. Metabolism. 2006 Jul;55(7):923-7; Influence of
chromium-enriched yeast on blood glucose and insulin variables, blood lipids, and markers of oxidative stress in subjects with type 2 diabetes
mellitus. Biol Trace Elem Res. 2006 Mar;109(3):215-30; Hypoglycemic potency of novel trivalent chromium in hyperglycemic insulin-deficient
rats. J Trace Elem Med Biol. 2006;20(1):33-9; An exploratory study into the effectiveness of a combination of traditional Chinese herbs in the
management of type 2 diabetes. Diabetes Care. 2006 Apr;29(4):945-6; Inhibition of diabetic nephropathy in rats by an oral antidiabetic material
extracted from yeast. J Am Soc Nephrol. 2006 Apr;17(4 Suppl 2):S127-31; Insulin-sensitizing and cholesterol-lowering effects of chromium
(D-Phenylalanine)3. J Inorg Biochem. 2006 Jul;100(7):1187-93;Chromium treatment has no effect in patients with poorly controlled,
insulin-treated type 2 diabetes in an obese Western population: a randomized, double-blind, placebo-controlled trial. Diabetes Care. 2006
Mar;29(3):521-5; Trivalent chromium inhibits protein glycosylation and lipid peroxidation in high glucose-treated erythrocytes. Antioxid Redox
Signal. 2006 Jan-Feb;8(1-2):238-4; Chromium chloride inhibits TNFalpha and IL-6 secretion in isolated human blood mononuclear cells exposed
to high glucose. Horm Metab Res. 2006 Jan;38(1):60-2;Effect of chromium picolinate on modified forced swimming test in diabetic rats:
involvement of serotonergic pathways and potassium channels. Basic Clin Pharmacol Toxicol. 2006 Feb;98(2):155-9;Chronic CO levels have
[corrected] a beneficial effect on vascular relaxation in diabetes. Biochem Biophys Res Commun. 2006 Feb 17;340(3):935-43; Chromium activates
glucose transporter 4 trafficking and enhances insulin-stimulated glucose transport in 3T3-L1 adipocytes via a cholesterol-dependent mechanism.
Mol Endocrinol. 2006 Apr;20(4):857-70; Mineral content of some medicinal plants used in the treatment of diabetes mellitus. Biol Trace Elem Res.
2005 Feb;103(2):109-15; Is chromium III a new key to effective diabetes management? Manag Care. 2005 Nov;14(11):78-80; Determination of
fourteen trace elements in chinese traditional medicines by atomic absorption spectrometry. Guang Pu Xue Yu Guang Pu Fen Xi. 2005
Sep;25(9):1510-3; Mineral contents of aloe vera leaf gel and their role on streptozotocin-induced diabetic rats. Biol Trace Elem Res. 2005
Winter;108(1-3):185-95; Effect of chromium on the insulin resistance in patients with type II diabetes mellitus. Folia Med (Plovdiv).
2005;47(3-4):59-62; A double-blind, placebo-controlled, exploratory trial of chromium picolinate in atypical depression: effect on carbohydrate
craving; J Psychiatr Pract. 2005 Sep;11(5):302-14; Effects of chronic chromium picolinate treatment in uninephrectomized rat. Metabolism. 2005
Sep;54(9):1243-9; Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic analysis.Dis Manag. 2005
Aug;8(4):265-75; Supplementation with chromium picolinate recovers renal Cr concentration and improves carbohydrate metabolism and renal
function in type 2 diabetic mice.Biol Trace Elem Res. 2005 Summer;105(1-3):229-48; Chromium supplementation shortens QTc interval duration
in patients with type 2 diabetes mellitus. Am Heart J. 2005 Apr;149(4):632-6; Regulation of chromium on gene expression of skeletal muscles in
diabetic rats.Wei Sheng Yan Jiu. 2005 Mar;34(2):184-7; Complementary therapies for diabetes: the case for chromium, magnesium, and
antioxidants.Arch Med Res. 2005 May-Jun;36(3):250-7;Cellular chromium enhances activation of insulin receptor kinase.Biochemistry. 2005 Jun
7;44(22):8167-75;Chromium picolinate may favorably influence the vascular risk associated with smoking by combating cortisol-induced insulin
33
resistance.Med Hypotheses. 2005;64(6):1220-4; Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic
analysis. Dis Manag. 2005 Aug;8(4):265-75. Mutat Res. 2006 Jul 24) Am Heart J. 2005 Apr;149(4):632-6. Med Hypotheses. 2005;64(6):1220-4. J
Psychiatr Pract. 2005 Sep;11(5):302-14.. Biol Trace Elem Res. 2005 Summer;105(1-3):229-48.
References: Magnesium
2010
Nuts, inflammation and insulin resistance. Asia Pac J Clin Nutr. 2010;19(1):124-30. Nuts, blood lipids and cardiovascular disease. Asia
Pac J Clin Nutr. 2010;19(1):131-6. Health benefits of nuts in prevention and management of diabetes. Asia Pac J Clin Nutr. 2010;19(1):110-6.Nuts,
metabolic syndrome and diabetes Br J Nutr. 2010 Aug;104(4):465-73. Relations of dietary magnesium intake to biomarkers of inflammation and
endothelial dysfunction in an ethnically diverse cohort of postmenopausal women. Diabetes Care. 2010 Feb;33(2):304-10. Oral magnesium
supplementation improves vascular function in elderly diabetic patients. Magnes Res. 2010 Aug 24. Magnesium intake and risk of self-reported
type 2 diabetes among Japanese. J Am Coll Nutr. 2010 Apr;29(2):99-106. Almond consumption improved glycemic control and lipid profiles in
patients with type 2 diabetes mellitus. Metabolism. 2010 May 22. Status of Copper and Magnesium Levels in Diabetic Nephropathy Cases: a
Case-Control Study from South India. Biol Trace Elem Res. 2010 Jun 16. Influence of Therapy with Metformin on the Concentration of Certain
Divalent Cations in Patients with Non-insulin-Dependent Diabetes Mellitus. Biol Trace Elem Res. 2010 Jun 22. Intracellular magnesium detection:
imaging a brighter future. Analyst. 2010 Aug;135(8):1855-66. Role of vitamins and minerals in prevention and management of type 2 diabetes
mellitus. Nutr Rev. 2010 Jun;68(6):341-54. Magnesium, inflammation, and obesity in chronic disease. Nutr Rev. 2010 Jun;68(6):333-40.
Magnesium and aging. Curr Pharm Des. 2010;16(7):832-9. Hypomagnesemia is a risk factor for nonrecovery of renal function and mortality in
AIDS patients with acute kidney injury. Braz J Med Biol Res. 2010 Mar;43(3):316-23. Low serum creatinine is associated with type 2 diabetes in
morbidly obese women and men: a cross-sectional study. BMC Endocr Disord. 2010 Apr 18;10(1):6..Magnesium and cardiovascular system.
Magnes Res. 2010 Jun;23(2):60-72.Natural therapeutic magnesium lithospermate B potently protects the endothelium from
hyperglycaemia-induced dysfunction. Cardiovasc Res. 2010 Sep 1;87(4):713-22. Magnesium supplements may enhance the effect of
antihypertensive medications in stage 1 hypertensive subjects. Magnes Res. 2010 Mar;23(1):27-40.
2009 and earlier The role of diet and lifestyle in primary, secondary, and tertiary diabetes prevention: a review of meta-analyses. Rev Diabet
Stud. 2010 Spring;7(1):26-35. Dietary fatty acid composition alters magnesium metabolism, distribution, and marginal deficiency response in rats
*. Magnes Res. 2009 Dec;22(4):280-8. Magnesium homeostasis and aging. Magnes Res. 2009 Dec;22(4):235-46.Long-term effects of maternal
magnesium restriction on adiposity and insulin resistance in rat pups. Obesity (Silver Spring). 2008 Jun;16(6):1270-6. The effect of
microelements supplementation on beta-oxidation activity in healthy and type 1 diabetic rats. Cent Eur J Public Health. 2008 Dec;16(4):205-8.
Effect of oral magnesium sulfate administration on blood pressure and lipid profile in streptozocin diabetic rat.Eur J Pharmacol. 2007 Apr
10;560(2-3):201-5. Jan 19; Magnesium metabolism in type 2 diabetes mellitus, metabolic syndrome and insulin resistance. Arch Biochem Biophys.
2007 Feb 1;458(1):40-7. The effect of magnesium deficit on serum immunoglobulin concentrations in type 1 diabetes mellitus. Rom J Intern Med.
2006;44(1):61-7; Serum magnesium and type-2 diabetes in African Americans and Hispanics: a New York cohort. J Am Coll Nutr. 2006
Dec;25(6):509-13. Magnesium intake is related to improved insulin homeostasis in the framingham offspring cohort. J Am Coll Nutr. 2006
Dec;25(6):486-92; Increased magnesium intake prevents hyperlipidemia and insulin resistance and reduces lipid peroxidation in fructose-fed rats
Pathophysiology. 2006 Dec 20; Relationship between serum magnesium values, lipids and anthropometric risk factors. Atherosclerosis. 2006 Dec
7; Dietary magnesium intake and risk of incident hypertension among middle-aged and older US women in a 10-year follow-up study. Am J
Cardiol. 2006 Dec 15;98(12):1616-21; Other relevant components of nuts: phytosterols, folate and minerals. Br J Nutr. 2006 Nov;96 Suppl
2:S36-44; Intracellular magnesium in elderly patients with heart failure: effects of diabetes and renal dysfunction.J Trace Elem Med Biol.
2006;20(4):221-6; Dietary magnesium and fiber intakes and inflammatory and metabolic indicators in middle-aged subjects from a
population-based cohort. Am J Clin Nutr. 2006 Nov;84(5):1062-9; Dietary calcium and magnesium, major food sources, and risk of type 2 diabetes
in U.S. black women. Diabetes Care. 2006 Oct;29(10):2238-43; Dietary fiber intake, dietary glycemic load, and the risk for gestational diabetes
mellitus. Diabetes Care. 2006 Oct;29(10):2223-30; Effects of oral magnesium supplementation on glycaemic control in Type 2 diabetes: a
meta-analysis of randomized double-blind controlled trials. Diabet Med. 2006 Oct;23(10): 050-6. Dairy, magnesium, and calcium intake in
relation to insulin sensitivity: approaches to modeling a dose-dependent association. Am J Epidemiol. 2006 Sep 1;164(5):449-58. The nerve-heart
connection in the pro-oxidant response to Mg-deficiency. Heart Fail Rev. 2006 Mar;11(1):35-44; A prospective study of dairy intake and the risk of
type 2 diabetes in women. Diabetes Care. 2006 Jul;29(7):1579-84; Serum ionized magnesium levels in relation to metabolic syndrome in type 2
diabetic patients. J Am Coll Nutr. 2006; Jun;25(3):210-5; Magnesium and diabetes mellitus: their relation. Clin Nutr. 2006 Aug;25(4):554-62.
Magnesium intake and incidence of metabolic syndrome among young adults. Circulation. 2006 Apr 4;113(13):1675-82; Dietary intake among
youth with diabetes: the SEARCH for Diabetes in Youth Study.J Am Diet Assoc. 2006 May;106(5):689-97.;Am J Epidemiol. 2006 Jul 21; J Am
Coll Nutr. 2006 Jun;25(3):210-5. Clin Nutr. 2006 Aug;25(4):554-62.. Arch Biochem Biophys. 2006 Jun 12; Magnesium urinary excretion in
diabetic adolescents. Acta Medica (Hradec Kralove). 2005;48(3-4):157-61
References: Vitamin K
34
2010 Clin J Am Soc Nephrol. 2010 Feb 4. The circulating inactive form of matrix GLA Protein is a surrogate marker for vascular calcification in
chronic kidney disease: a preliminary report. J Nutr Biochem. 2010 Feb 8. Vitamin K suppresses the lipopolysaccharide-induced expression of
inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor kappaB through the repression of
IKKalpha/beta phosphorylation.Clin J Am Soc Nephrol. 2010 Feb 18. Role of vitamins and minerals in prevention and management of type 2
diabetes mellitus. Nutr Rev. 2010 Jun;68(6):341-54.
2009 and earlier Vitamins K and D status in stages 3-5 chronic kidney disease.Clin Exp Immunol. 2009 Dec 17. Vitamin K(3) attenuates
lipopolysaccharide-induced acute lung injury through inhibition of nuclear factor-kappaB activation.J Mal Vasc. 2009 Apr 2. Origin of the
mediacalcosis in kidney failureNephrol Dial Transplant. 2009 Jul;24(7):2095-101. Origin of the mediacalcosis in kidney failure. J Mal Vasc. 2009
May;34(3):204-10. Association of kidney function and uncarboxylated matrix GLA protein: data from the Heart and Soul Study.J Thromb
Haemost. 2009 Feb;101(2):359-66. Uncarboxylated matrix GLA protein (ucMGP) is associated with coronary artery calcification in haemodialysis
patients.J Thromb Haemost 2009;Sept 28. Warfarin use and the risk of valvular calcification. Int J Artif Organs. 2009 Feb;32(2):67-74. Coagulation
meets calcification: The vitamin K system.J Bone Miner Res. 2009 Vitamin k and bone: past, present, and future.Br J Nutr. 2009 Apr 1:1-16
Minerals and vitamins in bone health: the potential value of dietary enhancement. Osteoporos Int. 2009Mar 12Prior treatment with vitamin K(2)
significantly improves the efficacy of risedronate.J Bone Miner Metab. 2009;27(3):333-40.Short-term menatetrenone therapy increases
gamma-carboxylation of osteocalcin with a moderate increase of bone turnover in postmenopausal osteoporosis: a randomized prospective study.
Bioorg Med Chem Lett. 2009 Feb 15;19(4):1054-7. Elucidation of the mechanism producing menaquinone-4 in osteoblastic cells. J Bone Miner
Res. 2009 Jun;24(6):983-91.Vitamin k treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in
healthy postmenopausal north american women. J Mal Vasc. 2009 Apr 2. Origin of the mediacalcosis in kidney failure. Am J Clin Nutr. 2008
Jul;88(1):210-5. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women.Atherosclerosis. 2008 Jul 19Thromb Res.
2008;122(3):411-7. High dietary menaquinone intake is associated with reduced coronary calcification. Effects of the blood coagulation vitamin K
as an inhibitor of arterial calcification. J Vasc Res. 2008 Apr 10;45(5):427-436. The Circulating Inactive Form of Matrix Gla Protein (ucMGP) as
a Biomarker for Cardiovascular Calcification. Arterioscler Thromb Vasc Biol. 2008 Apr;28(4):771-6. Vitamin K epoxide reductase complex
subunit 1 (VKORC1) polymorphism and aortic calcification: the Rotterdam Study. Am J Epidemiol. 2008 Feb 1;167(3):313-20. Vitamin K and
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healthy subjects in Jordan people. Prostaglandins Leukot Essent Fatty Acids. 2006 Jun;74(6):347-56; The relationship between tissue RBC n-3 fatty
acids and pulse wave velocity. In Vivo. 2006 Mar-Apr;20(2):307-10;Association between dietary fat and anti-oxidant status of Tunisian type 2
diabetic patients. Prostaglandins Leukot Essent Fatty Acids. 2006 May;74(5):323-9; Intake of fish and long-chain n-3 fatty acids and the risk of
coronary heart mortality in men and women. Br J Nutr. 2006 Apr;95(4):824-9; Sustained enrichment of liver phospholipids and triglycerides in
eicosapentaenoate after a bolus intravenous injection of a medium-chain triglycerides:fish oil emulsion to streptozotocin (Type 1) and
Goto-Kakizaki (Type 2) diabetic rats. Int J Mol Med. 2006 Apr;17(4):643-7; Nutrient intake of women with and without gestational diabetes with a
specific focus on fatty acids. Nutrition. 2006 Mar;22(3):230-6; A distinctive fatty acid profile in circulating lipids of Korean gestational diabetics: a
pilot study. Diabetes Res Clin Pract. 2006 Aug;73(2):178-83; N-3 fatty acids modulate antioxidant status in diabetic rats and their macrosomic
offspring. Int J Obes (Lond). 2006 May;30(5):739-50; Differential effect of saturated, monounsaturated, and polyunsaturated fatty acids on
alloxan-induced diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids. 2006 Mar;74(3):199-213; Effect of n-3 polyunsaturated fatty acids on
plasma lipid, LDL lipoperoxidation, homocysteine and inflammation indicators in diabetic dyslipidemia treated with statin + fibrate combination.
Cas Lek Cesk. 2005;144(11):737-41; Dietary fats, fatty acids and insulin resistance: short review of a multi-faceted connection. Med Sci Monit.
2005 Dec;11(12):RA359-67; A successful diabetes prevention study in Eskimos: the Alaska Siberia project. Int J Circumpolar Health. 2005
Sep;64(4):409-24; Omega-3 fatty acids improve glucose tolerance and components of the metabolic syndrome in Alaskan Eskimos: the Alaska
Siberia project. Int J Circumpolar Health. 2005 Sep;64(4):396-408; Fat food for a bad mood. Could we treat and prevent depression in Type 2
diabetes by means of omega-3 polyunsaturated fatty acids? A review of the evidence. Diabet Med. 2005 Nov;22 (11):1465-75. Mediation of
cognitive function by high fat diet following stress and inflammation. Nutr Neurosci. 2005 Oct-Dec;8(5-6):309-15; Nutrition in prediabetes. J
Indian Med Assoc. 2005 Nov;103(11):596, 598-9; C-reactive proteins and chronic disease: what role does nutrition play? Nutr Clin Pract. 2003
Jun;18(3):227-33; Molecular mechanisms of action and health benefits of polyunsaturated fatty acids] Rev Invest Clin. 2005
May-Jun;57(3):457-72; Effects of omega-3 fatty acids on eye health. Evid Rep Technol Assess (Summ). 2005 Jul;(117):1-6;Extending the
cardiovascular benefits of omega-3 Fatty acids. Curr Atheroscler Rep. 2005 Sep;7(5):375-80;The fats of life: type 1 diabetes mellitus,
athero-sclerosis, & omega-3 long-chain polyunsaturated fatty acids. Treat Endocrinol. 2005;4(4):261; The impact of age, body mass index, & fish
intake on the EPA & DHA content of human erythrocytes.Lipids. 2005 Apr;40(4):343-7; Structured dietary advice incorporating walnuts achieves
optimal fat and energy balance in patients with type 2 diabetes mellitus. J Am Diet Assoc. 2005 Jul;105(7):1087-96; Fetal erythrocyte membrane
lipids modification: preliminary observation of an early sign of compromised insulin sensitivity in offspring of gestational diabetic women. Diabet
Med. 2005 Jul;22(7):914-20; Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs. 2005;65(8):1051-9; Ratio of n-6 to n-3 fatty
acids & bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr. 2005 Apr;81(4):934-8; Long-chain omega 6
polyunsaturated fatty acids in erythrocyte phospholipids are associated with insulin resistance in non-obese type 2 diabetics. Clin Chim Acta. 2005
Apr;354(1-2):195-9; n-3 long-chain polyunsaturated fatty acids in type 2 diabetes: a review. J Am Diet Assoc. 2005 Mar;105(3):428-40; A few
more thoughts about fish and fish oil. J Am Diet Assoc. 2005 Mar;105(3):350-1; Red wine consumption improves insulin resistance but not
endothelial function in type 2 diabetic patients. Metabolism. 2005 Mar;54(3):306-13; Dietary linolenic acid is associated with a lower prevalence of
hypertension in the NHLBI Family Heart Study. Hypertension. 2005 Mar;45(3):368-73; Omega-3 fatty acids: molecular approaches to optimal
biological outcomes. Curr Opin Lipidol. 2005 Feb;16(1):11-8; Acute effects of monounsaturated fatty acids with and without omega-3 fatty acids
on vascular reactivity in individuals with type 2 diabetes. Diabetologia. 2005 Jan;48(1):113-22; The role of omega-3 long-chain polyun-saturated
fatty acids in health and disease of the retina. Prog Retin Eye Res. 2005 Jan;24(1):87-138; Including walnuts in a low-fat/modified-fat diet improves
HDL cholesterol-to-total cholesterol ratios in patients with type 2 diabetes. Diabetes Care. 2004 Dec;27(12):2777-83.
References: Carnitine
2010 Role of carnitine in disease. Nutr Metab (Lond). 2010 Apr 16;7(1):30. Sibutramine and L-carnitine compared to sibutramine alone on insulin
resistance in diabetic patients. Intern Med. 2010;49(16):1717-25. Orlistat and L-carnitine compared to orlistat alone on insulin resistance in
obese diabetic patients. Endocr J. 2010 Jul 30. Increased ROS production and lower abundance of complex I subunits and carnitine
palmitoyltransferase 1B protein despite normal mitochondrial respiration in insulin resistant human skeletal muscle. Diabetes. 2010 Aug 3. Effects
of acetyl-L-carnitine and oxfenicine on aorta stiffness in diabetic rats. Eur J Clin Invest. 2010 Jul 29 Managing diabetic peripheral neuropathic pain
in primary care. J Fam Pract. 2010 May;59(5 Suppl):S15-22. Caloric restriction and L-carnitine administration improves insulin sensitivity in
patients with impaired glucose metabolism. JPEN J Parenter Enteral Nutr. 2010 May-Jun;34(3):295-9. Metabolism. 2010 Apr 26. Effects of
combination of sibutramine and l-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients. Metabolism.
2010 Apr 26. Inspiratory muscle strength is correlated with carnitine levels in type 2 diabetes. Endocr Res. 2010 May;35(2):51-8. Type 2 diabetes
impairs pulmonary function in morbidly obese women: a case-control study. Diabetologia. 2010 Jun;53(6):1210-6. Acetyl-L-carnitine.
Monograph. Altern Med Rev. 2010 Apr;15(1):76-83. Comparison of vitamin E, L-carnitine and melatonin in ameliorating carbon tetrachloride and
diabetes induced hepatic oxidative stress. J Physiol Biochem. 2009 Sep;65(3):225-33. Dietary anthocyanin-rich bilberry extract ameliorates
hyperglycemia and insulin sensitivity via activation of AMP-activated protein kinase in diabetic mice. J Nutr. 2010 Mar;140(3):527-33.
2009 and earlier Inspiratory muscle strength is correlated with carnitine levels in type 2 diabetes. Diabetes Metab Res Rev. 2009 Sep;25
Suppl 1:S45-9.Carnitine and type 2 diabetes. Diabetol Metab Syndr. 2009 Oct 16;1(1):17.Effect of Carnitine and herbal mixture extract on obesity
induced by high fat diet in rats. J Biol Chem. 2009 Aug 21;284(34):22840-52. Carnitine insufficiency caused by aging and overnutrition
compromises mitochondrial performance and metabolic control. Diabetes. 2009 Mar;58(3):550-8. Overexpression of carnitine
39
palmitoyltransferase-1 in skeletal muscle is sufficient to enhance fatty acid oxidation and improve high-fat diet-induced insulin resistance.Curr Med
Res Opin. 2009 Sep;25(9):2223-8.Effect of propionyl-L-carnitine, L-arginine and nicotinic acid on the efficacy of vardenafil in the treatment of
erectile dysfunction in diabetes.Hypertension. 2009 Sep;54(3):567-74..Ameliorating hypertension and insulin resistance in subjects at increased
cardiovascular risk: effects of acetyl-L-carnitine therapy.Expert Opin Pharmacother. 2009 Aug;10(12):1875-82.Effects of simvastatin and carnitine
versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus.Metabolism. 2009 Nov;58(11):1618-23. Effect of L-carnitine on
the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin.Am J Clin Nutr. 2009 Jan;89(1):71-6.
L-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Nutr Metab (Lond). 2009 Jun 2;6:25.Effect of oral acetyl
L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics. Pathophysiology. 2009 Jun;16(1):53-56..Effect of short term
treatment of L-carnitine on tissue ACE activity in streptozotocin-induced diabetic rats. J Nutr. 2009 Jun;139(6):1073-81. Plasma acylcarnitine
profiles suggest incomplete long-chain fatty acid beta-oxidation and altered tricarboxylic acid cycle activity in type 2 diabetic African-American
women. Diabetes Metab Res Rev. 2009 Sep;25 Suppl 1:S45-9.Carnitine and type 2 diabetes. Asia Pac J Clin Nutr. 2008;17 Suppl 1:306-8.Effects of
L-carnitine on obesity, diabetes, and as an ergogenic aid. Ann Pharmacother. 2008 Nov;42(11):1686-91.Role of acetyl-L-carnitine in the treatment
of diabetic peripheral neuropathy. Clin Drug Investig. 2008;28(8):495-500.Thioctic acid and acetyl-L-carnitine in the treatment of sciatic pain
caused by a herniated disc: a randomized, double-blind, comparative study. Urol Int. 2008;81(3):340-6. L-carnitine treatment partially restores
urinary bladder function of streptozotocin diabetic rats. Pharmacol Ther. 2008 Nov;120(2):149-56. Carnitine in metabolic disease: potential for
pharmacological intervention. Ann Nutr Metab. 2008;52(4):335-8. Effect of oral L-carnitine administration on insulin sensitivity and lipid profile in
type 2 diabetes mellitus patients. Altern Med Rev. 2008 Jun;13(2):85-115.Alzheimer's disease, amnestic mild cognitive impairment, and
age-associated memory impairment: current understanding and progress toward integrative prevention. Eur J Pharmacol. 2008 Jul
7;588(2-3):213-6..The heterogeneity of diabetic neuropathy. Front Biosci. 2008 May 1;13:4809-16. Evaluation of the efficacy of
propionyl-L-carnitine versus pulsed muscular compressions in diabetic and non-diabetic patients affected by obliterating arteriopathy Leriche stage
II. Int Angiol. 2008 Jun;27(3):253-9. Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pac J Clin Nutr. 2008;17 Suppl
1:306-8. Preventive effect of acetyl-L-carnitine on the thermal hypoalgesia in streptozotocin-induced diabetic mice. Eur J Pharmacol. 2008 Jul
7;588(2-3):213-6. ATP production and TCA activity are stimulated by propionyl-L-carnitine in the diabetic rat heart. Drugs R D. 2008;9(2):83-91.
Protective effects of R-alpha-lipoic acid and acetyl-L-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid.
Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. CNS Drugs. 2007;21 Suppl 1:13-23; discussion 45-6. J Cell
Biochem. 2008 Jul 1;104(4):1232-43. Diabetes-induced bradycardia is an intrinsic metabolic defect reversed by carnitine. Metabolic agents in the
management of diabetic coronary patients: a new era. Int J Cardiol. 2008 Jun 23;127(1):133-4. Metabolism. 2007 Aug;56(8):1118-23. L-Carnitine
inhibits protein glycation in vitro and in vivo: evidence for a role in diabetic management. Acta Diabetol. 2007 Jun;44(2):83-90. Effects of
L-carnitine on RBC membrane composition and function in hyperinsulinemic rats. Ital J Biochem. 2007 Mar;56(1):53-60. Determination of free
L-carnitine levels in type II diabetic women with and without complications. Eur J Clin Nutr. 2007 Jul;61(7):892-5. Carnitine deficiency in children
and adolescents with type 1 diabetes. J Diabetes Complications. 2004 Sep-Oct;18(5):271-4 . Assessment of free L- carnitine levels in type II
diabetic women with and without complications. Asia Pac J Clin Nutr. 2004;13(Suppl):S155.]
References: alpha-Lipoic Acid
2010 alpha-Lipoic acid protects diabetic apolipoprotein E-deficient mice from nephropathy. J Diabetes Complications. 2010 Aug 26.
Complementary therapy in diabetic patients with chronic complications: a pilot study. Bratisl Lek Listy. 2010;111(4):205-11.
Pathomechanism of diabetic neuropathy: background of the pathogenesis-oriented therapy. Orv Hetil. 2010 Jun 13;151(24):971-81.
Protective effects of irbesartan and alpha lipoic acid in STZ-induced diabetic nephropathy in rats. Orv Hetil. 2010 Jun 13;151(24):971-81. Alpha
lipoic acid: a new treatment for neuropathic pain in patients with diabetes? Neth J Med. 2010 Apr;68(4):158-62.
Inflammation and apoptosis in aortic tissues of aged type II diabetes: amelioration with alpha-lipoic acid through phosphatidylinositol
3-kinase/Akt- dependent mechanism. Life Sci. 2010 Jun 5;86(23-24):844-53. Neuropathy in a rat model of mild diabetes induced by multiple low
doses of streptozotocin: effects of the antioxidant stobadine in comparison with a high-dose alpha-lipoic acid treatment. Gen Physiol Biophys. 2010
Mar;29(1):50-8. Effects of controlled-release alpha lipoic acid in lean, nondiabetic patients with polycystic ovary syndrome. J Diabetes Sci
Technol. 2010 Mar 1;4(2):359-64. Dietary fructose accelerates the development of diabetes in UCD-T2DM rats: amelioration by the antioxidant,
alpha-lipoic acid. Am J Physiol Regul Integr Comp Physiol. 2010 May;298(5):R1343-50. Alpha-lipoic acid improves vascular endothelial function
in patients with type 2 diabetes: a placebo-controlled randomized trial. Eur J Clin Invest. 2010 Feb;40(2):148-54. Antioxidant therapy in human
endocrine disorders. Med Sci Monit. 2010 Jan;16(1):RA9-24. alpha-Lipoic acid increases energy expenditure by enhancing adenosine
monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of
aged mice. Metabolism. 2010 Jul;59(7):967-76. Treatment with alpha-lipoic acid reduces asymmetric dimethylarginine in patients with type 2
diabetes mellitus. Transl Res. 2010 Jan;155(1):6-9.
2009 and earlier
Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J
Cardiovasc Pharmacol. 2009 Nov;54(5):391-8. Structural and functional condition of the left ventricle in patients with type 2 diabetes mellitus
complicated with diabetic autonomic neuropathy. Lik Sprava. 2009 Jan-Feb;(1-2):22-8. Attenuation of myocardial apoptosis by alpha-lipoic acid
through suppression of mitochondrial oxidative stress to reduce diabetic cardiomyopathy. Chin Med J (Engl). 2009 Nov 5;122(21):2580-6. Impact
of therapy with alpha-lipoic acid (ALA) on the oxidative stress in the controlled NIDDM: a possible preventive way against the organ dysfunction?
Arch Gerontol Geriatr. 2009;49 Suppl 1:129-33. A 52-year-old woman with disabling peripheral neuropathy: review of diabetic polyneuropathy.
JAMA. 2009 Oct 7;302(13):1451-8. lpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys
Acta. 2009 Oct;1790(10):1149-60. Oxidative stress and dysregulation of the taurine transporter in high-glucose-exposed human Schwann cells:
implications for pathogenesis of diabetic neuropathy. Am J Physiol Endocrinol Metab. 2009 Sep;297(3):E620-8. .A current update on the use of
alpha lipoic acid in the management of type 2 diabetes mellitus. Endocr Metab Immune Disord Drug Targets. 2009 Dec;9(4):392-8. Antioxidant
properties of alpha-lipoic acid: effects on red blood membrane permeability and adaptation of isolated rat heart to reversible ischemia. Mol Cell
40
Biochem. 2009 Jan;320(1-2):141-8. Lipoic acid synthase (LASY): a novel role in inflammation, mitochondrial function, and insulin resistance.
Diabetes. 2009 Mar;58(3):600-,8 Advances in the management of diabetic peripheral neuropathy. Curr Opin Support Palliat Care. 2009
Jun;3(2):136-43. Effects of alpha-lipoic acid on transforming growth factor beta1-p38 mitogen-activated protein kinase-fibronectin pathway in
diabetic nephropathy. Metabolism. 2009 May;58(5):616-23. Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced
oxidative stress to pancreatic beta cells. Free Radic Res. 2009 Jan;43(1):68-77. Alpha-lipoic acid reduces congenital malformations in the offspring
of diabetic mice. Diabetes Metab Res Rev. 2009 Mar;25(3):287-94. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol
clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. 2009 May 1;485(1):63-71. Effect of alpha lipoic acid on
oxidative stress and vascular wall of diabetic rats. Rom J Morphol Embryol. 2009;50(1):23-30. The role of alpha-lipoic acid in diabetic
polyneuropathy treatment. Bosn J Basic Med Sci. 2008 Nov;8(4):341-5. Nutritional supplementation for type 2 diabetes: a systematic review.
Ophthalmic Physiol Opt. 2008 Nov;28(6):503-23.. Effect of alpha-lipoic acid and mexidol on neuro- and the affective status in patients at early
stages of diabetic foot syndrome. Klin Med (Mosk). 2008;86(10):52-9. Alpha-lipoic acid supplementation and diabetes. Nutr Rev. 2008
Nov;66(11):646-57. The use of dipyridamole (curantyl) in combination with alpha-lipoic acid in the treatment of diabetic neuropathy with
retinopathy. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(7):23-6. Coenzyme Q(10) and alpha-lipoic acid supplementation in diabetic rats:
conduction velocity distributions. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):367-74.
References: CoQ10
2010 Coenzyme Q--biosynthesis and functions. Biochem Biophys Res Commun. 2010 May 21;396(1):74-9. Therapeutic use of
coenzyme Q(10) and coenzyme Q(10)-related compounds and formulations. Expert Opin Investig Drugs. 2010 Apr;19(4):535-54.
Coenzyme Q and mitochondrial disease. Dev Disabil Res Rev. 2010 Jun;16(2):183-8. Coenzyme Q10 is frequently reduced in
muscle of patients with mitochondrial myopathy. Neuromuscul Disord. 2010 Jan;20(1):44-8.
2009 and earlier Coenzyme Q10 improves endothelial dysfunction in statin-treated type 2 diabetic patients. Diabetes Care. 2009
May;32(5):810-2. Coenzyme Q10 deficiencies in neuromuscular diseases. Adv Exp Med Biol. 2009;652:117-28. Supplementation
of coenzyme Q10 and alpha-tocopherol lowers glycated hemoglobin level and lipid peroxidation in pancreas of diabetic rats. Nutr
Res. 2008 Feb;28(2):113-21. Antioxidant level and redox status of coenzyme Q10 in the plasma and blood cells of children with
diabetes mellitus type 1. Pediatr Diabetes. 2008 Dec;9(6):540-5. Coenzyme Q(10) and alpha-lipoic acid supplementation in
diabetic rats: conduction velocity distributions. Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):367-74. Hemodynamic effects
of fenofibrate and coenzyme Q10 in type 2 diabetic subjects with left ventricular diastolic dysfunction. Diabetes Care. 2008
Aug;31(8):1502-9.
41
Cathy Breedon 9-13
A very short scan of recent www.pubmed.gov listings
using just the words diabetes x carnitine.
(There are lots more.)
PLoS One. 2013 Jul 26;8(7)
Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in
Streptozotocin-Induced Diabetes in Male Wistar Rats. Wang CH, Wang SS, Ko
WJ, Dept of Surg, Nat TaiwanU Hosp, Taipei, Taiwan;Dept Physiol, College of Med, National Taiwan U,
Taipei, Taiwan. Introduction: In the treatment of patients with diabetes, one objective is an improvement
of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the
effects of acetyl-l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine
palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in
male Wistar rats, with a particular focus on the pressure-flow-volume relationship. Methods: Diabetes was
induced by a single tail vein injection of 55 mg kg(-1) streptozotocin. The diabetic animals were treated on
a daily basis with either acetyl-L-carnitine (1 g L(-1) in drinking water) or oxfenicine (150 mg kg(-1) by oral
gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure
and ascending aortic flow signals were recorded to calculate the maximal systolic elastance (E max) and
the theoretical maximum flow (Q max). Physically, E max reflects the contractility of the myocardium as
an intact heart, whereas Q max has an inverse relationship with the LV internal resistance. Results: When
comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was
characterized by a decline in E max associated with the unaltered Q max. Acetyl-l-carnitine (but not
oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However,
treating with acetyl-l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2
drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max
showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in
Q max corresponded to an increase in total vascular resistance when treated with oxfenicine.
CONCLUSIONS: Acetyl-l-carnitine, but not oxfencine, optimizes the integrative
nature of cardiac pumping mechanics by preventing the diabetes-induced
deterioration in myocardial intrinsic contractility associated with unaltered LV
internal resistance.
------------------------------------------------------------------------------------------------------------------------------J Pak Med Assoc. 2013 Mar;63(3):374-9. Effect
of cholecalciferol [vitamin D] and
levo carnitine on plasma glucose, plasma insulin and insulin
resistance in type 2 diabetic rats. Anwar MK, Hussain MM, Khan MA, Objective: To
compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on
plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised
controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi,
between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided
into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal
injection of streptozocin to induce type 2 diabetes mellitus. group I served as diabetic control; group II
was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo
carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and
samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated
by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis.
Results: Fasting plasma glucose levels were significantly decreased (p < 0.001) in the combined
supplementation group compared to the diabetic control and individual supplementation groups.
Combined supplementation showed a significant increase in fasting plasma insulin levels when compared
with diabetic control and levo carnitine groups (p < 0.001), and the effect of combined supplementation on
ameliorating insulin resistance was significantly better (p < 0.001) as compared to the individual
supplementation of cholecalciferol and levo carnitine.
CONCLUSIONS: The combined supplementation of cholecalciferol [vitamin D]
and levo carnitine for 6 days markedly improved the glycaemic control, insulin
secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A
prolonged supplementation by both the compounds along with caloric restriction
may yield a more promising outcome.
------------------------------------------------------------------------------------------------------------------------------Nutr Metab (Lond). 2013 Jul 10;10(1):48.
Carnitine supplementation to obese Zucker rats prevents obesityinduced type II to type I muscle fiber transition and favors an
oxidative phenotype of skeletal muscle.
Couturier A, Ringseis R, Mooren FC. Background: In the present study, we tested the hypothesis that
carnitine supplementation counteracts obesity-induced muscle fiber transition from type I to type II.
Methods: 24 obese Zucker rats were randomly divided into two groups of 12 rats each (obese control,
obese carnitine) and 12 lean Zucker rats were selected for lean control group. A control diet was given to
both control groups and a carnitine supplemented diet (3 g/kg diet) was given to obese carnitine group for
4 wk. Components of the muscle fiber transformation in skeletal muscle were examined. Results: The
plasma level of carnitine were lower in the obese control group compared to the lean control group and
higher in the obese carnitine group than in the other groups (P < 0.05). Plasma concentrations of
triglycerides and non-esterified fatty acids were increased in obese animals compared to lean animals
and the obese carnitine group had lower level compared to the obese control group (P < 0.05). The obese
carnitine group had an increased number of type I muscle fibers and higher mRNA levels of type I fiberspecific myosin heavy chain, regulators of muscle fiber transition and of genes involved in carnitine
uptake, fatty acid transport, beta-oxidation, angiogenesis, tricarboxylic acid cycle and thermo genesis in
M. rectus femoris compared to the other groups (P < 0.05).
CONCLUSION: The results demonstrate that carnitine supplementation to obese
Zucker a rat counteracts the obesity-induced muscle fiber transition and restores
the muscle oxidative metabolic phenotype. Carnitine supplementation is
supposed to be beneficial for the treatment of elevated levels of plasma lipids
during obesity or diabetes.
2014
Sanford Medical Center
Aunt Cathy’s Guide
to Nutrition:
SOME Drug / Nutrition
Interactions of Interest
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center, Fargo, ND
UND School of Medicine, Fargo, ND
This paper is not intended to be a complete review and it is presented here without
references. It is intended to be just a closer look at a collection of medication/nutrition
interactions that have been especially problematic for my patients, and some suggestions for
minimizing problems. There are (of course) many other drug/nutrition interactions that are not
covered here and that I don’t know a thing about. . Drug/Drug interactions are also not
included here. As always, it is not intended to take the place of advice from your health care
provider.
Anti- Seizure/Epilepsy Medications
All seizure medications cause vitamin D to turn over faster, so the intake needed to maintain
healthy blood levels of vitamin D are higher than usual.
Vitamin D inadequacy is common in the general population, and it is especially
prevalent among people taking seizure-control medications.
Vitamin D deficiency is associated with many health problems, including increased risk
of cancer, congestive heart failure, impaired immune function, depression, muscle weakness,
osteoporosis, falls, pain, and increased risk of all autoimmune disorders, such as Type I diabetes,
MS, arthritis, lupus and more.
RDA/RDI/AI levels at the moment are not associated with optimal vitamin D levels even
among healthy people, and they are very unlikely to assure adequacy among people using these
medications.
Recommended in general: maintain a blood level at about 40-50 mg/dL. Ideally, get a
blood level to determine current status and give a therapeutic dose to correct low levels (e.g.
50,00 iu/week x 8 weeks followed by a re-check.) Then provide an intake level sufficient to
maintain the 40-50 range (which may be found to require supplementation to provide 2000-5000
iu/day.) Please see my “Top Five” paper for more on this topic.
All seizure medications cause decreased absorption of biotin (vitamin B7).
Biotin is involved in many metabolic pathways, including the TCA Cycle to make ATP
(making usable energy from food), and gluconeogenesis (making glucose out of amino acids.)
Deficiency in general seems to be uncommon in healthy people, but when it does occur it has
been known to result in a number of serious problems. It has been shown to contribute to
depression, hallucinations, increased infections, poor muscle control, loss of hair, skin problems,
seizures and developmental delay in infants. Eggs, nuts and legumes like peanuts are among the
very best dietary sources. Eggs do contain a protein called avidin that makes biotin be poorly
absorbed if the egg is eaten raw, but cooked eggs are excellent sources of biotin … and also safer
to eat in terms of food-borne illness risk. The yolk has most of the biotin.
The intake of biotin assumed to meet the needs of most healthy people is about 30
mcg/day. In addition to all seizure medications, alcohol also impairs absorption of biotin.
Additionally, chronic antibiotic use decreases the biotin usually produced by bacterial activity in
the large intestine. People with intestinal absorption problems (such as inflammatory bowel
disease) have also been observed to become deficient in biotin. It appears that biotin
supplementation can be useful for people with diabetes in particular.
Because a very high biotin intake has no known detrimental effects, supplementation at
or above levels recommended for healthy people is very reasonable for anyone on chronic
seizure medications or in other situations described above. Not all multivitamins contain 30 mcg
biotin. However, it is easy to provide it singly if desired. For example, there are over-thecounter biotin supplements that provide 600 mcg, and it can also be found in variable amounts as
a part of “B-complex” vitamin supplements. The “B-100 Complex” type of supplement may
include 300 mcg of biotin along with many other B vitamins.
Some Specific Seizure Medications That Interact with Nutrients.
Phenytoin (Dilantin)
Folic acid deficiency is associated with use of this medication if appropriate
supplementation is not provided. However, there are some safety issues to consider:
When starting the prescription for phenytoin, it is recommended that people start folic
acid supplementation right away. If a person is already on the drug and found to be folic acid
deficient, generous and rapid folic acid supplementation can cause problems. In the latter case,
the physician can introduce supplemental folic acid slowly to avoid breakthrough seizures, and to
work up to achieving a normal blood folic acid level. This is important because it is clearly not
safe to simply let the person remain folic acid deficient. Folic acid deficiency is associated with
birth defects, poor DNA production, depression, high homocysteine level, increased risk of
stroke and impaired immune function.
The 1998 introduction of fortification of grain products with a well-absorbed form of
folic acid in the US improves the odds of preventing some of the folic-acid related problems in
the US today. However, requirements continue to be higher than for people not using phenytoin.
The usual intake suggested for most healthy people is 400 mcg folic acid /day, with 600 mcg
recommended in pregnancy. “Prenatal vitamins” often have 800 mcg of folic acid, but they
often do not contain many other nutrients. For that reason, just recommending a prenatal vitamin
is not a good solution to this problem. A better approach would be to provide as complete a
regular multivitamin with minerals daily as possible, and add one or more tiny 400 mcg folic
acid tablets.
Other food sources include leafy greens and orange juice, but it is not clear that folates in
the form found naturally in foods are as well absorbed as supplemental forms among people
using this medication. And, as it is well known that there is significant genetic variation in one’s
ability to obtain folic acid from non-supplemented food sources, it is reasonable to be generous.
Folic acid supplementation is simple, easy and safe at intake levels of 1000 mcg/day from
supplements and fortified foods. That “upper limit” is based on the possibility that higher
amounts might “mask” vitamin B12 deficiency, as recognized by elevated blood cell size. It
was not due to any observed toxicity of the vitamin. However, large red blood cell size (Mean
Cell Volume on a laboratory test) is a very late appearing symptom of vitamin B12 deficiency
and it should not be relied upon to detect deficiency. Instead, steps described later should be able
to prevent vitamin B12 deficiency, so the “masking deficiency of vitamin B12” concern is no
longer an issue. There is also no evidence that naturally occurring folates in foods pose any
threat to health.
In view of the well documented effect of phenytoin on folic acid status, it is reasonable to
monitor this, e.g. via erythrocyte folate levels, to determine the amount of supplementation
needed by an individual already on the drug. Before starting phenytoin, and in the absence of the
ability to monitor the situation with laboratory assessment, it is reasonable to just begin a
generous intake and maintain it … e.g. a regular intake of 1000 mcg supplement daily. This
amount can be provided in a tiny pill by prescription … and that level of supplementation is
available over-the-counter in Europe and elsewhere because of the excellent safety profile. One
could also achieve an intake level around that amount (1200) in the USA from, for example,
taking a standard multivitamin plus two tiny 400 mcg folic acid tablets without prescription.
The use of this medication is associated with birth defects and a Fetal Phenytoin
Syndrome has been described. Relative inadequacy of many B vitamins (including folic acid)
induced by use of this medication appears to be contributory to the degree of damage. For this
reason, optimizing nutrition status in women of childbearing age is especially important. But
really … it is mighty important for everyone. [Please see my “Folic Acid Absorption” cartoon
paper for further detail.]
Vitamin B12 absorption is also impaired, so monitoring adequacy of vitamin B12 is important.
As noted, normal Mean Cell Volume (red blood cell size) is NOT a useful assessment of
adequacy … by the time the cells are large, a lot of other damage has already occurred, and not
all of it is repairable. A serum B12 level would be a much better test. [To obtain the most
reliable and specific functional measure of vitamin B12 status, one could get a methylmalonic
acid (MMA) level, which is more sensitive than a serum vitamin B12 level. However, this is not
as available and it is more expensive.]
Vitamin B12 is affected by other medications as well, and by age and by certain
dietary practices. Please see more detail about vitamin B12 in the section below called “Gastroesophageal reflux (GERD) hyperacidity,” and see my “Vitamin B12” paper and “Vitamin B12
Absorption” cartoon paper for further details.
Thiamin (Vitamin B1) levels in the blood are depleted by the use of phenytoin.
Riboflavin (Vitamin B2) can also be depleted because the drug increases production of a liver
enzyme that destroys it. Supplementation of both is in order.
Vitamin B6 (pyridoxine) is also affected by intake of phenytoin, but there is a special caveat
about taking the “B-100 complex” type of supplement: with this particular medication 100
mg vitamin B6 may be too high. Vitamin B6 increases the breakdown rate of phenytoin, so
taking relatively high doses (e.g. 50-100 mg) may be a factor in decreased effectiveness of the
drug. As described earlier, the “B-100 Complex”-type of supplement would provide 100 mg, so
this would not be the best choice in this instance.
However, this does NOT mean that people should be made deficient of vitamin B6.
This vitamin is critical for many metabolic functions, including all protein metabolism, energy
metabolism, DNA production and nervous system function. The usual recommendation for most
folks is 1.5-2.0 mg/day. That amount should certainly be provided. If a person requires an
additional generous vitamin B6 for other medical reasons, it might result in needing a different
(higher) dose of Dilantin.
Phenytoin impairs production of carnitine, and carnitine adequacy is needed for the
drug to work most efficiently. Carnitine inadequacy effects on metabolism are described below
in the section on valproic acid, another seizure medication. Supplementation of carnitine is
strongly recommended. Please see my Carnitine handout for more details.
Primidone (Mysoline) This medication has also been shown to impair vitamin B12 status.
Phenobarbital
Vitamin B2 (riboflavin) can be depleted because the drug increases
production of a liver enzyme that destroys it. Supplementation is in order.
Valproate / Valproic Acid (Depekene) Inadequate carnitine increases the liver
toxicity of the drug and also contributes to very low blood sugar in certain contexts. Carnitine
deficiency contributes to the side effects of lethargy and excessive weight gain noted with this
medication. High triglycerides and poor control of insulin-treated diabetes have also been seen.
Impaired production of carnitine can also lead to “breakthrough seizures” because inadequacy
also impairs the utilization of the seizure medication itself. Please see my carnitine paper for
specific details.
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Stomach Acid Blockers for
Hyperacidity or Gastroesophageal Reflux Disease (GERD)
Proton Pump Inhibitors (PPIs) block production of stomach acid by over 90%.
However, the form of vitamin B12 found naturally in foods of animal origin requires
stomach acid for absorption.
The crystalline vitamin B12 form found in pills (e.g. multivitamins or just vitamin B12
alone) or in fortified foods bypasses this problem, so supplementation in pill form is strongly
advised. Vitamin B12 supplements are very tiny, very safe, cheap and easy to use. The form of
vitamin B12 added to food is also of this type so loss of stomach acid does not interfere with
vitamin B12 absorption from this source. This includes, for example, fortified cereals, infant
formulas and vitamin-supplemented beverages.
[The amount of vitamin B12 provided in these forms needs to be considered when
determining adequate intake. For example, if one drinks a fortified beverage, what number of
ounces would achieve the recommended amount? Eight ounces (1 cup) of some products
provide 100%, but many products provide that amount only in about a quart a day. Check the
label, or just add additional vitamin B12 via a multivitamin or a separate vitamin B12 pill.
Vitamin B12 is extremely non-toxic.]
As described earlier related to phenytoin (Dilantin) use, vitamin B12 deficiency is
associated with birth defects, poor DNA production, depression, high homocysteine level,
increased risk of stroke, and serious neurologic damage. Deficiency is often missed until
significant damage has occurred, in part because common blood tests like Mean Cell Volume
(that identify overt deficiency by enlarged cell size) only pick up very late- appearing symptoms.]
Vitamin B12 absorption can be impaired by factors other than
absent stomach acid, so the above recommendations related to PPI use
will NOT correct other factors that interfere.
For example, loss of production of ar stomach-produced substance called Intrinsic Factor (IF)
will impair absorption of vitamin B12 in the intestine. Intrinsic Factor may be inadequate among:
1. elderly people because of changes due to stomach atrophy affecting IF production.
2. people with a potentially debilitating autoimmune condition called “Pernicious Anemia,” that
causes inability to produce IF in the stomach.
3. people with surgical removal of the stomach (gastrectomy.)
4. people who have had certain forms of gastric bypass surgery.
Additionally, the terminal ileum (the last part of the small intestine) is the only location in the
GI tract where vitamin B12 can be absorbed. That means that damage or interference there can
also make even generous oral intake of vitamin B12 inadequate. People with intestinal conditions
such as inflammatory bowel disease or who have “short bowel” due to intestinal surgery will
generally need to obtain vitamin B12 via another route.
Vitamin B12 shots or special sublingual or nasal application forms are needed if the
absorption problems are not resolved. As discussed later, this may be also be needed when the
medication Metformin (Glucophage) is used. The interference with vitamin B12 absorption in
the intestine in this case is caused by a different type of problem, and estimates are that up to a
third of people using this medication chronically may be vitamin B12 deficient.
Vitamin B12 deficiency takes a long time (e.g. two years) to become evident, and the
consequences of inadequacy are very serious. For this reason, it is critical that people using
PPIS or who have “achlorhydria” (inadequate production of stomach acid for any reason) assure
an adequate oral intake of an absorbable form of vitamin B12.
Other conditions may require an administration route that bypasses the GI tract.
PPIs can also result in decreased absorption of inorganic iron and zinc
due to decreased acidity. Organic forms (like heme-iron and zinc in meat and lactoferrin in
mother’s milk) are not affected, but plant forms and pill/supplement forms (like ferrous sulfate,
etc.) can be significantly less well absorbed. However, other dietary features can modify this
effect in either direction. For example, adding meat to the meal improves absorption due to the
presence of “Meat Protein Factor,” and the addition of acidic foods (like orange juice and
vitamin C) also enhances absorption of inorganic iron and zinc somewhat in this context.
Conversely, substances naturally occurring in certain plant foods, such as phytates,
oxalates and tannins, will significantly impair absorption of inorganic iron and zinc.
Interestingly, milk consumption also significantly impairs absorption of inorganic iron and zinc.
Please see my “Nutrition Support of Iron Deficiency Anemia” paper for more details on this.
Calcium supplements are also less well absorbed, but a generous intake
and -- more importantly --assuring a generous vitamin D intake will prevent
problems. Most of the differences in absorption of various forms of supplemental calcium are
only clinically important in the absence of the normal hormonal regulation of calcium absorption
by vitamin D. When vitamin D status is adequate, the role of relative acidity in calcium
absorption is much less important.
Magnesium absorption can also be impaired by these medications, and
intake is often suboptimal in the US. Assuring a generous intake is a very good idea.
Poor magnesium status increases risk of insulin resistance, osteoporosis and leg cramps. [More
on this later … please see my Calcium and Magnesium papers for more detail.]
Bacterial overgrowth can result from use of PPI acid blockers, which can sometimes
lead to diarrhea and malabsorption of nutrients in general. This is also seen in achlorhydria due
to aging. Hydrochloric acid in the stomach is actually a part of the immune system because the
low pH kills many bacteria and other micro-organisms that may be consumed with food.
Acid Blockers: H2 Blockers These acid-reduction medications block production
of stomach acid by ~65-70%. They present less overt risk of impairment of vitamin B12 from
natural food sources than acid reduction with PPIs, but supplementation in pill or other
supplement form is strongly advised. Again, supplementation is very safe, cheap and easy to do.
Chronic Antibiotic Use
There are many types of antibiotics and many different reasons for using them.
For example, conditions associated with chronic use of antibiotics include:
Spinal Cord Injury including Spina Bifida, and others at risk of kidney/urinary tract
infections, Tuberculosis, Cystic Fibrosis, Inflammatory Bowel Disease, Chronic Ear
Infection, Immune System Issues (e.g. HIV/AIDS, Hypogammaglobulinemia, etc.) and
Severe Acne.
General for All Chronic Antibiotics:
Vitamin K
Antibiotics impair the expected vitamin K production by intestinal bacteria. This is
not new. However, that source is now known to be generally poorly available for everyone.
This is fairly new.
However, people taking chronic antibiotics will be getting absolutely none from that
source. Supplementation with generous vitamin K is recommended for everyone, and for this
population in particular. Vitamin K is very NON-toxic, although people often assume that it is
toxic because it is fat soluble. No upper end of safety has ever been established for it because no
one has ever taken enough to cause problems. [The only safety issue involving vitamin K is the
(often misunderstood) interaction with the drug warfarin (Coumadin) which will be discussed
later.]
The current recommended intake of vitamin K levels for the healthy population appears
to underestimate the amount needed to assure optimal blood levels of this vitamin. See my
Vitamin K papers for more detail. Vitamin K deficiency contributes to osteoporosis, arterial
calcification, kidney calcification, risk of diabetes and certain cancers. Note that these health
risks all are increased long before coagulation time is effected so one’s coagulation time is not a
good way to monitor a person’s vitamin K adequacy.
Impairment of Absorption of Folic Acid
The 1998 introduction of fortification of grain products with a well-absorbed form of
folic acid in the US improves the odds of preventing some of the folic-acid related problems.
However, requirements continue to be higher for people chronically taking antibiotics than for
people not using these medications. Generous supplementation is recommended. It is also safe,
easy and inexpensive. As described earlier, the results of folic acid inadequacy includes birth
defects, poor DNA production, depression, high homocysteine level, increased risk of stroke, and
serious neurologic damage.
Two Specific Interactions of Interest:
Tetracycline
Tetracycline reduces absorption of folic acid, but B vitamins in general also reduce
absorption of tetracycline, so they should not be taken at the same time. As always, this
does not mean that a person should be made to be vitamin deficient in order to optimize drug
absorption. It just means that attention should be paid to maintaining both general vitamin
adequacy and efficacy of the tetracycline dose used.
Isoniazid (Nydrazid, Laniazid)
Vitamin B6 (pyridoxine) levels in the blood are decreased by these TB medications.
It used to be a well known interaction when tuberculosis was very common, but it fell off our
radar when TB became quite rare. Only we old guys remember it from that time period.
However, TB is now back (for a variety of reasons) and the awareness of vitamin B6
supplementation also needs to come back whenever these medications are used. Some of the
neurologic and birth-defect symptoms described as side effects of isoniazid appear to be related
to the relative vitamin B6 deficiency associated with its use.
In any case, assuring adequacy of vitamin B6 is very important in this situation, and as is
the case for other B vitamins, this can be done easily, cheaply and safely. It does not impair the
efficacy of the drug. Pyridoxine is known to be safe at up to 200 mg/day. The usual
recommended intake is between 1.5-2 mg/day. It is usually given at 10-50 mg/day to patients on
isoniazid.
There are many interactions with nutrition seen with chronic antibiotic
use, but this is a quick overview so I have focused on only a few examples. Health care
professionals will want to familiarize themselves with the ones they see often in their practice
and that will be far more than can be covered here. Luckily, this kind of specific information is
now easy to get on the Internet. 
Anti-coagulants: Warfarin (Coumadin)
Since 2005, our understanding about the role(s) of vitamin K and the natural means
by which we get it have undergone tremendous change. As described earlier (in the section
on antibiotics,) it is now known that there are many important functions of vitamin K besides the
well-recognized role in blood coagulation, making us aware that inadequacy of the vitamin is
very detrimental to health. [For example, vitamin K is a cofactor necessary to activate
osteocalcin/calcitonin to allow calcium to be moved from the bloodstream into the bones. Failure
to manage calcium levels in blood and bone contribute to a variety of health problems.]
Additionally, during this same period our assumptions about the availability of vitamin K
made by intestinal bacteria have changed markedly. And even the importance of assuring
ADEQUACY of vitamin K (and not just consistency of intake) as a key factor in the safety of
warfarin use has now been shown. That is, persons with adequate/normal vitamin K status have
been shown to be far less vulnerable to extremes of coagulation volatility that is a danger
associated with the use of this drug.
Misunderstandings about the interaction of warfarin with vitamin K are extremely
common and they result in very serious health consequences. This particular anticoagulant
works by interfering with the availability of vitamin K as a cofactor in the cascade of events that
produces a blood clot. The official recommendations from the manufacturers are that people
should take a consistent and adequate amount of vitamin K.
A consistent and adequate vitamin K intake will do much to prevent volatility in blood
clotting that can be associated with wide swings in vitamin K intake. That is, maintaining
adequacy of vitamin K seems to buffer the degree of variation in coagulation associated with
daily differences in vitamin K intake.
However, the official recommendation above is very often misinterpreted by users of
the medication and by health professionals, and the belief continues to be commonly
expressed that one should “avoid all sources of vitamin K.” Some people are even told that
they should avoid taking vitamins … even if the vitamin product did not contain vitamin K!
(Until very recently, MANY common multivitamin brands did NOT contain vitamin K.)
Interestingly, as noted above, providing a daily standard amount of vitamin K
actually makes the drug safer to use, especially in elderly people. Additionally, it prevents
the serious (but not uncommon) consequences of accidentally (or intentionally) inducing a
Vitamin K deficiency that results in increased risk of the following health problems:
Osteoporosis
Calcification of kidneys and kidney stones
Artery damage (Calcification of arteries, increased arterial inflammation and risk of
plaque build-up, high blood pressure and varicose veins.)
Cancer of the liver and colon
Type II Diabetes
Pre-eclampsia in pregnancy
The Role of Vitamin K in Blood Clotting:
Remember that vitamin K does not MAKE you clot your blood …
it just needs to be available if you WANT to clot your blood.
[If it MADE people clot their blood, we could expect to have big problems after
eating a big spinach salad. Vitamin K is just a cofactor (a tool)
needed to do the job, not the thing that initiates the process.]
Recommendations for people not using warfarin:
People not using warfarin (that is … most everyone):
Take a generous amount of vitamin K. A good daily amount would be about twice the current
recommendation for most healthy people (because that level appears to be set too low to assure
optimal blood levels.) Dark leafy greens are great foods for many reasons, and they are the
richest dietary source. Supplemental vitamin K is an option as well. Remember that vitamin K is
NOT toxic and no upper tolerance level has ever been set because no one has ever had problems.
The ONLY vitamin K safety issue is the potential interaction with the drug warfarin.
Recommendations for people who may be going to start taking warfarin
People not using warfarin yet but who may starting it:
Before starting the drug do as described above for people not on the medication to assure an
adequate vitamin K level. The doctor will set the appropriate drug level needed to control
coagulation for a person (you) who has adequate vitamin K status.
[This prevents setting the drug prescription based on a person’s unrecognized inadeaquate
vitamin K level.] Then continue to take in a consistent but adequate amount as a vitamin K
supplement while on the drug. Now, many doctors are regularly prescribing a daily vitamin K
supplement when they initiate any warfarin prescription in order to reduce the health risks
associated with this medication.
Recommendations for people currently using warfarin:
Do not make any changes in your vitamin K intake without the approval of your physician.
If your vitamin K level is low, he/she will want to gradually “walk up” the vitamin K intake until
you are in the healthy range. This can be monitored just as it was when one initially starts on the
medication. Abrupt changes from low to normal-high vitamin K are not safe when one is on
warfarin. There may be other factors to consider in a person’s particular situation
Once the low vitamin K level is corrected by the physician, he/she will want you to continue to
take in a consistent but adequate amount as a vitamin K while on the drug. As noted, this will
often include a prescription for daily vitamin K supplement in order to maintain the health risks.
Additionally, there is no reason to discontinue assuring a consistent and adequate amount of
vitamin K if the warfarin is discontinued.
An additional reason to avoid banning dark leafy greens from the diet:
Inducing a vitamin K deficiency by banning vitamin K-rich foods also decreases intake of
lutein, the dark green pigment of the foods that provide vitamin K. It is a potent antioxidant
with important roles in prevention of oxidative damage to cell membranes, especially in macular
degeneration and the development of complications of diabetes.
Vitamin K-rich foods are naturally very low in fat and calories, and they are very “nutrient
dense.” Removing them unnecessarily from people’s diet is not in their best interests.
Similarly, telling people to “stop taking a multivitamin to avoid taking in vitamin K” means that
one has just removed all the other nutrients they would have received by taking the multivitamin.
This includes 400 iu vitamin D, and although the 400 iu amount in the multivitamin is not even
sufficient as a maintenance level in terms of blood vitamin D level, in many people it may be the
ONLY vitamin D they do get. It is especially not benign to remove this source of vitamin D and
other nutrients such as vitamin B12 in a form that is absorbed best by elderly people or those on
PPIs.
Other types of anti-coagulants
Many other anticoagulants (e.g. Plavix, Aspirin, Aggrinox) do not work by means of
interacting with vitamin K. They operate entirely differently, in a way that does not involve
tinkering with vitamin K availability. That means that there is absolutely no reason at all
to restrict vitamin K for these patients. Encourage intake of foods rich in vitamin K for many
reasons, including the other nutrients and lutein that are well-represented in those foods. A
multivitamin with minerals that also includes vitamin K is a very good idea as well, in part
because there are a lot of people who don’t go anywhere near those dark leafy greens even if we
nag at them. Additionally, it appears that the amount of vitamin K needed to assure a healthy
blood level is higher than 90-120 mcg, the amount currently recommended for healthy people.
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Diuretics: Furosemide (Lasix) Use
Magnesium is a mineral cofactor in over 300 metabolic pathways, including energy
and protein metabolism, bone health and nervous system function. Use of furosemide
(Lasix) increases losses of potassium and also magnesium. The potassium part is well known
to health professionals so I won’t address it here, but the magnesium losses are much less well
known. At a cellular level, potassium metabolism cannot operate normally in the absence of
adequate magnesium. The foods that are well-known to be rich in potassium (e.g. potatoes,
milk, bananas, orange juice, etc.) do not happen to be rich in magnesium.
The best foods sources of magnesium are the part of the plant that will be “the baby
plant” … that is, the part that is a seed, bean, germ, or nut. Increasing intake of these foods can
be very helpful for many health reasons. This includes, for example, decreasing risk of
developing Type II diabetes, and improving management of diabetes if it is already established.
The fairly recent recognition of these foods as the best magnesium sources and the importance of
magnesium adequacy is a main reason why “whole grains” … the kind that still have the germ
included … and eating nuts are being encouraged.
Most multivitamins contain 0- 25% of the recommended magnesium intake. (Most
contain zero potassium, by the way.) For people not on furosemide, the amount of magnesium
provided in a multivitamin may be sufficient if food magnesium sources are generally good.
However, it is unlikely to be sufficient if furosemide is in the picture as well.
In this context, supplementation of a separate magnesium oxide or magnesium chloride to
provide about 400 mg/day more is a good idea for people on this medication, unless the person
has poorly functioning kidneys. Four hundred is just the usual recommended amount for healthy
people and readily available over the counter … it is not a high “therapeutic” level. [Note that
magnesium sulfate and magnesium citrate are poorly absorbed sources of magnesium, and they
contribute to loose stools. That is why they are used for constipation problems and for cleansing
the bowel prior to having a colonoscopy. The unabsorbed particles attract water to the intestine.
They are not as effective as dietary supplements.]
The addition of a medication that increases urinary losses of magnesium can result in
very low levels. Consider that magnesium intake is generally low in many Americans (e.g.
NHANES: Most Americans obtain less than 2/3 of the recommended amount of magnesium.)
This is not good because, as noted, magnesium inadequacy contributes to diabetes (because
insulin receptors are magnesium dependent) and also to energy metabolism in general, all protein
metabolism, and nerve function. It is hugely important in pregnancy.
At the same time, we rarely look closely at a nutrient that is not easy to evaluate
meaningfully. For example, blood magnesium levels in general do not reflect cellular
magnesium levels, so an “OK” blood magnesium level does not tell us about magnesium intake
adequacy. The blood Mg level is controlled by the kidney, and it will stay in the normal range
even if cells are not getting enough for optimal functioning.
My experience has been that most people are given advice about bananas for potassium
(courtesy of a successful advertising campaign of the Chiquita people.) But the magnesium loss
is left out of the conversation in part because it is hard to measure with a lab. The other reason is
that people have not been told what foods are rich sources of magnesium and how to assess
magnesium intake meaningfully.
The practical answer is to ask about the amount of those “baby plant” foods that a
person eats. Regularly eating a good amount of nuts, seeds, legumes (like beans, peanuts,
peas and lentils ) and whole grains is the best indication that one has a healthy dietary
magnesium intake. [One large study from Harvard, for example, found that eating an ounce of
nuts or peanuts four times a week or more was associated with 25% less risk of developing type
II diabetes in a 16 year period.] These foods are also very rich sources of many other nutrients in
addition to magnesium.
The asking about these foods is key because details of a person’s actual diet are rarely
evaluated in the brief amount of time allotted to a clinic visit. Just saying “eat a balanced diet and
exercise!” does not provide enough specific information to protect people from the increased risk
of magnesium inadequacy associated with this medication.
Encouraging a generous intake of these same foods (along with a multivitamin with
minerals) is especially important for your patients on furosemide or any other diuretic that is
described officially as causing potassium loss in the urine. If the patient is unable or unwilling to
eat a generous amount of these foods, consider adding a 400-500 mg magnesium supplement as
described (unless there is a question of kidney failure.)
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For more on these nutrition issues, please see my other papers, which include:
Overview Papers:
My Current Top Five Easy Ways to Improve Your Family’s Nutrition (subject to change at any moment! )
Thinking about Other Nutrition Issues in Diabetes
Top Ten Pregnancy Nutrition Recommendations
Why Are Children with Chronic Illnesses or Handicapping Conditions at High Risk of Receiving
Suboptimal Nutrition?
Single Nutrient Topics:
Magnesium
Calcium
Folic Acid
A Short Carnitine Discussion that Might Be Helpful
Vitamin B12
Nutrition Support of Iron Deficiency Anemia
Vitamin K: New Issues in Cardiovascular Health, Renal Health, Osteoporosis, Liver & Colon
Cancer, Diabetes, Pregnancy and Varicose Veins
Vitamin K: Focus on the Vitamin K and Warfarin/Coumadin Anticoagulant Drugs Issue
MeritCare Medical Center
Department of Pediatrics
Aunt Cathy’s Guide to Nutrition:
Cathy Breedon PhD, RD, CSP, FADA
Perinatal/Pediatric Nutrition Specialist
MeritCare Children’s Hospital, Fargo, ND
and UND School of Medicine
What is Galactosemia?
Children with galactosemia have a problem handling a type of sugar called “galactose”
that is found in some foods. It can build up in their bodies and cause some serious problems. If
you look up galactosemia on the internet, you will find some frightening information. However,
there are different forms of galatosemia, and the kind your child has is not the more serious
“classic” galactosemia, but a much milder form called the “Duarte variant galactosemia”
Having galactosemia of the “Duarte” type means that the children may only have
this problem while they are babies. We must carefully limit their intake of their intake of
galactose sugar, at least for the first year of life. At about that age, their doctors will do a test to
see if they have outgrown their problem in coping with this sugar.
Fortunately, it is pretty easy during that first year to limit galactose. Unfortunately,
mother’s milk contains galactose, so babies with any kind of galactosemia may not be breastfed. They cannot use regular milk-based formulas either like Enfamil, Good Start and
Similac (the major brands in alphabetical order.) Your doctor will have prescribed one of the
common soy-based baby formulas like Good Start Soy, Isomil and Prosobee. All are fine.]
For any of these products, the powdered form is better than the liquid products because
all the liquid soy formulas contain a small amount of carrageenan, a kind of naturally occurring
thickener/stabilizer made out of red seaweed. Carrageenen is about 27% galactose, so it could
contribute a small amount of galactose. This potential source of galactose is avoidable just by
using the powdered form of soy formula.
Where is Galactose found in food?
Galactose is found in dairy products, so it can be largely avoided by removing all dairy
foods from the baby’s diet. But since dairy products are often used in food preparation and in
commercial products especially, it is important to carefully examine all food labels for
sources of galactose. In 2006, labeling laws were implemented for processed foods in the US
to assist people with management of a variety of allergies. Now many commercially made
foods that contain milk products will have the word “milk” on the label, not just the scientific
name of some component of milk. This has been VERY helpful.
"Milk sugar" is the common name for lactose, a combination sugar made out of
galactose and a different sugar called glucose. Glucose is not a problem for children with
galactosemia, but the galactose is so we need to take lactose out of your baby’s diet too.
Small amounts of galactose are also found in organ meats (liver, brains, kidneys,
sweetbreads, pancreas and heart,) so they must also be excluded from the diet. These are
generally not thought of as common elements of the American diet, but they are found in hot
dogs, sausage, cold cuts, paté and in giblet gravy. Many commercial sausage products also can
contain "milk solids." Luckily, it is not hard to avoid these foods while children are little.
Some fruits and vegetables contain some galactose in an absorbable form.
In general, the amount is very small, and if we introduce strained fruits and vegetables
only after 6 months of age, it is not likely to be a problem for the baby who has the Duarte type
of galactosemia. The fruits and vegetables with the most galactose by far are persimmons and
tomatoes. Both are very easy to avoid in a baby’s diet, so it is reasonable to avoid just these two
fruit/vegetable foods during this first year.
Words on labels that indicate that it may contain galactose:
acidophilus milk cream
butter
buttermilk
buttermilk salad dressings
(like ranch dressing)
casein
cheese
cream soups
creamed anything
dairy
dry milk solids
ice cream
ice milk
lactose
margarines with milk solids
or "a touch of butter"
milk (any kind)
milk chocolate
pudding
sherbet
sour cream
whey
whipping cream
yogurt
Read labels for all commercial products or ask the manufacturer. Watch for:
Many crackers, cookies, cakes, muffins, biscuits and frostings are made with milk
or butter, including some baby products like Zwiebach.
Most white bread is made with milk. (French bread and whole wheat breads are
usually not, but check the labels. Sometimes the tops are brushed with butter.)
Pancakes, waffles, and French toast made from mixes or commercially prepared
(If made from scratch with soy formula instead of milk, they are fine.)
Instant mashed potatoes or potato dishes made with milk.
These suspicious-looking words on labels actually are safe for children with galactosemia:
lactalbumin
lactate
lactic acid
Although it can feel overwhelming to think about all the foods like breads and crackers
that might have galactose in them, remember that you really only have to know the names of
one or two brands that are safe. It doesn’t matter what any other products out there may
contain if you only buy the one brand that you have looked at carefully and that you know is
safe. So, when you travel to Grandma’s house, just take along your own brand of safe crackers
and you don’t have to worry about what is in the brand at her house.
Galactose in Medications
Many common medications contain lactose. Always check with the pharmacist before
using any medication. Sometimes labels do not list the "inactive" ingredients like lactose; it may
be referred to as a flavoring or a carrier substance.
Be sure that the pharmacist you talk with understands how very important it is to
be sure that a product is free of galactose and lactose. I emphasize this because galactosemia
is quite rare, and so the pharmacist may also think that your baby is simply "lactose intolerant.”
If the pharmacist assures you that the small amount of lactose in a product should cause no
problem during the first year, it means that he/she is confusing a serious metabolism problem
(galactosemia) with a mild digestive difficulty. If this happens, I will be happy to explain things
to your pharmacist, so feel free to call. Or, give him/her this explanation. If the pharmacists are
not sure if a product is lactose free, they or you can email or write to the manufacturer.
Other People
As your baby gets older, it will be important to make sure that well-meaning people do
not feed your little sweetie inappropriate foods. Since it is so rare, when you are in a situation
of having to discuss it with people around you who do not know about galactosemia, it is often
easier to just say that the baby is very allergic to some foods. People know about allergies, and
they understand that they can be very serious. There is so need to try to explain more than that.
There is really just one more thing to watch out for: If other babies are around, (as is
common at family gatherings or at day care centers) little ones who have started to move
around independently can sometimes grab the wrong bottle. While we obviously try to
prevent this kind of thing as much as possible, it can (and does) happen. But do keep in mind
that, especially as your baby gets older and is crawling or toddling, if she/he somehow takes a
few swigs of someone else’s bottle, it is not a crisis. Just take away the bottle and give your
baby the right bottle and a great big hug. That takes care of it.
Not all nutrition professionals will be familiar with this very special diet for very
special babies. However, there will often be a registered Dietitian (“RD”) at your regional
Children’s Hospital who specializes in this kind of unusual diet and he/she can answer
additional questions and provide assistance.
Mer itCar e Medical Center
Aunt Cathy’s Guide to:
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical Nutrition Specialist,
MeritCare Medical Center, Fargo, ND
& UND School of Medicine Dept. of Pediatrics
Nutr ition for People with
Epider molysis Bullosa
Epidermolysis bullosa is a family of genetic diseases that primarily affect the health of
body surfaces including the skin, the mouth and the digestive system. Skin is extremely
fragile and easily blistered from even minor trauma or friction. The degree of severity is
quite variable and nutrition concerns will vary with the degree and type of injury. This
paper is a summary of my presentation at the 2006 National DEBra Patient Care
Conference in Nashville. (DEBra is the Dystrophic Epidermolysis Bullosa Research
Association of America.) I have arranged the issues with a problem-solving focus, with
the needs of the most seriously affected people in mind. Many issues overlap, so various
aspects of important issues may be discussed in several places within the paper.
The general suggestions made here are intended to be of use to patients
and their families with the approval and assistance of their health care
professional and not in isolation. They are based on my very best guess
about what aspects of normal and therapeutic nutrition might be especially
helpful or important for people with EB. My best guesses are based on the
most resent scientific literature and by what I would do to optimize the health
of a family member fighting these battles. Please note that I do not sell anything
and I never will. There is very little EB-specific nutrition information available
in the scientific literature, so the recommendations are primarily based on the
role of nutrition in managing wound healing, inflammation, constipation, dental
problems, anemia, osteoporosis, and other conditions associated with EB.
Some parts of this paper may focus on issues for infants and children, but in almost
all cases the information or concepts will apply to adults as well (so don’t skip over the
“kids” parts.  ) Although this paper was written primarily for people who have EB and
their families, you will find that some parts will be primarily of use to the health care
professionals. I included this information not to “blind you with science,” but because I
want to be sure that the underlying scientific principles are clear enough to let people use the
information creatively to solve new problems that may arise.
You may share this paper with anyone, but please do not alter it in any way. Copies
can be downloaded for free along with other articles cited here from MeritCare’s website.
Go to www.meritcare.com and type my name in the search box. You can then click a button
that says “Cathy Breedon’s Handouts.” My sincere hope is that you will find some useful
information here and that you will share it with others who may benefit. And now . . .
1
1. Getting enough calories
People with severe EB often have higher than usual needs for energy
(calories.) In part this is because of the need to continually heal wounds. At the same time,
they may have decreased ability to take in food because of difficulty with eating due to oral
problems. These may include decreased ability to open the mouth wide, blisters in the mouth,
esophageal strictures, or significant dental problems. Many people with EB struggle with
constipation, which can greatly decrease appetite. As a result, as children they often fail to
grow optimally and at any age the ability to heal wounds and to be active can be impaired.
Their intake of vitamins, minerals and protein can also be compromised by poor total food
intake. This leads to poor immune function, inadequate energy to participate in activities,
additional compromise of skin integrity, impaired wound healing, anemia and other problems.
Increasing the calories of formulas for infants usually involves concentrating the
product to make a higher caloric density. For example, using only 9 oz of water instead of the
usual 13 oz when preparing a 13 oz can of infant formula concentrate will make the formula
have 24 calories per ounce instead of the usual 20. The nice thing about this approach is that it
provides ALL nutrients in higher amounts (not just calories,) it does not distort the ratios of
nutrients per calorie, it contributes no additional cost, and it is safe to use. Sometimes fat or
carbohydrate calories will still need to be added, but these should generally be used only to
add calories beyond the 24 calories per ounce concentration. Infants would rarely if ever be
fed a product with more than 30 calories per ounce. How to increase calories beyond the 24
calories per ounce mixture described above should be determined with the help of a person
familiar with these issues, as there are sometimes important reasons to use one additive over
another in a particular child’s case.
Boring Science Alert:
This next section will likely be of interest only to health care professionals, and probably not
even to them. But if I don’t include the explanation they might not trust trying it. 
Everyone else gets to skip to page 5.
Issues and suggestions for increasing an infant’s formula to 25 - 30 calories
per oz when necessary.
Sometimes some oil or carbohydrate is used to add additional calories above the 24
calories per oz level. This is because if lots more protein is taken in than is needed, the
nitrogen waste from the excess protein may be more than the kidneys can easily handle.
Unlike extra protein, neither oil nor carbohydrate contribute to this “(potential) Renal Solute
Load” (RSL) – the work the kidney has to do if all the nitrogen in that protein had to be
excreted. As a rule of thumb, this number should (ideally) be around 300 mOsm (particles)
per kg of water available to excrete the waste through the kidney, especially in the first three
months of life. Maturity of kidneys reduces the risk of this problem. Note, however, that the
Potential Renal Solute Load of a product becomes much less important for an infant
2
who is growing or who is continually trying to heal wounds. This is because the protein
nitrogen consumed (the biggest contributor to RSL) will be most likely be used to make tissue
rather than needing to be excreted as a waste product.
Carbohydrate can contribute quite a lot to the “osmolality” of a feeding (the
number of tiny particles floating in the amount of water available in the intestine (not in
the kidney.) The same <300 mOsm per kg water (or expressed as “osmolarity” – 300
mOsm per liter of formula) is the rule of thumb. However, people concerned about an
osmolality of a feeding being over 300 will be comforted to know that the reason it is set
there is because sometimes higher osmolalities may contribute to looser stools and even
result in an “osmotic diarrhea” in some infants.
However, for infants troubled by constipation, this effect can actually be helpful!
The higher number of particles per volume (the osmolality) of a formula tends to attract
water which helps keep water in the intestines to keeps stools softer. Many constipation
treatments work the same way, like milk of magnesia, lactulose, Miralax® (Braintree Labs) and
prune juice. For example, the osmolarity of regular prune juice is reported in some
references as being 800-1265 mOsm/liter!
For all of these reasons, it can be reasonable to consider a different approach to
increasing the caloric density of an older infant’s formula (or some of a younger infant’s
formula) in a somewhat nonstandard – but maybe a better – way, especially for an infant with
constipation and wounds to heal. Instead of adding all those empty calories from fat and
carbohydrate to a 24 calories/oz infant formula to make it have 30 calories per oz.,
consider using a mix of infant formula with some of a “complete nutrition” type of liquid
formula designed for children.
Most “complete nutrition” formula products for people ages one through adulthood
provide 30 calories per ounce. With appropriate professional supervision these products can
also be useful for helping children younger than one year, although they are not marketed for
this use. For example, nutrition professionals will be interested to know that the Renal Solute
Load and the Osmolality of the products designed for children are quite comparable to the
levels found in infant formulas, especially when the infant formulas have needed to be
concentrated to a higher calorie level per oz. The reason that they are not marketed for use
with older infants is related primarily to the considerable cost of submitting and getting the
products “approved” to be called infant formulas, and the fact that the companies would then
be competing with their own infant-focused products in that age-group.
Table 1. on the next page will be especially likely to be of interest only to health care
professionals. It shows a sample of the osmolality and potential renal solute load of some of
the products made by major manufacturers compared with one of their own standard infant
formulas at different caloric densities. The osmolality and renal solute load of infant
formulas concentrated to 24 kcal/oz plus additional carbohydrate or fat calories to make a 30
kcal/oz feeding is not much different from the better-tasting children’s products, and the
children’s products provide considerably more protein. They also contribute important
vitamins and minerals not provided by carbohydrate and oil additives.
3
Of course, it is always important to review the entire feeding regimen for
appropriateness of all nutrients. For infants and children length and weight growth progress
can serve somewhat as markers that intake of calories and protein is likely too low, adequate,
or excessive. Growth alone, however will not necessarily detect inadequacies of many other
nutrients that have less of a direct effect on calorie and protein utilization. Also, the use of
standard growth charts can be helpful in charting a child’s growth against his earlier measures,
but the grids themselves may not reflect what is typical or ideal or even possible growth for a
child with severe EB.
Table 1: The protein content, osmolality and potential renal solute load
of some of the “complete type” children’s liquid formula products made by
major manufacturers compared with one of their own standard infant
formulas at different caloric densities. (This table subject to being
outdated about every five minutes because of continuing product changes.
Consider this table as reflecting just one moment in time, but as an
example of what to look at in products.*
Company
Mead
Johnson
Calories Protein Osmolality Potential Renal
per oz
grams per oz mOsm/Kg
Solute Load
(usual goal <300
Children’s
Product
30
0.89
Enfamil®
Nestle
Children’s
Product
mOsm/Liter
(usual goal <300 ideally)
440-520
270
vanilla/choc
345
Kindercal®
Infant Product
ideally)
tube feeding
20
-------24
-----30
0.42
-----0.50
-----0.50
300
-----360
------
181
----217
30
1.0
350
204
20
-------24
-----30
0.42
-----0.50
-----0.50
265
----318
------
135
----162
30
1.0
430
276
20
-------24
-----30
0.47
-----0.56
-----0.56
300
----360
------
187
---224
higher with added
carbohydrate
Nutren Jr®
Infant Product
Good Start
Supreme®
Ross
Children’s
Product
higher with added
carbohydrate
PediaSure®
Infant Product
Similac®
4
higher with added
carbohydrate
-------------------------------------------------------------------------------------------------------------
Back to everybody:
Many of the substances added to foods or formulas to add calories can seriously
distort the nutritional balance unless the protein, vitamins and minerals are
carefully adjusted. For example, corn syrup, sugar, glucose polymers products like
Polycose® (Ross), butter/margarine, cream, regular vegetable oil, MCT oil® (Mead
Johnson/Novartis), and emulsified fat products like Microlipid (Mead Johnson/Novartis) and Intralipid®
(Pharmacia & Upjohn) all have one thing in common. They all just add empty calories. In
small amounts there is no concern, but if a significant percentage of the person’s calories
is contributed by these products there is potential for distorting the ratio of calories
relative to the nutrients needed to metabolize them.
People trying to grow or to heal wounds will have higher needs for all nutrients, not
just generous calories and protein. In this situation it is important to recognize that just
adding protein and/or calories will not work well in the absence of the critically important
vitamins and minerals that the body needs to convert fuel (calories) to make usable energy,
and/or to construct tissues. This is key in conditions that require extra production of tissue,
such as wound healing and have an increased need for immune system activity. Interestingly,
skin, intestinal, and immune system cells are the ones with the greatest need for rapid growth.
Failure to assure adequacy of micronutrients can make other efforts unsuccessful.
Unfortunately, this issue often does not get the attention it deserves and it is not
uncommon for people to be given calories-only or protein-only supplements without
assuring adequacy of the necessary vitamins and minerals to use the protein. Also,
giving just protein in the absence of adequate calories will result in the protein being burned
as an energy source instead of using it for construction. I think of this as like living in North
Dakota in the winter: if we run out of fuel we start burning the furniture! Most nutrients have
many additional important roles, some of which will be described further a bit later.
One should keep in mind that the usual recommended amounts of calories and
nutrients such as the RDAs or RDIs are based on the needs of “most healthy people.”
They do not address the needs of people with illness or other health conditions. The health
care professionals will need to think through the particular challenges of an individual’s
situation and make adjustments in goals accordingly. A good example is zinc, a mineral
needed in over 200 different places in a person’s body. Every time we try to make a new cell,
we need zinc to make the DNA in the center of it. That means that people who need to
make a lot of new tissue will need a more generous intake of zinc.
Poor zinc status impairs growth in children, and it limits the ability to heal wounds –
another situation that requires a lot of new tissue formation. Recovery from wounds and
staying healthy in general also depend on adequacy of zinc because the production of T-cells
of the immune system is very dependent on adequate zinc. At the same time, excessive
amounts of zinc can cause problems. Determining the right amount requires a close look at
the individual’s situation.
5
2. How much zinc?
Some recommendations for zinc intakes needed for healing serious burns in hospitals have
been about the same on a “per body weight” basis as the levels recommended for healthy
infants. [For example, the RDA tables show 5 mg zinc for a baby with an average weight of 9
kg (about 20 lbs.) Using that ratio of 5-to-9, the zinc for a 90 kg (198 lbs) man would be 50
mg, which happens to be a very typical supplemental dosage for healing serious wounds.]
This is not surprising since both the injured person and the infant are trying to
produce a lot of cells in a hurry. It led me to think the best nutritional model for optimal
wound care would be to “baby the wound.” In other words, think of providing the amount of
a nutrient per body weight needed in infancy as being a reasonable guide for the amount per
weight in a child or adult with serious burns or wounds. The 5-to-9 ratio can be rounded to an
easier 0.5 mg per kg (or 0.25 mg zinc per lb) for wound healing. Many standard
multivitamins provide 12-15 mg zinc and additional zinc can be supplemented alone.
However, the very best absorbed form in the greatest amount is found in meat, and
especially red meat. [Meat is actually color coded . . . red meat has more than white meat!]
Other foods (except for oysters) never even come close. My “Iron and Zinc” handout has
more details, but here’s a tiny peek:
Table 2:
The very best sources of well-absorbed and utilizable zinc and iron are the same foods.
1 oz
Zinc mg
Iron mg
beef liver
1.5
2.2
beef
1.3
1.0
pork
0.8
0.9
chicken
0.7
0.3
fish
0.5
0.3
(Data Source: Agriculture Handbook No. 8-4 US Dept. of Agriculture Science & Education Admin.)
Other factors that may affect the amount of supplemental zinc that may be
recommended for an individual include:
1. Whether he/she is presumed to have adequate or poor zinc stores to start with;
2. The amount of construction work needing to be accomplished; and
3. Dietary factors such as meat consumption.
For people with poor stores or increased needs, it is not uncommon for them to be
prescribed 50 mg zinc/day or more for fairly short periods. As a general rule, avoid long-term
supplementing over that amount without the physician’s knowledge and approval. Problems
have been noted in some folks with long-term supplementation at that level, sometimes
because of impaired absorption of copper – the two minerals compete for absorption in the
intestine. People taking higher than usual zinc as supplements should be sure that their
multivitamin with minerals also contains copper. Interestingly, the competition effect is much
less when the zinc source is meat instead of supplements. Some disturbance in cholesterol
levels has also been reported occasionally in people in the general public taking high dose
6
zinc supplements for a long time. However that effect is unlikely to be a concern in EB
because the actual zinc requirements are higher than average, and zinc losses can also be
much higher from the “weeping” of wounds.
3. How Much Protein for Wound Healing?
A very similar situation turned out to be the case in determining a good amount of
protein for individuals with wounds. The World Health Organization suggests that healthy
adults should get at least 0.8 g protein per kg body weight (about 3.6 g protein per pound.).
Americans typically eat considerably more than this minimum guideline, however.
A number of reference books about wound care have suggested that 2.2g protein per
kg (1.1 g per pound) would be a reasonable amount for optimal healing. It caught my
eye because I work primarily in pediatrics so I recognized that 2.2g protein per kg body
weight is the level often suggested as a reasonable amount for healthy normal infants!
This turns out to be a suggested increase to about 2.75 times the WHO figure for average
adults. This intake amount is clearly safe and not excessive, since many Americans eat 2-3
times the WHO level normally! To the best of my knowledge, my “Baby the Wound!”
system of determining nutrient needs in serious burns or other wounds has not been
adopted by any big official agency. Again, it’s just my best guess for a safe but effective
intake level to start with, and a way to think about the best nutrient to promote healing
instead of just providing RDA levels.
Aunt Cathy’s “Baby That Wound!” Theory
(Remember: I made this up – this is not official science!)
This little baby elephant* is a good model for the “Baby That Wound” concept:
A lot of food is needed every day in order to grow as fast has she should!
Some examples are shown on the next page.
*This cute baby elephant is called Tamani (a Swahili word for “Hope”)
www.lowryparkzoo.com/ baby_elephant/photos.html
used by permission of the Lowry Park Zoo in Tampa, Florida,
with best wishes for children with EB.
7
Protein grams
per kg body wt
9 kg Baby
Wound Healing Man
70 kg Average Man
70 kg Average Man
2.2
2.2
Zinc mg per kg
body wt
0.5
0.5
0.8
0.11
(W.H.O)
(new RDA)
0.9-1.0
(new RDA)
0.17 – 0.21
(former RDAs of 12-15mg)
What about other vitamins and minerals?
A generous intake of vitamin B12 and folic acid (another B vitamin) is also required for
making DNA (for making all cells) and in particular for making new red blood cells.
Sometimes “anemia” is not caused by inadequate iron but by a relative inadequacy of
these nutrients, or others (like vitamin E and other antioxidants) that are needed to keep
red blood cells from being broken apart too soon. This blood cell breakage can be more
likely to happen because of the higher production of free radicals related to inflammation.
Antioxidants and free radicals will be discussed in more detail later, as will anemia issues.
Vitamin C also helps protect the white blood cells of the immune system to let them live
longer to keep on killing germs. Vitamin C and copper are also players on the team that lets
us build connective tissue for wound healing, and both are also required to use iron in the
body. And on and on. These are just a few of many examples of the critical role played by
vitamins and minerals in health, and why this aspect of a person’s nutrition cannot be ignored.
For some specific additional information, please see my handouts on folic acid, vitamin B12,
magnesium, chromium, vitamin D, copper, zinc and iron. A recent report in the scientific
literature specifically about vitamins and trace mineral adequacy in EB reached the following
conclusion:
Vitamin and trace metal levels in recessive dystrophic epidermolysis bullosa. J Eur Acad Dermatol Venereol.
2004 Nov;18(6):649-53.Conclusion: Vitamin and trace metal deficiencies are frequent in RDEB, even in patients
receiving gastrostomy feeding, and often go unrecognized. Regular nutritional evaluation is necessary. Dietary
advice and supplements should be given. Enteral feeding by gastrostomy should be discussed in early childhood.
Another issue in supplementing calories and protein in the diet is cost.
The “regular food” items are many times cheaper than the commercial additives.
For example, consider fat additives commonly used: MCT oil (Mead Johnson) is about $1.00 an
ounce ($65 per quart) and the calories are about 5 calories less per teaspoon than most food
fats and oils. It is specially designed for use in certain digestion problems that involve
inadequate bile production or poor ability to “recycle” bile. Unless an individual is known to
have a digestive problem involving bile, it is unlikely to provide any special benefit to warrant
the high cost. Comparing prices, today in Fargo, canola oil (a good choice) costs less than
$0.06 an ounce ($1.82 per quart.)
8
The advantage of using special “emulsified products” is that they are better at
staying mixed into formulas. That is what emulsification means . . . keeping the oil and
water in a food from separating. But unless that is a major problem in an individual’s
situation, it is useful to know that they are even higher in cost. This is because they are
primarily designed to be used for intravenous (i.v.) feedings. “Intralipid” (Pharmacia & Upjohn)
and Microlipid” (Novartis/Mead Johnson) cost about 88 cents per oz, but they have only half the
calories of other fats, so you need to use twice as much. Again, compare these with the
cost of canola oil shown earlier – it is MUCH more expensive. Some other issues about
the use of particular forms of fat will be discussed later.
Protein additives are also much more expensive than excellent quality protein in foods.
At about 7 g of protein per egg, egg protein costs about a penny a gram and it contains
some additional nutritional value. Milk protein (in milk, yogurt, cheese and cottage cheese)
and eggs are extremely useful in EB because they are much easier for some people to eat than
many meats. The whey protein supplements used by body builders provide very nice protein
and I have found prices of various products on line, some of the lowest between $10-$30 for a
two pound can. Prices in stores appear to be more. These products provide ONLY protein –
no other nutrients, but they might have some benefit for people who find the casein in milk
protein to be constipating, however. Milk protein normally is about 82% casein and 18%
whey. (More on this in the discussion of constipation later.)
The liquid pasteurized “no yolk” egg protein products available in grocery stores are
more expensive than eggs, but cheaper than the special additive products. For example,
“EggBeaters” provides 6 g protein per ¼ cup, at about 7 cents a gram at a grocery store
here in Fargo. It has the advantage of being pasteurized so it can be added to foods that
are not intended to be cooked, such as a smoothie or eggnog. An ounce of milk has about
a gram of protein. Powdered milk is another very inexpensive product that can be added
to foods or beverages. It provides 1.5 g protein per tablespoon, and some calcium and
other nutrients are provided with it. It can be stirred into many different foods, such as
puddings, soups, and smoothies, etc., but it doesn’t have to be a dairy food that you add it
to. Try adding it to hot cereal, jello, mashed potatoes and even meatloaf! (I add
EVERYTHING to meatloaf . . . you should see it!) If lactose intolerance is an issue,
lactase enzyme can be used to minimize this problem. Some brands of lactase enzyme
are: Dairyease®, Lac-Dos®, Lactaid®, Lactrase®, RiteAid® Dairy Relief™, Surelac®,
Walgreens® and Dairy Digestive.™
Adding Carbohydrate Calories:
“Glucose polymers” (such as “Polycose” by Ross) are simply starch in
solution and they have no advantage over regular food carbohydrates like sugar or
food starch. They are designed primarily as a carbohydrate that can be added to
beverages without adding a sweet taste. There is usually no reason to avoid sweetness in
children’s feedings. The risk of tooth decay is identical because any carbohydrate fed
orally is food for bacteria in the mouth. The bacteria then produce acids that attack the
tooth enamel. The main factors that increase risk of tooth decay are frequency of
feedings and contact time with the teeth, not whether it was sugar or starch. Because of
9
difficulty of dental care in EB, however, the whole issue of tooth decay is not to be
taken lightly. Some dental issues will be discussed later.
Back to the issue of using sugar versus glucose polymer products: There is no danger of
causing a “sweet tooth” to be developed in a child. Children just come that way . . . human
milk is sweet and it is all part of the design to make babies want to nurse. I have found that
using regular table sugar can often make many foods and formulas more palatable for
children, and therefore it is more effective because they eat more. And, of course, the dental
and sweet tooth concerns are even less of a concern when the child is fed through a tube
instead of orally.
A teaspoon of glucose polymer products
weighs 2 grams and provides only
8 “empty calories” from carbohydrate.
Price per 100 calories: $5.00
A teaspoon of sugar weighs 4 grams
and adds 16 “empty calories”
from carbohydrate;
Price per 100 calories: $0.05
That means you need only half as much sugar to get the same calories. A 12.3 oz
(350 grams) can of a glucose polymer product costs about $7-$8.30 from the cheapest on-line
sources. That is equal to about a half cent per calorie provided. Compare that with table
sugar, which in Fargo today costs $4.29 for a 10lb. bag. That is only five 100th of a cent per
calorie. Looked at another way, the Polycose costs 100 times as much for an equal
amount of calories.
In most circumstances there is no need to use these expensive special products at all.
“MCT oil,” an example noted earlier, is designed for special needs related to certain liver
diseases or intestinal malabsorption problems such as Cystic Fibrosis. It is often inappropriate
for other uses because besides being very costly, it is all saturated fat (from coconut oil) and
it therefore provides none of the “essential” fats or any omega-3 and omega-6
polyunsaturated fats at all . . . just calories. I have also found that using regularly available
food products from the grocery store also has the psychological advantage of
“de-medicalizing” at least one part of a person’s care.
Sometimes health care professionals are not familiar with these issues, because they
have to know so much about everything else. It might be beneficial to share this paper with
them if these very costly products are suggested in order to use them only when regular
carbohydrates and fats available at the grocery store will not do. In addition, remember that
just adding fat or carbohydrate calories or “just protein” from any source will contribute no
other nutrients and so they should be used as only a small part of a higher calorie or “nutrient
dense” feeding regimen.
Energy to grow and to go!
10
A daily “complete” type standard multivitamin with minerals
It is very reasonable to add a standard multivitamin with minerals to the diet of a person with
EB, and I strongly encourage it for many reasons. [Please note that I do not sell anything – I
just think it is a very good idea, based on what we know about the usual nutrient density of
people’s diets, and the increased requirements for many nutrients because of EB.] A
multivitamin/mineral supplement is a good idea even if a “complete nutrition” formula
product is used. It is also a good idea for everyone in the family – with EB or not. These
products can be swallowed, chewed or crushed and added to foods. A mortar and pestle can
do a fine job of turning pills to powder fine enough to be used with gastrostomy tubes. You
can find a mortar and pestle for less than $10 in the kitchenware section of all the large
discount stores – people use them to grind spices.
None of the multivitamin/mineral products is truly “complete,” however. Most have no
potassium, only about 200 mg of calcium, and just 10-25% of the recommended amount of
magnesium. They are not intended to take the place of food, but to be used in addition to food.
Most liquid products are even less complete, often containing much lower amounts of folic acid
and minerals. They also add no calories, no protein and little if any beneficial “phytochemicals”
(plant chemicals) available from foods. Supplementation is very wise, but of course it is only
a part of the regimen to improve the health of people with EB or other serious conditions.
Some people with EB have severe physical eating problems.
This may include pain and blistering in the mouth, a very small mouth opening, esophageal
strictures, and severe dental problems resulting in problems chewing and swallowing enough
food or an adequate variety of foods. They often have inadequate intakes because of the time
and effort required to eat even a small amount of food. Sometimes the entire diet must be
blenderized to a puree texture because the ability to chew is so impaired. In this situation, the
use of commercial baby foods is fast but certainly not flavorful or enticing, and in general
these foods have very low caloric and nutrient density. They are usually pureed with water.
Pureeing regular foods with taste-appropriate and nutritious liquids (like milk, cream soups,
commercial formulas, juices, etc.) is a much better solution.
It may be necessary to use other feeding routes in order to achieve
appropriate growth and the best possible health.
In some (non-EB) situations this may involve feeding through a tube from the nose to the
tummy. This is an “NG”– a “naso-gastric” tube. But in EB there is potential injury to the
face and other tissues with this approach so it is not recommended. Often this kind of tube
placement is secured with tape to a person’s cheek, and this is definitely not reasonable to do
in EB. In addition, NG tube feedings are used in circumstances where the expectation is that
the tube feeding will be needed only for a fairly short period of time. The expectation with
severe EB is that a person would benefit from aggressive nutrition assistance throughout
life.
11
For all of these reasons, the tube is placed directly into the stomach or sometimes
into the small intestine. Some tubes are placed through the skin to go directly into the
tummy. They may be called a PG tube, a PEG tube, or another variation. PG stands for
“Percutaneous” (through the skin) “gastrostomy” (through an opening into the stomach.)
Sometimes it is positioned into the jejunum of the small intestine instead. There are
important issues in EB regarding which technique is used to place the tube. The health
care professionals will know the benefits and problems associated with using one approach
over another for a particular individual. Whether such a placement can be accomplished with
local instead of general anesthesia (as is sometimes the case in people with other medical
conditions) is a question that needs to be discussed with the individual’s physician.
Sometimes it must be done under general anesthesia, but it may be able to be done at the same
time as another necessary procedure.
In my experience with many (non-EB) children who have ultimately required a
gastrostomy tube to assure adequate nutrition, it has been shown repeatedly that it is far better
to place the tube before the person has become poorly nourished from months of trying and
failing to take in enough orally. Acting before the situation becomes critical and the child
debilitated and immune-suppressed is very important. Additional factors such as the
expected brain growth and development during this period make it critical that the child not be
allowed to fail nutritionally. Many children fail to take in enough nutrition in spite of great
effort on the part of families to provide appropriate oral feedings. Studies of the growth and
health of children with severe EB specifically have shown that it is much better and
more effective to recognize the need for a tube placement and to place it proactively.
Sometimes parents are hesitant about having a feeding tube placed because they perceive
that it is somehow “admitting defeat” or that it is an indication that they are not willing to do
what it takes to get food into the child. Some people just hate the idea of yet another
procedure or adding yet another way in which the child will be different from other children.
However, time after time I have been told by the family when they finally agreed to having
the tube placed after months of huge effort and poor success, that “we should have done this
months ago.”
It is reasonable to assume that an infant or child with severe EB will need a feeding
tube. Delaying placement only increases the period of discomfort, frustration on the part of
both child and caretaker, “feeding wars,” and feelings of failure. Most importantly, it also
results in an insufficient intake of nutrients for the baby to grow and develop and to be as
healthy as possible in spite of this devastating condition. Parents can “cash in” all that time
they were spending struggling with very difficult feeding and use it to do something much
more pleasurable … like playing with the baby. 
If an individual can eat but just cannot eat enough, the tube feeding can be an excellent
help because it allows the individual to be passively fed as needed, and it can also help
administer medications. This approach also lets the person eat just preferred foods and the rest
of the nutrition can be easily fed passively. I think of this as contributing to another important
feeding issue: the “happiness factor.”
12
Certainly the skin care at the site of the tube placement is an important
consideration and communicating with a health care professional familiar with the very
special skin issues in EB is very important. DEBra of America, Inc. is the best contact for help
with this issue. The website is http://www.debra.org/index.php and the phone and email
addresses are: (212) 868-1573 or (866) DEBRA76 (866-332-7276) or [email protected].
As described earlier, many of the commercial tube-feeding products for children
and adults provide about 30 calories per ounce and about 0.9 g protein per ounce.
However, there are many products on the market that provide more concentrated calories
(up to 60 calories per ounce) and higher amounts of protein per ounce. The vitamins
and minerals will vary as well. Many provide “RDA” levels of nutrients at about a quart
a day but they are quite diverse so read the label. And since RDA levels in general are not
sufficient to meet the needs of people with severe EB, additional micronutrient
supplementation is advisable.
For help with choosing a tube-feeding product or setting up a tube-feeding
regimen, contact a registered dietitian with expertise in tube feedings. Many of them
have the special certification “CNS” after their name and the “RD” in their credentials.
This stands for “Certified Nutrition Support Dietitian” and it means that the dietitian will
have been certified by the National Board of Nutrition Support Certification, established
in 1984 by the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) To
find a dietitian with this level of tube-feeding expertise you can call a local hospital (or a
large teaching hospital) and ask one of the clinical dietitians there for help in locating
someone. There may even be one on staff locally. If looking for help with tube feedings
for an infant or child, you can also find help from dietitians who have “CSP” after their
name and the letters “RD.” CSP means Certified Specialist in Pediatric Nutrition. Most
children’s hospitals will have at least one on staff. You can also go to one of these
websites for help in finding someone with the special skills that you need:
http://www.nutritioncertify.org or www.eatright.org.
Many people with EB have major troubles with constipation.
Contrary to popular belief, simply increasing water or other fluids will not resolve
constipation unless inadequate fluid intake was a contributing problem. Extra fluid is
clearly needed if fiber is being added, but in the absence of added fiber any additional fluid
is simply absorbed from the intestine and excreted via the kidney. As described in more
detail later, many liquids like prune juice help with constipation for reasons unrelated to just
their fluid content. In addition, adding fiber may not be a helpful approach to constipation
for a person whose ability to push food through the lower intestinal tract may be impaired;
in fact, it may actually contribute to bowel obstruction. Some types of fiber actually slow
transit time through the intestine instead of moving things along, and some forms may be
too physically rough on the intestinal lining for a person with EB. Ask your health care
professional for specific guidance about fiber types. Some tube feeding products come in
versions that are fortified with non-abrasive fiber.
13
Limitations on types of foods tolerated can certainly result in a relatively low fiber diet
however. In addition, pain with elimination can be very severe and delicate rectal tissues can
be torn. Sometimes this can lead to a child intentionally withholding stool to avoid the pain
of elimination. Serious bowel impactions and colon enlargement can result. A plan for
keeping stools soft and for minimizing pain is essential.
In many conditions with severe rectal pain keeping a very soft towelette with a specially
formulated (and elegantly named) “butt paste” on it can be helpful. For example, I am
personally very aware that many cancer chemotherapy patients suffer from what I call
“flame-thrower diarrhea.” In that situation, it was extremely helpful to mix zinc oxide and
lidocaine (a pain killer) on a soft tissue or paper towel and to keep it in place by the rectal
opening until it is lost the next time the person went to the bathroom. However, the very
special skin problems of EB may make some of these common approaches unhelpful or
inappropriate. I described it here as something that worked well for me for control the pain
from chemotherapy . . . and I mention it particularly because no one told me what could be
done to help until weeks of pain had gone by! I am not a pharmacist, a physician or a nurse,
so the best sources of specific help with this kind of pain for people with EB are the folks at
DEBra of America, Inc. My point here is: be sure to ask for their help . . . do not suffer in
silence because of the embarrassment of talking about this “end” of the natural fooddigestion process.
For people with constipation problems for whom a nutrient-dense high-calorie diet is
needed, it is useful to know that there are pretty generous calories in some of the foods and
beverages we commonly use for constipation. Examples include “cranberry juice cocktail”
and prune juice which have 20 calories per ounce – as high as whole milk. Corn syrup has
60 kcal per Tablespoon. They contribute to keeping stools soft by keeping water in the colon.
This is called an “osmotic effect.” Prune juice has some additional properties that help. Fruit
juices also provide a variety of beneficial phytochemical antioxidants which are discussed
later.
When trying to “increase fluids” for constipation, remember that juices are 99.9% water.
That means that they contribute essentially the same amount of fluid as plain water would,
but they have the advantage of adding some calories, some beneficial phytochemicals and a
few nutrients. It makes little sense to concentrate a child’s formula or tube feeding and
then feed plain water . . . it just re-dilutes the feeding. A common estimate of “normal”
fluid needs is about 1 ml fluid per calorie you eat, so if you eat 2000 calories a day, then
2000 ml (2 liters – a bit over 8-1/3 cups) of total fluid would be general goal. This is not
just water, though . . . it includes all liquids. Sometimes people erroneously interpret this to
think it means we must drink 8 glasses of water PLUS several more cups of milk, juice, and
other beverages. This can be pretty unreasonable . . . and also unnecessary. Other factors
such as heat and fluid lost from wounds, etc., may increase our fluid needs above average,
however, and usually problems arise from taking in too little total fluid, not from taking in
too much. So, it is best to stay on the generous side. And remember to try to pick fluids that
are a source of calories and nutrients . . . not just water.
14
Also, consider whether some of the ways we add extra calories are possible
contributors to the constipation. For example, “casein” is a curd-forming milk protein
that can be quite constipating for some people. Whey protein is not curd-forming, and
therefore it is often less constipating. There are several generally available commercial
nutritional beverage products used for children, such as Boost or KinderCal (by Mead
Johnson), Carnation Instant Breakfast or Nutren Jr. (by Nestle), or PediaSure (by Ross) and
many “adult” products. [Again, commercial products change their names and contents on a
regular basis, so this list may no longer be up-to-date.]
If using these products, check the label to see if the protein is primarily in the form of
casein. You may see the word “caseinate” on the label. This is a perfectly fine protein
source for growth and healing, but for the chronically constipated individual it would be
worth trying one that had less of the protein in the form of casein. Powdered products such
as various brands of “instant breakfast” that are added to milk often include powdered milk
as the protein source of the powder, too, so the protein would still be 82% casein.
This is also an issue in infant feeding. Mother’s milk is very useful for MANY
reasons, including fat blend, immune-boosting factors and better absorbability of many
nutrients. In addition to these great benefits, it is unusual for babies to be constipated
when exclusively fed mother’s milk. It can be fed directly by having the baby nurse (if
able) or the milk can be expressed and fed via a bottle or a tube. However, some children’s
health situations can result in a degree of constipation even with mother’s milk.
Soy formulas are milk-free and so they have no casein, although for some children
soy is constipating, too. Of the milk-based products, a variety of protein sources are
available: Nestle Good Start Supreme is all whey (no casein) and the whey is partly
chopped up. This product has been helpful for use with chronically constipated babies.
Standard Enfamil (Mead Johnson) and Similac (Abbott) products have adjusted the caseinto whey ratio from 82%-to-18% (regular milk) to an easier to digest 40% to 60% ratio in an
effort to try to approach the ratios in human milk. None of these has been studied in EB
specifically, however, and as noted, the formula features and names change all the time.
The protein in all the “lactose free” milk-based infant formulas is 100% casein.
Enfamil’s “GentleEase” infant formula product has less lactose than their Enfamil and it
has both casein and whey in the same ratio as cow’s milk (82% casein to 18% whey.) The
difference is that they have hydrolyzed (chopped up) both of these proteins. This may be
helpful for constipation although it is too new a product (6/06) for users to have had much
experience with it.
Dairy fat (butterfat) can also be quite constipating. Butterfat is the fat in cream,
whole and 2% milk, butter and cheese. Besides the constipation issue, it is a saturated fat
and (like MCT oil) always a very poor source of the essential fatty acids or other omega-3
or omega-6 polyunsaturated fats. In spite of this, some diets, such as the ketogenic diet for
seizure control, may contain a very high amount of cream. That diet is (not surprisingly)
constipating for many children. Using other forms of fat in place of at least some of the
cream can help a lot, both for constipation relief and for good nutrition.
15
Some iron sources can contribute to constipation, and it is not uncommon to find that
the heavily iron-fortified infant cereal can contribute to the problem. High doses of
“inorganic” iron (that is, the “ferrous” or “ferric” forms found in plants or in pills) can be
constipating and since it is also far less well absorbed, it is actually not the best route to
improving iron deficiency in an individual. Iron in breastmilk is “organic.” It is not
constipating and it is very well absorbed.
The standard amount of inorganic iron in infant formula is not constipating. For
example, “Nestle Good Start Supreme” formula (a “chopped up” whey-based product) is
often very useful for helping constipated babies and it only comes with iron. Using “low
iron” infant formula to assist with constipation is not recommended because it is not the iron
that is causing the problem. However inadequate iron can cause lots of problems, so the
American Academy of Pediatrics recommends iron fortified formulas when formulas
are used in infant feeding. In addition, philosophically, even if removing the iron did help
with constipation (which it doesn’t,) I find it puzzling that some parents or physicians would
be willing to remove a high priority critical nutrient like iron from a child’s diet in order to
form the “perfect stool.”
Highly absorbable and non-constipating “organic” iron is the kind found in meat.
It is called “heme” iron (like in the word hemoglobin in red blood cells,) and there is also a
substance in meat called “Meat Protein Factor” that improves absorption of the inorganic
iron in the meal as well. Both iron and zinc are most generous and best absorbed from meat,
and as noted, the foods are actually “color coded.” Red meats have more of both than white
meats like chicken. But all meats have better amounts of available non-constipating iron
than the inorganic iron in supplements, formulas and plants. See my iron and zinc handout
for more information on this. A discussion of the problem of anemia will follow, as well.
Products to relieve constipation: Milk of Magnesia (magnesium hydroxide,)
Lactulose and MiraLax (polyethylene glycol) all work by attracting water to the bowel by
osmosis and so they can be useful for keeping stools from hardening. Both contribute no
calories. Prune juice and corn syrup add considerable calories, but they act the same way
(an osmotic effect), and the prune juice naturally has additional phytochemical substances
that encourage defecation. The prunes themselves are helpful . . . not just the juice.
Glycerol suppositories act locally at the rectum, but whether these should be used by a
person with EB should be decided with your health care provider. Other products such as
those containing senna can work by means of irritating the bowel to stimulate activity. For
this reason it is important to talk with your pharmacist or other health care provider about
the usefulness or safety of the many constipation treatment or prevention products available.
16
Some nutrients of special interest in EB:
As mentioned earlier, increased nutrient excretion or turnover, or decreased
absorption will alter nutrient requirements so that the "normal" guidelines of adequacy
or safety (such as the "RDA" or “RDI” level) or expected patterns of “normal” growth rates
may not apply. They may not apply for other reasons as well, such as altered body
composition or the effects of medications. Many guidelines only address intake goals and
growth expectations for "healthy" people.
In many cases, special levels of certain nutrients can greatly affect the risk of
complications and worsening of chronic conditions. One area of encouraging nutrition
research is in the area of helping to control inflammation in inflammatory diseases. Also,
looking promising is the use of antioxidants to help reduce the injury to tissues resulting
from the excessive inflammation and higher metabolic rates due to wound healing. The term
“antioxidant” includes vitamins E and C, and important substances made in the body that
use minerals like selenium (“glutathione peroxidase”) and zinc (“zinc-copper superoxide
dismutase.”) It also includes some “phytochemicals” (like all the brightly colored pigments
naturally occurring in fruits and vegetables) and some “conditionally essential” nutrients
like alpha lipoic acid, CoQ10 and carnitine. The same patterns are emerging for many
conditions that feature altered metabolism and/or inflammation, so it is reasonable to
look closely at them in EB as well.
Other “conditionally essential” nutrients that may actually be essential in EB include biotin
and choline … both of these are provided most generously in egg yolk, so don’t be afraid to
give cooked (or pasteurized) egg yolk. Interestingly, one of the things a person needs to
repair injuries to cells is cholesterol … so there is no reason to be gun-shy about giving
egg yolks.
Antioxidants
For many autoimmune diseases like diabetes, lupus, juvenile rheumatoid arthritis,
inflammatory bowel disease, down syndrome, and apparently many other conditions
including EB, the medical condition itself (or the therapy) results in increased
production of damaging “free radicals.” This leads to increased frequency and severity of
complications beyond those due to the condition or medication use alone. For this reason,
appropriate generous antioxidant supplementation is advisable. In addition to
vitamin/mineral antioxidants, there are many potent antioxidants available in brightly
colored fruits and vegetables. The food pigments themselves are often antioxidants.
Examples include orange colored “beta-carotene” in carrots and squash, red “lycopene” in
tomatoes and watermelon, green “lutein” in dark leafy greens, red/blue “anthocyanins” in
blueberries and beets, yellow xeazanthin in corn and kale, and white/yellow “flavones” in
onions and garlic. The simple rule of thumb about all these colorful vegetables and
fruits is “Eat as much of ’em as you can!”
17
This class of color-pigment substances is usually called “phytochemicals,” which simply
means “plant chemicals.” (But it sounds so very scientific!) Many vegetables and fruits have a
wide variety of phytochemicals that have benefits in addition to the generous antioxidant
content, so children’s diets (and the diets of adults) should be as generous in these foods as
possible. A great example: Lycopene, the red pigment in tomatoes, is 200 times as potent as a
protective antioxidant than vitamin E. There is much to be gained from including brightly
colored fruits and vegetables in the diets of everyone in the family. (More information on this
topic is available in my “Eye Health” handout.)
Adding these foods can sometimes be a problem for anyone. I have had some success
using pureed fruits and vegetables that are frozen in an ice-cube tray and then popped out and
stored as cubes in a freezer bag. These are then quick and easy to add to foods like soups,
spaghetti sauce, chili, meatloaf, etc. I have found that if the fruits and vegetables are pureed to
the point where no identifiable “vegetable carcass” is discernible, people are unaware that they
have been added.  For a tube-fed child, any combination of fruits and vegetables can be
pureed all together with formula or other nutritious liquids (e.g. prune juice) and frozen as
described. Blenderizing the “veggie cubes” with the formula to be fed will usually thin it down
enough, but it can also be strained if there is a concern about clogging the tube.
This sounds time-consuming, but some families find it can be done all at once for a month’s
supply. One can use canned, frozen or fresh (use low sodium vegetables if using the canned
type.) Some folks have a routine of freezing any leftover fruits and vegetables immediately after
a meal in a freezer bag and then blenderizing them all at once when a good amount has been
stored up. Also, many Grandmas or friends who keep asking how they can help are very happy
to take on this kind of project. It is something very concrete to do to really help. For everyone,
of course, clean and safe food-handling techniques are very important. (Please see my FoodBorne Illness handout for more on this topic.)
Another option is to add readily available fruit and/or vegetable juices (e.g. cranberry juice,
Carrot juice, prune juice, low sodium “V-8” type) as part of the liquid used to reconstitute infant
or other concentrated formula. Variety is very beneficial because the various phytochemicals are
not all in the same foods. There are also many new products to investigate now that the public is
becoming aware of the importance of these phytochemicals for health. Some are powders or
juice concentrates . . . but some are really pricey. The products themselves are usually just fine
to use, but some clearly give the buyer the impression in their advertising that they are much
more potent and all-encompassing than they really are. They do this by comparing their product
with foods that are poor sources of various nutrients.
Example: One product advertises itself as having “The vitamin C of 20 peaches!” It
sounds impressive, but they are counting on people not knowing that peaches are rich in vitamin
A, but they are not among the best sources of vitamin C. An orange has about 80 mg of vitamin
C, but a typical peach has only 6 mg.* Twenty peaches provides the vitamin C of just 1-1/2
oranges. Using this kind of logic, I could claim to be amazingly tall because I tower over nearly
all of my patients! Sounds impressive, too, until you note that I work in pediatrics and my
patients are babies and children. I am still only 5’4” no matter whom I compare myself to.
* Data from Pennington & Church: “Food Values of Portions Commonly Used.”
Anyway, you get the idea.
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Omega-3 / Omega-6 Oils
Along with antioxidant supplementation, manipulation of the inflammatory response by
altering the ratio of omega-3 to omega-6 fatty acids is also looking very promising in the
autoimmune and inflammatory diseases in particular. This ratio also appears to be very
important in other areas of health research as well, such as risk of heart disease, cancer,
HIV, depression, epilepsy, and degenerative eye diseases. In each case, the direction of
change that shows benefit is increasing the proportion of dietary fats that are rich in
oils of the omega-3 family in relation to the intake of fats from the omega-6 family.
Vegetable oils that are high in “omega-6” (such as corn oil) contribute to a strong
inflammatory response. Adjusting the intake of dietary fat to have a better proportion of oils
from the “omega-3” family can significantly reduce the strength of an inflammatory
response. In addition to the ratio, there is a minimum amount of omega-3 oil intake
suggested, and as discussed below, some suggestions for the forms of omega-3 oils to use.
This can be particularly important in conditions characterized by excessive
inflammation, like EB. Compared with corn oil, other vegetable oils like canola oil,
flaxseed oil, walnut oil and soy oil (only if non-hydrogenated) contribute to a much better
balance of omega-3 to omega-6 oils. Ground flax seeds, soybeans, walnuts and other nuts
and seeds have other nutritional befits that the oil alone will not have, but your health care
provider may want you to avoid the intact forms of these foods unless they are processed
enough to eliminate rough edges.
Olive oil and peanut oil are mostly “friendly” monounsaturated oils. They are not rich
in either omega-3 or omega-6 polyunsaturated oils, but if they replace the high omega-6
corn oil in the typical US diet, they can have a big beneficial effect on the ratio of the
remaining omega-6 to omega-3 oils. This contributes to decreasing the strength of
inflammatory substances that the body makes out of these two families of oil. It has the
added advantage of displacing some of the less beneficial fats in the diet, like the saturated
fats in coconut oil, palm oil and butterfat.
Fish oils contain a generous amount of the omega-3 oils, and they are in a form that
is especially easily utilized in the effort to control inflammation. It is becoming very clear
that many individuals benefit greatly from having the fish oil form in particular provided
because it contains “ready-to-use” EPA and DHA. This is a really big deal because these
two fats both have direct anti-inflammatory effects. DHA is also a critical fat of brain tissue
(yes, we are all truly “fat-heads,”) and shown to have benefits in infant development, and in
solving problems such as depression and alzheimers disease. More information is available
in my handout on lipids and oils. EPA is key to decreasing inflammation. EPA stands for
“Eicosa Pentaenoic Acid” -- but I like to think of it as standing for “Environmental
Protection Agency,” because it really helps to protect our internal environments! More
information is available in my handout on lipids and oils.
19
How Much EPA and DHA Omega 3 Oil?
There are no official guidelines for EB, but
the American Heart Association does have
recommendations fof levels of intake by
level of heart disease (CHD) risk, and it
might be a good guide for our use as well .
Going FISHing . . .
My best guess is that for many reasons, people with very severe EB would benefit from
an intake of EPA+DHA of 2-4 grams daily, and for those with milder forms at least a
gram daily. Note that some “omega 3” supplements contain DHA only. DHA does some
very important things, but for EB the anti-inflammatory effects of providing generous
ready-made EPA are potentially very important. For that reason, find a supplement with
both EPA and DHA.
AHA Recommendations for Omega-3 Fat Intake (2002)
People without
documented heart disease
People with
documented heart disease
People with high triglycerides
Eat a variety of (preferable oily) fish at least twice a week.
Include oils and foods rich in alpha-linolenic acid (flaxseed,
canola and soybean oils; flaxseeds; and walnuts.
Eat about a gram of EPA+DHA daily. This can come from oily fish or
from fish-oil supplements.*
Take 2-4 grams of EPA+DHA provided as fish oil supplements.*
* As always, you should discuss this with your physician, since in certain situations (like people on
certain medications) there may be reasons to do things differently. But a good thing to remember
about fish oil in general is that it is just a food, not a drug. If you eat more than you need for EPA
and DHA, it is just a source of calories. Consider, for example, what would happen if you ate 3 oz of
salmon (“a serving”) and then you ATE SOME MORE! Well, you would be in no danger because it
just adds some protein and calories. 
Another BIG DEAL for people with EB: Vitamin D
Vitamin D is a very special problem in EB. It has traditionally been a thought to
be of special concern for everyone in northern latitudes where making vitamin D in the skin
can be poor many months out of the year. However, it is now recognized as a world-wide
problem even in sunny places. It is also a concern among those who drink little milk (or
who use unfortified milk) and those who do not take typical vitamin supplements, although
the amount in multivitamins and milk is now recognized as far too low to correct this
problem in most cases. Vitamin D inadequacy is especially a serious problem
among those whose skin is often covered up or injured, and those who are
usually indoors. It is also very injurious.
20
Vitamin D deficiency greatly increases
risk of many serious health problems,
such as arthritis, MS, diabetes, muscle
weakness (sarcopenia) and falls, muscle
pain, congestive heart failure, asthma,
wheezing, lung problems, osteoporosis,
impaired immune function to fight
infection and many types of cancer.
And that’s just the “short list.”
Vitamin D functions as a key steroid
hormone in over 200 different tissues
and there is an unrecognized epidemic of
vitamin D deficiency in the US.
PEOPLE WITH EB NEED TO STAY IN THE SHADE,
SO THEY ARE AT GREAT RISK OF VITAMIN D DEFICIENCY
The best way to deal with this is to get a blood test called a 25-hydroxy vitamin
D level. (Not a “1,25-DiHydroxy vitamin D level” … that measures something else.)
The current level of “OK” is to have a blood level at 30 mg/dL or more. But many
researchers have now determined that a blood level of at least 40 to 50 is associated with
the best health outcomes. For that reason, for people with EB in particular, I strongly
recommend getting a blood test, and then getting it up to 40-50 mg/dL. This is just the
middle of the normal range and not at all excessive. The vitamin D level should be reevaluated to assure that this level is attained, and then measured again at least annually.
A key new finding is that for many people (especially those with certain health
problems,) the amount they need to take in to maintain that blood level goal is much
higher than we thought. For example, a treatment dose to get a low level up to speed is
often 50,000 iu vitamin D each week for 8 weeks followed by a recheck. Some people need
to do this whole thing twice. Then, the amount needed to keep their vitamin D level in the
best range is often at least 2000 iu/day. I have had some patients who clearly required a
daily intake of 5,000 iu/day to keep from dropping back down to the inadequate level.
The point is, there is no way to know if a particular individual is getting enough
vitamin D (even if it is quite generous in the diet or using supplements) without
actually doing the blood test. Vitamin D levels are now THE most commonly ordered
blood test in America because doctors keep finding severe deficiency in surprising situations
when they actually check. So they start to check everyone, and that is really where we need
to go with this. But in the meantime, PLEASE be sure the people you know and love with
EB have this checked and fixed if necessary with appropriately generous supplementation .
Regarding appropriate calcium intake:
21
It appears that assuring adequacy of vitamin D can allow a much lower intake of calcium to
be sufficient. [JAMA. 2005 Nov 9;294(18):2336-41] This is important in EB in part because some of the
calcium supplements and certain dairy foods can contribute to constipation. Being able to
take in less calcium but still meet one’s nutrient needs may be very helpful. And, of course,
adequacy of BOTH calcium and vitamin D are critical for dental and bone health. A recent
report again pointed out that bone problems are common in the EB population, so we need
to direct additional attention in that direction.
Fortunately, providing adequate vitamin D is not difficult. The generous amounts
described above come in many forms … liquid vitamin D drops, gummy vitamin D
products, and tiny gel caps with 2000 to 5000 iu in each one. The 50,000 iu/week
therapeutic dose is a prescription product but still very easy to take. Happily, vitamin D is
also extremely inexpensive. NOT assuring vitamin D adequacy is VERY expensive.
Bone mineralization in children with epidermolysis bullosa. Br J Dermatol. 2006 May;154(5):959-62.
Conclusions: Children with RDEB and JEB have low bone mass after adjusting for their smaller size, which may
put them at risk for fragility fractures. Low bone mass was best predicted by the level of mobility, raising the
hypothesis that improving activity or bone loading may be a potential preventive intervention in these children.
However, as low bone mass may be multifactorial in these children, more detailed investigation of potential
aetiological factors is required before interventions are planned.
------------------------------------------------.
“Conditionally Essential Nutrients”
In the study of nutrition, a substance is said to be “essential” if one has to take it in
from outside. Substances that are classified as “non-essential” are needed just as much in the
body, but we usually have the ability to make enough ourselves and therefore we do not have
to eat them. However, it is well known that some substances can become essential in certain
conditions, like when one needs to continually heal wounds. We can make enough of a
substance for running things under normal circumstances, but when there is higher than
average demand related to a severe health condition, the amount we can make for ourselves is
simply inadequate to do the job. These substances are therefore regarded as “Conditionally
Essential.” Many substances fall into this category, including the amino acids arginine and
glutamine, and the nucleotides used to make DNA for the center of every new cell.
Carnitine is a conditionally essential substance made of two amino acids needed
for the body to make useable energy out of body fat or dietary fat. Several cases of
serious and sometimes fatal heart damage (“cardiomyopathy”) from carnitine inadequacy
have been reported specifically in children with EB, underscoring the importance of
assuring adequacy, and not just assuming it.
Lethal cardiomyopathy in epidermolysis bullosa associated with amitriptyline. Arch Dis Child. 2005.
Aug;90(8):871-2. Dilated cardiomyopathy in dystrophic epidermolysis bullosa: a lethal complication of
epidermolysis bullosa. Eur J Anaesthesiol. 2002 Sep;19(9):689-90. Dilated cardiomyopathy in dystrophic
epidermolysis bullosa. Arch Dis Child. 2000 Jul;83(1):59-63. Review.
22
Alpha lipoic acid is an antioxidant but it also has an important role in making energy
out of food. [For all you science people out there, alpha lipoic acid is part of the TCA cycle in
two separate reactions.] It is also the subject of considerable interest in wound healing and
nerve function, especially in diabetes. Similarly, it may evolve that there may be applications
for CoQ-10 (ubiquinone), another antioxidant substance that is also active in an energy
production pathway. As yet I have seen nothing specific to EB in the scientific literature on
this topic, but they may turn out to be a substances of considerable interest here, too, as they
have been in other health conditions.
Research in using these substances to improve wound healing in general has been ongoing for many years, and in many cases very promising results have been obtained. Some
special tube-feeding products designed specifically to encourage wound-healing already
incorporate generous amounts of some of these conditionally essential nutrients in their
formulations. However, much is not yet known about the circumstances in which
supplementing these substances would have the greatest likelihood of helping, the amounts
that may be needed, the safety of using them in various situations, and the cost. This exciting
topic is too big to include in detail here, but you will be seeing more attention to these
conditionally essential substances in the news.
Dental Issues
Dental problems are common in
EB, and they can result in pain, tooth loss,
tooth decay, enamel issues, eating
problems, and malnutrition. Even brushing
with a soft brush or swab may contribute to
injury in the mouth. A dentist should be
consulted to determine if some protective
treatments might be useful (such as
coatings or fluoride treatments) and for
guidance on safe cleaning of the teeth and
gums. Inadequate vitamin D is a big
contributor to the poor bone and tooth
formation and osteoporosis often seen with
severe EB.
Without adequate vitamin D the calcium
in the diet is poorly absorbed. That means
that what might look like a good amount of
calcium intake on paper will actually not be
enough to meet the body’s requirements.
Saliva and some foods are more alkaline or “acid-neutralizing” in nature and they
may help decrease the bacterial “acid bath” to which teeth are exposed when any
carbohydrate is eaten (as discussed earlier in the section on carbohydrate additives.)
Cheese, with its high calcium and low carbohydrate content has been shown to decrease
cavities in rats fed sugar water when the feeding was followed by a bit of cheese.
Similarly, sugar-free gum or similar products that increase production of (alkaline) saliva
have been found to decrease cavities in a number of situations. Whether these
approaches are useful or safe (or constipating) for an individual with EB has not been
studied, but there may be something using similar principles that could be helpful.
23
And of course, the development of healthy teeth is also very dependent on our
ability to assure adequacy of the many nutrients involved in tooth production, including
not only calcium, phosphorus and fluoride but vitamin D, magnesium and vitamin C as
well. Vitamin D issues were addressed earlier. Vitamin C is extremely important for the
connective tissue that keeps teeth attached to the jaw and for wound healing, but it is best
to avoid regularly chewing or sucking on vitamin C supplements because vitamin C is
itself acidic (“ascorbic acid”) and it can contribute to tooth decay when in direct content
with teeth for a period of time. Swallowing it in pill form does not have the acidifying
effect on teeth, and as part of a meal eaten orally the effect is also less.
Anemia
Anemia (low hemoglobin in blood) is a common problem in EB and in any
condition with a major inflammatory component. Sometimes this kind of anemia is called
“the anemia of chronic disease” because it is not just a “nutritional” anemia. In this situation,
inadequate iron may not be the problem at all. As described earlier, high production of free
radicals from inflammation can damage red blood cells so they have a much shorter functional
life. So, even if iron is available, the body’s production of new red blood cells just can’t keep
up with the red blood cell destruction from free radical damage. The red blood cell breaking is
called “hemolysis.” As described earlier, providing generous antioxidant protection and
decreasing inflammation via altering the omega-6 to omega-3 fat ratio will help red blood cells
live longer to do their work.
Iron deficiency can certainly cause anemia. Iron absorption, iron sources and ironrelated constipation issues were discussed earlier. People do not normally “lose” much iron
unless there is blood loss, but a significant amount can be lost in the sloughing of skin from
wounds or intestinal injury. Therefore, actual requirements for iron will be higher in severe EB.
Blood tests for “ferritin” can normally help the physician determine if iron stores are truly
low, but unfortunately, chronic inflammation can cause the ferritin level to be artificially
elevated. The doctor can use other evaluations (like iron saturation) to determine whether or
not a person’s body is truly “iron hungry” or if it is just having trouble keeping up with red
blood cell production for other reasons. These different causes should result in different
therapeutic approaches. Just adding more and more supplemental iron in this situation
may not only be unhelpful but it can contribute to problems like constipation, and
increased free radical production.
In addition to iron deficiency and the anemia caused by red blood cells breaking,
anemia can develop because of inadequacy of several other nutrients, including folic acid,
vitamin B12, vitamin C, copper, zinc and protein. For that reason, just adding supplemental
iron to a person’s diet is unlikely to solve the problem. Assuring adequacy of all of these
nutrients is central to the prevention of anemia. As with the zinc issues described earlier, iron
from meats is much better absorbed than the iron used in supplements, and the presence of meat
also makes the supplement iron be better absorbed. (See my iron and zinc handout.)
Therapeutic diets that eliminate certain foods or entire food groups are in need of
careful attention to the nutritional adequacy provided by the foods remaining. This
24
includes special diets for allergies, celiac disease (“gluten-sensitive enteropathy”), autism, or the
ketogenic diet for seizure control and also those that have eliminated many foods because of
texture problems as may occur in EB. It is critical that the nutritional adequacy of the diet is not
compromised. Sometimes small adjustments in the foods offered can solve any problems caused
by food group limitation, but in the more restrictive diets it is virtually impossible to obtain
appropriate levels of vitamins and minerals without careful supplementation. As the nutrient
content of supplement products on the market can be quite variable, it is reasonable to
have the diet and supplement plan evaluated carefully by a credentialed nutrition
professional (e.g. an RD – a Registered Dietitian) using a computer analysis program.
Such programs are available in many hospitals and clinics and in many university
settings. They allow for the clinician and the family to be very sure that there are no accidental
nutrient inadequacies or excesses in the feeding regimen that could harm the child’s overall
health. Most computer programs in stores that sell health products and vitamin supplements,
however, are inadequate for the kind of careful micronutrient assessment that is needed in this
situation, and in addition, they are often primarily programmed to promote and increase sales
of particular nutrition products. Appropriate supplementation can be quite inexpensive and as
effective as the higher priced products. Often various products are promoted as much superior
simply because the individual promoting it is also selling it.
Drug/Nutrition Interactions
Like anyone else with a serious medical condition, people with EB may use a
number of medications with important nutritional implications. A short list of
medications with important nutrition interactions is shown below. For the details on the
nature of these particular drug interactions, please see my handout on “Nutrition for Special
Needs Kids.”
Seizure (epilepsy) medications like phenobarbital, valproate (Depekene®,) phenytoin
(Dilantin®,) and Tegretol®
Anti-inflammatory (Hydrocortisone)
Infection treatment (many antibiotics)
Broncho-dilator for asthma (Theophyllin)
Anidepressants: Serotonin Re-uptake Inhibitors, Zoloft®)
Stomach Acid Reducers:
(H2 blockers: Zantac®, Tagamet®, ranitidine and cimetidene)
(Proton Pump Inhibitors: Prilosec®, Nexium® Protonix® Pepcid® Prevacid®)
Diabetes medication (Glucophage®, Metformin)
ADHD control (Methylphenidate, Ritalin®)
Amytriptaline
Drugs can also affect intake by causing nausea, vomiting, constipation, taste
changes, lethargy, or altered appetite. In EB it is important to know that narcotic pain
medications often cause severe constipation and appetite loss. When these drugs are
necessary, plan ahead to minimize the development of constipation as described earlier.
25
Herbal remedies and the term “Dietary Supplement”
“Herbal remedies” are not nutrients but many people have been given the
impression that they are. They are often marketed as “dietary supplements” because by
law, the people selling them do not have to prove that their product is safe or effective. It is
a loophole in the Food and Drug Administration’s laws that many people are unaware of.
People assume that in America a company could not package and sell health products that
were inadequately tested (or not tested at all.) But although labeled as “dietary supplements”
in order to avoid having to test them, these products are often actually in the category of
drugs and medications, not food. This is because whether they are in a natural state or
packaged as a pill, the implied goal of using them is to achieve some pharmacologic
reaction like pain relief, treatment for diseases, cancer prevention, etc.
For people with complex medical conditions and especially those who must use
medications of various types, there can be significant and dangerous interactions when
unknown to the physician, herbal products (or any “over-the-counter” products) are
added to the mix. As one example, the herbal supplement “St. John’s wort” which has
been promoted as a “natural antidepressant with no side effects” actually interacts with a
wide variety of medications and causes the medications to stop working sooner than they
should. This effect of St. John’s wort has been found with medications for heart disease,
HIV/AIDS, birth control pills, and drugs that prevent the rejection of transplanted organs.
Very serious injury has resulted.
This is just one example of why it is very important to discuss the use of ANY
herbal product or “dietary supplement” with your primary care provider. “Natural”
products certainly CAN have side effects – after all, some of the most potent (and also
dangerous) drugs actually come from plants. For example, digitalis (an important heart
medicine) comes from the foxglove plant, and even heroin, cocaine and marijuana are
“herbal” products. Here is a recent comment on the problem from the scientific literature:
Herbal product-drug interactions mediated by induction. Br J Clin Pharmacol. 2006 Jun;61(6):677-81.
Despite their common use, it is not widely recognized that herbal medicines can alter the efficacy of
coadministered prescription drugs. Constituents in herbs interact with nuclear receptors to enhance
metabolizing enzyme and/or transporter activity leading to reduced drug concentrations. Although St John's
wort was the first and most frequently reported source of induction-style herb-drug interactions, this
knowledge has not yet changed its current availability. This type of interaction is likely to be relevant to other
herbal products. Caregivers need to be aware of the issues and options for therapeutic management.
When looking at the label of a product that is being marketed as a “dietary
supplement,” ask yourself whether this substance is a nutrient (that is . . . is it part of your
diet? . . . of your dinner? . . . like a vitamin would be) or are they are really promoting a
substance as having certain medicinal properties? Interestingly, the label may say (or
imply) that a substance has been used for generations for depression or sleeplessness or hair
loss or cancer prevention, or heart disease, etc. etc. It often very clearly implies that a
product is a proven useful and safe product for solving a particular health problem.
26
However, look closely at the small print and you will usually find a legal
disclaimer that says something like this: “The claims on the label have not been evaluated
by the FDA” and “The use of this product is not intended to prevent, diagnose, treat, cure,
or help any health problem.” [Hmmm . . . Then why did you name this product “CancerFree?”] Anyway, we all need to read labels closely, and be sure to show any product
you are taking (or considering taking) to your health care provider, as many of these
substances can interact with other medications, or they may present special problems for
folks with particular health problems.
Another technique used by “dietary supplement” marketers is to label a product as
“supporting” or “promoting” the health of some body system. This is a special type of legal
claim – a “function” claim” – because it really just states that the nutrient has a role in some
bodily function. An example would be saying “Vitamin B2 has a role in energy
metabolism.” (It does.) However, although that statement is true, it does not necessarily
follow that one’s intake of the substance is likely to be inadequate and in need of
supplementation, or that taking extra will “give you energy.” (It won’t.) They usually fail to
note that the amount needed by an individual is already adequate in most situations or that it
can easily be provided with a small diet adjustment or an inexpensive general supplement as
described earlier. It also implies (but will not outright state) that taking more of the
substance than usual would be beneficial for treating problems with the body function it
“supports.”
For example, I once saw a sign on a table in a store displaying a very expensive
protein powder that said: “Protein is Essential for LIFE!” Now, that is certainly true … with
no protein we would not survive. Same with oxygen and water!  However, in this case the
implication was clearly that one had better be on the safe side and buy protein supplements,
since the alternative appears to be death. However, there was no mention of the fact that
most Americans eat about three times the amount of protein they need just from food, and
there is no need at all for most of them to take extra supplemental protein.
So, while in this case eating the protein powder would generally not be harmful, I
am always irritated by the use of baseless fears or tricky wording to sell expensive and
questionably helpful health and nutrition products. When these techniques are used to trick
people already struggling with serious medical conditions, I find it unconscionable.
This kind of tricky marketing also has a tendency to make health care professionals
“throw the baby out with the bath water.” When there is so much that is “iffy” in the
marketing of nutrition (or non-nutrition products labeled as “dietary supplements”) the use
of truly helpful and scientifically sound nutrition information does not get the attention it
deserves.
So, now I’ll get down off my soapbox and summarize all this rambling:
Summary:
Providing optimal nutrition for the individual with EB can:
• promote healing of wounds.
27
•
•
•
•
•
•
•
•
optimize physical, intellectual and psychological development.
prevent serious complications like osteoporosis.
decrease problems like constipation, anemia and poor dental health.
optimize immune function to reduce the incidence/severity of illness
decrease pain due to inflammation or nutritional inadequacy
optimize the safety and effectiveness of any medications used
facilitate the care of the individual
improve the quality of life of the individual and caretakers
These goals will only be realized when health professionals are able to take a
close look at this important aspect of care. Please feel free to share this paper with
others, including your health care professionals.
I was very pleased to meet many people in the EB community at the conference in
Nashville, and I am grateful for the opportunity to learn more about living with this
condition. I wrote this paper as the result of that experience. However, please remember
that this entire paper is just my best guess (based on the most recent scientific literature)
about aspects of nutrition may be helpful for people with severe EB. It does not represent
the official recommendations of any facility or organization, and it is intended to be
used only with the involvement and approval of one’s primary health care provider.
(Sounds like one of those tricky legal disclaimers, doesn’t it? – Well, it sort of is one
because people’s health conditions are just too variable for the suggestions included here to
be optimal for all, and there is still a lot to be learned. So, please think of this paper as just
a little well-intentioned meddling from your Aunt Cathy.
Also remember that this paper was written in June of 2006 . . . check the
MeritCare Website [www.meritcare.com] for updates. Just type my name in the search
box and then pick “Cathy Breedon’s handouts.”
You can also find the other papers there that I referred to earlier as sources of more
specific nutrition details. You will also find more of my “Best Guess” information there
about nutrition for other health conditions that someone in your family may be dealing with,
such as diabetes, multiple sclerosis, celiac disease and hemochromatosis.
Cathy B.
Baby elephants courtesy of:
www.wildlife-pictures-online.com
www.africaguide.com
www.iucn.org
www.lowryparkzoo.com/baby_elephant/photos.html
28
MeritCare Health System
2012
Aunt Cathy’s Guide to: Nutrition and Eye Health
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical Nutrition Specialist
MeritCare Health Systems, Fargo, ND
and UND School of Medicine
Your mother said carrots are good the
eyes, and she was right. There are other
foods and nutrients that are important for
eye health as well. Here are a few in the
news:
CATARACT
One threat to vision is cataract, a clouding of the lens. In some studies, a generous intake
of antioxidant vitamins like vitamins E and C can decrease the likelihood of cataract
formation. Other studies have not shown a protective effect in terms of cataract prevention,
but they did show benefits in other aspects of general health, and in eye health in particular.
Certain other vitamins, such as vitamins B-2 (riboflavin) and B-6 (pyridoxine) can decrease
the likelihood of cataract formation. Adequate selenium (a mineral) also has a role in
protecting against cataract. Smoking increases risk of cataract. Recently, research has
suggested that supplementation of substances called “carnitine” and “alpha-lipoic acid”
(which one’s body normally makes) may be a factor in cataract production. It is also looking
interesting in diabetes, macular degeneration and other eye health problems. They are also
found in certain foods, but the amount being used in the research trials is more than one would
normally take in from food.
Because many of these issue are so new, I have attached a few references for health
professionals from the scientific literature at the end of this paper.
DIABETES
Diabetes is the major cause of blindness in American adults, and good control of
blood sugar significantly reduces the risk of this complication. People with diabetes have a
higher need for antioxidant protection, so antioxidant nutrients are extremely important to
people with diabetes. There is evidence that a generous intake of vitamins E and C and
assuring adequacy of the minerals selenium and zinc may be especially helpful in helping
people with diabetes experience fewer or milder health complications from the disease,
including its effects on vision. Vitamin B-6 may be especially important in people with
diabetes, along with alpha-lipoic acid, a B-vitamin-like substance that is a very potent
antioxidant. Many other antioxidant substances in plants are being explored, such as
“pycnogenol,” a pine bark extract.
MACULAR DEGENERATION
The other major cause of blindness in adults in this country is macular degener-ation.
A part of the retina, in the back of the eye where incoming light and visual images are
received, gradually becomes less able to do its job. This appears as a central "blind spot" in
one's field of vision. A number of antioxidants may protect against the develop-ment of
macular degeneration, but the emphasis here is on prevention, since nutrients do not appear to
correct the damage once it has occurred. However, good nutrition can decrease the
progression of the condition. The nutrition of children and younger adults will help determine
whether they develop this condition in later life. Recent research suggests that combinations
of several of the substances described earlier may be much more effective than any one
supplement alone. For example, this year a study reported that a blend of acetyl-carnitine,
omega-3 fats, and the antioxidants CoQ10 and vitamin E may improve retinal functions in
early macular degeneration.
“Phytochemicals” are naturally occurring chemical compounds in plants that have
important health effects. Many are natural antioxidants. A substance called lutein in dark
leafy green vegetables seems to be especially protective against macular degeneration.
Lutein is a cousin of beta-carotene (the coloring agent in carrots that can be converted to
vitamin A.) Lutein apparently filters out damaging light rays that otherwise injure the retina.
It also acts as an antioxidant. Interestingly, lutein is not in carrots. So Mom was right, but so
was Shirley Temple when she sang "You gotta eat your spinach, baby." The richest source
of lutein is kale, which has 10 times more lutein than spinach, the second best source.
Spinach has about 10 times more lutein than romaine lettuce (the next best).
Eating Kale: Traditionally, kale is made into soup and served in salads, but for some people
it tastes bitter. People often send me recipes for their mother’s delicious kale soup, but
unfortunately the recipes often start out with “Fry a pound of bacon, retaining the bacon fat.
Add kale.”) Hmmm . . . maybe not a good approach to a healthy diet. Instead, try
experimenting with adding kale to less traditional foods – I dry it in a food dehydrator and
crumble it into a jar in the refrigerator. Then I add a Tablespoon here and there in highly
flavored foods like spaghetti sauce, chili, meatloaf, etc.
I even sneak a little finely ground kale into brownie mix! We want to teach children to eat
greens (and model “good kale-eating behavior”) but while we are waiting for them to decide
that kale is yummy, it is reasonable to try to slide some by them. These are not mutually
exclusive goals!
(By the way, kale is also a really rich source of vitamin K … another nutrient that is often
inadequatre in the diets of Americans. Remember: “K is for Kale!”)
Another potentially helpful phytochemical antioxidant that has a role in filtering blue
light waves in the retina is called zeaxanthin (zee-a-ZAN-thin.) Like lutein, this yellowish
pigment is found in the dark leafy greens, and it is also in corn.
Other rich food sources of powerful antioxidant phytochemicals are tomatoes and
watermelon (lycopene), tea (polyphenols), strawberries, blueberries, red grapes (anthocyanins), and many others. The lycopene in tomatoes is especially helpful and it has also
been shown to decrease risk of prostate cancer and heart disease. Cooking these foods does
NOT destroy these beneficial substances. In fact, MORE lycopene is obtained from
tomatoes when they are cooked because it becomes easier to absorb.
Enjoy a great variety of fruits and vegetables and you will be getting lots of terrific
substances that we may not have even learned about yet! A good rule is to try to eat a variety
of lots of highly colored vegetables and fruits, because many important protective
phytochemicals are actually the naturally occurring pigments that color the food. Even
“white” foods like garlic, onions and mushrooms have useful phytochemicals. After all, in the
fruit and vegie world, white counts as a color too!
Adequacy of selenium and zinc is important in macular degeneration (and in a number
of health conditions). Both minerals are important as components of antioxidants, and both
have other roles as well. Selenium intake can be low in the diets of some people because
certain areas of the country have selenium-poor soil. Other places have a very high selenium
level in the soil. Meats and oysters are the best-absorbed sources of zinc in the diet, and some
people obtain too little zinc from food. Both of these nutrients can cause problems in high
doses (well above the usual recommended level). Do not take "megadoses" of these
nutrients — more is not better. Specific recommendations will be summarized at the
end of this article.
Vitamin A and Beta-Carotene
Vitamin A and beta-carotene are critical for eye health. Beta-carotene is a
phytochemical, too. It is a pigment in dark orange and green colored fruits and vegetables
that your body can convert to vitamin A. Serious inadequacy of vitamin A is a major cause of
blindness in children around the world, causing a dry-eye condition called “xeropthalmia”.
Without normal eye moisture to bathe the surface of the eye, it can thicken, and eyes can
become infected with the cornea melting away, resulting in blindness.
Inadequacy is usually not that severe in the USA, but at low intakes people here
experience "night blindness," a condition in which the ability to recover vision after seeing a
flash of light is too slow. The group at highest risk of vitamin A deficiency night blindness
here are people who abuse alcohol. This is partly because a poor diet may be involved, but
also because of some metabolic competition between vitamin A and alcohol that disturbs the
usual processing of vitamin A..
Vitamin A is critical for the entire immune system and the ability to fight infections, but
too much can be toxic. The plant form (beta-carotene) is NOT toxic; if you eat a lot of
carotene-rich plants your skin may have an orange tint, but no harm is done. In fact, where I
live up north, this can even pass as a tan! The form of vitamin A that can become toxic in
high doses is called “retinol” and it appears on the labels of foods and vitamin pills as the
word “retinylpalmitate” or “retinylacetate.” Taking too much in this form may cause some
problems with bone health. Many products are now combining the retinyl forms with the
safer beta-carotene form of vitamin A, so check the label. The combination is a good idea.
Other than taking too many vitamin pills, there is little danger of overdose. The only way
to take in too much vitamin A from food would be to eat a great deal of liver. One food is so
high in vitamin A that it is actually poisonous . . . so don’t buy polar bear liver even if it IS on
sale! 
Choosing a multivitamin/mineral supplement:
An inexpensive generic product may cost only a few pennies a day. Highly priced
supplements sold in specialty stores or by neighbors are often very good products. But in spite
of the claims of people trying to sell things to you, they are not significantly better than the
standard (cheaper) products available everywhere. In addition, they are often extremely
expensive and overpriced.
Men and postmenopausal women may want to look for a product with 10 mg iron or
less (the "silver" type) because they do not need as much iron as young women need.
Recommendations for younger women are usually between 15 and 18 mg/day. Note,
however, that some men and older women CAN become iron deficient if their diet is poor or
if certain other health problems are present. That’s why it is generally a better idea to take a
multivitamin that has 8-10 mg iron (the men’s recommended intake level) instead of zero.
Some vitamin products now contain very small amounts of one or more of the plant
antioxidants discussed earlier, like lutein or lycopene. Unfortunately, the amount is usually
very small, and while not at all harmful, in no way does including them in the vitamin pill
replace the need to eat brightly colored fruits and vegetables.
Some multivitamins are described as formulated especially for eye health. They may
contain more generous zinc than the usual amount of 15 mg, and they will usually have more
antioxidants than usual (like extra vitamins C and E, and maybe some of the phytochemical
pigments like lutein and zeaxanthin.) Whether you need this kind of product is a question for
your doctor, and also depends on what else you are eating or taking. Some with very generous
zinc content will make it wise to avoid taking a lot of other supplemental zinc. One has to
check the labels because there are many products available.
RECOMMENDATIONS
•
Adequacy of all nutrients supports eye health, so the best course of action is that same
old advice: eat a balanced diet with a wide variety of foods. All the food groups are
important, because they all contain critical nutrients for overall health. Inadequacy of
ANY nutrient can result in serious health problems. Often some amount or type of nutrient
supplementation is needed for situations involving dsease treatment. Assuring adequacy
(and not assuming adequacy) of all nutrients is a key factor in staying well.
•
Eat lots of fruits and vegetables, and especially look for those leafy greens and bright
colors. This practice appears to have MANY health benefits.
•
Take a general multivitamin with minerals as described above (choose one with zinc,
selenium and chromium in the amounts near the RDA, RDI or “safe and adequate range”
on the product label). This practice alone is associated with better eye health and it has
many other health benefits as well. Treat the vitamin pill as if it were a prescribed
medicine . . . a product that you don’t “forget” to take, or one that you skip because “it’s
just one more pill” and you already take plenty of pills. Do not take more than one
standard multivitamin with minerals daily unless told to do so by your physician.
•
The amount of selenium in a multivitamin product varies from none to as high as 200
mcg. The standard amount recommended “for healthy people” is about 60–70 mcg day.
However, for people with diabetes, cancer and diseases of the eye, a level of 150 to 200
mcg may be helpful. Selenium is also available separately in small 50 mcg pills.
Selenium can be toxic when long-term intake levels are around 800 mcg/day, so most
experts recommend staying well below 600 mcg. Since some selenium is in food, a 150200 mcg daily intake in supplement form may be a good goal for people with eye diseases
and for most people it is well within the safe range. The selenium in foods varies with
where it was grown. As a general rule, if you live in a very high selenium region, limit
supplemental selenium intake to the 60-70 mcg “normal level” unless advised
differently by your physician.
[How do you know if you live in a high or low selenium region? Ask your County
Extension Agent if selenium is added to the animal feed locally. If it is low, it will be
added because the farm animals (like people)are always healthier if their nutrition needs
are met; if it is a high selenium region they will not be adding it to the feed.]
•
An additional 250 - 500 mg of vitamin C and 200-400 iu vitamin E may be helpful.
These are generous-but-safe levels for which there is evidence of a number of health
benefits. Do not take more than this without first checking with your physician. For
comparison, the usual amount assumed to meet the needs of healthy folks is 90 mg
vitamin C and 30 iu vitamin E daily. However these usually recommended levels are not
designed to meet the needs of people with eye health issues.
•
Zinc is most abundant and well absorbed into the body from meats. It is much more
readily absorbed from meats than from supplements. Standard multivitamins vary from
providing 0 to 20 mg zinc (check the label). The usual recommended intake amount for
healthy adults is about 12 mg daily. In diabetes and macular degeneration, research
suggests that a more generous intake may be helpful. Recent studies of macular
degeneration showed some promise in slowing its progression with a product that
contained 50mg zinc day. This intake level is often used to treat certain conditions in
which extra zinc is needed, but for some people it may be too high.
•
If 20-50mg zinc is taken in supplement form, be sure that supplemental copper is
also provided because high supplemental zinc intakes can interfere with absorption of
copper, increasing requirements. The resultant copper inadequacy can contribute to
anemia, heart disease and poor wound healing. Zinc supplementation at 50 mg daily has
also been found to cause some problems in the cholesterol levels of some people in a
study. This is just one more reminder that it can be dangerous to “self-medicate”
with anything – medications, nutrients, or herbal products – in excessive amounts.
•
Be sure to tell your physician if you are taking nutriient supplements, and to get
her/his approval before using the higher dosages. Also, report all over-the-counter
and prescription medications or herbal products that you take. Some can interfere
with other prescription medications or cause other harm. The doctor will need to see the
whole picture to provide the best treatment for you.
•
For people battling diabetes or macular degeneration I always recommend
supplementation of some additional specific antioxidants that are usually not in standard
multivitamin products. These are:
Alpha-lipoic acid (at least 600 mg/day)
Acetyl Carnitine (usually 50-100 mg/kg body weight daily, with an upper end for most
eople at 3000 mg/day. However, really large people have been shown to need more to
achieve the same benefits,
CoQ10 is showing benefit in many neurologic, cardiovascular and other health problems,
and there is evidence of benefit in eye health. There is no standard recommendation for
CoQ10 for healthy people. However, many research studies have shown benefits with
experimental intake levels of 60 to 150 mg/day. .that have other benefits as well
Vit d
• And finally, for general eye health. . . Don't play with sharp sticks! As Mom ALSO
said, "You could put somebody's eye out with that!"
------------------------------------------------------------------------------------------------------------
Some references from the scientific literature
(primarily of interest to health professionals):
2006
The evidence for efficacy of omega-3 fatty acids in preventing or slowing the progression of
retinitis pigmentosa: a systematic review. Can J Ophthalmol. 2006;41(4):481-90
Effect of niacin on retinal vascular diameter in patients with age-related macular degeneration.
Curr Eye Res. 2006 Jul-Aug;31(7):629-34.
Dietary fatty acids and the 5-year incidence of age-related maculopathy. Arch Ophthalmol.
2006 Jul;124(7):981-6.
Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with agerelated macular degeneration: the US Twin Study of Age-Related Macular Degeneration.
Arch Ophthalmol. 2006 Jul;124(7):995-1001.
Dietary antioxidants influence macular degeneration risk. Mayo Clin Health Lett. 2006
May;24(5):4.
Antioxidant vitamin and mineral supplements for slowing the progression of age-related
macular degeneration. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000254.
The burden of age-related macular degeneration.Pharmacoeconomics. 2006;24(4):319-34.
Effect of short-term, high-dose retinol on dark adaptation in aging and early age-related
maculopathy. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1310-8.
C-reactive protein and homocysteine are associated with dietary and behavioral risk factors
for age-related macular degeneration. Nutrition. 2006 Apr;22(4):441-3.
2005
Improvement of visual functions and fundus alterations in early age-related macular
degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, &
coenzyme Q10. Ophthalmologica.2005;219(3);154-66.
Effects of antioxidant treatment on normal and diabetic rat retinal enzyme activities. J
Ocul Pharmacol Ther. 2005;21(1):28-35.
The protective effect of alpha-lipoic acid against oxidative damage in rabbit conjunctiva and
cornea exposed to ultraviolet radiation. Ophthalmologica. 2005;219(1):49-53.
Effect of advanced glycation end products on accelerated apoptosis of retinal capillary cells
under in vitro conditions. Life Sci. 2005;76(9):1051-60.
Neuroprotectin D1 (NPD1): a DHA-derived mediator that protects brain and retina against
cell injury-induced oxidative stress. Brain Pathol. 2005;15(2):159-66.
The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina.
Prog Retin Eye Res. 2005;24(1):87-138.
Hypothesis on the role of nutritional factors in ocular hypertension and glaucoma. J Fr
Ophtalmol.2005;28(3):312-6.
2004
Carnitine level in human lens and density of cataract Klin Oczna. 2004;106(3 Suppl):409-10.
Effect of long-term administration of alpha-lipoic acid on retinal capillary cell death and the
development of retinopathy in diabetic rats. Diabetes. 2004;53(12):3233-8.
Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving
vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004;122(9):1306-14.
Nutritional manipulation of primate retinas, II: effects of age, n-3 fatty acids, lutein, and
zeaxanthin on retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2004;45(9): 324456.
Nutrition and age-related macular degeneration. J Fr Ophtalmol. 2004;27(9 Pt 2):3S38-56
2003
Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic
approach and a pilot study. Ophthalmologica. 2003;217(5):351-7.
Protection of the retina from ischemia-reperfusion injury by L-carnitine in guinea pigs. Eur J
Ophthalmol. 2003;13(1):80-5.
Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes:
role of oxidants and protein kinase-C activation. Diabetes. 2003;52:829-37.
Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Exp Eye Res. 2003
Feb;76(2):241-8.
2002 and earlier
The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental
diabetes. Diabetes. 2002;51(9):2826-32
L-carnitine in experimental retinal ischemia-reperfusion injury. Ophthalmologica.
2002;216(2):144-50.
Antioxidants attenuate early up regulation of retinal vascular endothelial growth factor in
streptozotocin-diabetic rats. Diabetologia. 2001;44(9):1102-10.
Carnitine protects the molecular chaperone activity of lens alpha-crystallin and decreases the
post-translational protein modifications induced by oxidative stress. FASEB J.
2001;15(9):1604-6.
Early changes in lipid peroxidation and antioxidative defense in diabetic rat retina: effect of
DL-alpha-lipoic acid. Eur J Pharmacol. 2000;398(1):139-46.
Modelling cortical cataractogenesis 22: is in vitro reduction of damage in model diabetic rat
cataract by taurine due to its antioxidant activity? Exp Eye Res.1999;69:291-300.
In experimental diabetes the decrease in the eye of lens carnitine levels is an early important
and selective event. Exp Eye Res. 1997;64(2):195-201.
References: Coenzyme Q10 (CoQ10) & Eye Health Search
Cathy Breedon 9/12
Coenzyme Q10 protects retinal cells from apoptosis induced by radiation in vitro and
in vivo. Lulli M, Witort E, Papucci L. J Radiat Res. 2012 Sep 1;53(5):695 703.
Coenzyme Q10 reduces ethanol-induced apoptosis in corneal fibroblasts.
Chen CC, Liou SW, Chen CC. PLoS One. 2011 Apr 27;6(4):e19111.
Protective effect of Coenzyme Q(10) against oxidative damage in human lens epithelial cells
by novel ocular drug carriers. Wang S, Zhang J, Jiang T. Int J
Pharm. 2011 Jan 17;403(1-2):219-29.
Nonsense mutations in CABC1/ADCK3 cause progressive cerebellar ataxia and atrophy.
Gerards M, van den Bosch B, Calis C, Mitochondrion. 2010 Aug;10(5):510-5.
Coenzyme Q10 prevents human lens epithelial cells from light-induced apoptotic cell
death by reducing oxidative stress and stabilizing BAX / Bcl-2 ratio. Kernt M,
Hirneiss C, Neubauer AS, Acta Ophthalmol. 2010 May;88(3):e78-86.
Neuroprotection for optic nerve disorders.
Bessero AC, Clarke PG. Curr Opin Neurol. 2010 Feb;23(1):10-5
Coenzyme Q10 vitreous levels after administration of coenzyme Q10 eyedrops in
patients undergoing vitrectomy. Fato R, Bergamini C, Leoni S. Acta Ophthalmol.
2010 Jun;88(4):e150-1.
Topical use of coenzyme Q10-loaded liposomes coated with trimethyl chitosan:
tolerance, precornea retention and anti-cataract effect. Zhang J, Wang S. Int J
Pharm. 2009 May 8;372(1-2):66-75.
Coenzyme Q10 in the human retina.
Qu J, Kaufman Y, Washington I.Invest Ophthalmol Vis Sci. 2009
Apr;50(4):1814-8.
Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for
retinal protection. Russo R, Cavaliere F, Rombolà L.Prog Brain Res.
2008;173:575-82.
Assessment of neuroprotection in the retina with DARC.
Guo L, Cordeiro MF. Prog Brain Res. 2008;173:437-50.
Coenzyme Q10 protects retinal cells against oxidative stress in vitro and in vivo.
Nakajima Y, Inokuchi Y, Nishi M. Brain Res. 2008 Aug 21;1226:226-33.
Metabolic therapy for early treatment of age-related macular degeneration
Fehér J, Kovács B, Kovács I. Orv Hetil. 2007 Dec 2;148(48):2259-68.
Retinal damage caused by high intraocular pressure-induced transient ischemia is
prevented by coenzyme Q10 in rat. Nucci C, Tartaglione R, Cerulli A. Int Rev
Neurobiol. 2007;82:397-406.
CoQ10 supplementation elevates the epidermal CoQ10 level in adult hairless mice.
Ashida Y, Yamanishi H, Terada T. Biofactors. 2005;25(1-4):175-8.
Improvement of visual functions and fundus alterations in early age-related macular
degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, &
coenzyme Q10. Feher J, Kovacs B, Kovacs I. Ophthalmologica. 2005 MayJun;219(3):154-66.
Leber's hereditary opric neuropathy: a case report.
Chang CW, Chang CH, Peng ML. Kaohsiung J Med Sci.2003 Oct;19(10):516-21.
Mitotropic compounds for the treatment of age-related macular degeneration. The
metabolic approach and a pilot study. Feher J, Papale A, Mannino G.
Ophthalmologica. 2003 Sep-Oct;217(5):351-7.
The mechanisms of apoptosis in biology and medicine: a new focus for ophthalmology.
Tempestini A, Schiavone N, Papucci L. Eur J Ophthalmol. 2003 Apr;13 Suppl
3:S11-8.
Concomitant effect of topical ubiquinone Q10 and vitamin E to prevent keratocyte
apoptosis after excimer laser photoablation in rabbits. Brancato R, FioreT,
Papucci L. J Refract Surg. 2002 Mar-Apr;18(2):135-9.
Prevention of corneal keratocyte apoptosis after argon fluoride excimer laser irradiation
with the free radical scavenger ubiquinone Q10.Brancato R, Schiavone N, Siano
S. Eur J Ophthalmol.2000 Jan-Mar;10(1):32-8.
Pediatric ophthalmology.
Carruthers J. Curr Opin Ophthalmol. 1996 Oct;7(5):3-7.
Reversible ophthalmoplegia in CPEO.
Dunlop IS, Dunlop P. Aust N Z J Ophthalmol. 1995 Aug;23(3):231-4.
MeritCare Medical Center
Aunt Cathy's Guide to Nutrition
for Health Care Professionals:
Thinking about
Prenatal Nutrition and
Fetal Alcohol Syndrome
(FAS)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Prenatal/Pediatric Nutrition Specialist
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
and Clinical Associate Professor of Pediatrics
UND School of Medicine, Fargo, ND
I. Introduction:
Why Do Some Babies Have Fetal Alcohol Syndrome (FAS)
and Others Do Not?
In 1995 a hypothesis was suggested to explain why only relatively few women who
drink alcohol during pregnancy give birth to children with FAS. Epidemiological, clinical
case, and basic biomedical research was evaluated, and the authors concluded that specific
sociobehavioral risk factors such as Low SES (Socio-Economic Status) are permissive of
FAS in that they provide a context for increased vulnerability.
[Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences. Neurotoxicol
Teratol. 1995 Jul-Aug;17(4):445-62.]
Poor nutritional status of the mother is one of many environmental risk factors,
and it deserves some attention because nutrition is one factor that we may be able to alter
to improve the outcome of pregnancy. Poverty and poor nutritional status are clearly related,
so it can be difficult to tease out any unique contribution of nutrition. However subsequent
FAS research has demonstrated that there are nutrition influences on FAS in humans
unrelated to poverty, and animal research has demonstrated the ability of certain
nutrition deficits to exacerbate the effects of perinatal alcohol.
As one example, decreased maternal antioxidant status in conjunction with alcohol
provokes FAS in vulnerable fetuses. Research in this area involves examinations of the relative
availability of vitamins A and C, beta-carotene (and other antioxidant phytochemicals), zinc
and selenium.
Other nutritional factors are also being found to contribute to the degree of
damage induced by maternal alcohol use. These include the relative availability of a
number of vitamins and minerals whose functional role in metabolism is affected by the
1
presence of alcohol. Significant alcohol intake alters the amount of certain nutrients required
to metabolize alcohol as an energy substrate (fuel source). The B vitamins have been the
focus of much interest in this area, along with mineral co-factors like magnesium and
chromium.
Excessive alcohol consumption also alters the requirement for nutrients that have a
role in detoxifying potentially harmful substances. In the latter scenario, alcohol
dehydrogenase enzyme and the Cytochome p40 system are examples of this “garbage
disposal” function that has much more work to do when alcohol intake is excessive. Both
depend significantly on the adequacy of certain nutrients such as iron and zinc, and the
requirement for these nutrients may increase as well.
It is useful to remember that the usual recommended intakes of nutrients (like the
RDAs, DRIs, AIs, etc.) are based on the best guess about the needs of the “healthy”
population. Excessive alcohol intake can alter people’s actual nutrient requirements
substantially so the usual recommendations may no longer be optimal or even adequate. This
paper will focus on research into this issue.
Additionally, while it is clearly the case that avoiding alcohol abuse during pregnancy
(or at any time of life) is the goal, we are a long way from reaching it. While efforts continue
to be made in that direction, it seems to me that right now we should still do all we can to
make maternal alcohol consumption hurt the babies less.
II. Historical Perspective on Nutrition Aspects of FAS:
Although the term FAS was not coined until the early1970s, the damage associated
with alcohol use in pregnancy has been noted at least as long ago as early Bible times.
Dietary interventions have been seen as potential factors in the treatment of children of
alcoholics for at least 100 years.
[Fetal alcohol syndrome: historical perspectives. Neurosci Biobehav Rev. 2007;31(2):168-71.]
Over 100 years ago (in 1890) a report in the Journal of the American
Medical Association made the following dietary regimen recommendations:
"No fact is more firmly established than that alcoholic ancestors will transmit
to their children a defective brain and nerve power. The form and shape of
this defect and its manifestations will vary widely.
The general principles which should govern in the treatment may be grouped
as follows:
2
1) “No form of alcohols are safe, and narcotics of all kinds should be used with great care.”
2) “The diet should not include meats, because of their stimulating character; while meats
contain much food force, they act as stimulants to a brain already over-stimulated and
exhausted, and increase the peril of nervous disease.”
3) “The pathological tendency of all these cases is to become alcohol-takers and meateaters, hence the diet should always be non-stimulating and farinaceous [grain-based],
and should be carried out with military regularity."
[100 years ago: alcoholic heredity in diseases of children. JAMA Oct 1990;264:1888.]
This diet is (of course) no longer advised, although
FAS does effect growth and nutritional needs.
III. ALCOHOL and NUTRITIONAL STATUS
Alcohol has its most profound negative effect on nutritional status once alcohol
intake exceeds 30% of daily calories on a regular basis. At this level, intakes of protein,
fat, vitamin A, vitamin C, thiamine, calcium, iron, zinc and fiber usually fall below 75% of the
(non-pregnancy) RDA.
Malabsorption, alcohol-nutrient and nutrient-nutrient interactions aggravate the
nutritional profile. Additionally, the “RDA” (or RDI or DRI or AI or similar recommended
intake levels) no longer directly applies when the population is not a member of the
“healthy” population. Deficiencies in many B-complex vitamins are frequently seen among
alcoholics. Thiamine and folic acid deficiency are the most common (or at least the most
commonly looked-for or recognized), leading to cardiac and neurologic complications.
[Medical and Nutritional Complications of Alcoholism: Mechanisms and Management, 1992]
Many studies have examined the role of a number of nutrients or diet
features relative to:
1)
2)
3)
alcohol use in general,
the effects of alcohol on the fetus, and
the health of children with FAS.
This paper will focus on the possibility of minimizing fetal damage
from alcohol exposure with an emphasis on
prenatal vitamin and mineral nutrition factors.
3
Evaluating the effects of alcohol on fetal development in humans is extremely difficult.
Many types of studies are simply impossible for ethical reasons. Much of the research
therefore involves laboratory animals and our ability to generalize study results to humans is
always an issue.
However, studies in laboratory animals are demonstrating several areas of specific
interactions between nutrients and alcohol exposure that modify the developmental injury
associated with the alcohol exposure. There are very likely similar relationships in humans, as
has been well documented for certain nutrients such as the effect of alcoholism on vitamin B-1
(thiamin) and folic acid status, requirements and utilization.
Specific Nutrients of Interest in FAS:
Thiamin (Vitamin B-1)
A number of mechanisms may be involved in the pathogenesis of thiamin
deficiency in the alcoholic:
1. inadequate dietary intake;
2. impaired intestinal transport; and especially
3. decreased conversion of the dietary or supplement form to the
active coenzyme form (i.e. TPP).
In rats, both functional and structural studies showed that neurotoxic effects of
developmental alcohol exposure were not reversed by thiamin administration. However,
adverse effects of undernutrition following developmental alcohol exposure were suppressed
by thiamin administration. In a more recent study (2009) the results indexed thiamin
deficiency related to alcohol or to dietary inadequacy as a potent risk factor for
stillbirths.
[Alcohol and B1 vitamin deficiency-related stillbirths. J Matern Fetal Neonatal Med. 2009;22(5): 452-7. Delayed
language development due to infantile thiamine deficiency. Develop Med & Child Neurol. 2009;51(8):629-634.
Thiamin administration during chronic alcohol intake in pregnant and lactating rats: effects on the offspring
neurobehavioural development. Alcohol Alcohol. 1996;31(1):27-40.]
The recommended thiamin (vitamin B-1) intake for non-pregnant chronic
alcoholics is 15 mg/day (DRI = 1.4). That is, the person who abuses alcohol benefited from
taking in ten times the usual amount of thiamin. This is a good illustration of a situation in
which the usual recommended intake level is not adequate in certain “non-healthy”
populations. There is currently no specific recommendation for pregnant women who are
alcoholics, but it is likely to be more because of increased need.
[Individual susceptibility to Wernicke-Korsakoff syndrome and alcoholism-induced cognitive deficit: impaired thiamin
utilization found in alcoholics and alcohol abusers. Psychiatr Genet. 2002 Dec;12(4):217-24. ]
4
But how safe would it be to provide over ten times the usual amount of
thiamin in pregnancy?
The Food and Nutrition Board did not set a tolerable upper level (UL) of intake for
thiamin because there are no well-established toxic effects from the consumption of excess
thiamin in food or through long-term oral supplementation (up to 200 mg/day).
[http://lpi.oregonstate.edu/infocenter/vitamins/thiamin/]
A recent study investigated the tolerable upper intake levels of vitamin B-1 and
vitamin B-2 in weaning rats. The results showed that feeding a diet containing up to 1.0%
thiamin-HCl or 1.0% riboflavin (vitamin B-2) did not induce apparent adverse effects, and the
“no-observed-adverse-effect-levels” (NOAELs) for thiamin and riboflavin in rats might be
1.0% in diet, corresponding to 900 mg/kg body weight/day.
[Effects of excess vitamin B1 or vitamin B2 on growth and urinary excretion of watersoluble vitamins in weaning rats Shokuhin Eiseigaku Zasshi. 2009;50(2):70-4.]
While this was not a human study or a pregnancy study, it is useful as an indicator of
how unlikely it would be that providing simply generous thiamin (like the 15 mg described for
non-pregnant alcoholics above) in alcoholic pregnancy would be harmful.
Consider that:
1. The current prenatal recommendation (DRI) is 1.4 mg/day of thiamin, but it is
extremely unlikely to be toxic at levels far above this, (e.g. there is no recognized
upper limit of safety, as described earlier.
[Dietary Reference Intakes: Recommended Intakes for Individuals (PDF|87 KB)
National Academy of Sciences. Institute of Medicine. Food and Nutrition Board.
Dietary Reference Intakes: Summary of Applications I dietary assessment. Public
Health Nutr. 2002 Dec;5(6A):843-9.]
2. The DRI reference weight for (non-pregnant) women is 126 lbs (57 kg).
3. The “no observed effect in rats” level of 900 mg/kg/d described above would
correspond to a 57 kg (~125 lb) human’s intake of 51,300 mg thiamin /day.
This makes the 15 mg thiamin /day suggested earlier for (non-pregnant)
alcoholics not look so very high.
It is well known that thiamin deficiency in pregnancy is very injurious to both
mother and baby, and fetal development in the presence of both alcohol abuse and
thiamin deficiency is worse than either exposure alone.
There are many reports of Wernicke’s encephalopathy (also called Wernicke-Korsakoff
Syndrome) in pregnancy. This is a very serious life-threatening and neurologically damaging
5
condition caused by thiamin deficiency. It is one manifestation of a life-threatening condition
from thiamin deficiency called beriberi – a condition unexpected in the general US population,
and therefore rarely recognized when it develops.
Thiamin deficiency during pregnancy is particularly injurious to mother and baby. It has
also been described as a side effect during pregnancy of hyperemesis gravidarum (very severe
nausea and vomiting in early pregnancy,) history of maternal gastric bypass (bariatric) surgery,
and some eating disorders. (Please see my “Prenatal Top 10” handout for more on this.)
As the most common contributing cause of thiamin deficiency in the developed world is
alcohol abuse, it is reasonable to consider a person who abuses alcohol as being at significant
risk of being thiamin deficient, even in the absence of any symptoms or lab tests. When that
person is pregnant or planning a pregnancy, it would be very prudent to recognize the
potential for fetal damage from the relative inadequacy, and to address it.
General: The Korsakoff syndrome: clinical aspects, psychology and treatment. Alcohol Alcohol. 2009 Mar-Apr; 44
(2):148-54. Risk of thiamine deficiency in the non-alcoholic: Tracking ID # 153103. J Gen Intern Med. 2006;21
(Suppl. 4):265. Wernicke's encephalopathy: beyond alcoholism. Nat Clin Pract Neurol. 2006 Jan;2(1):54-8.
Functional Limitations in Thiamine Deficiency Neuropathy: FIM Score Improvement With Treatment. J Clin
Neuromusc Dis. 2006;7(3):104-109. Ophthalmoplegia & Nystagmus in Infants Fed a Thiamine-Deficient Formula:
An Epidemic of Wernicke Encephalopathy. J Neuro-Ophthalmol.2005; 25(3):169-172.
Bariatric surgery: Wernicke's encephalopathy presenting as acute psychosis after gastric bypass. J Emerg Med.
2009 Apr 28. Wernicke’s encephalopathy after subtotal gastrectomy for morbid obesity. Rev Neurol (Paris). 2008
May;164(5):463-7. Wernicke Encephalopathy After Bariatric Surgery: A Systematic Review. Ann Surg. Nov
2008;248(5):714-720. Nutritional consequences of bariatric surgery. Current Opin Clin Nutr & Metabol Care.
2006;9(4):489-496. Wernicke Encephalopathy Post Gastric Bypass: 668. Am J Gastroenterol. 2005;100 (Suppl
1):S251-S252. Wernicke-Korsakoff Encephalopathy & Polyneuropathy After Gastroplasty for Morbid Obesity:
Report of a Case. Arch Neurol. 2000 Sep;57(9):1356-9.]
Hyperemesis gravidarum: Hyperemesis gravidarum induced Wernicke’s encephalopathy: serial clinical,
electrophysiological and MR imaging observations. J Neurol Sci. 2009 Sep 15;284(1-2):214-6. Wernicke's
encephalopathy associated with hyperemesis gravidarum] Rev Neurol. 2008 Sep 1-15;47(5):274-6. Hyperemesis
gravidarum: a rare cause of Wernicke encephalopathy] Presse Med. 2007 Dec;36(12 Pt 1):1759-61. Pregnant woman
with hyperemesis, confusion, ataxia and nystagmus] Tidsskr Nor Laegeforen. 2006 Apr 6;126(8):106971.Wernicke's Encephalopathy with Hyperemesis & Ketoacidosis. Obstet Anesth Dig. 2006;26(2):97. Hyperemesis
Gravidarum Complicated by Wernicke Encephalopathy: Background, Case Report, and Review of the Literature.
Obstet & Gynecol Surv. 200661(4):255-268. Acute Wernicke's encephalopathy induced by hyperemesis gravidarum
Acta Neurolog Scandinav. 1999;99(3):196-198.]
Identifying alcohol-related thiamin deficiency:
Researchers have described early diagnosis of alcohol-related thiamin deficiency as an
important aspect of effective intervention and treatment. Alcohol biomarkers exist that provide
a direct and indirect way of estimating the amount of alcohol being consumed, the duration of
ingestion and the harmful effects that long-term alcohol use has on body functions.
Appropriate use of these markers can be very helpful when considering a diagnosis of alcoholrelated thiamin deficiency.
[Biomarkers in alcohol misuse: their role in the prevention and detection of thiamin deficiency. .Alcohol
Alcohol. 2009 Mar-Apr;44(2):177-82.]
6
CB Note:
However, we do not need to diagnose deficiency before recommending a generous
thiamin intake in women at risk. The simple expedient of providing a generous (safe and
cheap) thiamin intake to all women with a history of alcohol abuse may help prevent fetal
damage. The idea would be to prevent injury by NOT waiting until overt deficiency has caused
enough serious damage to be recognizable.
Thinking further along this line, though … many women’s alcohol use/abuse goes
undetected and unadmitted. Providing generous thiamin to all would provide some protection
to those individuals and their infants, plus those with a history of bariatric surgery.
An additional advantage to this approach is that no one must be singled out as being an
alcoholic, or made to admit alcohol abuse before we provide any help in this area. In
populations with a high prevalence of alcohol abuse this kind of simple intervention would
likely be a quite cost-effective way to minimize fetal alcohol severity to some degree, and to
protect the adult drinker from serious injury as well with no harm to others. As always, this is
not the official recommendation of any official health group … it’s just my best guess.
Riboflavin (Vitamin B-2)
Riboflavin deficiency is very common in alcoholism because of poor diet but also
because alcohol impairs absorption of riboflavin in the intestine. Absorption of dietary sources
is more impaired by alcohol than absorption of riboflavin in vitamin supplements. Milk is the
richest dietary source. Riboflavin is involved in all energy and protein metabolism so it is
important in fetal development. It may be especially important in mood.
[Mechanisms underlying the differential effects of ethanol on the bioavailability of
riboflavin and flavin adenine dinucleotide. J Clin Invest. 1987 May;79(5):1343-8.]
Niacin (Vitamin B-3)
Chronic alcoholics are also at risk of unrecognized pellagra (niacin deficiency)
which is a condition that can, if uncorrected, result in dementia, severe skin problems, and
even death. Niacin is involved in many metabolic functions, so deficiency can result in a wide
range of problems.
A form of niacin called nicotinamide was found to prevent some of the
deleterious effects of alcohol on the developing mouse brain when given shortly after
alcohol exposure. The authors concluded that nicotinamide may hold promise as a preventive
therapy of FAS.
[Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in
the developing mouse brain. PLoS Med. 2006 Apr;3(4):e101. Pellagra among
chronic alcoholics: clinical and pathological study of 20 necropsy cases. J Neurol
Neurosurg Psychiatry. 1981 Mar;44(3):209-15.]
7
Vitamin B6 (Pyridoxine)
Deficiency has been reported in alcoholics and even in the general public. High
alcohol intake may be associated with inadequate intake, and in addition, alcohol increases B6
destruction so one’s requirements would be higher than usual. Vitamin B-6 is a cofactor for all
protein, amino acid and neurotransmitter metabolism. It can also result in an elevated
homocysteine level.
[Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics.
Alcohol Clin Exp Res. 2005 Jun;29(6):1044-8.]
Folic Acid and Vitamin B12:
Folic acid is a nutrient of well-documented prenatal importance. It works with
vitamin B12 and vitamin B6 in certain pathways related to making DNA, which means that all
three need to be adequate for fetal development to proceed normally. Lower serum folate
levels have often been reported in alcoholic populations.
Since 1998 folic acid has been added to grain products in the US which has improved
the birth defects rates significantly. However, the amount added for the general public is
unlikely to prevent deficiency in alcohol abusers because alcohol directly impairs folate
absorption in the intestine. Additionally, malnourished alcoholics do not absorb folate as
well as well-nourished alcoholics do.
Once folate depletion occurs, alcohol accelerates the production of megaloblastic
anemia, and suppresses the hematologic response to folate. Folic acid deficiency is also related
to mental health issues (e.g. depression.) It now appears that supplementing folic acid and
vitamin B12 together may help prevent some fetal damage from exposure to alcohol.
[Effect of folic acid on prenatal alcohol-induced modification of brain proteome in
mice. Br J Nutr. 2008 Mar;99(3):455-61. The maternal combined supplementation of
folic acid and Vitamin B(12) suppresses ethanol-induced developmental toxicity in
mouse fetuses. Reprod Toxicol. 2006 Jul;22(1):56-61.]
Choline:
Disturbances in choline metabolism cause neural tube defects in mouse embryos in
vitro. Maternal choline availability is critical in the developing fetal rat brain hippocampus –
an area of the brain responsible for memory and much affected by fetal alcohol exposure.
Inhibitors of choline uptake and metabolism cause developmental abnormalities in mice.
[An overview of evidence for a causal relationship between dietary
availability of choline during development and cognitive function in
offspring. Neurosci Biobehav Rev. 2006;30(5):696-712. Periconceptional
dietary intake of choline and betaine and neural tube defects in offspring. Am
J Epidemiol. 2004;160(2):102-109.]
8
Choline is an essential nutrient in methylation, acetylcholine and phospholipid
biosynthesis, and in cell signaling. The demand by an embryo or fetus for choline may place a
pregnant woman and, subsequently, the developing fetus at risk for choline deficiency.
Several studies have shown that providing prenatal or neonatal
choline supplementation can ameliorate some of the effects of prenatal
alcohol … findings with important implications for children of women who
drink alcohol during pregnancy.
[Prenatal choline supplementation mitigates the adverse effects of prenatal alcohol
exposure on development in rats. Neurotoxicol Teratol. 2009 Jul 16. Choline
supplementation attenuates learning deficits associated with neonatal alcohol exposure
in the rat: effects of varying the timing of choline administration. Brain Res. 2008 Oct
27;1237:91-100. Choline supplementation following third-trimester-equivalent alcohol
exposure attenuates behavioral alterations in rats. Behav Neurosci. 2007
Feb;121(1):120-30.]
What are the best sources of dietary choline?
This is a nutrient that has not been in our radar until fairly recently, and it is turning out to have
important roles in a wide variety of tissues. It deserves closer attention because inadequacy is
a problem for some people, and deficiency is now known to be associated with serious medical
problems.
By far the richest dietary sources are:
egg yolk
~125 mg/yolk
beef liver
~120 mg/1oz
wheat germ ~85mg/half cup
There is an excellent overview with references and lots of information about
choline at this website: http://lpi.oregonstate.edu/infocenter/othernuts/choline/
The following excerpts are from that site:
“Most choline in foods is found in the form of phosphatidylcholine. Milk, eggs, liver, and
peanuts are especially rich in choline.”
[CB note: peanut butter has only 10 mg choline per Tblsp., so I’m not sure
why it was mentioned here.]
“Phosphatidylcholine, also known as lecithin, contains about 13% choline by weight.
9
Presently, national surveys do not provide any information on the dietary intake of choline, but
it has been estimated that the average intake by adults is between 730 and 1,040 mg/day.
Lecithins added during food processing may increase the daily consumption of choline by
about 115 mg/day.
Strict vegetarians who consume no milk or eggs may be at risk of inadequate choline
intake.” …
“Supplements: Choline salts, such as choline chloride and choline bitartrate are available as
supplements. Phosphatidylcholine supplements also provide choline; however, they are only
13% choline by weight. Therefore, a supplement providing 4,230 mg (4.2 grams) of
phosphitidyl choline would provide 550 mg of choline. Although the chemical term, "lecithin"
is synonymous with phosphatidylcholine, commercial lecithin preparations may contain
anywhere from 20-90% phosphatidylcholine. Thus, lecithin supplements may contain even less
than 13% choline.”
Here’s another good resource:
“Good Sources of Dietary Choline Now a Mouse Click Away
http://www.ars.usda.gov/IS/pr/2004/040316.htm
A new specialty database is now available to help people get healthful amounts of the
nutrient choline in their diets. The database can be accessed online, free of charge, at
the
Agricultural Research Service's Nutrient Data Laboratory (NDL) web site:
http://www.ars.usda.gov/main/site_main.htm?modecode=12-35-45-00”
Life stage
Infants
Infants
Children
Children
Children
Adolescents
Adults
Pregnancy
Breast-feeding
Adequate Intake (AI) for Choline
Age
Males (mg/day)
0-6 months
125
7-12 months
150
1-3 years
200
4-8 years
250
9-13 years
375
14-18 years
550
19 years and older 550
All ages
All ages
-
Females
125
150
200
250
375
400
425
450
550
http://fnic.nal.usda.gov
10
CB Note -- Practical application to FAS:
The cheapest and most available food to encourage pregnant women to eat to
improve choline intake is clearly egg yolk. The WIC program already provides eggs as
part of the food package for low income pregnant women, so the missing step is actively
encouraging generous egg consumption for pregnant women in general, and those with
potential alcohol issues in particular.
Remember to advise the NON-low income pregnant women about this as well.
Alcohol problems are found at all levels of socio-economic status (SES.) However, women are
more likely to be identified or labeled as alcohol abusers if they are from a lower income
population. Similarly, the likelihood of an infant receiving a diagnosis of Fetal Alcohol
Syndrome is significantly less in whites and in higher SES populations, even when alcohol use
is suspected or evident.
[Fetal alcohol syndrome: maternal and neonatal characteristics. J Perinat Med.
1998;26(4):263-9. By Bagheri MM, Burd L, Martsolf JT, Klug MG …
North Dakota researchers!]
----------------------------------------------------------------------------------------------------------For people concerned that the cholesterol content of some extra egg yolks might
present a problem: In our society we tend to equate the word cholesterol with serious health
problems. It is important to realize that in pregnancy women actually work very hard to make
a lot more cholesterol than normal. Trying to make more cholesterol available during
pregnancy is physiologically normal. This is because cholesterol is required to make
important perinatal substances like myelin (the greasy nerve-coating that speeds up
messages), steroid hormones and the membranes of all cells. As she is trying to produce
about a trillion cells, a little extra dietary cholesterol at this time is likely to actually be helpful.
B-Vitamin Summary:
Thiamin is among the most studied vitamins affected by alcohol abuse,
but as a good rule of thumb, one clearly should consider the status of all the
B vitamins to be at risk as well. No B vitamin is ever found to be the only
one compromised when deficiency is recognized and other co-existing B
vitamin deficiencies are then looked for.
Unfortunately, at present the looking-for-other-deficiencies part is quite uncommon in
actual practice. It is costly and not always even possible to do this in a patient-care setting.
“Evidence Based” is a very desirable goal, but an additional problem we have is that the nature
of most nutrition research is modeled on identifying the effect of an intervention with a single
nutrient while holding all else constant (as much as possible.)
11
This research model would tend to miss any potential effect of adjusting intake of one
B-vitamin. As an over-simplified analogy, it would be like concluding that giving oxygen, food
and water is not beneficial because giving any one of them to a rat deprived of all three would
not result in improvement in its state of health.
Research methods aside, it seems reasonable to at least attempt to assure the adequacy
of as broad a scope of nutrients as possible within safe limits. However, this requires health
care professionals to become more familiar with what the safe limits actually ARE for
each nutrient. In general, in “application-to-real-people” terms it would mean something as
simple as thinking about providing a multivitamin instead of just the one nutrient that was
evaluated and found to be inadequate. Similarly, one might supplementation with all the B
vitamins (e.g. as a B-complex supplement of whatever strength is indicated by the situation.)
Typically the broader-scope products are no more costly than single-nutrient products,
the safety of the interventions described above is not an issue, and there is the potential to do
more good than just focusing on providing the one nutrient known to be deficient. [And --- do
I have to say this? -- of course, no supplements are truly “complete,” they don’t take the place
of “eating right,” and they don’t make it OK to abuse alcohol. I am just looking for something I
can do that is at least easy, safe, cheap, more helpful and actually do-able without a
prescription in a very terrible situation.]
Vitamin A and FAS:
Vitamin A in one of its hormonal forms (RA -- retinoic acid) is a key director of the
process of “differentiation” in which a fertilized egg begins to differentiate into various body
parts and organs. Too little RA or too much RA are both associated with poor fetal outcome.
There are many phenotypic similarities between fetal alcohol syndrome and malformations of
both vitamin A toxicity and deficiency. Some vitamin A derivatives like the acne medication
Accutane are also known to cause birth defects if taken during early pregnancy.
One interaction that appears to have a role in altering fetal development is that the
synthesis of RA from retinol catalyzed by alcohol dehydrogenase. Researchers have suggested
that excessive alcohol intake competes for this enzyme, leading to RA deficiency. In other
words, using up all one’s alcohol dehydrogenase enzyme trying to protect ones body from
alcohol toxicity, may result in having substantially less available to make vitamin A retinol
into the key RA form.
In FAS, vitamin A metabolism is severely affected, and cell differentiation can be
compromised. Hepatic (liver) stores are low in chronic alcoholics but replacement therapy
may be toxic to the liver and to the fetus. Chronic alcohol use depletes hepatic vitamin A
stores regardless of intake because alcohol breaks down vitamin A and promotes its
mobilization from the liver. In other words, it is a big problem but the solution is not easy.
[Ethanol induces embryonic malformations by competing for retinaldehyde dehydrogenase
activity during vertebrate gastrulation. Dis Model Mech. 2009 May-Jun;2(5-6):295-305. Alcohol
and pregnancy: diagnostic aspects and abnormalities in the placental vitamin A pathway ] Ann Biol
Clin (Paris). 2008 Sep-Oct;66(5):509-13. Ethanol exposure affects gene expression in the embryonic
12
organizer and reduces retinoic acid levels. Dev Biol. 2005 Mar 1;279(1):193-204. Ethanol increases
retinoic acid production in cerebellar astrocytes and in cerebellum. Brain Res Dev Brain Res. 2004
Nov 25;153(2):233-41. Amelioration of ethanol-induced growth retardation by all-trans-retinoic acid
and alpha-tocopherol in shell-less culture of the chick embryo. Reprod Toxicol. 2004
May;18(3):407-12. Cigarette smoking, alcohol use and adverse pregnancy outcomes: implications
for micronutrient supplementation.J Nutr. 2003 May;133(5 Suppl 2):1722S-1731S. Prenatal ethanol
consumption increases retinol and cellular retinol-binding protein expression in the rat fetal snout.
Biology of the Neonate. 80(2):152-7, 2001 The effect of maternal ethanol ingestion on fetal rat heart
vitamin A: a model for FAS. Pediatr Res. 1995 Apr;37(4 Pt 1):418-23 Ethanol inhibition of retinoic
acid synthesis as a potential mechanism for FAS FASEB J. 1996 Jul;10(9):1050-7.]
CB comment: Reminder about vitamin A interactions with alcohol abuse:
This is a metabolic interaction of alcohol and vitamin A that occurs regardless of vitamin A
nutritional status. Inadequate or excessive vitamin A intake would clearly be potentially
contributory, of course. However, it is important to emphasize that simply providing more than
RDA levels of vitamin A in the retinol form will not correct the problem, and it could be
detrimental. The beta-carotene (the precursor to vitamin A retinol) is not a problem in this
regard because one controls the conversion of beta-carotene to retinol based on need.
Antioxidant Nutrients and FAS:
Normal metabolism produces waste products called by many names but commonly
called “free radicals.” Other terms are “singlet oxygen” and “reactive oxygen species (ROS).”
In 25-words-or-less [could I EVER say anything that briefly? ☺], free radicals can injure cell
membranes by stealing electrons from the surface. This electron theft is called “oxidation.”
An antioxidant prevents that damage and protects the cell membranes … sometimes by
donating an electron of its own so the free radical is “quenched.”
In nature, many different antioxidants work together. For example, inadequate vitamin
E can be compensated for by a generous selenium intake … and vice versa. Similarly, after
vitamin E has donated an electron to quench a free radical, vitamin C can reactivate vitamin E
by giving it a brand new electron. Simplified, this means that when studying the effect of
inadequacy or supplementation of vitamin E, the vitamin C and selenium status of the subjects
could significantly affect the findings.
As described earlier regarding research problems with sorting out the effects of the B
vitamins, this sort of complex interaction among many antioxidant substances makes it
difficult to identify the specific effect of a certain amount of just one particularantioxidant. To
correctly interpret the results, one would need to know about the status of other
antioxidant/pro-oxidant substances at the time of the evaluation. This can make it difficult to
carry out high quality research with clearly interpretable results.
Free radical injury from failure to have adequate antioxidants available is called
“oxidative stress” and it is associated with a very wide range of problems such as
complications of diabetes, macular degeneration, and rancid butter.
13
As noted, free radical production is a NORMAL part of metabolism and free
radicals NORMALLY get handled by NORMAL amounts of antioxidants from foods and
supplements such as:
1. Well known antioxidant vitamins like vitamins A, C, and E
2. Less well-known vitamin-related substances like alpha-lipoic acid, CoQ-10
(ubiquinone)
3. Minerals such as selenium and zinc are used to produce important antioxidant
enzymes like (respectively) “glutathione peroxidase” and “zinc-copper superoxide
dismutase.”
1.
Some “phytochemicals” (“substances in plants”) such as the pigments called
“carotenoids” are very potent antioxidants. Examples include the orange-colored
pigment beta-carotene, red lycopene, green lutein, red/blue anthocyanin, and
yellow zeaxanthin. For example, lycopene in tomatoes is 200 times as potent as an
antioxidant the more familiar vitamin E. There are over 500 known carotenoids, so
we are only just beginning to mine these vegetable/fruit treasures.
5. MANY other phytochemicals such as polyphenols, pycnogenol (from pine bark) and
resveratrol (in red wine and red grapes) are being found to have important
antioxidant (and other beneficial) activity. Research in this area is simply
exploding.
KEY ISSUE: Any condition in which fuel (or other) metabolism is not proceeding in a
standard manner will result in more free radical production, so the person will
have an increased need for antioxidant protection. This is true for many health
conditions such as diabetes, inflammatory diseases, and alcohol abuse as well.
Obtaining a large percentage of calories from alcohol is not part of “normal”
operations. This is another example of the usually adequate nutrient intake levels no
longer being sufficient to meet the needs of people who are not members of the group
called “the healthy population.”
Application to FAS in particular:
It appears that at least some of the fetal damage from alcohol
abuse is related to the excessive production of free radicals that
accompanies high alcohol use.
2005-2009
Early exposure to ethanol but not red wine at the same alcohol concentration induces behavioral
and brain neurotrophin alterations in young and adult mice. Neurotoxicol. 2009 Jan;30(1):59-71.
Black ginseng inhibits ethanol-induced teratogenesis in cultured mouse embryos through its effects
on antioxidant activity. Toxicol in Vitro. 2009 Feb;23(1):47-52. Nrf2-mediated transcriptional
induction of antioxidant response in mouse embryos exposed to ethanol in vivo: implications for
the prevention of fetal alcohol spectrum disorders. Antioxi & Redox Signal. 2008 Dec;10(12): 2023-
14
33. Novel molecular targets for the prevention of fetal alcohol syndrome. Recent Patents on CNS
Drug Discov. 2007 Jan; 2(1):23-35. Effects of maternal administration of vitamins C and E on ethanol
neurobehavioral teratogenicity in the guinea pig. Alcohol. 2007 Dec;41(8):577-86. Review of
neurobehavioral effects of alcohol-related neuro-developmental disorder in an animal model.
Nihon Arukoru Yakubutsu Igakkai Zasshi. 2006 Feb; 41(1):15-22. Neurotoxic effects of alcohol and
acetaldehyde during embryonic development. J Toxicol Environ Health Part A. 2005 Dec; 68(2324):2147-62. Antioxidant pretreatment does not ameliorate alcohol-induced Purkinje cell loss in
the developing rat cerebellum. Alcoholism: Clin Experi Res. 2005 Jul; 29(7):1223-9.Ascorbic acid
inhibits ROS production, NF-kappa B activation and prevents ethanol-induced growth retardation
and microencephaly. Neuropharmacol. 2005 Mar.;48(3):426-34.
1999-2005
Vitamin E protects against alcohol-induced cell loss and oxidative stress in the neonatal rat hippocampus. Internat J Developmental Neuroscie. 2004 Aug-Oct; 22(5-6):363-77. Protection from ethanolinduced limb malformations by the superoxide dismutase/catalase mimetic, EUK-134. 2004
Aug:FASEB Journal. 18(11):1234-6.Protection of Xenopus laevis embryos against alcohol-induced
delayed gut maturation and growth retardation by peroxi-redoxin 5 and catalase. J Molec Biol. 2004
Jul 16. ;340(4):819-27. Catalase and peroxiredoxin 5 protect Xenopus embryos against alcoholinduced ocular anomalies. Investig Ophthalmol & Visual Science. 2004 Jan;45(1):23-9. Ethanolinduced reduction of neurotrophin secretion in neonatal rat cerebellar granule cells is mitigated by
vitamin E. Neurosci Let. 2004;Nov;370(1):51-4. Ethanol effects on neonatal rat cortex: comparative
analyses of neurotrophic factors, apoptosis-related proteins, and oxidative processes during
vulnerable and resistant periods. Brain Research. Developmental Brain Research. 2003 Nov;145(2):24962.Antioxidants and fetal protection against ethanol teratogenicity. I. Neurotoxicol Teratol. 2003 JanFeb;25(1):1-9. Protective effect of folic acid against oxidative stress produced in 21-day postpartum
rats by maternal-ethanol chronic consumption during pregnancy and lactation period. Free Radical
Research. 2001 Jan;34(1):1-8. Amelioration of ethanol-induced neurotoxicity in the neonatal rat central
nervous system by antioxidant therapy. Alcoholism: Clin Experi Research. 2000; 24(4):512-8. Ethanol, oxidative
stress, reactive aldehydes, and the fetus. 1999 Jun; Frontiers in Biosci. 4:D541-50. Vitamin E and beta-
carotene protect against ethanol combined with ischemia in an embryonic rat hippocampal culture model of
fetal alcohol syndrome. Neurosci Let. 263(2-3):189-92, 1999. The antioxidants vitamin E and beta-carotene
protect against ethanol-induced neurotoxicity in embryonic rat hippocampal cultures. Alcohol 1999; 17(2):163-8.
Zinc and Fetal Alcohol Syndrome:
The antioxidant function of zinc was described above. In addition to that role, there
are more than 200 zinc-dependent enzymes that will function poorly in the presence of
zinc deficiency. This includes decreased function of alcohol dehydrogenase, an enzyme
described earlier as important for detoxifying alcohol and for producing retinoic acid
from retinol.
Zinc is of critical reproductive importance (e.g. DNA production), and it has specific
roles in immune functions. For example, the production of T-cells by the thymus gland is very
zinc-dependent. The diet of alcohol abusers is often poor and lacking in zinc along with many
other nutrients. There also appear to be altered requirements for zinc, due to:
1)
possible impaired absorption,
2)
higher metabolic requirements, and
3)
increased excretion of zinc.
15
Zinc Adequacy in the General Population:
An “average” 1500 calorie diet provides about 40% of the (non-pregnancy) adult DRI
for zinc. Many women regularly take in 1500-1600 kcals daily. Vegetarianism and trends
toward eating less meat (and especially red meat) decrease it further. High fiber diets include
phytates, which like tannins in tea and oxalates in leafy greens, decrease absorption of both
zinc and iron from plant and supplement sources.
The zinc content of foods and its absorbability correspond fairly well to the naturally
occurring iron content of food. However, it is not generally added to foods that are fortified
with iron. We regularly check people’s iron status and iron deficiency is known to be a
common health problem. However, we rarely evaluate zinc intake or labs.
So here’s the question:
If people’s diets are often found to be low in iron (even in spite of iron
fortification of many foods), why would we assume that their zinc intake is
adequate? (We do.)
------------------------------------------
There is continuing evidence that inadequacy of zinc has
the potential to exacerbate fetal damage associated with
alcohol abuse.
[Dietary zinc supplementation throughout pregnancy protects against fetal dysmorphology and improves
postnatal survival after prenatal ethanol exposure in mice. Alcohol Clin Exp Res. 2009 Apr;33(4):591-600.
Dietary zinc supplementation during pregnancy prevents spatial and object recognition memory
impairments caused by early prenatal ethanol exposure. Behav Brain Res. 2008 Jan
25;186(2):230-8. Syndromes, disorders and maternal risk factors associated with neural tube
defects (VI). Taiwan J Obstet Gynecol. 2008 Sep;47(3):267-75. Zinc supplementation does not
attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period. 2001
Apr; Alcoholism: Clinical & Experimental Research. 25(4):600-5. Effects of prenatal or postnatal
ethanol consumption on zinc intestinal absorption and excretion in rats. Alcohol & Alcoholism.
2007 Jan;42(1):3-10. Prenatal zinc treatment at the time of acute ethanol exposure limits spatial
memory impairments in mouse offspring. Pediat Res. 2006 Jan;59(1):66-71.Critically timed
ethanol exposure reduces GABAAR function on septal neurons developing in vivo but not in
vitro. Brain Res. 2004May; 1008(1):69-80. Human class IV alcohol dehydrogenase: kinetic
mechanism, functional roles and medical relevance. Chemico-Biolog Interact. 2003 Feb 1;143144:219-27. Kinetic mechanism of human class IV alcohol dehydrogenase functioning as retinol
dehydrogenase. J Biol Chem 2002 Jul; 277(28):25209-16.]
The initial discovery of this relationship is still fascinating:
16
Interesting Observations:
Zinc deprived rats were noted in 1971 to “look like” rat pups with FAS. The number
and severity of defects dramatically increased when the alcohol (ETOH) is administered to
zinc-deprived pregnant rats.
Both alcohol exposure and zinc deficiency result in fetal harm. But there is a
synergistic teratogenic effect … the damage was much more severe when zinc deficiency
and alcohol exposure occurred together. This is a very good illustration of the notion
introduced at the beginning of this paper that other environmental variables clearly have a role
in determining the developmental damage associated with fetal alcohol exposure.
Representative Rat Pups
Zinc
No alcohol
(control)
Zinc
15% Kcals
as alcohol
Low Zinc
15% Kcals
as alcohol
Low Zinc
20% Kcals
as alcohol
[Zinc nutrition in fetal alcohol syndrome. Pediatr Res. 1985 Sep;19(9):944-7.]
Remember that “at 30% of kcals as alcohol the intake of many
nutrients drops below 75% of the RDA” statement? The serious fetal effects
shown above occurred at only 15-20% of calories from alcohol!
Clearly a diet that provides 75% or more of the RDA should not be our “comfort zone”
when discussing FAS. Even brief periods of inadequate zinc intake during critical periods can
cause birth defects, because of an inability to mobilize maternal zinc stores for use by the fetus.
17
In 1989 a study of the hair zinc content at birth in FAS babies showed no difference
compared with controls. Did this prove that zinc status had no role in the development of fetal
alcohol syndrome? This is an example of the importance of asking the right questions at the
right time. This issue should be evaluated before conception if possible, and in early
pregnancy at the latest. Zinc status during the critical first two months of pregnancy (when
dysmorphic changes might occur) may not be reflected in zinc status of baby in later
pregnancy (when the pregnancy has been recognized and prenatal vitamin/mineral supplements
are often provided or the mother makes a greater effort to “eat right.”)
Protein and Zinc Interaction in FAS:
Protein synthesis is impaired by alcohol regardless of dietary protein intake. Zinc is
also essential for protein synthesis. Alcohol clearance is decreased in individuals consuming
diets with inadequate protein content. Diets with inadequate protein content are also likely to
be inadequate in zinc and other nutrients.
Altered zinc metabolism contributes to the developmental toxicity of alcohol and also
of the seizure-control medication valproic acid and other drugs. The developmental toxicity of
certain compounds is, in part, due to maternal toxicity resulting in alterations in zinc (Zn)
metabolism that affects the developing baby. As noted earlier, this may include a relative
inadequacy of alcohol dehydrogenase, a key zinc-containing enzyme in the detoxification of
alcohol and many drugs and an important substance in production of retinoic acid. It appears
that the teratogenic effects of several chemicals can be modulated by dietary Zn intake.
Since the study with the rat pups shown above was published, a number of studies have
attempted to improve outcomes by supplementing zinc – in general, the results are mixed –
some factors seemed to be improved, and others did not. This likely reflects the huge role of
zinc in many areas of metabolism … it is a cofactor for the function of over 200 enzymes in
the body. It also reflects the influence of other factors (besides intake) that alter zinc
metabolism in the alcoholic state. There is no evidence that supplementing zinc at levels
above the usual recommended level is beneficial, and giving more than that amount in
supplement form may even be harmful.
However, the notion of assuring RDA/DRI level adequacy of zinc is very
reasonable, since overt deficiency is clearly permissive of greater teratogenic effects from
alcohol exposure. The use of a standard multivitamin with minerals will usually provide this
amount (i.e. 12-15 mg) and it will not be excessive even if the mother eats a diet rich in zinccontaining foods. The richest foods in zinc content and in zinc absorbability are meats, which
also provide excellent protein and absorbable iron. [Please see my handout on “Nutrition
Support of Iron Deficiency” for more details on the iron and zinc content and availability in
foods and supplements.]
Zinc deficiency acts as a co-teratogen with alcohol in fetal alcohol syndrome.
Neurotoxicology. 1990 Summer;11(2):375-80.
18
Iron Deficiency and Fetal Alcohol Syndrome:
Iron deficiency may play a role in increased fetal damage from alcohol exposure for
several reasons beyond its well-known oxygen-carrying function. As described earlier, the
Cytochrome P450 system is an iron-dependent system that can be thought of as a garbage
disposal. It is responsible for breaking down many substances that would be harmful if they
built up in the body. It is a factor in the disposal of many medications and potential
environmental toxins like alcohol. Poor iron status can compromise the functioning of the
garbage disposal. As a result, an iron deficient person may fail to metabolize alcohol (and
other drugs) in a timely manner. That means that when the mother drinks alcohol, both she
and her baby are exposed to alcohol longer than usual, which may increase its teratogenic
effects.
The reverse may also be true. Fetal alcohol exposure produces some defects that
parallel the abnormalities associated with early iron deficiency. Researchers looked at amounts
of iron, transferrin and ferritin in three CNS regions in rats (cerebral cortex, subcortical
forebrain and brainstem). The pattern of brain iron distribution was delayed by alcohol
exposure by up to 2 weeks. Alcohol-induced alterations in iron homeostasis persisted into
adulthood. The net result: timely delivery and bioavailability of iron was compromised by
alcohol exposure. The defects in iron regulation are permanent and may underlie
alcohol- induced abnormalities in iron dependent growth processes such as myelination.
Iron regulation in the developing rat brain: effect of in utero ethanol exposure.
J Neurochem. 1995 Jul;65(1):373-80.
CB question:
Mother rats in this study received normal dietary iron. What if maternal initial iron
status were poor and/or the diet were inadequate in iron as well?
Could that ever happen? In any case, assuring adequacy (instead of assuming it) has the
potential to benefit both mother and baby.
---------------------------------------------------------------------------------------------------------
So what can we do to provide some protection to the fetus
being exposed to alcohol.
Improving the regular diet of chronic alcohol users can of course be very useful if it can
be achieved. In particular, encouraging intake of brightly colored fruits and vegetables is very
safe and it provides terrific antioxidants and key nutrients. However, I would be VERY
surprised if women who abuse alcohol had not already heard somewhere that fruits and
vegetables are “good for you.” Many may even already be eating lots of fruits and vegetables.
19
Others (like everybody else) may not ordinarily eat them for reasons of flavor, cost,
time or whatever. Increasing intake in this situation is most likely to occur if one could
help her identify some specific key foods that she enjoys that are rich in antioxidants.
These might include things not always thought of as key providers of antioxidants, like tomato
sauce, canned peaches, red grape juice, etc. Many generous-antioxidant foods like these are
now being provided through the WIC Program. Other foods like ketchup are surprisingly good
sources of lycopene. If money is not the problem, the grab-and-go fruits and vegies now in
many grocery stores can be very helpful.
A standard prenatal multivitamin/mineral supplement should be encouraged (for
many reasons) as well as more generous vitamins C and E. Remember that her need for
antioxidants is much higher than usual, so higher than RDA/DRI intake levels would be a good
idea. This concept has been studied much more in other oxidative stress-inducing conditions
such as diabetes with good results. Antioxidant adequacy has been shown to help to decrease
the incidence of birth defects in infants of mothers with diabetes. This situation (FAS) is quite
comparable in terms of oxidative stress, but less studied.
Most multivitamin/mineral supplements have RDA/DRI levels of zinc and iron, but
iodine, vitamin K and selenium levels are quite variable between brands. All three have
great importance in pregnancy. For example, fetal alcohol syndrome is the number one cause
of preventable mental retardation in the US. Iodine deficiency syndrome is the number one
cause of preventable mental retardation in the WORLD.
New concerns have recently been raised about IODINE inadequacy during
pregnancy, even in the US and other areas where salt has been iodized to provide iodine.
This has prompted the World Heath Organization (WHO) to increase the recommendations for
iodine during pregnancy from 200 to 250 microg/d and suggested that a median urinary iodine
(UI) concentration of 150-249 microg/L indicates adequate iodine intake in pregnant women.
Many multivitamins, including prenatal vitamins, contain little or now iodine. Clearly a
combination of alcohol exposure plus relative iodine deficiency does not bode well for the
developing fetus.
[Please see my “New Attention to an Old Problem: Iodine Deficiency in Pregnancy and Lactation,” “Top
Five Easy Ways to Improve Your Family’s Nutrition” and “Top Ten Nutrition Plan for Optimizing Pregnancy
Outcome” for more on these and related issues.]
[Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the
offspring: a review. Am J Clin Nutr. 2009 Feb;89(2):668S-72S. Iodine levels and thyroid
hormones in healthy pregnant women and birth weight of their offspring. Eur J Endocrinol. 2009
Mar;160(3):423 Iodine Content of prenatal multivitamins in the United States. NEJM.
2009;360:939-940. Iodine status of the U.S. population, National Health and Nutrition
Examination Survey 2003-2004. Thyroid. 2008 Nov;18(11):1207-14.]
Some products are missing a lot of minerals. SELENIUM is one that is highly variable
so check the label. The usual recommendation is a daily intake of 60-70 mcg/day. The
advisable upper limit is 600 mcg/day, so providing RDA-ish levels is safe and a very good idea
in view of its key role as an antioxidant component and the increased requirements for
20
antioxidant protection in fetal alcohol exposure. If a person’s multivitamin with minerals
contains inadequate selenium, 50 mcg supplements are available over the counter.
A new “likely-to-be-inadequate-but-out-of-our-radar” vitamin is VITAMIN K.
1. We are much more dependent on an outside source of vitamin K than was earlier believed.
2. Many people in the US are now being found to be vitamin K deficient when we check …
but it is rarely checked because it has traditionally been assumed to be made in adequate
amounts by intestinal bacteria.
3. It is often left out of multivitamin pills (check the label) – it is even omitted as an important
nutrient to consider in the 2,000 kcal suggested meal pattern in the new Food Guide Pyramid.
4. Inadequacy of vitamin K increases risk of several problems in pregnancy, including
toxemia.
5. Dark leafy greens are the richest food sources, and many folks eat very little of these foods
… which of course also includes people who abuse alcohol.
The AI for vitamin K for pregnant women is 90 mcg/day but some groups are now
being found to have needs higher than AI recommended levels. It would not surprise me to
find that women who abuse alcohol are among those with different requirements. In spite of a
common belief that vitamin K is potentially toxic because it is fat soluble, it is now very clear
that vitamin K is extremely NOT toxic. In fact, there is no upper limit of safety
established for vitamin K because no one has ever gotten into trouble from taking too
much. [The business with certain anticoagulant drugs is a drug/nutrient interaction issue, and
unrelated to the safety of the vitamin in people not using this kind of medication.]
Food and Nutrition Board, Institute of Medicine. Vitamin K. Dietary
Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium,
Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium,
and Zinc. Washington D.C.: National Academy Press; 2001:162-196.
[See my “Top Five Easy Ways to Improve Your Family’s Nutrition” and “Vitamin K” handouts for more on
these and related issues.]
------------------------------------------------------------------
It is reasonable to identify several brands of multivitamins with minerals that are
satisfactory and generally low in cost, with some attention to the problems above regarding
iodine, selenium and vitamin K. However, instead of just advising her to buy and take a
multivitamin, physically providing the appropriate supplement(s) is far more likely to
achieve the goal of trying to protect that baby. Some places do this, but most do not.
Developing a program that provides this link in the chain would be very cost effective
in protecting against fetal damage of many types … even for women who do not use alcohol!
This calls for a big paradigm shift from the “just eat right” advice we are more comfortable
with. [See my “Top Ten Nutrition Recommendations for Pregnancy” for more on these issues.]
21
Additionally, many insurance programs do not cover nutrition supplements because
they are “over the counter.” For people on a tight budget, this alone can be a deal-breaker. If
the mother is also addicted to drugs/nicotine/ alcohol etc., the likelihood of her limited funds
being saved to buy vitamin pills seems to be unrealistic.
To keep your eye on the prize … that is, to help protect that baby … the most
likely way to achieve success is to both physically provide the vitamin/mineral, and to
explain that taking it as directed may help protect the baby from some of the effects of
her drinking. Of course we do not give her the impression that it will make it OK to drink …
we should continue to make it plain that stopping alcohol consumption is the absolutely best
thing she can do. But I have found that most women with an alcohol or other drug problem
would very much prefer not to be addicted. Most of the women are also very worried about
their baby’s health, even as they continue to abuse alcohol or drugs. I have found that many
of these women are actually quite willing to take their vitamins (even when they have
been unable to stop drinking) when strongly encouraged, the benefits to the baby are
explained and they are also provided with the bottle of vitamins.
Will she take it?
Isn’t this just a big waste of time? Many will take supplements (especially if the
supplements are provided and the women are educated about the reasons for their use.) Some
won’t. Should we decide not to try with any of the women because some will not follow
through? Don’t pre-judge that she “does not care about her baby” just because she is addicted
to alcohol . . . many would like to quit drinking but just can’t.
One health professional actually told me at a conference that if we gave them
multivitamins, the women would “just sell the vitamins on the black market.” (Hmmm … what
IS the street value of generic multivitamin pills these days, especially when many other people
will be receiving them for free as well?) I think this exposes an unfortunate tendency to be
more ready to judge her rather than to help her. Remember to “Keep your eye on the prize:”
the healthiest baby possible in spite of a suboptimal pregnancy situation. In addition to
the baby’s health, there are also potential for many positive benefits in terms of the
mother’s health and health care costs.
Beyond the multivitamin-with-minerals and encouraging
consumption of nutritious foods in place of the alcohol:
What might be helpful and won’t be harmful?
Consider additional:
Vitamin E (e.g. 400 iu)
22
Vitamin C (e.g. 250-500 mg)
Selenium (e.g. add a 50 mcg tablet if her multivitamin has less than 30 mcg.)
Magnesium (e.g. RDA-ish levels of 250 mg as magnesium oxide or chloride.)
Magnesium deficiency has not been studied as a particular interactive factor in
FAS, but it IS recognized as suboptimally represented in the diets of the
majority of even healthy Americans. Most multivitamins have only 10-25% of
the recommended amount, so a person with poor diet (as is common in people
wit alcohol problems) would likely not have her needs met by the amount in the
multivitamin. Inadequacy during pregnancy has serious consequences for
pregnancy outcome in general.
Iodine Help her make sure that the salt she uses at home is the iodized kind, and check
the iodine cotent of her multivitamin with minerals. The new WHO
recommendation for iodine intake in pregnancy is 250 mcg/d
Thiamin (at least 15 mg)
Folic acid (100-800 mcg extra) Generous B vitamin supplementation in general as
a “B-Complex” is a good idea, but the folic acid content of those remains at
400 mcg, and the level of thiamine suggested is higher than would be
provided by most B-complex products.
Choline Check that diet and food provide AT LEAST 450 mg (the recommended
amount for a healthy pregnancy.) I would be inclined to double it in an alcoholabuse situation, based on knowing that that intake is not at all harmful and she
certainly could need more. Whether or not an additional supplement form is
needed depends on things like how much is in the multivitamin and her egg
yolk intake, as described earlier.
Vitamin D (1000-2000/day). There are many reasons why alcohol abusers are at
risk of being overtly deficient in vitamin D, and the DRA/RDA level of 400 iu
is insufficient even for maintenance in a large proportion of the general
population. (This is especially true if you happen to live in North Dakota!)
Ideally, one should check her vitamin D level because deficiency in pregnancy
is itself looking like it has some serious damaging effects. If she is low the
doctor will want to give her a much higher therapeutic dose rather than a
maintenance dose.
Vitamin K (at least 100 mcg/day)
[See my “Top Five Easy Ways to Improve Your Family’s Nutrition” and “Top
Ten Nutrition Plan for Optimizing Pregnancy Outcome” and “Vitamin K” for
more on these and related issues.]
23
Identifying Whom to “Treat”
Except for the really generous thiamin, the recommendations described are not
unsuitable for women in general. For example, the same interventions apply to optimize
pregnancy outcome if she has diabetes. Or even if she has no medical problems. But when you
want to indentify those who are specifically at risk of ETOH abuse . . .
Final thoughts:
In view of the vagaries of “detection” (at what stage of pregnancy or pre-pregnancy is
she “screened,” the large variability in the likelihood of detection by current methods, the
effectiveness of interventions that rely on detecting alcohol abuse in women already several
months pregnant, etc.) it makes more sense to focus nutrition interventions as if all women
were potentially at risk of these common nutritional inadequacies … not just those
identified as alcohol abusers; both the Risk : Benefit ratio and Cost : Benefit ratios are
clearly in that direction.
Also, it has often been said that alcohol abusers are rarely only using alcohol. Many
are “polypharmacy” users/abusers, so there is the potential for other drug effects (nicotine,
caffeine, cocaine, inhalants, etc.) whenever the population being studied is human. This can
complicate interpretation of the data obtained about the effects of nutrition on fetal alcohol
syndrome specifically. There is a lot more to learn, but the suggestions presented here have
resonance with other abuse other substances as well.
The papers referred to in this handout (and others) can be found at no cost at
www.meritcare.com
Top Five Easy Ways to Improve Your Family's Nutrition
Pregnancy
Iron Deficiency
Antioxidant Phytochemicals: Ideas for adding them to the diet
Vitamin K -- New issues in cardiovascular health, osteoporosis, pre-eclampsia and
cancer of the liver and colon.
Just type Cathy Breedon in the search box in the upper right.
Click the item that pops up that says: “Handouts from Cathy Breedon
…for Cathy Breedon's workshop topics.…”
24
Sanford Medical Center
Aunt Cathy’s
Guide to Nutrition:
Folate
(Vitamin B9)
Part I: Food Sources
Usual Adult Goal = 400 mcg daily
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center, Fargo, ND,
UND School of Medicine Dept. of Pediatrics
Pregnancy Goal = 800 mcg daily
Folate per 1/2 cup (unless noted)
100 mcg or more
10-30 mcg
Asparagus, Brussels sprouts,
Black-eyed peas, Spinach,
Soybeans, Black beans,
Broad beans,
Fortified cereals (see label)
Cantaloupe, Strawberries, Pears,
Grapefruit, Grapefruit juice,
Potatoes, Corn, Carrots, Onions,
Bananas, Squash, Cabbage
Tomato,Raspberries, Cherries
40-90 mcg
Fruits and vegetables with
little or no folate*:
Lima beans, Peas, Collard greens,
Sweet potato, Romaine lettuce,
Broccoli, Oranges and Orange juice,
Wheat germ, Oatmeal, Tempeh,
Miso, Peanuts (1 oz) Wild rice,
Sunflower seeds (1 oz ), Beets,
Apples and Apple juice,
Plums, Prunes, Cranberries,
Grapes and Grapejuice,
Watermelon, Kiwi,
Raisins, Peaches, Apricots,
*Although these fruits have little folate they are sources of other important nutrients.
Grain Products:
Since 1998 the folic acid form of folate has been added to “enriched” grain
products in America. The FDA requires that 40 mcg of folic acid be added per 100
grams (3.5 ounces) of enriched bread and other grain products.
Comparing the five years before and after initiating this supplementation
demonstrated a significant reduction in the incidence of birth defects and strokes.
So it has been well demonstrated that many people were clearly failing to get enough
folate, or a usable form of folate, prior to 1998. People with certain genetic traits were
even more positively affected by this fortification. For example, while the overall
reduction of neural tube defects was about 50%, the groups with the highest incidence of
these birth defects experienced a reduction of 60-70%! This is a tremendous victory. For
example, since 1998 here at Sanford Medical Center we have seen a dramatic drop in the
number of new patients in our spina bifida clinic … how great is THAT??!!
The folic acid fortification mandate does not include whole grains, as they
are presumed to still contribute some folate in the intact germ.
Remember that it is useful to always think of “Enriched” grain on a food label as
“UNriched” grain, since only three vitamins (B1, B2 and B3) and iron are traditionally
added back when the germ was removed.
Refining removes the bran and the germ of the grain. The germ is the “Baby
Plant” where the bulk of the nutrients are kept … and the absence of the many nutrients it
WOULD have provided is not made up by enriching the refined grain with those four
nutrients. Magnesium, chromium and vitamin E are some examples of nutrients removed
but NOT replaced, and this has serious health implications. But at the time this
enrichment process was first designed, these other nutrients were not in our radar.
(Please see my “Top Five Recommendations” paper for a discussion of the magnesium
inadequacy issue, and more detail in my “OTHER Nutrition Issues in Diabetes” paper.)
Adding folic acid as described above is actually called a “fortification” and not
“enrichment” because the amount added is more than would be provided by the whole
grain. Additionally important is the fact that the FORM now added to grain products
provides a major benefit for people with conditions in which other naturally occurring
forms of folate are not well utilized.
An example of this is a genetic condition called having the MTHFR* gene. For
people with this gene, providing the “folic acid” form can be instrumental in protecting
against stroke and birth defects like spina bifida and anencephaly (“neural tube defects”.)
It also is protective against many other types of birth defects like shortened limbs, cleft
lip/palate, and certain prenatally established brain tumors.
Vitamin supplements:
Most multivitamin pills for children and adults have 200-400 mcg folic acid.
Prenatal vitamins have 800 mcg because of the increased requirements during pregnancy.
Liquid vitamin products (such as vitamin drops for infants or liquid vitamin tonics for
adults) usually have no folic acid because it will not stay in solution. This is also true of
the form added to foods like certain “vitamin fortified cereals” with labels that say
something like: “fortified with eight essential vitamins!”
(*MTHFR refers to genetically inadequate availablility or function of an enzyme called
MethyleneTetraHydroFolateReductase. Now you can see why we just call it “MTHFR.”)
Aunt Cathy's Guide To:
Folate (Vitamin B9)
Part II: Absorption
(not scientifically correct)
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
Odds and Ends:
Genetic factors: People with the MTHFR gene benefit from the “kite only”
form. Found in some people Irish heritage and others as well.
Inadequate folic acid increases the incidence of many birth defects and also
stroke, depression and some cancers. It results in an elevated homocysteine
level. Correcting deficiency reduces these risks
Chronic use of alcohol or certain medications affects absorption or interacts
with folic acid: antibiotics, some seizure medications and antidepressants
Certain medical conditions affect absorption of or requirements: celiac
disease, cystic fibrosis, inflammatory bowel disease , bacterial overgrowth,
short bowel etc.
Sanford Medical Center
Aunt Cathy’s Guide to
Nutrition Support of
Hemochromatosis Therapy
For Patients, Their Families, and
Their Health Care Providers:
My Specific “Best Guess” Suggestions –
(Subject to Change at Any Moment! ☺)
Cathy Breedon PhD, RD, CSP,FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine Dept. of Pediatrics
Fargo, ND
People with hemochromatosis have too much iron stored in the liver and other
body organs. Sometimes this is caused by a genetic problem in regulating how much iron is
absorbed from foods. In other people, it can be due to a need for frequent blood transfusions.
Regardless of the cause, excessive iron causes serious damage that leads to cirrhosis of the liver,
liver cancer, heart damage, and other problems. [Hemochromatosis--from an underdiagnosed curiosity to a
common disease. Tidsskr Nor Laegeforen. 2009 Apr 30;129(9):863-6. Hereditary haemochromatosis.Best Pract Res Clin
Gastroenterol. 2009;23(2):171-83]
The primary treatment to remove excess iron is the removal of red blood cells (erythrocytes)
because they contain an iron-rich substance called hemoglobin that carries oxygen to the tissues.
The removal of red blood cells is called “phlebotomy,” the same process that is used when
donating blood. There are some medications that your doctor may use as well to help remove
excessive iron.
In the past, removing iron from the diet was the primary treatment to minimize damage from
hemochromatosis, but that approach (besides being quite difficult) does not have the advantage
of removing excess iron that has already been deposited in the body.
However, nutrition still plays an important role in hemochromatosis because it can:
1.
2.
3.
4.
Support the phlebotomy therapy by optimizing production of red blood cells to improve
the effectiveness of phlebotomy treatments and to allow for more frequent treatments as
needed.
Decrease the anemia and fatigue that are common problems related to regular phlebotomy
treatments.
Decrease some of the damage to organs from having too much iron.
Prevent serious nutritional deficiencies that can result from regular phlebotomy and/or
attempts to decrease dietary iron absorption. 1
The following suggestions are not the official recommendations of any medical group, but
they are simply a collection of things that I would do today if a family member had
hemochromatosis. They will likely help and they will do no harm beyond the added cost of the
supplements. Most of the supplements described can be obtained inexpensively in warehouse or
discount stores. These nutrition suggestions are to be used in addition to phlebotomy or other
treatments ordered by the physician, and they are not intended to be used instead of phlebotomy.
The specific recommendations may change as more is learned about hemochromatosis. As
always, discuss any diet plan and supplement use with your physician, including any herbal
products that you may be taking.
Sometimes the general suggestions given here for helping to manage hemochromatosis need to
be modified if a person has other issues that interact with nutrition, such as the use of certain
medications, or if one already has serious liver disease. Additionally, some herbal products are
particularly risky for people with any condition that injures the liver – some examples of herbs to
avoid for this reason are kavakava, chaparrel and comfrey.
[Review of abnormal laboratory test results and toxic effects due to use of herbal medicines. Am J Clin Pathol. 2003;120(1):12737.]
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1. Starting point: Take a daily multivitamin/multimineral
supplement with no iron.
Several products are iron-free, such as: "One a Day 55-plus," "Certa-Vite Golden," and
“Centum Silver.” There are many appropriate and inexpensive products. Besides "no
iron", the minerals that should be included in the product are zinc and copper at the RDA
levels, and magnesium at least at about 25% of the RDA. More information on zinc
issues is found on pages 6-7.
2. Extra nutrients specifically to help make hemoglobin and red
blood cells:
A. Extra Folic Acid: 2 to 4 tiny folic acid 400 mcg (microgram) tablets. These are
cheap, very easy to take and very safe.
B. Extra Vitamin B12 and Vitamin B6: take one "B-100 Complex" tablet daily
-- it provides very generous amounts of these nutrients and other important vitamins,
and all are well within the safe range. This is true even though RDA levels of these
vitamins are also present in the multivitamin. (Note -- extra vitamin B2 -- riboflavin - will make urine a very bright yellow. No problem.)
C. Copper is involved in transporting iron in the body. The RDA amount of copper in your
multivitamin should be adequate to move iron from the storage areas to the hemoglobin
factories. Just check the label to be sure that it DOES contain about 2 mg.
D. Get adequate protein. (More on this later) The “globin” part of hemoglobin is
7
made of protein, as are a number of substances (like “transferrin”) needed to move
iron from the storage area to the bone marrow where the red blood cells are made.
Protein is also central to the operations of everything in your body, so inadequacy is
never a good idea. Most Americans eat a very generous amount of protein, but
whenever one tries to follow a diet with a lot of exclusions, it is a good idea to check
the appropriateness of protein in the diet.
E. Get adequate (appropriate) calories. Without adequate calories, the protein
you eat will be burned as fuel to make energy instead of being used to make the
important protein substances described above. It’s like living in North Dakota in the
winter and running out of fuel . . . we start burning the furniture!
2. Generous antioxidants to decrease tissue damage from having
extra iron on board:
One way that excessive iron causes serious injury is by a process called oxidation, the
same process that causes metal tools to rust, and cooking oil to turn rancid. To prevent or
minimize this kind of damage, the body has a need for substances that act as
“antioxidants.” When people have a condition that causes increased oxidation, more
antioxidant protection than usual is needed. This is true for hemochromatosis, but also for
many other health conditions like diabetes, arthritis and MS. Here are some suggestions
for optimizing antioxidant defenses:
A. Vitamin E: Take a 400 iu capsule of this important antioxidant also called
“alpha-tocopherol.” The “RDA” is 30 iu, but the RDA levels are designed to
meet the needs of “98% of the healthy population,” This kind of general
recommendation often does not apply when one is dealing with chronic health
problems. The “natural” vitamin E products are usually more expensive than
synthetic forms. The natural form of alpha-tocopherol will have the letter “d” in
front of the name. Forms labeled “dl” are synthetic, and they have about ½ the
strength of the d-alpha tocopherol. It appears, however, that there may also be
advantages to using products that contain a natural source of “mixed tocopherols”
instead of just d-alpha-tocopherol alone. These include substances like “gammatocopherol.” Vitamin E supplementation at high doses can interact with statin
drugs, so as always, check with your doctor if you are taking these medications.
There are supplements that provide “the mixed” form, and good food sources of
mixed tocopherols are nuts, peanuts and the germ of grains. These food sources
also contain generous magnesium and chromium, which is very beneficial. They
contain some inorganic iron as well, but it is not absorbed efficiently enough to
discourage eating these nutrient-rich foods. More on iron absorption later.
B. Selenium (part of a critically important antioxidant made in the body called
“glutathione peroxidase”): Aim for 100-200 mcg/day. If your multivitamin has
about the RDA level of 60 mcg (mcg is the abbreviation for micrograms), take a
small 50 mcg tablet in addition. If your supplement has only a little (e.g. some
7
products have none or only about 20 mcg), take two of the 50 mcg tablets. Some
products already have as much as 200 micrograms – in that case no additional
selenium is needed. Selenium is potentially toxic: the recommended upper limit
is 600 mcg/day, and the toxic dose is a chronic intake of 800 mcg/day. As you can
see, the amount recommended here is not anywhere near the toxic level.
There is evidence that adequacy of selenium and vitamin E may work together to
protect against some iron-overload-related heart muscle damage. The synergistic effects
of vitamin E and selenium in iron-overloaded mouse hearts. Can J Cardiol. 1998 Jul;14(7):937-41
Some areas have high amounts of selenium in the soil so people who eat plants or
animals grown on that soil may actually be getting too much selenium. A good
way to find out if your area is high in selenium is to ask the local county
Agricultural Extension Service staff. Someone there will know whether a region
has low selenium because farmers there have to add selenium to animal feed
C. Eat lots of brightly colored fruits and vegetables. Many of the pigments that
give plants their colors are also very potent antioxidants. These substances are
some-times called “phytochemicals” – which just means “plant chemicals.”
Examples that are being studied extensively now are lycopene in tomatoes, lutein
in dark leafy greens, anthocyanins in blueberries and beets, and many others. Even
seemingly colorless fruits and vegetables (such as onions, garlic and mushrooms)
contain important antioxidants. Eating lots of fruits and vegetables has many
important health benefits. Interestingly, the iron that is found in leafy greens and
may other plants is very poorly absorbed, so enjoy your spinach! (Factors affecting
iron absorption will be discussed more later.)
D. Vitamin C issues: Any acid substance like vinegar or vitamin C can enhance iron
absorption from sources of inorganic iron (the form of iron in pills or plants.)
That effect is a much less important as a source of iron than the highly absorbable
and generous iron found in meat (especially red meat). In spite of this, people with
hemochromatosis are often erroneously advised to stop taking all vitamin pills that
contain vitamin C, and to avoid fruits and vegetables that contain it.
One person’s story: One man that I saw was so conscientious about following
this advice (given to him elsewhere) that he had developed actual evidence of
scurvy, the vitamin C deficiency disease! He was also deficient in many other
nutrients because of his efforts to avoid vitamin C, and inadequacy of those
nutrients made it impossible for him to make red blood cells. That meant that his
phlebotomy treatments to remove extra iron had to be put on hold. His anemia
(lack of red blood cells) also made him feel extremely weak and fatigued.
In addition to the absorption of inorganic iron issue, there has been concern that
high doses of vitamin C may become a “pro-oxidant” (the opposite of the usual
antioxidant role) in situations in which iron stores are excessive or in conditions
like alcoholism. This has not been identified as a problem by subsequent
research. Your multivitamin should contain about 100 mg of vitamin C, and it is
8
very likely safe to take an 100 –200 mg of vitamin C in addition in supplement
form. Some will also be provided by the fruits and vegetables and you are
strongly encouraged to continue to eat them. If you take extra vitamin C as a
supplement, take it with milk or cheese to minimize or negate any increase in
absorption of iron from plants or pills (that is, inorganic iron.)
5. Foods to eat MORE of because they can decrease absorption
of (inorganic) iron:
A. Dairy foods are notoriously poor sources of iron that also decrease absorption of the
iron in plants and pills taken at the same time. Drinking milk daily will also help to
provide some of the vitamin D you need. A multivitamin provides 400 iu of vitamin D,
and there is 100 iu of vitamin D in an 8-oz cup of fortified milk.) This is a reasonable
amount for some people, although people in the northern latitudes have been
shown to need 1000-2000 iu. to assure adequacy because of the diminished ability
to make vitamin D in the skin at high latitudes. The higher risk of vitamin D
deficiency is also associated dark skin, old skin, being indoors much of the time,
sunscreen use, being covered up, or using seizure-control medications.
Vitamin D deficiency is now regarded as “an unrecognized epidemic” in the
northern half of the USA and certainly in Canada. It is a big contributor to a
wide variety of health problems. [See my Top Five Recommendations handout for
more detail on this.] Other dairy foods like cheese and yogurt are often NOT
supplemented with vitamin D, but they do help reduce iron absorption as milk does.
If you are not fond of milk you can use these foods and you can easily add extra
vitamin D as separate 400-2000 iu capsules to solve the important vitamin D problem.
New information about checking for vitamin D deficiency:
For everyone (and especially those with serious metabolism issues like
hemochromatosis) it is a good idea to have a serum vitamin D level measured at
least once in the winter every year. This is because the doctor will want to see
whether a “maintenance” intake level is enough (1000-2000) or if the individual
actually is vitamin D deficient and in need of a “therapeutic” or treatment amount to
correct inadequacy before switching to the maintenance amount. This may be done
several ways, but as an example, it may require 50,000 iu/week for 8 weeks.
As noted earlier, actual vitamin D deficiency is much more common than previously
thought and it is very common in people with liver damage of the type associated
with hemochromatosis. And although deficiency is very harmful it is also generally
invisible except when we look for it with a blood test. The test is called a “25hydroxycholecalciferol” level. [Vitamin D and parathyroid hormone in outpatients with noncholestatic
chronic liver disease. Clin Gastroenterol Hepatol. 2007 Apr;5(4):513-20]
Back to the discussion of dairy foods:
9
Milk actually decreases absorption of iron, and each cup provides a nice 8 grams
of protein. (Remember that ice cream, and most yogurt and cheeses do not have
vitamin D added at this time.) Some types of yogurt have vitamin D added and others
do not. Other than the ice cream, these foods do provide good protein, so milk,
yogurt and cheese are good replacements for meat in meals. For example, have a
cheese sandwich instead of a meat sandwich. An ounce of meat has 7 grams of
protein but lots of easily absorbable iron. Cheese has the same amount of protein, and
a cup of yogurt or milk has 8 grams of protein, but much less iron, and as noted
above, in addition it interferes with iron absorption from other foods. Low fat or skim
milk products are usually best for other reasons.
B. Tea contains “tannins,” plant substances that bind (inorganic) iron in the
intestinal tract very well and significantly reduces its absorbability. This has
been shown to be effective in hemochromatosis specifically (see the excerpt below.)
Tea is looking good for a lot of other reasons as well (e.g. anti-cancer qualities,
antioxidant properties,) in addition to having the marked effect of decreasing
absorption of plant iron.
Clinical trial on the effect of regular tea drinking on iron accumulation in genetic
haemochromatosis. Gut. 1998;43(5):699-704. “A significant reduction in iron absorption was
observed when the test meal was accompanied by drinks of tea instead of water. In the tea drinking
group, the increase in storage iron was reduced by about one third compared with that of the control
group. Conclusions: Regular tea drinking with meals reduces the frequency of phlebotomies
required in the management of patients with haemochromatosis.”
C. Leafy greens. Many foods like spinach contain “oxalates” that bind up iron in the
intestinal tract and make it too big a molecule to be absorbed well. This is true even
though the iron and vitamin C content are generous! These foods also contribute
many terrific nutrients as well. Interestingly, broccoli is low in oxalate, so the iron
and other minerals like calcium are pretty well absorbed from this vegetable. So,
although broccoli is a leafy and green vegetable, and a very nutritious food, it does
not decrease absorption of iron.
D. Bran (the fibrous outer part of grain) contains “phytates” which impair iron
absorption as tannins and oxalates do.
E. Eggs Interestingly, although egg yolk used to be fed to infants as an iron source,
the form of iron in eggs has been found to be very poorly absorbed. Eggs are an
excellent source of protein (the protein in an egg is like 1 oz of meat) and other
nutrients as well such as choline. Further, the egg white has most of the protein (6 of
the 7 grams) and essentially none of the iron at all. So, substituting egg dishes for
meats is another way to decrease the amount of iron available to absorb.
5. Things to eat LESS of (not necessarily to "never" eat):
10
A. Meats of all kinds contain iron in an especially absorbable form called “heme”
iron. This is also sometimes called “organic iron.” (Think of organic iron as coming
from “organisms” – animals and not plants. Absorption of organic iron is not
affected by the presence or absence of vitamin C or acid the way plant iron is. That
means that severely restricting vitamin C is not at all effective in reducing absorption
of the greatest sources of iron in foods, and as described earlier, it can cause harm.
Iron in the “organic” (animal) form is about 20% absorbed. Twenty percent
absorption does not sound very high, but “inorganic iron” (the kind in supplements or
plants) is less than 2% absorbed. Some plant forms of iron, in foods like spinach that
contain oxalates, are only 0.025% absorbed!
In addition to being a generous source of absorbable iron, meat also has a special
property of causing increased absorption of iron from the inorganic iron sources!
In other words, the iron found in chili beans will be much more easily absorbed if
there is meat in the chili. This effect is called “Meat Protein Factor.”
Of all the food-related factors that affect iron absorption, limiting meat intake is
one of the most influential, but even that appears to be less of an issue if a person
is able to undergo phlebotomy regularly. And, as described earlier, maintaining a
generous intake of all the OTHER nutrients needed to make red blood cells is key to
being able to continue to have the phlebotomy treatments.
B. Of the different types of meat, liver is extremely high in very absorbable iron,
so it would be best to avoid it. This includes foods made from liver like paté, or
liverwurst. Scandinavian/German “blood sausage” would also be a poor choice.
C. Red vs white meat: Next to liver, red meat is the highest in absorbable iron, but
unless phlebotomy is not working, complete avoidance of red meat does not appear to
be necessary. Poultry and fish have much less iron than red meat, but what they have
is still more than in plant foods, and like the iron in red meat, the iron is also well
absorbed. Additionally, the white meat of chicken and turkey has less iron than dark
meat. The iron content can be thought of as somewhat “color-coded” in meats.
However, all meats have the ability to increase absorption of iron from OTHER foods
in the meal as described above (the “Meat Protein Factor”)
D. Alcohol should generally be avoided. Iron overload is a cause of serious liver
injury, and alcohol can make the damage worse.
[Alcohol Clin Exp Res. 2007 Jan;31(1):138-43. Effects of alcohol consumption on iron metabolism in mice with
hemochromatosis mutations. J Nutr Sci Vitaminol (Tokyo). 2004 Apr;50(2):78-86. Low dose-ethanol modulates toxic effect of
iron-overloading in the liver.]
E. Raw seafood: As with people who abuse alcohol, people with hemochromatosis or
11
anyone with potential liver damage from any cause should be especially careful to
avoid raw seafood like raw oysters and sushi. It often contains micro-organisms of
the “Vibrio” family that cause cholera and other serious diseases. It is extremely
dangerous to anyone with liver problems, even in amounts that would be considered
safe for other people.
[Necrotizing fasciitis from Vibrio vulnificus in a patient with undiagnosed hepatitis and cirrhosis. J Clin Microbiol. 2007
Mar;45(3):1058-62. Vibrio vulnificus-necrotizing fasciitis in patient with cirrhosis. Intern Med. 2007;46(3):143. A fatal case of
Vibrio vulnificus septicemia from a nongulf state: a public health alert for patients with chronic liver disease.
Am J Emerg Med. 2006 Sep;24(5):621-4. Chronic liver disease and consumption of raw oysters: a potentially lethal
combination--a review of Vibrio vulnificus septicemia. Am J Gastroenterol. 2005 May;100(5):1195-9.]
F. Sometime one can decrease iron intake by choosing a similar plant food that
contains less iron. The form of iron in all of the following foods is “inorganic” iron
and therefore not highly absorbable, but the total amount in some of these foods make
them less desirable products for people with hemochromatosis.
However, this suggestion is way down on the list in terms of importance as long as
phlebotomy is working. I mention them here because invariably someone asks
about them.
Iron-fortified foods: Example: “Quick” iron-fortified cream-of-wheat has over 15
mg iron per cup, but unfortified cream-of-wheat or oatmeal only has about 2 mg.
Iron fortified foods will indicate that they are fortified or enriched with iron if you
check the label. The words “ferrous” or “ferric” in the ingredient list is an
indication of iron being added.
“Enriched” means that the iron was added back to the original level in a food after it
was removed during processing. Enriched flour is an example of this.
“Fortified” means that the iron (or another nutrient) was added to achieve a level
higher than would naturally be in the food. “Total” cereal is an example of this: it is
fortified to provide 18 mg of iron per cup compared with 4.5 mg iron in a cup of a
similar but unfortified whole wheat cereal like “Wheaties.”
Legumes like lima beans and peas have 5-6 mg of iron per cup, but vegetables like
corn and carrots have only about 1 mg.
Prune juice is not the best choice of juice – it contains quite a lot of iron (over 9 mg
per cup compared with about 1 mg per cup of other fruit juices.) It may have other
effects as well. ☺
Iron Content of Food in General: The chart on the last page shows the iron content
of a number of types of foods and some factors that affect its absorption. As you can
see, the foods that are highest in absorbable iron tend to also be highest in
absorbable zinc, and vice versa. This relationship is the reason that the multivitamin
with minerals for people with hemochromatosis should provide the RDA level of zinc:
if people are cutting back on dietary iron, they will also be accidentally cutting back
12
on zinc intake as well. This is particularly important because inadequate zinc can also
impair the production of red blood cells needed for phlebotomy to continue.
6.
A.
Miscellaneous:
Acid-blocker drugs. Proton pump inhibitors are medications that suppress acid
production in the stomach, and they have been shown to decrease absorption of
inorganic iron for that reason. This effect has been employed in the management of
hemochromatosis. People who use this kind of medication must be sure to take
vitamin B12 in a supplement form, because absence of stomach acid impairs
absorption of vitamin B12 from food sources. The amount described earlier is fine …
the issue is that it must be in the crystalline form found in vitamin supplements, and
one cannot rely on the vitamin B12 naturally present in animal foods. Inadequate
vitamin B12 will limit production of red blood cells, so this is particularly important.
[Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007 Mar 7.]
B.
Increased absorption of lead: The same mechanism that results in excessive iron
absorption appears to also increase risk of absorption of lead. Lead seriously injures
the brain and other organs, and is a great contributor to high blood pressure. It also can
contribute to hearing loss. [Examples: Variants in iron metabolism genes predict higher blood lead levels
in young children. Environ Health Perspect. 2008 Sep;116(9):1261-6. Low-level environmental exposure to lead
and progressive chronic kidney diseases. Am J Med. 2006 Aug;119(8):707.e1-9.]
Sources of lead can include:
Calcium supplements made from oyster shells, bone or clay (dolomite.)
[Lead in pharmaceutical products and dietary supplements. Regul Toxicol Pharmacol. 2007;48(2):128-34.
Lead content in 70 brands of dietary calcium supplements. Am J Public Health. 199 ;83(8):1155-60.]
Water from wells that have brass or bronze immersible pumps or water that flows
through old lead pipes.
(For these reasons, a water filter that removes lead from the water would be a very good
idea.) Drinking water is not a major contributor to total lead exposure ordinarily but it
appears that lead in drinking water is probably absorbed more completely than lead in food.
Adults normally absorb 35-50 percent of the lead they drink and the absorption rate for
children may be greater than 50 percent. People with hemochromatosis will absorb even
more. [More information about lead in water, pumps and filters can be found at:
http://extoxnet.orst.edu/factsheets/leadpump.quest]
Old lead-based paint and the dust from it when it disintegrates.
Older homes may have been painted with it, and paint chips and dust can be significant
sources of lead. Remodeling and demolition work will stir up the lead to increase exposure
via the lungs but indirectly through the digestive tract as well. The person with
hemochromatosis will absorb much more than others exposed to the same situation.
13
Some imported pottery, pewter and lead crystal.
The lead content of crystal appears to only become a factor when acidic beverages are in
contact with the lead in the crystal for quite a while, or if the lead crystal is used on a daily
basis. However, many folks use it only about twice a year, so it is not a big problem to toast
the New Year using the heirloom crystal. [Estimation of lead intake from crystalware under conditions of
consumer use. Food Addit Contam. 2000;17(3):205-18. Lead migration from lead crystal wine glasses. Food Addit
Contam. 1996;13(7):747-65.]
Miscellaneous Sources of Lead:
Although the issue of increased absorption of lead in hemochromatosis is related only to lead
that is consumed, sometimes it is accidentally taken in via other routes. Here are a few
examples to be aware of. Most are not common problems, but they are of interest:
Some Cosmetics:
There have been reports recently of lead being found in several brands of lipstick, and many
women do end up swallowing quite a lot of lipstick. Another example is kohl, is a leadbased eye make-up common in other countries that finds its way to the US.
[http://www.4woman.gov/faq/cosmetics.pdf. www.safecosmetics.org;
http://www.leadsafe.org/elements/uploads/files/fileManager/Cosmetics distributorceaseslead_basedeye_liner.pdf. ]
Many folk remedies contain lead:
There is an excellent resource on line. [http://www.oregon.gov/DHS/ph/lead/docs/ homeremedies.pdf. ]
Hunting related: [Intoxication from an accidentally ingested lead shot retained in the gastrointestinal tract.
Environ Health Perspect. 2005 Apr;113(4):491-3.]
Pica (a craving that results in eating or chewing on non-food items): [Pica-associated
cerebral edema in an adult. J Neurol Sci. 2004 Oct 15;225(1-2):149-51.] Happily, “pencil lead” is not
really lead so chewing on pencil lead will not lead to lead absorption from that source.
However, based on recently identified problems with lead-based paint on toys and other
products imported from China, it might be prudent for pencil-chewers to ask where that
pencil came from before proceeding.
14
Sanford Medical Center
Aunt Cathy’s
Guide to Nutrition:
Iron and Zinc in Food
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
University of ND School of Medicine
Fargo, ND
(Data Source: Agriculture Handbook No. 8-4 US
Dept. of Agriculture Science & Education Admin.)
7
Aunt Cathy’s Guide for
Problem Solving:
How Much Should
This Baby Eat?
Troubleshooting in the Front Lines
Cathy Breedon, PhD, RD, CSP, FADA
Perinatal/Pediatric Nutrition Specialist
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
It is well kn own that healthy, t ypically developing infants will te nd to take the am ount of breast
milk, formula and/or food needed to m eet their en ergy (calorie) needs. When lower energy foods are
provided, these babies increase their intake; when hi gher energy foods are provide d, they will eat less.
Of course, this depends on a few major factors:
1.
The food must not be SO LOW in energy that th e baby cannot possibly eat the volum e of food
required to get enough, or SO HIGH in energy th at the amount needed to quench thirst carries
with it exorbitant calories.
2.
The feeder must make the food easily accessible to the baby.
3.
The feeder must not coax, prod or force baby to take more than the amount needed to meet hunger
needs, or fail to feed enough in an effort to prevent having a “fat baby.”
4.
The baby must be able to eat, to keep the food down, and to digest and absorb it adequately.
This article will provide some tools for judging the adequacy and appropriateness of an infant’s or
child’s inta ke, includin g checklis ts to aid in the de tective work needed to identify the reason for a
particular growth pattern or reported intake. W hile these tools can be useful in working with healthy
infants and children, they can be especially helpful in evaluating the nutritional status of those children
with special health care needs and for identifying appropriate nutrition interventions.
A regis tered dietitian (R D) can ev aluate in de tail a ch ild’s intake by working together with the
primary care provider (PCP), nurse or oth er h ealth care p rofessionals. Som e RDs are also b oard
certified as pediatric nu trition specialis ts. They will h ave the cred ential CSP af ter their nam es in
addition to the letters RD.
GUIDLEINES FOR EVALUATING
AN INFANT’S INTAKE
Caregivers are often concerned about finding th e magic number of ounces or spoons of food
that a baby “should” take. Once a m other’s milk supply is established, a breast-fed baby has much
more control over the amount of food taken than a fo rmula fed infant. The breast-fed infant’s mother
cannot see h ow much is taken and how m uch is le ft. Bottle feeding tends to encourag e “empty bottle
syndrome”: m aking baby take every last drop or
bite w hether it’s needed or not. (“Come on,
Baby….finish this stuff! It’s too expensive to waste!”) This can teach a child to ignore internal
hunger cues and it also teaches that the best way to m ake Mom and Dad happy is to eat ev erything in
sight!
This sort of learning may contribute to late r obesity, as suggested by studies assessing the
effects of internal and external clues for eating among normal weight and overweight adults. In som e
studies it was found that ove rweight individuals tended to eat more in response to external cues to eat
(the sight of food, the time of day when one usually ea ts) rather than in response to an actual sensation
of hunger. Breast-feed ing as well as bottle-feeding could contribu te to this same pattern if one uses
feeding as a pacifier and cure for all upsets and discomforts.
Many of us have learned to use food as a
therapy for stress, de pression, boredom or
nervousness. These eating patterns can contrib ute to weig ht problem s because we are not eating in
response to a physical hunger stimulus, but to meet a psychological need.
If a baby is growing appropriate ly we do not need to be so over-concerned about the am ounts
an individual infant consumes. Since each baby has his/her own pattern and rate of growth, period s of
growth spur ts and v ariable ac tivity levels, it is r easonable to try to let hea lthy babies se t th eir own
energy intake on a daily basis.
For example: a record o f normal intakes at 6 m onths of age indicated that the average intake
was 37 oz/day of formula or m ilk, with an a dditional 9% of calories com ing from other foods. 1
However, the range of norm al intakes (between the 10 th and 90 th percentiles) at th is age was 30 to 50
oz per day. There is no reason to suppose that an individual 6 m onth old infant should take the
“average” amount of formula, especially when the amount of other food eaten by the baby could be far
less or far greater than 9% of calories.
There is also no pressing scientific reason behind the “rule” that a baby should never be given more
than a quart (32 ounces) of for mula a day. Thi s non-helpful guideline proba bly evolved from four
factors:
1. By the tim e m ost babies drink a quart of for mula daily they have reached a developm ental age
when it is appropriate to begin to take solids. That is, the baby is usually 4-6 m onths old, so the
rule is a good reminder to begin introducing other foods.
2. A quart (32 oz) of formula provide s the RDA for vitam ins, minerals and protein, so healthy babies
do not need to take more than that volum
e to m eet those guidelines. At this point, if
developmentally ready, infants can very safely wo rk on learning to eat other foods. The nutrient
balance of baby’s sometimes unpredictable beginning food choices will not be a problem.
3. Because a quart of formula does p rovide for adequate levels of vitamins, minerals and protein, and
since formula can be quite expensive, it is financia lly reasonable to use no m ore than 32 ounces of
formula each day and provide the additional energy baby needs as other foods.
2
4. Some confusion on this point has also arisen
from the fact th at the W IC Program (Special
Supplemental Food Program for Wom en, Infants and Children) provides formula for infants in an
amount each month that m akes about 26 ounces per day (one can of form ula concentrate per day,
or a sim ilar amount mixed from formula powder.) Pe ople sometimes fail to realize that W IC is a
supplemental food program , not a pr ogram that purports to meet all of the nutritional needs of its
clients.
When infants reach a size when 26 ounces of for mula no longer meets their needs, their caregivers
are expected to eith er purchase some additional formula or, if age-appro priate, other foods can be
offered to the baby. This W IC program limit of formula provided is based on funding limitations.
It is not intended to be used as the upper lim it of for mula an infant may safely or appropriately
take.
So, although the commonly heard “32 ounce lim it” of for mula daily m ay be a us eful guide, it is
certainly no t a Rule. Consum ing over 32 ounces is not harmful or dangerous.
Many infants
regularly take over 32 oz/day without any problem s. As long as the child is growing appropriately
and being given opportunities to acquire developm entally appropr iate eating skills, a form ula
intake above 32 oz/day is of no concern.
However, the quantity of hum an milk or for mula consumed can be a lim iting factor in the nutrient
quality of an infant’s diet even if the baby’s energy needs are bein g appropriately met. Babies who
are healthy, growing norm ally a nd taking the great m ajority of their nutrition as a nutritionally
complete or near-com plete p roduct (e.g. hum an milk or commercial for mula) will likely be
obtaining the right am ount of food and individual nu trients. [Vitamin D needs closer attention, of
course.] With the introduction of other foods however, the complete nutrition product will begin to
be displaced. This is reflected in the average milk or formula intake at age eleven months dropping
to 18-24 oz/day from the peak intak e at around 6- 7 months of age. Addition ally, the content o f
iron, zinc and vitamin B6 decreases markedly in human milk after 6 months.
The nutrient quality of the diet then becomes more dependent on th e particular foods offered and
consumed. Many infants are fed an appropriate amount of a variety of foods, but it is at this point
that a more careful look at diet proportions is warranted. For example, it is sometimes erroneously
assumed that the baby’s diet will be balanced as long as formula or human milk is provided, even
when the volume consumed is extremely low.
A quick-and-easy estimate of the
“typicalness” of a formula intake volume
for screening healthy infants:
Multiply the ounces taken in by 20 kcal/oz
(this assumes the formula is prepared
following the usual directions ) and divide
by the infant’s weight.
3
In the first year of life, an intake of about 90-120 kcal/kg (kilocalor ies per kilogram of body
weight) which is the sam e as 41-50 kcal/lb (kilocal ories per pound of body weight) is typical, w ith the
numbers in the higher end of the range mort often seen in the first half of the year. In the past, 100-120
kcal/kg (45-50 kcal/lb) have been used as guidelin es, but more recently it was found t hat many infants
will grow normally and thrive on the smaller caloric intake levels as well.2
The key of energy (caloric) adequacy will always be :
Look at the baby’s growth, especially weight for length (weight/length) ratio
and apparent body fat stores.
If other food sources ar e included in the infant’s diet, you
can easily calculate the energy
contribution of baby foods using the tables of averag e values from manufacturers’ product information
or food nutrient tables. New labeling laws also make this much easier than in the past. Additionally, a
simplified system like the old diabetic exchange system can be used for table foods.
Calculating the en ergy intake and th en comparing it with the “typical” range is a useful screening
tool to help identify problem s not i mmediately apparent. Values abov e or below this range, even in
apparently healthy inf ants, cer tainly warrant a closer look since th ey m ay be indicators of certain
problems. However, the typical range is not be to used as a feeding rule that a particu lar child must
conform to on a regular basis.
This method to interpret the appr opriateness of a baby’s energy inta ke for its weight assum es that
the baby is of fairly norm al weight for age and length . Remember that very thin or very chubby babies
will not play by the sam e rules because their unusua l weight for length and age significantly changes
the denominator in the ratio:
•
Very thin babies will appear to have a more generous caloric intake than they actually do.
•
Conversely, a high caloric intake in a chubby baby may appear to be within the usual range because
there are so many pounds or kilograms to spread the calories over.
To correct for this effect, it can be helpful to recalculate kcal/kg or kcal/lb
using the average weight for a child of the baby’s length.
(See Case Studies 1 and 2 for examples.)
4
TROUBLESHOOTING ON THE FRONT LINES
Looking for Explanations when Unusual Intake Patterns are Reported
Note: All of the case studies and scenarios presented here have come from
actual experiences with babies for whom these questions and considerations
detected the real cause of inappropriate growth.
Things to Consider in Assessing All Intake Records:
1. How accurate is the intake record?
Is the person describing the intake:
ƒ
Providing first-hand information (e.g. is baby fed by others part of the day?)
ƒ
Guessing?
ƒ
ƒ
Clear about arithmetic and the actual size of the bottle or cup used?
Remembering to count night feedings, all beverages and all snacks?
ƒ
Able to accurately describe formula preparation?
2. How typical is the intake record?
ƒ
Is the record from the weekend at home but baby is fed at a sitter’s house five days a week?
ƒ
Is the child ill or just now recovered from an illness and weight loss?
3. Check that the total day’s intake volume reported is consistent with estimates obtained
through other approaches.
For example, compare a reported estim ate of tota l ounces of for mula consumed per day with both
the number of ounces prepared daily and the sum obtained when asking the caregiver to go through
a typical day describing each feeding.
In addition you m ay ask the num ber of cans of con centrate used in a day or how many days one
can of powdered form ula feeds the baby. This type of cross-checking will pick up errors like
missed night feedings, and it can cl arify complex situations like Case Study 3 (a very thin infant
who was reported to take a lot of formula but who never seemed to be satisfied.)
5
Things to Consider in Assessing Specific Patterns of Unusual Intake:
Figure 1 below describes four scenar ios that often are seen when eval
Explanations of each of four scenarios follows the figure.
uating the intake of infants.
Authors Note: I often use the term “fluffy” instead of obese when discussing a child with caregivers
because it is less judgmental. Our society equates generous adiposity with many negative personal
qualities. In order to optimize the therapeutic relationship it is important for the family to know that
I care about and like their child. Although this term is not scientific or technical, I find that it works
well for me and my clients, and it fits my Aunt Cathy patient-care style.
Figure 1:
Four scenarios to consider when the
reported intake seems to be at odds
with the baby’s appearance
Infant
Appearance
Reported Intake
High
Low
1
3
2
4
Thin
Fluffy
SCENARIO 1:
A very high reported intake, especially for a slim or normally proportioned baby
BABY Problems to Consider
•
Is baby experiencing any malabsorption? Ask about stool patterns.
•
Is baby vomiting excessively or does the baby have reflux?
Ask about the frequency, forcefulness and volum
e. Note that volum e of vom itus is often
overestimated even by health professionals. To better estimate am ounts lost, one can pour a small
amount of water on a table surface or cloth and ask the caregiver to com pare it w ith the reported
volume. (“Is it about this much?”) It is surprising how a small amount can appear to be quite a lot.
6
If vomiting is reported to be significant, has pyloric stenosis or gastro esophageal reflux (GER)
been ruled out by the physician? In infants reflux can be relate d to im maturity of the lower
esophageal sphincter.
•
Does baby vomit consistently or only under certain circumstances, such as:
ƒ
Only when left alone after a feeding, as has been reported in cases of rumination associated with
nonorganic failure to thrive.
ƒ
Only when made to intake more than a certain volume.
ƒ
Only when fed certain foods or when certain water is used to prepare formula.
ƒ
Only when fed in an “infant seat.”
ƒ
Only when a certain person is the feeder.
•
Is the baby much more physically active, irritable and/or jittery than usual?
•
Is baby “hypermetabolic”?
Higher metabolic rates are sometimes seen when babies are working hard to breath, born sm all for
gestational age, f ighting inf ections, trying to achieve catch-up gr owth, recovering from an acute
illness and sometimes when they have been exposed to significant mounts of alcohol or other drugs
in utero.
•
Is the baby adequately oxygenated?
Progressing to a state of health in which extra oxygen is no longe r needed is seen as highly
desirable by caregivers both as a s ignificant marker of progress for the baby and because it m akes
infant care and transpor tation much easier. For this reason, there can be a tendenc y for families
and health care professionals to want to get the baby off oxygen as soon as possible.
However, som etimes adequate food intake and gr owth are only able to be achieved because of
assisted oxygenation. P rematurely removing oxygen support can result in a baby having to use so
much energ y to bre athe that g rowth is im paired. Also, exhaustion from the excessive breathing
effort can make a baby stop eating before nutritional needs are met.
Providing oxygen when it is needed assures that the child does not have to choose between eating
and breathing. Helping all concerned understand these concepts is very important.
CAREGIVER Problems to Consider
•
Is the formula mixed incorrectly?
If too m uch water is added, ba by must drink a very large volum e to try to get enough calories.
He/she mail fail to get enough to maintain appropriate weight for length.
7
SCENARIO 2:
A very high reported intake, especially “fluffy” baby
BABY Problems to Consider
•
Is baby truly fluffy (having a very high weight/length ratio) or just large for age
(weight/length ratio normal)?
If the weig ht/length ratio is with in norm al lim its then the baby lik ely is m anaging his/her ow n
intake appropriately. Do not attempt to make baby take less to match some average intake for age.
•
If baby is truly fluffy and also consuming a very high caloric intake, is he able to sense satiety
normally?
Some children with brain injury (such as congen ital hydrocephalus) can e xperience problems with
this even a s infants. Other children (such as those with P rader-Willi Syndrome) are more like ly to
experience this problem later in childhood.
CAREGIVER Problems to Consider
•
Is food being used as a pacifier?
•
Does the caregiver understand that babies often cry for reasons other than hunger?
•
Does the caregiver believe that baby needs to take in a particular amount regardless of
appetite?
•
Is there pressure from family members or other to:
•
ƒ
Keep that kid quiet!
ƒ
Put some meat on his bones!
ƒ
Giver her a lot of food or formula to make her sleep through the night!
Is formula being prepared correctly?
Failure to add enough water to the form ula can contribute to dehydration. Babies may be forced by
thirst to take more formula than they are hungry for (calorically,) creating a vicious cycle.
•
Is baby being kept too warm and sweating a lot, leading to taking extra formula in an effort
to meet fluid needs?
If so, and if the heat situation cannot be adjust ed, give guidelines for a reasonable formula intake
and provide additional water in some form as appropriate.
8
SCENARIO 3:
A low reported intake, especially for a slim or normally-proportioned baby
BABY Problems to Consider
•
Is the baby much more physically active, irritable and/or jittery than usual?
Does this behavior use up energy quickly and also
distractibility or exhaustion?
•
interfere with baby’s ability to eat becaus e of
Is the baby hypermetabolic?
Higher metabolic rates are sometimes seen when ba bies are working hard to breathe. Some babies
in this situation are thos e with heart or lung c onditions. Some were born sm all for gestational age
and they may be trying to achieve catch-up growth.
Babies f ighting inf ections, or rec overing f rom an acute illn ess m ay f all into this c ategory.
Sometimes babies who have been exposed to significant amounts of alcohol or other drugs in utero
will have this problem.
•
Is baby adequately oxygenated?
(See Scenario 1)
•
Is there anything physically interfering with the baby’s ability to suck and swallow
adequately?
Poor lip closure, structural t ongue or lip problem s, and poor coordination of sucking, swallowing
and breathing can all interfere with getting enough in. They can make feeding very time consuming
and also quite unpleasant for the baby. Evaluation and recomm endations by a pediatric speech
therapist or occupational therapist can be very helpful in this situation.
•
Is tummy capacity adequate?
If a higher caloric density feeding were used, woul d the baby continue to take the same volum e or
would he/she decrease intake to maintain the same caloric level?
How long does baby take to finish a feeding?
How often does baby eat?
Does baby seem to experience early satiety?
9
•
Does the baby perceive hunger?
Can baby communicate hunger adequately?
Does baby ever cry to be fed or does the caregiver have to initiate the feedings?
Is baby taking any m edications that can suppress appetite or cause
drowsiness?
ga strointestinal dis tress o r
CAREGIVER Problems to Consider
•
Can the caregiver recognize baby’s signals that he/she wants to eat?
•
Does the caretaker have realistic expectations about baby’s feeding abilities and needs?
•
Does the feeder stop feeding too soon, when baby is only catching his/her breath?
•
Does the feeder engage the baby during feeding? Is there eye contact and cuddling?
•
Are the feeding utensils appropriate?
For example, is the type of nipple appropriate and the nipple hole the right size so baby does not
become exhausted or frustrated, or choke when eating?
•
Does the feeder have an eating disorder?
Does the caretaker eat regularly ? Does he/she have extrem e vi ews about fitness or about not
wanting to have a fat baby?
•
Is the caregiver very young and/or inexperienced in basic baby care?
•
Are there other children to care for, or other obligations? Who actually feeds this baby?
•
Is the caregiver afraid that frequent feeding or cuddling with “spoil” the baby?
•
Does the caregiver think that snacking between meals is bad and so feeds baby only three
times a day?
•
Is the feeder engaged in a “Food War,” -- a battle of wills -- with an infant that has resulted
in disordered eating (e.g. near total food refusal) on the part of the infant?
•
Is being fed unpleasant for the baby?
A history of having been intubated or forcibly fe d can caus e a baby to associate oral eating with
unpleasant experiences. Children who have experi enced only m inimal oral feeding because of
10
health problem s can also find the introduction of an oral feeding regim en to be quite unpleasant
and frightening. Those with som e degree of dysphagia (“unsafe swallowers”) may experience oral
food intake as a terrifying exercise in trying not to choke and aspirate food into the lungs.
Some babies and children are ex tremely sensitive to certain textures and oral sensations. Som e
have a “hypersensitive gag reflex.” Again, the RD can assist the fa mily as they talk with the PCP
to consider a feeding evaluation by a Pediatric Occupation al Therapis t and/or Spe ech Therap ist.
Many of them have special programs and experience in overcoming this type of feeding aversion.
SCENARIO 4:
Low reported intake, especially for a very fluffy baby
BABY Problems To Consider
•
Is baby hypotonic or less active than usual?
A baby with low ene rgy requ irements will often take less form ula than ave rage becau se of
decreased hunger, especially when fat sto res are quite gen erous. But even so, baby m ay still get
more calo ries than are required because of th e drive to m eet fluid needs. Som etimes only high
calorie fluids are available.
Baby may also be coaxed or forced to take m ore than he/she would choose because caregiv ers are
concerned about an unusually low intake volum e. Chubby children with Down Syndrom e or
certain types of nerve and/or muscle diseases can sometimes present this way
Tube-fed children with m inimal energy expenditure are especially vulnera ble to overfeeding when
caregivers or health p rofessions set goals based on the usual caloric intake levels observed for the
“average” baby’s age, activity/movement or size. Weight gain goals can som etimes be set at levels
that are that are inappropriate when baby’s body composition is atypical.
CAREGIVER Problems to Consider
•
Is the formula mixed incorrectly?
As noted above, if too little wate r is added, baby m ay appear to be taking a relatively low volume
of formula but he/she actually may be getting quite a lot of calories.
•
Is baby receiving substantial amounts of corn syrup (60 kcal/oz) for constipation problems?
•
Is a lot of cereal or other thickener added to the formula in an attempt to prevent spitting up
or gastroesophageal reflux, or because of dysphagia concerns?
11
The caloric contribution of thickeners and corn syr up can b e substantial: infant cereals are 9 kcals
per level teaspoon, and corn syrup contributes 10
kcals per teaspoon. Thes e additives can also
seriously alter the ratios of carbohydrate and/or fa t to protein, som etimes leading to a relative
inadequacy of protein. The micronutrient content of the diet is also quite likely to be disturbed
unless carefully assessed and adjusted.
CASE STUDY 1:
A “fluffy” baby with a reported intake in the typical kcal/kg range
DATA: At age 3 m onths, LS is a very fluffy-looking baby. He weighs 6.6 kg (14 lb 8 oz) and is 57
cm long (22.5 in). His weight/length is above the 95th percentile.
He takes about 760 kcal da ily, all from for mula, which is 115 k cal/kg, and well within the norm al
range for his age.
Question: Why is he gaining weight at an excessive rate on this apparently normal intake?
ANSWER: Since his weight/length ratio is not in the normal range; the Rule-of-Thumb kcal/kg range
will not apply directly. It assumes a normal distribution of lean body mass and fat stores.
Children with a disp roportionately high am ount of fat relative to lean body m ass will need fewer
Kcal/kg than average to support themselves. This is because lean body mass is the most metabolically
active tissue, and the caloric requirements to maintain fat stores are much lower.
12
One can use this alternate calcula tion to get a sense of the energy ne eded to support his (tentatively
presumed to be normal “non-fat” tissues) plus a more typical amount of fat stores for age.
1. On the weight/length N CHS growth chart above fi nd L.S.’s length along the bottom of the page.
Follow a straight line upward at that point until it intersects the 50th percentile. Then go to the side
to find the average weight for children of that length.
The average weight for this length is _________(a).
2. Recalculate the kcal/kg (kcal/lb) using this weight as the denominator. Is the intake still in the
typical range? Depending on the situation, it m ay or m ay not be. This calculation can provide a
clue to help you assess the situation correctly.
760 kcals= kcal/kg average wt for length
(a)
For example, if the inta ke is now above the usual range, it m ay be tha t the child has norm al c aloric
requirements and he is “fluffy” due to higher than usual caloric intake. In this case continue your
assessment using Scenario 2.
However, if his recalculated intake is still in the typical range, it may be a clue that the child has lower
than norm al caloric requirem ents. This m ay occur with children who are hypotonic (who have low
musle tone,)those who move less than usual for any reason and in certain forms of muscle disease. In
this case, continue your assessment using Scenario 4.
Which scenario is suggested by L.S.’s history?
(answers on page 16)
If a lower weight/length is desirable (e.g. for a child whose condition results in decreased physical
activity or decreased lean body mass, such as spine bifida or certain neuro-muscular conditions), pick a
percentile that would decrease the risk of overfeeding and of inducing what could be very debilitating
“over-fatness.” These children can be quite overfat but not look especially overweight on the charts.
Depending on the child’s degree of mobility or muscular impairment, a weight-to-length ratio between
the 10th to 25th percentile may actually be optimal for continued independence. Use that weight to
calculate the caloric intake goal.
[Please see my handout “Why Are Children With Chronic Illnesses or Handicapping Conditions at
High Risk of Receiving Suboptimal Nutrition?” for more specific information.]
As always, it is critical to:
•
follow each child’s individual growth pattern since all of these Rules -of-Thumb are just starting
guesses. Assessm ent of body fat stores is an important adjunct for children with unusual body
composition, in order to assure that fat stores
are not depleted or excessive. T his m ay be an
“official” as sessment – using a caliper and followi ng skinf old thicknes s – or som etimes just a n
13
educated eye and a “finger pinch” can be just as helpful. Many neurologically-affected children can
have a slim appearance but actually have adequate-to-generous fat stores. In such cases, it is not in
their best interests to push for a somewhat arbitrary weight gain that would only make it harder for
them to move themselves or to be cared for my others.
•
assess the adequacy of protein, vitamins, minerals and fluid es pecially wh en low caloric
requirements result in decreased total food intake or when certain food groups m ust be elim inated
due to allergies or texture problems.
•
consider the potential for altered nutrient requirements. These m ay accom pany a particu lar
medical condition or therapeutic regimen such as drug nutrient interactions, nutrient malabsorption
or excessive losses.
CASE STUDY 2:
A very thin baby with an intake in the typical kcal/kg range.
DATA: at 7 kg and 72 cm (15 lb 6 oz; 28.3 in), AG is quite thin. Her weight -to-length is below the
5th percentile and yet she appears to take 100 kcal/kg (45.5 kcal/lb), which is a typical intake.
Why does she fail to gain well on what appears to be a normal intake?
ANSWER: As with L.S., this baby has an unusual body composition th at makes the Rule-of-Thum b
not apply. She is virtually all lean body mass (with minimal fat,) so her metabolic rate for her length is
higher than would be expected.
1. Use the alternate calculation: Find the average weight for her length. The average weight for
this length is __________ (a). (See Figure 3 on the next page.)
2. Recalculate kcal/kg (or kcal/lb) using this weight as the denominator.
700 kcals = ______ kcals/kg
(a)
Is the intake still in the typical range? If it is, this would be a clue that something else is gettin g in
her way, so continue your assessment using Scenario 1.
If the intake now looks low, it appears that something is preventing her from taking enough volume to
meet her needs, so continue your assessment using Scenario 3.
Which Scenario is suggested by A.G.’s history?
(answers on page 16)
--------------------------------------------------------------------------------------------------14
This alternate calculatio n can also assist in setti ng intake g oals f or children with s pecial m edical or
physical problems when it is clinically appropriate to do so.
Example: In Case Study 2, if this ch ild’s nutrition care plan established a caloric and protein intake
based on her actual weight, she would continue to be underfe d. Instead, choose a w eight denominator
(using the weight/length ratio on the NCHS growth chart) that is more desirable.
If an average weight/length is desirable (e.g. for a child with nutrition al needs in the typical range,
but whose intake is con trolled by o thers becaus e all feedin gs are via a tube), base the energy and
protein recommendations on an average weight for a child of that length. Then follow up by
monitoring growth car efully and ad justing the f eeding as n eeded. For catch -up growth, even higher
intakes m ay be needed on a tem porary basis. It is not uncomm on for child ren to “outgrow” their
feeding unless som eone checks this periodically. W hat was once adequate per kg of body weight
drops to a level that fails to support appropriate gr owth, so follow-up is crucial. Som etimes caregivers
can be taught to do this calculation and progress the feeding volume themselves as the child grows.
CASE STUDY 3:
A thin infant with a very large reported formula intake volume.
DATA: B.W., a very thin-appearing 6.2 kg baby boy, w
as reported by his m other to have had a
regular intake for many weeks of five 8 oz bottles of form ula daily and no solids (40 oz x 20 kcal/oz =
800 kcal/day; 800 kcal/6.2 kg = 129 kcal/kg) which is a hi gher intake than usual, especially for such a
thin baby.
15
B.W.’s m other repo rted that h e “seem s to want to e at a ll the tim e” and is “nev er satisf ied” with a
feeding. This pattern could reflect a serious m edical problem and if found to be a true representation
of the situation, it should result in a referral for medical evaluation.
ANSWER: On further questioning however, the mother was asked to describe formula
preparation and feeding in greater detail and from several different angles. She then described
preparing only one can of for mula concentrate da ily. Formula concentrate contains 40 kcal/oz and
comes in 13 oz cans, providing a maxim um of only 84 kcal/kg for a 6.2 kg baby) . It was discovered
that mother was not comf ortable with ar ithmetic or measurement, and that the bo ttles she was using
held only 4 to 5 oz each rather than 8 oz.
B.W.’s mother had been afraid to give the baby more in spite of his evident hunger. She was told by a
person staffing a professional pediatric health phone consultation line at a loca l clinic that giving him
40 oz (as she had been) was “probably over feeding since 32 ounces was the lim it.” The health care
professional indicated that the chil d’s reported d esire for m ore to e at when his in take was alr eady so
high was “probably just attention-getting behavior.”
If the health care professional had asked about the child’s appearance (very thin), and obtained
a more thorough description of formula preparation, the problem would have been immediately
apparent and easily resolved.
A similar picture m ight have occurred with the overd ilution of the for mula, and there is an additional
threat of water intoxication. This mother avoide d that measuring problem by using the em pty formula
concentrate can as the measuring device for adding water 1:1. Over- and under-dilution of for mula are
actually fairly comm on m istakes. One study f ound th at as up to 5% of pe ople preparing form ula
misunderstand the directions and dilute the form ula twice; another 5% fail to dilute the form
ula
concentrate at all. However, only very careful questioning will detect the real problem.
SUMMARY
A good understand ing of the und erlying as sumptions ab out growth and body com position which
provide the basis for the usual nutritional recomm endations for infants and children is very im portant.
It m akes it possible for the health care professional to m ake “intelligent departures” from the usual
feeding recommendations in order to meet the needs of children with special health problems.
Careful questioning can be of gr eat valu e in helping to dif ferentiate between the ser ious health
problems that require m edical car e, and th e problem s which are co rrectable by sim ple dietary
adjustments. Knowing th e righ t q uestions to ask can m ake it eas ier to be a su ccessful nu trition
detective and an advocate for these young children.
Answers to Case Studies 1 and 2
Case 1
L.S. Intake = 160 kcal/kg (72 kcal/lb)
Scenario 2
Case 2
A.G Intake = 78 kcal/kg (36 kcal/lb)
Scenario 3
16
Sanford Medical Center
Aunt Cathy's Guide To:
The Importance of
Vitamin/Mineral Cofactors
(not scientifically correct)
What happens if
vitamin / mineral cofactors
are not available?
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
MeritCare Medical Center
Aunt Cathy’s
Industrial Strength
“Instant” Oatmeal Recipe
(By popular demand . . . one person ☺)
Cathy Breedon PhD, RD, CSP, FADA
Clinical Nutrition Specialist
MeritCare Health Systems, Fargo, ND
and UND School of Medicine
There are just the two of us, but on the weekends one of us will cook up a big batch of hot
cereal. Depending on what we have around, it usually contains something like the
following. Measurements are certainly not exact (we use the time-honored scoop and fling
method,) but it often comes out sort of in this ratio:
1 cup of stone-ground oats
½ cup oat bran
½ cup wheat bran
½ cup of wheat germ
½ cup of ground flax
-about a cup of raw almonds that come with the brown coating on them (cheapest at
warehouse-type stores), chopped up. Slivered almonds are easy but much more
pricey. You could use walnuts instead, or in addition.
-about a cup of raisins (especially yummy: the big red-grape raisins also available in
those stores) Be creative . . . how about dried apricots or mango bits?
Add anything else you want in any amount and leave out anything above you don’t want.
Usually I start with about a quart or so (i.e. unmeasured) of water in a big heavy pot
(something like a small size pressure cooker bottom – the heaviness keeps it from having
hot spots and sticking.) Add the raisins and chopped nuts. Bring to boil. Add everything
else in any order, but the oat bran does best if you don’t just dump it in but stir it in a bit
more gradually. You could even mix it all together in a bowl first and add it all at once to
the water, but I am never clever enough to think so far ahead.
Bring it back to a boil on low or medium and stir and cook it as long as it says on the
stone-ground oat package. If it gets too dry or starts to stick, just add more water. The
water just depends on how you like your hot cereal – thin or thick. Your call!
We eat some on the day we make it (usually Sunday) and put all the rest in a covered
plastic container in the refrigerator. Then, while racing around in the morning to get to
work, we just microwave a “slab” of the cold cereal and it is the very best tasting
“instant” oatmeal in the world. It has lots of great nutrition (magnesium, protein, omega3 fats, vitamin E, B vitamins, soluble fiber to lower cholesterol, non-soluble fiber to keep
things moving, a variety of beneficial phytochemicals, etc., etc.) and really fast.
I put milk and a packet of sugar substitute or sugar on mine. Dan puts a “heart healthy”
margarine (no trans, etc.) and brown sugar on his. A friend puts jelly or syrup in it. Go
wild! ☺
Some folks are not really good breakfast eaters. In that case, you can also take it cold in
a plastic container to work and microwave it to have it as a coffee-break snack or for
lunch. You could even pre-fill several small containers the day you make it and just “grab
one and run out the door.”
One could also do kind of a “Master Mix” approach to make preparation even easier and
faster. Just add all the dry ingredients (including the nuts and raisins) and put them in a
freezer bag. You want to keep the mixture refrigerated or frozen in order to keep the flax
and wheat germ happy. Anyway, when you experience the urge to cook a big pot of
cereal, just grab one of your ready-to-go bags of mixed ingredients from the freezer, boil
water and dump in the cereal combo. For the truly home-economically gifted, one could
set aside one day a year and fill a small chest freezer with a year’s supply of ready-to-add
cereal mix. Impress your friends. It would certainly impress me!
One other idea: Sometimes I actually cook dinner (“Gasp!”) and I find that it is pretty
easy to make up a batch of this cereal for the next day while preparing an evening meal.
You can do it while the Tater Tots are baking! ☺
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
New Attention to an Old Problem:
Iodine Deficiency in
Pregnancy and Lactation
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center Dept. of Pediatrics and
UND School of Medicine Dept. of Pediatrics
Fargo, ND
Bibliography and some abstracts
2005- Jan. 2011
2011
Hypothyroxinemia and Pregnancy. Endocr Pract. 2011 Jan 17:1-24. Objective: To evaluate the peer-reviewed
literature on iodine deficiency and hypothyroxinemia in pregnancy. … An adequate amount of iodine intake has to
be recommended pre-conception or starting early in pregnancy.
Neonatal Age and Point of CareTSH Testing in the Monitoring of Iodine Deficiency Disorders:
Findings from Western Uganda. Thyroid. 2011 Feb;21(2):183-8. Background: Iodine deficiency is a major
public health problem throughout Africa. Although salt for human consumption is said to contain adequate amounts
of iodine in Uganda, iodine intake may not be optimal. … Based on the percentage of neonates with TSH values
>5 mIU/L, presumptive iodine deficiency persists in western Uganda. This finding suggests that continued
monitoring of iodine nutrition in the area surrounding the Rwenzori Mountains in Uganda and Congo is
needed. …
Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: A
common practice in some Asian cultures to promote breast milk supply. J Paediatr Child
Health. 2011 Jan 31. Mild iodine deficiency is a recognised problem in Australia and New Zealand. However,
iodine excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of
excess dietary iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of
consuming seaweed soup to promote breast milk supply. Although most attention recently has been on the
inadequacy of iodine in Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is
desirable.
2010
Iodine deficiency in infancy - a risk for cognitive development. Dtsch Med Wochenschr. 2010
Aug;135(31-32):1551-6. Severe iodine deficiency during pregnancy seriously influences fetal brain development
and in the worst case induces cretinism. Recent studies have shown that even a mild iodine deficiency during
pregnancy and during the first years of life adversely affects brain development. The World Health
Organisation (WHO) considers iodine deficiency as the most common preventable cause of early childhood
mental deficiency. In this context, the insufficient production of the four iodine atoms containing thyroxine seems
to play a causal role, i. e., due to the iodine substrate deficiency the neuronally particularly relevant free-thyroxine
level falls. Due to the very limited iodine storage capacity, the infantile thyroid is eminently dependent on an
adequate and steady iodine supply. In the first month of life, when milk is the only energy- and nutrient
provider, infants fed a commercial formula regularly have a sufficient iodine supply. However, breastfed
infants, who depend on maternal iodine status, frequently show an inadequate iodine intake. Furthermore,
iodine intake is critical when complementary food (CF) is introduced. Especially homemade CF is poor in
iodine, but also commercial CFs are only partly fortified. A simultaneous inadequate iodine supply of the
breastfeeding mother and the preferential use of mostly iodine-poor organic milk cannot ensure an adequate iodine
supply of the infant. In terms of an improvement of nutrient supply, especially concerning an unhindered
brain development, the corresponding German reference value for iodine intake of infants until age 4 month
should be raised from currently 40 microg/d to at least 60 microg/d (WHO-reference: 90 microg/d).
Some subgroups of reproductive age women in the United States may be at risk for iodine
deficiency. J Nutr. 2010 Aug;140(8):1489-94. Consuming an adequate amount of iodine during pregnancy is
critical for fetal neurologic development. Even a mild deficiency can impair cognitive ability. Important sources of
iodine in the United States include dairy products and iodized salt. Although the U.S. population has
traditionally been considered iodine sufficient, median urinary iodine concentrations (UIC)
have decreased 50% since the 1970s. We analyzed 2001-2006 NHANES data from urine iodine spot tests
for pregnant (n = 326), lactating (n = 53), and nonpregnant, nonlactating (n = 1437) women of reproductive age (1544 y). We used WHO criteria to define iodine sufficiency (median UIC: 150-249 microg/L among pregnant
women; >or=100 microg/L among lactating women; and 100-199 microg/L among nonpregnant, nonlactating
women). The iodine status of pregnant women was borderline sufficient (median UIC = 153 microg/L; 95% CI
= 105-196), while lactating (115 microg/L; 95% CI = 62-162) and nonpregnant, nonlactating (130 microg/L;
95% CI = 117-140) women were iodine sufficient. … Iodine levels among U.S. women should be monitored,
particularly among subgroups at risk for iodine deficiency.
Serum thyroid hormone levels in preterm infants born before 33 weeks of gestation and
association of transient hypothyroxinemia with postnatal characteristics. J Pediatr Endocrinol
Metab. 2010 Sep;23(9):899-912.: Fetal thyroid function and the hypothalamopituitary-thyroid axis continue to
mature throughout pregnancy. Therefore, thyroid hormone levels of premature infants differ from those of mature
ones. Our primary objective was to evaluate the reference values of serum thyroid hormones in preterm infants born
before 33 wk gestation. The second objective was to define a cut-off value for transient hypothyroxinemia of
prematurity (THOP) according to gestational age and association of THOP with postnatal characteristics in these
infants…. CONCLUSIONS: In preterm infants below 30 wk, thyroid hormones were lower and urinary iodine
values were higher compared to infants with older gestational age. THOP at the first wk of life may convey
important prognostic information about neonatal morbidity and length of hospitalization stay.
Iodine status of pregnant women from central Poland ten years after introduction of iodine
prophylaxis programme. (Pol J Endocrinol 2010; 61 (6): 646-651).2010 Nov-Dec;61(6):646-51. Introduction:
Until 1997, Poland was one of the European countries suffering from mild/moderate iodine deficiency. In 1997, a
national iodine prophylaxis programme was implemented based on mandatory iodisation of household salt with 30 ±
10 mg KI/kg salt, obligatory iodisation of neonatal formula with 10 μg KI/100 mL and voluntary supplementation of
pregnant and breast-feeding women with additional 100-150 μg of iodine. Our aim in this study was to evaluate the
iodine status of pregnant women ten years after iodine prophylaxis was introduced. … Conclusion: Iodine
supplements with 150 μg of iodine should be prescribed for each healthy pregnant woman according to the
assumptions of Polish iodine prophylaxis programme to obtain adequate iodine supply.
Patterns of iodine intake and urinary iodine concentrations during pregnancy and blood
thyroid-stimulating hormone concentrations in the newborn progeny. Thyroid. 2010
Nov;20(11):1295-9. Background: Appropriate maternal intake of iodine during pregnancy is essential for maternal
thyroxine production and thyroid status of the fetus. It should be possible to enhance iodine intake during pregnancy
by using iodine fortified salt or taking iodine supplements. In the present report we determined the status of iodine
nutrition in pregnant women who were stratified on the basis of their history of taking or not taking iodized salt or
iodine supplements. The study was performed in Toledo (Spain), a region in which prior studies have noted
borderline iodine sufficiency. Iodine nutrition was assessed by measuring urinary iodine concentration (UIC) and
neonatal thyrotropin (TSH).… Conclusions: In a region with a history of borderline iodine deficiency the UICs
were below 150 μg/L in a substantial percentage of pregnant women who did not take iodine supplements,
regardless of whether or not they took iodized salt. Our results support the use of iodine supplements from
the start of the pregnancy, or even before pregnancy in women who live in regions with a history of even
small degrees of iodine deficiency. In addition, neonate TSH screening is not the best tool to assess whether the
iodine status in populations is ideal.
Iodine-induced neonatal hypothyroidism secondary to maternal seaweed consumption: A
common practice in some Asian cultures to promote breast milk supply. J Paediatr Child
Health. 2011 Jan 31. Mild iodine deficiency is a recognised problem in Australia and New Zealand. However, iodine
excess can cause hypothyroidism in some infants. We highlight two cases which illustrate the risks of excess dietary
iodine intake during pregnancy and breastfeeding. They also describe a cultural practice of consuming seaweed
soup to promote breast milk supply. Although most attention recently has been on the inadequacy of iodine in
Australian diets, the reverse situation should not be overlooked. Neither feast nor famine is desirable.
Hypothyroxinemia and Pregnancy. Endocr Pract. 2011 Jan 17:1-24. Objective: To evaluate the peer-reviewed
literature on iodine deficiency and hypothyroxinemia in pregnancy. … An adequate amount of iodine intake has
to be recommended pre-conception or starting early in pregnancy.
Neonatal Age and Point of CareTSH Testing in the Monitoring of Iodine Deficiency Disorders:
Findings from Western Uganda. Thyroid. 2011 Feb;21(2):183-8. Background: Iodine deficiency is a major
public health problem throughout Africa. Although salt for human consumption is said to contain adequate amounts
of iodine in Uganda, iodine intake may not be optimal. … Based on the percentage of neonates with TSH values
>5 mIU/L, presumptive iodine deficiency persists in western Uganda. This finding suggests that continued
monitoring of iodine nutrition in the area surrounding the Rwenzori Mountains in Uganda and Congo is
needed.
Iodine intake in Portuguese pregnant women: results of a countrywide study. Eur J Endocrinol. 2010
Oct;163(4):631-5. Iodine is the key element for thyroid hormone synthesis, and its deficiency, even moderate, is
harmful in pregnancy, when needs are increased, because of its potential deleterious effects on fetal brain
development. In Portugal, no recent data on iodine intake exists. The objective of this countrywide study was to
analyze iodine status in pregnant Portuguese women in order to propose adequate measures to the health
authorities…. women assisted in most Portuguese maternity hospitals. Considering the potential deleterious
effects of inadequate iodine supply in pregnancy, iodine supplementation is strongly recommended in this
period of life.
Poor iodine status and knowledge related to iodine on the eve of mandatory iodine fortification
in Australia. Asia Pac J Clin Nutr. 2010;19(2):250-5. Background: Mandatory fortification of bread with
iodised salt is proposed to address the re-emergence of iodine deficiency in Australia and New Zealand. …
These data add support to the need for a national approach to address iodine intake which includes an
accompanying consumer education campaign.
The Swiss iodized salt program provides adequate iodine for school children and pregnant
women, but weaning infants not receiving iodine-containing complementary foods as well
as their mothers are iodine deficient. J Clin Endocrinol Metab. 2010 Dec;95(12):5217-24.
BACKGROUND: If children and pregnant women in the population are iodine sufficient, it is generally assumed
infants are also sufficient. But weaning infants may be at risk of iodine deficiency because iodized salt contributes
little dietary iodine during this period. To fill this gap, iodine fortification of infant formula milk (IFM) and
complementary foods (CF) is likely important. OBJECTIVES: The objective of the study was to first confirm that
Swiss school children and pregnant women remain iodine sufficient and then to assess iodine status in infancy and
the relative contribution of breast milk and IFM/CF to their iodine intakes. … RESULTS: Median (m) UICs in
pregnant women (162 μg/liter) and school children (120 μg/liter) were sufficient, and 80% of the household salt was
adequately iodized (≥15 ppm). However, mUICs in infants not receiving IFM/CF were not sufficient: 1) mUIC in
breast-fed infants (82 μg/liter) was lower than in non-breast-fed infants (105 μg/liter) (P<0.001) and 2) mUIC in
breast-fed weaning infants not receiving IFM/CF (70 μg/liter) was lower than infants receiving IFM (109 μg/liter)
(P<0.01). mUIC was low in lactating mothers (67 μg/liter) and median breast milk iodine concentration was 49
μg/kg CONCLUSIONS: In countries in which iodized salt programs supply sufficient iodine to older children
and pregnant women, weaning infants, particularly those not receiving iodine-containing IFM, may be at risk
of inadequate iodine intakes.
Effect of iodine deficiency and hypothyroidism on the protein expressions of CaMK II in the hippocampus of
pups. Wei Sheng Yan Jiu. 2010 Mar;39(2):180-3. Objective: To observe the effect of iodine deficiency and
hypothyroidism on the protein expressions of CaMK II in the hippocampus of pups. … Conclusion: Iodine
deficiency and hypothyroidism may decrease the protein expression of CaMK II.
Dietary iodine: why are so many mothers not getting enough? Environ Health Perspect. 2010
Oct;118(10):A438-42.
Iodine deficiency in Australia: is iodine supplementation for pregnant and lactating women warranted? Med J
Aust. 2010 Apr 19;192(8):461-3. Recent research has confirmed that Australian children and pregnant women are
mildly iodine deficient. A considerable proportion of the pregnant population is moderately to severely iodine
deficient. Even subclinical hypothyroidism in the mother, occurring as a consequence of iodine deficiency,
can cause irreversible brain damage in the fetus, making it essential to avoid iodine deficiency in pregnancy.
The proposal of Food Standards Australia and New Zealand (FSANZ) - Mandatory Iodine Fortification for
Australia (P1003) - has been implemented. FSANZ openly admits P1003 is inadequate for covering the needs
of pregnant women. Therefore, health professionals and the public must be properly informed about the limitations
of this proposal. Views differ about the most effective measures to prevent iodine deficiency in Australia. We
propose that women planning a pregnancy, and pregnant and lactating women should be advised to take an
iodine supplement. Women with pre-existing thyroid disease should exercise caution and seek medical advice
before taking a supplement.
Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary
deficienty or excess. Part II - Vitamin D, Vitamin A, Iron, Zinc, Iodine, Essential Fatty Acids. J Matern Fetal
Neonatal Med. 2010 Apr 14. Part II of this review considers additional micronutrients. … To assure adequate
iodine, food is fortified worldwide with iodated salt. If urinary iodine levels are low, supplementation is
needed. Essential fatty acids requirements can be met by one to two portions of fish per week.
CB Note: The iodine-related section of the above report says that “To assure adequate iodine, food is fortified
worldwide with iodated salt. If urinary iodine levels are low, supplementation is needed.” It sounds a bit like things
are OK because “food is fortified worldwide with iodated salt.” As described elsewhere in this paper, many places
that have low iodine in the soil still do not have access to iodized salt. Additionally, the newest evaluations are
showing that the amount added to salt is insufficient for many women and especially for pregnant and lactating
women. And the likelihood is quite low that women around the world (and here) normally get their urinary
iodine level evaluated in order to determine whether “supplementation is needed.”
Iodine intake in Portuguese pregnant women: results of a countrywide study. Eur J Endocrinol. 2010
Oct;163(4):631-5. …urine iodine concentration (UIC) was evaluated 3631 pregnant women followed in 17
maternity hospitals from hinterland and coastal areas in Continental Portugal and the Portuguese islands of Açores
and Madeira. Results: Median UIC value was 84.9 μg/l (range 67.6-124.1) in Continental Portugal, 69.5 μg/l in
Madeira, and 50.0 μg/l in Açores. The percentage of satisfactory values (>150 μg/l) was 16.8, ranging from 8.8 to
34.1 in the Continent, and being 8.2 in Madeira and 2.3 in Açores. The percentage of values below 50 μg/l was 23.7,
ranging from 14.0 to 37.4 in the Continent, 33.7 in Madeira, and 50.0 in Açores. Conclusions: Our results point
to an inadequate iodine intake in pregnant women assisted in most Portuguese maternity hospitals.
Considering the potential deleterious effects of inadequate iodine supply in pregnancy, iodine
supplementation is strongly recommended in this period of life.
Iodine intake and maternal thyroid function during pregnancy. Epidemiology. 2010 Jan;21(1):62-9. Background:
An adequate iodine intake during pregnancy is essential for the synthesis of maternal thyroid hormones and normal
brain development in the fetus. Scant evidence is available on the effects and safety of iodine supplementation
during pregnancy in areas with adequate or mildly deficient iodine intake. We examined the association of maternal
iodine intake and supplementation with thyroid function before 24 weeks of gestation in population-based samples
from 3 different areas in Spain. Methods: A cross-sectional study of 1844 pregnant women (gestational age range
8-23 weeks) was carried out in 3 areas in Spain (Guipúzcoa, Sabadell, Valencia), during the period 2004-2008. We
measured levels of free thyroxine and thyroid-stimulating hormone (TSH) in serum, iodine in a spot urine sample,
and questionnaire estimates of iodine intake from diet, iodized salt and supplements. Adjusted associations were
assessed by multiple linear regression and logistic regression analyses. Results: There was an increased risk of
TSH above 3 muU/mL in women who consumed 200 microg or more of iodine supplements daily compared
with those who consumed less than 100 microg/day (adjusted odds ratio = 2.5 [95% confidence interval = 1.2 to
5.4]). We observed no association between urinary iodine and TSH levels. Pregnant women from the area
with the highest median urinary iodine (168 microg/L) and highest supplement coverage (93%) showed the
lowest values of serum free thyroxine. (geometric mean = 10.09 pmol/L [9.98 to 10.19]). CONCLUSIONS:
Iodine supplement intake in the first half of pregnancy may lead to maternal thyroid dysfunction in iodinesufficient or mildly iodine-deficient populations.
Thyroid disorders and pregnancy. Internist (Berl). 2010 May;51(5):620-4. Disorders of the thyroid in women are
common during the reproductive years. Incorrect or delayed treatment during pregnancy can adversely affect the
health of mother and child. Knowledge of the physiological changes during this time is essential. … [CB note: This
paper is looking at women who have medical conditions involving the thyroid gland, and not at public health
iodine-in-pregnancy issues.].
Lifestyle factors in people seeking infertility treatment - A review. Aust N Z J Obstet Gynaecol. 2010 Feb;50(1):820. Background: Clinical infertility is a prevalent problem with significant financial and psychosocial costs.
Modifiable lifestyle factors exist that may affect a person's time to conception and their chance of having a healthy,
live birth. … Results: A person's time to pregnancy and their chance of having a healthy, live birth may be
affected by factors such as weight, vitamin and iodine intake … Conclusion: Advice on modifiable lifestyle
factors should be given to people presenting for infertility treatment to help them make positive changes that may
improve their chances of pregnancy and delivering a healthy, live baby. Developing a guideline for this would be a
prudent step towards helping clinicians to implement this aspect of preconception care.
The challenges of iodine supplementation: a public health programme perspective. Best Pract Res Clin Endocrinol
Metab. 2010 Feb;24(1):89-99. An adequate iodine intake during pregnancy, lactation and early childhood is
particularly critical for optimal brain development of the foetus and of children 7-24 months of age. While the
primary strategy for sustainable elimination of iodine deficiency remains universal salt iodisation, the World
Health Organization and the United Nations Children's Fund recommend a complementary strategy of
iodine supplements as a temporary measure when salt iodisation could not be implemented. This article aims
to review current evidence on efficacy and implications of implementing iodine supplementation as a public health
measure to address iodine deficiency. Iodine supplementation seems unlikely to reach high coverage in a rapid,
equitable and sustained way. Implementing the programme requires political commitment, effective and efficient
supply, distribution and targeting, continuous education and communication and a robust monitoring system. Thus,
universal salt iodisation should remain the primary strategy to eliminate iodine deficiency.
Cretinism revisited. Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):39-50. Endemic cretinism includes two
syndromes: a more common neurological disorder with brain damage, deaf mutism, squint and spastic
paresis of the legs and a less common syndrome of severe hypothyroidism, growth retardation and less severe
mental defect. Both conditions are due to dietary iodine deficiency and can be prevented by correction of
iodine deficiency before pregnancy. Endemic cretinism is now included in the spectrum of the effects of iodine
deficiency in a population termed the 'iodine deficiency disorders (IDDs)', which also includes a wide range of lesser
degrees of cognitive defect that can be prevented by the correction of iodine deficiency. Iodine deficiency is now
recognised by the World Health Organization (WHO) as the most common preventable cause of brain
damage with in excess of 2 billion at risk from 130 countries. A global United Nations (UN) programme of
prevention has achieved 68% household usage of iodised salt by the year 2000 compared with less than 20%
prior to 1990.
Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab. 2010
Feb;24(1):13-27. Depending on the availability of iodine, the thyroid gland is able to enhance or limit the use of
iodine for thyroid hormone production. When compensation fails, as in severely iodine-deficient populations,
hypothyroidism and developmental brain damage will be the dominating disorders. This is, out of all comparison,
the most serious association between disease and the level of iodine intake in a population. In less severe iodine
deficiency, the normal thyroid gland is able to adapt and keep thyroid hormone production within the normal range.
However, the prolonged thyroid hyperactivity associated with such adaptation leads to thyroid growth, and during
follicular cell proliferation there is a tendency to mutations leading to multifocal autonomous growth and function.
… Monitoring and adjusting of iodine intake in a population is an important part of preventive medicine.
Epidemiology of iodine deficiency: Salt iodisation and iodine status. Best Pract Res Clin Endocrinol Metab. 2010
Feb;24(1):1-11. Universal salt iodisation (USI) and iodine supplementation are highly effective strategies for
preventing and controlling iodine deficiency. USI is now implemented in nearly all countries worldwide, and twothirds of the world's population is covered by iodised salt. The number of countries with iodine deficiency as a
national public health problem has decreased from 110 in 1993 to 47 in 2007. Still one-third of households
lack access to adequately iodised salt. Iodine deficiency remains a major threat to the health and development
of populations around the world, particularly in children and pregnant women in low-income countries. Data
on iodine status are available from 130 countries and approximately one-third of the global population is estimated
to have a low iodine intake based on urinary iodine (UI) concentrations. Insufficient control of iodine fortification
levels has led to excessive iodine intakes in 34 countries. The challenges ahead lie in ensuring higher coverage of
adequately iodised salt, strengthening regular monitoring of salt iodisation and iodine status in the population,
together with targeted interventions for vulnerable population groups.
Iodine deficiency in the prenatal period may form learning ability deficiency in the postnatal period.
Georgian Med News. 2010 Jan;(178):65-8. The present study analysis the changes in learning ability of the progeny
of rats suffered from iodine deficiency. … We can conclude that the diet with very low iodine content results in
a low level of thyroxin in maternal serum and neurological deficiency in progeny manifested by learning
disability during maze testing. Addition of the iodine to the diet prevents development of mentioned
neurological deficiency.
Suboptimal iodine status of Australian pregnant women reflects poor knowledge and practices related to iodine
nutrition. Nutrition. 2010 Oct;26(10):963-8. OBJECTIVE: To assess the iodine status and knowledge and
practices related to iodine nutrition of Australian women during pregnancy. …CONCLUSION: Public health
strategies, including nutritional education and supplementation, are urgently required to improve the iodine
status of pregnant women. Currently, no readily accessible information on iodine is available to women
attending antenatal clinics in Australia.
The influence of dietary status on the cognitive performance of children. . Mol Nutr Food Res. 2010 Apr;54(4):45770. The rapid rate of growth of the brain during the last third of gestation and the early postnatal stage
makes it vulnerable to an inadequate diet, although brain development continues into adulthood and
micronutrient status can influence functioning beyond infancy. Certain dietary deficiencies during the first 2
years of life, for example iodine and iron, create problems that are not reversed by a later adequate diet. ….
In particular, attention has been directed to protein-calorie malnutrition and more specifically the intake of iron,
iodine and vitamin A …
Iodine intake is still inadequate among pregnant women eight years after mandatory iodination of salt in Turkey.
J Endocrinol Invest. 2010 Jul-Aug;33(7):461-4. … Conclusion: Our study revealed that iodine deficiency still
remains a serious problem for pregnant women. Based on our results, antenatal follow-up protocols in the
primary care setting in Turkey must include iodine supplementation.
Iodine deficiency in pregnancy, infancy and childhood and its consequences for brain development.
Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):29-38. Iodine deficiency during foetal development and
early childhood is associated with cognitive impairment. Randomised clinical studies in school-aged children
encountered in the literature indicate that cognitive performance can be improved by iodine supplementation, but
most studies suffer from methodological constraints. Tests to assess cognitive performance in the domains that are
potentially affected by iodine deficiency need to be refined. Maternal iodine supplementation in areas of mild-tomoderate iodine deficiency may improve cognitive performance of the offspring, but randomised controlled studies
with long-term outcomes are lacking. Studies in infants or young children have not been conducted. The best
indicators for iodine deficiency in children are thyroid-stimulating hormone (TSH) in newborns and thyroglobulin
(Tg) in older children. Urinary iodine may also be useful but only at the population level. Adequate salt iodization
will cover the requirements of infants and children as well as pregnant women. However, close monitoring remains
essential.
[CB note: This particular discussion is about research design and the need for more research. Of course more
research is always needed. However, as most of the people who read my materials are not epidemiologists (nor am I)
some fine points of interpretation of this report may be helpful.
First, the type of research designs described here as “lacking” are “randomized controlled studies with long-term
outcomes” including “studies in infants or young children.” Although desirable from a statistical confidence
level sense, obtaining the results of this kind of study design with infants, children, or ANYBODY would most
likely be unethical and therefore not likely to ever become available. (If we are pretty darn sure that iodine
deficiency is not good for people, we can never do the kind of study where some folks are randomly assigned
to not receive the supplemental amount presumed to provide adequacy … especially for “long-term” outcome
measures.)
I think it is important to realize that although we will likely never have this kind of definitive data, there is a ton of
other kinds of research evidence that the problem of Iodine Deficiency Disorders (IDD) is huge and that correcting it
to the best of our ability is worthwhile.
Second is a comment about the interpretation of the second to the last statement: “Adequate salt iodization will
cover the requirements of infants and children as well as pregnant women.” My reaction is, well, of course
“ADEQUATE” salt iodization will cover everyone’s requirements. That’s like saying “taking in enough food
prevents starvation.” It sounds like there is no problem. Here’s the problem:
1) Many people who need additional iodine do not get it for many reasons even if local iodization levels in
salt are “adequate.” The reasons for this are discussed in detail in several of my other papers.
2) It is apparent by the recent upward adjustment in the amount of iodine now recommended by the WHO that the
previous (recent) iodization level has in fact been “INadequate” for pregnant women in particular.
3) About 1/3 of the world’s population still does not have access to iodized salt. “Epidemiology of iodine deficiency:
Salt iodisation and iodine status.” Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):1-11.
Neonatal TSH screening: is it a sensitive and reliable tool for monitoring iodine status in populations? Best Pract
Res Clin Endocrinol Metab. 2010 Feb;24(1):63-75. Conclusion … these researchers do not think it is very useful and
they explain why they think this.
Thyroid function at the third trimester of pregnancy in a Northern French population. Ann Endocrinol (Paris).
2010 Sep 29. … Conclusion: The hypothyroxinemia at the third trimester of pregnancy was more prominent in
the Parisian population and insufficient iodine intake could be responsible for the deficient increase in TT4. It is
therefore concluded that the inability of the thyroid to establish the required equilibrium could be corrected
by systematic iodine supplementation before pregnancy. Finally, the strong correlation between FT4 and FTI
suggests that the quality of FT4 test immunoassay is appropriate for estimating FT4 serum levels during pregnancy.
Inadequacy of nutrients intake among pregnant women in the Deep South of Thailand. BMC Public Health. 2010
Sep 24;10(1):572.
Universal screening detects two-times more thyroid disorders in early pregnancy than targeted high-risk case
finding. Eur J Endocrinol. 2010 Oct;163(4):645-50. … CONCLUSIONS: Over half (55%) of pregnant women
with abnormalities suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if only those with
high-risk criteria were examined. A more extensive screening of thyroid autoimmunity and dysfunction seems
warranted.
An approach to a sanitary and social problem: urinary iodine excretion in pregnant women from a iodine
deficient region. Arch Latinoam Nutr. 2009 Dec;59(4):378-82. The urinary iodine excretion (UIE) assay is an
effective method to detect reduced iodine intake. … 45% of pregnant women with UIE < 100 ug/l showed impaired
thyroid function. …
Post-production losses in iodine concentration of salt hamper the control of iodine deficiency disorders: a case
study in northern Ethiopia. J Health Popul Nutr. 2010 Jun;28(3):238-44.
Parameters of thyroid function throughout and after pregnancy in an iodine-deficient population.
Thyroid. 2010 Sep;20(9):995-1001. Background: The thyroid hormone milieu is of crucial importance for the
developing fetus. Pregnancy induces physiological changes in thyroid homeostasis that are influenced by the iodine
status. However, longitudinal studies addressing thyroid function during pregnancy and after delivery are still
lacking in mild-to-moderate iodine-deficient populations. Here we characterize the serum parameters of thyroid
function throughout pregnancy, and until 1 year after delivery, in a population of pregnant women whom we have
previously reported to be iodine deficient (median urinary iodine levels below 75 microg/L). … Conclusion: The
pregnant women in this study had an absence of the usual free T(4) spike and a smaller than expected increment in
total T(4), described during pregnancy in iodine-sufficient populations. A greater number of women had subclinical
hypothyroidism compared with iodine-sufficient populations. This hormonal profile, most likely due to iodine
insufficiency, may result in inadequate thyroid hormone supply to the developing fetus. We conclude that
care should be taken when reviewing the results of thyroid hormone tests in iodine-insufficient populations
and when no gestation-specific reference values have been established. In addition, we recommend iodine
supplementation in our population and populations with similar iodine status, particularly during pregnancy
and lactation.
Perinatal iron and copper deficiencies alter neonatal rat circulating and brain thyroid hormone concentrations.
Endocrinology. 2010 Aug;151(8):4055-65. Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies
lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common
mechanism contributing to the observed derangements. … These results indicate that at least some of the brain
defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH
levels.
Effect of selenium on hypothyroidism induced by methimazole (MMI) in lactating rats and their pups. Acta Biol
Hung. 2010 Jun;61(2):145-57. The present study was undertaken to assess the effect of selenium (Se) on
hypothyroidism induced by methimazole (MMI) in lactating rats and their pups. … In the MMI-treated group,
thyroid iodine contents and plasma thyroid hormone levels significantly decreased, while plasma TSH levels
increased in pups and their mothers. These biochemical modifications corresponded histologically to closed
follicles, increased vascularity and a reduction in colloid volume. Co-treatment with Se ameliorated these
parameters. We concluded that the supplementation of Se in diet had beneficial effects on hypothyroidism
during a critical period of life.
CB Note: Both Selenium and iodine are required for production of thyroxine, and both are quite variable in foods
depending on the content in the soil in which the foods are grown. In some areas of the world, particularly
mountainous areas, selenium deficiency is common. Examples of areas that automatically supplement selenium
include New Zealand and the Alpine region of Europe. It is likely that people with a combination of iodine AND
selenium deficiency would experience much greater thyroid –related problems.
[Selenium status, thyroid volume and multiple nodule formation in an area with mild iodine deficiency. Eur J Endocrinol. 2011 Jan 17. Trace
elements status in multinodular goiter. J Trace Elem Med Biol. 2010 Apr;24 (2):106-10. The impact of common micronutrient deficiencies on
iodine and thyroid metabolism: the evidence from human studies. Best Pract Res Clin Endocrinol Metab. 2010 Feb;24(1):117-32. Selenium and
thyroid. Best Pract Res Clin Endocrinol Metab. 2009 Dec;23(6):815-27. Selenium and the thyroid: a close-knit connection. J Clin Endocrinol
Metab. 2010 Dec;95(12):5180-8. Fenvalerate exposure alters thyroid hormone status in selenium- and/or iodine-deficient rats. Biol Trace Elem
Res. 2010 Jun;135(1-3):233-41.Selenium & iodine supplementation: effect on thyroid function of older New Zealanders. Am J Clin Nutr. 2009
Oct;90(4):1038-46. Role of iodine, selenium and other micronutrients in thyroid function and disorders. Endocr Metab Immune Disord Drug
Targets. 2009 Sep;9(3):277-94. Selenium levels in first-degree relatives of diabetic patients. Biol Trace Elem Res. 2009 May;128(2):144-51.
Effect of trace elements on thyroid structural and functional state (a review). Gig Sanit. 2008 Sep-Oct;(5):79-81.On the importance of selenium
and iodine metabolism for thyroid hormone biosynthesis and human health. Mol Nutr Food Res. 2008 Nov;52(11):1235-46.Environmental
factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab. 2008 Aug;4(8):454-60. Environmental triggers of autoimmune thyroiditis.
J Autoimmun. 2009 Nov-Dec;33(3-4):183-9. Trace element levels in hashimoto thyroiditis patients with subclinical hypothyroidism. . Biol Trace
Elem Res. 2008 Summer;123(1-3):1-7. Trace elements in growth: iodine and selenium status of Turkish children. . J Trace Elem Med Biol.
2007;21 Suppl 1:40-3.]
The impact of transient hypothyroidism on the increasing rate of congenital hypothyroidism in the United States.
Pediatrics. 2010 May;125 Suppl 2:S54-63.
Therapeutic drug monitoring during pregnancy and lactation: thyroid function assessment in pregnancychallenges and solutions. Ther Drug Monit. 2010 Jun;32(3):265-8.
Iodine intake in a population of pregnant women: INMA mother and child cohort study, Spain.
J Epidemiol Community Health. 2010 Aug 15. Background Monitoring iodine status during pregnancy is essential
to prevent iodine-related disorders. The objectives of this study are to estimate iodine intake and excretion, to assess
their association and to evaluate the compliance of the recommendations in a multicentre cohort of pregnant women.
…. Results 1522 women were included in the study. Median UIC was 134 (IQR 80-218) mug/l in Valencia, 168
(IQR 108-272) mug/l in Gipuzkoa and 94 (IQR 57-151) mug/l in Sabadell. 48.9% of Valencian women consumed
iodine supplements, 93.3% in Gipuzkoa and 11.0% in Sabadell. Prevalence of iodised salt consumption was 50.5%
in the whole sample. UIC was associated with intake of supplements, iodised salt, dietary iodine and water. UIC
levels were lower than expected according to the estimated iodine intake. Conclusion Median UIC reflected iodine
deficiency according to WHO reference levels, except in Gipuzkoa where supplements are widely consumed.
It is necessary to strengthen iodised salt consumption since it is already far from the objective proposed of
coverage of 90% of households. More data would be valuable to assess the correspondence between iodine
intake and excretion during pregnancy.
Iodine intake and maternal thyroid function during pregnancy. Epidemiology. 2010 Jan;21(1):62-9. [Data from
same study in Spain as above.]Background: An adequate iodine intake during pregnancy is essential for the
synthesis of maternal thyroid hormones and normal brain development in the fetus. Scant evidence is available on
the effects and safety of iodine supplementation during pregnancy in areas with adequate or mildly deficient iodine
intake. We examined the association of maternal iodine intake and supplementation with thyroid function before 24
weeks of gestation in population-based samples from 3 different areas in Spain. Methods: A cross-sectional study
of 1844 pregnant women (gestational age range 8-23 weeks) was carried out in 3 areas in Spain (Guipúzcoa,
Sabadell, Valencia), during the period 2004-2008. We measured levels of free thyroxine and thyroid-stimulating
hormone (TSH) in serum, iodine in a spot urine sample, and questionnaire estimates of iodine intake from diet,
iodized salt and supplements. Adjusted associations were assessed by multiple linear regression and logistic
regression analyses. Results: There was an increased risk of TSH above 3 muU/mL in women who consumed 200
microg or more of iodine supplements daily compared with those who consumed less than 100 microg/day
(adjusted odds ratio = 2.5 [95% confidence interval = 1.2 to 5.4]). We observed no association between urinary
iodine and TSH levels. Pregnant women from the area with the highest median urinary iodine (168 microg/L)
and highest supplement coverage (93%) showed the lowest values of serum free thyroxine. (geometric mean =
10.09 pmol/L [9.98 to 10.19]). CONCLUSIONS: Iodine supplement intake in the first half of pregnancy
may lead to maternal thyroid dysfunction in iodine-sufficient or mildly iodine-deficient populations.
Plenary Lecture 3: Food and the planet: nutritional dilemmas of greenhouse gas emission reductions through
reduced intakes of meat and dairy foods. Proc Nutr Soc. 2010 Feb;69(1):103-18. Legally-binding legislation is
now in place to ensure major reductions in greenhouse gas emissions in the UK. Reductions in intakes of meat and
dairy products, which account for approximately 40% of food-related emissions, are an inevitable policy option. The
present paper assesses, as far as is possible, the risk to nutritional status of such a policy in the context of the part
played by these foods in overall health and well-being and their contribution to nutritional status for the major
nutrients that they supply. … However, overall protein intakes would probably fall, with the potential for intakes to
be less than current requirements for the elderly. Whether it is detrimental to health is uncertain and controversial.
Zn intakes are also likely to fall, raising questions about child growth that are currently unanswerable. Milk and
dairy products, currently specifically recommended for young children and pregnant women, provide 30-40% of
dietary Ca, iodine, vitamin B12 and riboflavin. Population groups with low milk intakes generally show low intakes
and poor status for each of these nutrients. Taken together it would appear that the reductions in meat and
dairy foods, which are necessary to limit environmental damage, do pose serious nutritional challenges for
some key nutrients. These challenges can be met, however, by improved public health advice on alternative
dietary sources and by increasing food fortification.
Symposium on 'Geographical and geological influences on nutrition': Iodine deficiency in industrialised countries.
Proc Nutr Soc. 2010 Feb;69(1):133-43. Iodine deficiency is not only a problem in developing regions; it also
affects many industrialised countries. Globally, two billion individuals have an insufficient iodine intake, and
approximately 50% of continental Europe remains mildly iodine deficient. Iodine intakes in other
industrialised countries, including the USA and Australia, have fallen in recent years. Iodine deficiency has
reappeared in Australia, as a result of declining iodine residues in milk products because of decreased iodophor use
by the dairy industry. In the USA, although the general population is iodine sufficient, it is uncertain whether iodine
intakes are adequate in pregnancy, which has led to calls for iodine supplementation. The few available data suggest
that pregnant women in the Republic of Ireland and the UK are now mildly iodine deficient, possibly as a result of
reduced use of iodophors by the dairy industry, as observed in Australia. Representative data on iodine status in
children and pregnant women in the UK are urgently needed to inform health policy. In most industrialised countries
the best strategy to control iodine deficiency is carefully-monitored salt iodisation. However, because
approximately 90% of salt consumption in industrialised countries is from purchased processed foods, the
iodisation of household salt only will not supply adequate iodine. Thus, in order to successfully control iodine
deficiency in industrialised countries it is critical that the food industry use iodised salt. The current push to
reduce salt consumption to prevent chronic diseases and the policy of salt iodisation to eliminate iodine
deficiency do not conflict; iodisation methods can fortify salt to provide recommended iodine intakes even if
per capita salt intakes are reduced to <5 g/d.
The current salt iodization strategy in Kyrgyzstan ensures sufficient iodine nutrition among school-age children
but not pregnant women.Public Health Nutr. 2010 May;13(5):623-30. Although goitre and cretinism were brought
under control in Kyrgyzstan during the 1960s by centrally directed iodized salt supplies, iodine-deficiency disorders
(IDD) had made a comeback when the USSR broke up in 1991. Upon independence, Kyrgyzstan started developing
its own salt processing industry and by 2001 the Government enacted a law on IDD elimination, mandating
universal salt iodization (USI) at 25-55 mg/kg. The present study [in 2007] aimed to evaluate the effectiveness of the
USI strategy on the iodine consumption, iodine status and burden of IDD in the population of Kyrgyzstan. …
CONCLUSIONS: The iodine nutrition status of the Kyrgyz population is highly responsive to household
salt iodization. Although the results in children suggest adequate iodine nutrition, the iodine consumption
among pregnant women did not assure their dietary requirements. In-depth analysis of the survey data
suggest that excess iodine intake is not likely to become a public health concern in Kyrgyzstan when the salt
supply meets agreed standards.
Iodine: it's important in patients that require parenteral nutrition. Gastroenterology. 2009 Nov;137(5 Suppl):S3646. Iodine deficiency has multiple adverse effects on growth and development because of inadequate thyroid
hormone production. Four methods are generally recommended for assessment of iodine nutrition: urinary iodine
concentration, thyroid size, and blood concentrations of thyroid-stimulating hormone and thyroglobulin. Iodine
intakes < or = 1 mg/d are well tolerated by most adults, because the thyroid is able to adjust to a wide range of
intakes. A daily dose of 1 microg iodine/kg body weight is recommended for infants and children receiving
parenteral nutrition (PN), but this is far below their requirement. Daily iodine requirements in adults
receiving enteral nutrition or PN are estimated to be 70-150 microg, but most PN formulations do not contain
iodine. Despite this, deficiency is unlikely because absorption from iodine-containing skin disinfectants and other
adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing
disinfectants for catheter care, iodine deficiency may occur during long-term PN, and periodic testing of
thyroid functions may be prudent. Infants may be particularly vulnerable because of their small thyroidal
iodine store, but available data do not yet support routine supplementation of preterm infants with iodine.
Adults may be less vulnerable because thyroidal iodine stores may be able to support thyroid hormone production
for several months. More studies to clarify this issue would be valuable.
Fetal and neonatal thyroid function: review and summary of significant new findings. Curr Opin Endocrinol
Diabetes Obes. 2010 Feb;17(1):1-7. The purpose of this review is to briefly summarize current knowledge of fetal
and neonatal thyroid function, and then to summarize the most significant new findings over the last year that add to
our knowledge of the cause, diagnosis, and management of fetal and neonatal thyroid disorders…. [CB note: This is
about managing certain types of thyroid disorders in newborns, and not generally about iodine intake issues in
pregnancy.]
Impact of pregnancy on prevalence of goitre and nodular thyroid disease in women living in a region of
borderline sufficient iodine supply. Horm Metab Res. 2010 Feb;42(2):137-42. An interplay of genetic, epigenetic,
and environmental factors contributes to thyroid disease. In a cross-sectional study, we aimed to determine the
influence of parity in combination with other risk factors on the prevalence of goitre and nodular thyroid disease
(NTD) in women living in a region of previous overt iodine deficiency, which experienced a continuous
improvement in alimentary iodine supply in the last two decades. Thyroid ultrasonography (7.5 MHz; Merck
Thyromobil) was performed by the same investigator in 736 women living in Thuringia and Saxony [Germany]..
Goitre prevalence was 19.1%. Solitary thyroid nodules were detected in 21.5%, and multiple nodules in 23.8% of
women. In a multivariate analysis, neither age nor parity was positively correlated with goitre prevalence and NTD.
A significant correlation was detected between BMI and goitre and multinodular disease. Goitre was found in
25.3% of women with a positive family history for thyroid disease, as opposed to 16.1% goitre in women with
a negative family history. Neither goitre nor NTD were associated with a history of smoking in the whole
study population. Thyroid nodules and/or goitre are present in up to 45% of women in an area of previous
overt iodine deficiency. Whereas BMI and family history are positively correlated with the presence of NTD and
goitre, no such correlation could be detected for pregnancy and smoking after processing our data with multivariate
analyses.
Clin Endocrinol (Oxf). 2010 Jan;72(1):81-6. Iodine sources and iodine levels in pregnant women from an area
without known iodine deficiency. An adequate iodine intake during pregnancy is essential for normal development
of the foetus. The World Health Organization (WHO) recommends that the median urinary iodine
concentration (UIC) in a population of pregnant women should range between 150 and 249 microg/l. The aim
of this study was to evaluate iodine status and to examine the main sources of iodine in pregnant women from an
apparently iodine-sufficient area. Methods: Six hundred pregnant women in the third trimester completed a food
frequency questionnaire, and iodine was measured in urine samples. Urinary iodine concentrations were described in
the whole population and in subgroups according to their frequency of intake of milk, fish, eggs, bread and iodized
salt, as iodine supplements. Results: The median UIC was 104 microg/l (n = 600), however, the median was higher
among women who had a high milk intake (117 microg/l), used iodized salt (117 microg/l) or who were
supplemented with iodine (141 microg/l). Women receiving iodine supplementation who also consumed more than
one cup of milk per day had median UIC higher than 150 microg/l. In multivariate models, women with moderate
and high milk intake had lower risk of having UIC below 150 microg/l [OR (95% CI): 0.42 (0.22-0.82) and 0.29
(0.15-0.55) respectively], after adjustment for potential confounders. Conclusions: On the basis of WHO
criteria, the iodine status of pregnant women was inadequate in this area. Milk was the most important
dietary source of iodine, and iodine supplementation was also an important source of iodine, although not
enough to reach the current recommendations.
2009
Prevalence of iodine deficiency in pregnant women in the health area of Palencia (Spain). Endocrinol Nutr. 2009
Dec;56(10):452-7. BACKGROUND: Iodine deficiency in pregnant women may result in substantial and
irreversible impairment in fetal brain development, even from the first few weeks of pregnancy.
OBJECTIVE: To assess the nutritional iodine status of pregnant women in our health area and its relationship
with dietary factors and thyroid function and to suggest treatment guidelines. … CONCLUSIONS:
Seventy-eight percent of pregnant women in our health area were iodine deficient. Iodized salt intake is
related to iodine sufficiency and to increased urinary iodine concentrations. Measures to increase intake of
iodized salt among the population should be implemented. Iodized salt supplements should be systematically
prescribed in women from the beginning of pregnancy.
A framework to explore micronutrient deficiency in maternal and child health in Malawi, Southern Africa.
Environ Health. 2009 Dec 21;8 Suppl 1:S13. Global food insecurity is associated with micronutrient deficiencies
and it has been suggested that 4.5 billion people world-wide are affected by deficiencies in iron, vitamin A and
iodine. Zinc has also been identified to be of increasing concern. The most vulnerable are young children and
women of childbearing age. …
Perinatal goiter with increased iodine uptake and hypothyroidism due to excess maternal iodine ingestion. Horm
Res. 2009;72(6):344-7. AIMS: To review cases of fetal/newborn goiter due to excess maternal iodine ingestion. …
We reviewed the medical records of all patients that presented with congenital goiter in 2003. We used the PubMed
search engine to conduct a review of publications addressing congenital goiter and excessive iodine intake.
…Maternal ingestion of large amounts of iodine due to an error in the manufacturing of a prenatal vitamin
caused a goiter in her fetus. Seven other women who received the same prenatal vitamin had newborn children with
goiters. Three of these children were hypothyroid at the time of initial examination. Three patients (2 hypothyroid
and 1 euthyroid) had thyroid scans with radioactive iodine; iodine uptake was elevated (>80%) in all 3, and in 1 the
perchlorate washout test was positive. …The finding of congenital goiter and increased iodine uptake in a newborn
is considered diagnostic of dyshormonogenesis, a permanent form of hypothyroidism. Our description is important
because it demonstrates that iodine excess during pregnancy may mimic some forms of dyshormonogenesis.
The differentiation between the two causes of newborn goiter may prevent the lifelong use of supplemental
levothyroxine in patients with a transient abnormality.
Breastfeeding and maternal and infant iodine nutrition. Clinical Endocrinology. 70(5):803-9, 2009 May.
Adequate concentration of iodine in breast milk is essential to provide for optimal neonatal thyroid hormone
stores and to prevent impaired neurological development in breast-fed neonates. In many countries of the world,
low iodine content of the breast milk indicates less than optimum maternal and infant iodine nutrition. The
current WHO/ICCIDD/UNICEF recommendation for daily iodine intake (250 microg for lactating mothers) has
been selected to ensure that iodine deficiency dose not occur in the postpartum period and that the iodine
content of the milk is sufficient for the infant's iodine requirement
Iodine status and thyroid function of pregnant, lactating women and infants (0-1 yr) residing in areas with an
effective Universal Salt Iodization program. Asia Pacific Journal of Clinical Nutrition. 18(1):34-40, 2009.
Pregnant women, lactating women and infants were selected randomly in the regions where iodized salt
coverage rate is more than 90% since 2000. Median Urinary Iodine (MUI) of infants, three groups of pregnant
women (first, second and third trimester) and two groups lactating women (breastfeeding less than or more than
six months) were 233, 174, 180, 147, 126 and 145 microg/L, respectively. Median milk iodine of lactating
women was 163 microg/L. Percentage of milk iodine < 150 microg/L of early lactating women was 40%
less than that of late lactating women (p < 0.01). There was a positive correlation between urine iodine of
infants and milk iodine of lactating women (r = 0.526, p = 0.000)…. Total 15.4% women's TSH were
abnormal. Most of these women's urinary iodine were lower than 150 microg/L.
Iodine Content of prenatal multivitamins in the United States. NEJM. 2009;360:939-940. The amount of iodine
on the label was found not to be a good indicator of the amount in the product; in most cases it was less than
stated and in some cases more. Kelp-based products were less reliable than products using potassium iodide.
127 non-prescription and 96 prescription prenatal vitamins were identified. 69% of non-prescription but only
28% of prescription products contained iodine at all, according to the label. 13 brands contained levels that were
discordant by 50% or more with the amount on the label.
Iodine levels and thyroid hormones in healthy pregnant women and birth weight of their offspring.
Eur J Endocrinol. 2009 Mar;160(3):423-9. Studied 239 women who had thyroid function and UIC at the first
and third trimesters available. Conclusions: The present study suggests that iodine status during pregnancy may
be related to prenatal growth in healthy women.
A study for maternal thyroid hormone deficiency during the first half of pregnancy in China. Eur J Clin Invest.
2009 Jan;39(1):37-42.
Prenatal induced chronic dietary hypothyroidism delays but does not block adult-type Leydig cell development.
Am J Physiol Endocrinol Metab. 2009 Feb;296(2):E305-14.
Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review.
Am J Clin Nutr. 2009 Feb;89(2):668S-72S. The World Health Organization (WHO) recently increased
their recommended iodine intake during pregnancy from 200 to 250 microg/d and suggested that a
median urinary iodine (UI) concentration of 150-249 microg/L indicates adequate iodine intake in
pregnant women. Thyrotropin concentrations in blood collected from newborns 3-4 d after birth may be a
sensitive indicator of even mild iodine deficiency during late pregnancy; a <3% frequency of thyrotropin values
>5 mU/L indicates iodine sufficiency. New reference data & a simple collection system may facilitate use of the
median UI concentration as an indicator of iodine status in newborns. In areas of severe iodine deficiency,
maternal & fetal hypothyroxinemia can cause cretinism and adversely affect cognitive development in children;
to prevent fetal damage, iodine should be given before or early in pregnancy. Whether mild-to-moderate
maternal iodine deficiency produces more subtle changes in cognitive function in offspring is unclear; no
controlled intervention studies have measured long-term clinical outcomes. Cross-sectional studies have, with
few exceptions, reported impaired intellectual function & motor skills in children from iodine-deficient areas,
but many of these studies were likely confounded by other factors that affect child development. In countries or
regions where <90% of households are using iodized salt & the median UI concentration in school-age children
is <100 microg/L, the WHO recommends iodine supplementation in pregnancy and infancy.
Iodine status of pregnant women and their progeny in the Minho Region of Portugal. Thyroid. 2009
Feb;19(2):157-63. … in Portugal, a country that the International Council for Control of Iodine Deficiency
Disorders considered, in 2004, to have probably reached iodine sufficiency. … [Results of this study] suggest
that iodine supplementation should be implemented throughout pregnancy and lactation in Portugal.
Gestational thyroid function abnormalities in conditions of mild iodine deficiency: early screening versus
continuous monitoring of maternal thyroid status Eur J Endocrinol. 2009 Jan 29. Conclusions: In mildly ID
areas thyroid function testing early in gestation seems to be only partly effective in identifying thyroid
underfunction in pregnant women. Indeed, in our series more than 40% hypothyroid women would not have
been diagnosed had we limited our observation to early thyroid function tests alone. Although thyroid
autoimmunity carried a 5-fold increased risk of hypothyroidism, iodine deficiency seems to be a major
determinant in the occurrence of thyroid underfunction. Adequate iodine supplementation should be strongly
recommended to meet the increased hormone demand over gestation.
Colostrum iodine and perchlorate concentrations in Boston-area women: a cross-sectional study. Clin Endocrol
(Oxf). 2009 Feb;70(2):326-30 OBJECTIVE: To measure levels of colostrum iodine, which has not been previously
measured… RESULTS: Sufficient colostrum was obtained to measure iodine in 61 samples … . Median colostrum
iodine content was 51.4 micromol/l (range 21.3-304.2 microg/l)., CONCLUSIONS: Iodine is present in human
colostrum and thus available for breastfeeding infants immediately after birth.
CB Note:
These researchers report that the median colostrum iodine content was 51.4 micromol/l, with a very wide range
(21.3-304.2). As described earlier (Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf).
2008 Oct 6.) in areas of iodine sufficiency breast milk iodine concentration should be in the range of 100-150
mug/dL. That means that we must interpret this research as indicating that colostrum can and does contain iodine,
but the amount is generally often well below the level found in the milk of women who are iodine sufficient. It
would be interesting to evaluate the colostrum iodine content among women who have biochemical evidence of
being iodine sufficient versus those who are not. In any case, it appears that like milk, the iodine content of
colostrums varies significantly, most likely depending on the mother’s state of adequacy or inadequacy. Iodine is
clearly one more nutrient for which we must not assume that mother’s milk or colostrum will automatically
deliver the necessary level to the baby if mother’s own iodine status is poor. At the same time, it is also now
clear that we must not assume that her iodine status is adequate. This will require some serious re-thinking of
our current maternal-child nutrition recommendations in order to assure iodine adequacy for all.
Thyroid disorders during pregnancy .Dtsch Med Wochenschr. 2009 Jan;134(3):83-6.
Is maternal diet supplementation beneficial? Optimal development of infant depends on mother's diet.
Am J Clin Nutr. 2009 Feb;89(2):685S-7S . … Whatever the limitations of our current state of knowledge, it is
apparent that pregnancy and lactation are periods during which good nutrition is exceptionally important. The infant
is not protected from the inadequate diet of the mother.
Maternal milk concentration of zinc, iron, selenium, and iodine and its relationship to dietary intakes. Biol Trace
Elem Res. 2009 Jan;127(1):6-15. … Rio Grande WIC: The lactating mothers consumed significantly less Zn, Se,
and I when compared to the Recommended Dietary Allowances (RDA) even though Fe intake was higher than the
RDA value. Breast milk concentration of Zn, Fe, and Se were in agreement within the range of representative values
for Constituents of Human Milk but Iodine was at significantly lower concentration than the representative value.
2008
Iodine status of the U.S. population, National Health and Nutrition Examination Survey 2003-2004. Thyroid. 2008
Nov;18(11):1207-14. BACKGROUND: Since 1971, the general U.S. population has been monitored for dietary
iodine sufficiency by urinary iodine (UI) measurements through the National Health and Nutrition Examination
Survey (NHANES). This report presents the UI levels for the population participating in NHANES 2003-2004. It is
the third assessment of the U.S. population since NHANES III (1988-1994), when the median UI level was observed
to decrease from NHANES I (1971-1974). METHODS: In 2003-2004, a stratified, multistage, probability sample of
approximately 5000 participants per year were selected to participate in NHANES Household interviews, and
specimen collection were performed. UI level was measured by inductively coupled plasma mass spectrometry on a
random subsample of 2526 participants aged 6 years and older. RESULTS: The median UI level for the general
U.S. population in 2003-2004 was 160 microg/L (95% confidence interval [CI] 146-172), and 11.3 +/- 1.8% of the
population had a UI level below 50 microg/L. Children had a higher UI level than adolescents and adults. Among
all (pregnant and nonpregnant) women of reproductive age, the median UI level was 139 microg/L (95% CI
117-156), 15.1 +/- 3.2% women had a UI level <50 microg/L, and Non-Hispanic blacks in this group had a lower
UI level than other racial/ethnic groups. CONCLUSIONS: These findings affirm the stabilization of the UI level
and the adequate iodine nutrition in the GENERAL U.S. population since 2000. Future surveys designed to
achieve UI levels representative of pregnant women can improve the estimate of iodine sufficiency in this
population subgroup. Continued monitoring of the population for iodine sufficiency is warranted because of
groups at risk for iodine deficiency disorders.
CB note:
Some key points from the above report that I don’t want to get lost: Although the average UI in this large US study
(160 mcg/L) was interpreted as reflecting adequacy of iodine, the median UI level for women was 139; in
several studies a UI of <150 is described as indicating iodine deficiency. There are many issues about how
iodine sufficiency is assessed, but it looks like an important observation to mark that even if the “general” US
population is fine, women (pregnant or not) are much less likely to achieve the value the NHANES researchers
describe as adequate iodine status. Additionally, note that they also report that about 15% of women had a UI of
<50! Fifteen percent of the women is a lot of people (some at reproductive age) with seriously poor iodine status.
Iodine status and thyroid volume changes during pregnancy: results of a survey in Aran Valley (Catalan Pyrenees,
Spain.) J Endocrinol Invest. 2008 Oct;31(10):851-5 The Aran Valley has a long-standing history of iodine
deficiency. … As of 2000, iodine deficiency among pregnant women in the Aran Valley was still very high…
preconceptional supplements with iodine are required for its prevention.
Perinatal and chronic hypothyroidism impair behavioural development in male and female rats. Exp Physiol. 2008
Nov;93(11):1199-209.
Perinatal iodine deficiency in the Far East. Vopr Pitan. 2008;77(5):65-8.
Maternal and infant thyroid disorders and cerebral palsy. Semin Perinatol. 2008 Dec;32(6):438-4. … A major
research priority should be to assess the effects on CP risk of thyroid supplementation in transient hypothyroxinemia
of prematurity. Iodine deficiency can be addressed by inexpensive and well-established public health measures, and
thyroid hormone deficiency can be addressed by inexpensive and well-established clinical measures. If a causal
chain can be established that links iodine and thyroid hormone to risk of CP, the potential for introducing very costeffective ways of reducing the burden of CP will be considerable.
Iodine balance, iatrogenic excess, and thyroid dysfunction in premature newborns. Semin Perinatol. 2008 Dec;32(6):
407-12 … The iodine intake of newborns is entirely dependent on the iodine content of breast milk and the formula
preparations used to feed them. An inadequate iodine supply (deficiency and excess) might be especially dangerous
in the case of premature babies. The minimum recommended dietary allowance is different depending on age
groups. The iodine intake required is at least 15 microg/kg/d in full-term infants and 30 microg/kg/d in
preterms. Premature infants are in a situation of iodine deficiency, precisely at a stage of psychomotor and neural
development that is extremely sensitive to alterations of thyroid function.
Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull. 2008 Sep;29(3):195-202 Conclusions: Global
progress in controlling iodine deficiency has been made since 2003, but efforts need to be accelerated in order to
eliminate this debilitating health issue that affects almost one in three individuals globally. Surveillance systems
need to be strengthened to monitor both low and excessive intakes of iodine.
Micronutrient status, cognition and behavioral problems in childhood. Eur J Nutr. 2008;47 Suppl 3:38-50.
Reference values for neonatal thyroid volumes in a moderately iodine-deficient area. J Endocrinol Invest. 2008
Jul;31(7):642-6. The reference ranges of thyroid volumes in neonates vary according to the iodine status of a
specific region. In different studies, it ranged between 0.47 and 1.62 ml. It has been previously shown that Bursa
city was a moderately iodine-deficient area. We therefore aimed at determining normal reference ranges of neonatal
thyroid volumes in our moderately iodine-deficient area. … Conclusion: Normal thyroid volumes in neonates vary
between different regions. Local reference values should be used in thyroid volume assessment. Our results are in
concordance with the literature and can be used as reference values for our region.
CB note:
These researchers (above) found that in their “moderately iodine -deficient area” neonates have evidence of poorer
iodine status (i.e. larger thyroid volume) than elsewhere. They appear to suggest using a local regional average to
assess inadequacy to better reflect their population. However, just re-labeling poor iodine status as “OK for around
here” is unlikely to be helpful. Establishing lower iodine reference values as regionally “normal” because they
are commonly seen seems like a recipe for missing infants at risk. It reminds me of the old vitamin D tables that
gave significantly lower blood levels as “normal” if the measurement was done in the winter. It was “normal” only
in the mathematical sense of the word because deficiency was in fact very common in the winter especially.
However, as we have been learning in the vitamin D world, “averages” and “normal values” in this situation are not
the same thing as “healthiest” values.
Iodine deficiency, more than cretinism and goiter. Med Hypotheses. 2008 Nov;71(5):645-8. Recent reports of the World
Health Organization show iodine deficiency to be a worldwide occurring health problem. … iodine deficiency may
give rise to clinical symptoms of hypothyroidism without abnormality of thyroid hormone values. [Hypothesis
discussed here that there may be a relationship] between iodine deficiency and obesity, attention deficit
hyperactivity disorder (ADHD), psychiatric disorders, fibromyalgia, and malignancies.
Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency.
J Clin Endocrinol Metab. 2008 Jul;93(7):2616-21.
Inadequate iodine nutrition of pregnant women from Extremadura [Spain] Eur J Endocrinol. 2008 Oct;159(4):439-45.
Iodine deficiency disorders and their prevention in India. Rev Endocr Metab Disord. 2008 Sep;9(3):237-44. New
insights on the high prevalence of functional decompensation of the thyroid among newborn and children from
several states of India as well as neighbouring countries of Nepal and Bhutan helped to prevent nutritional iodine
deficiency and iodine deficiency disorders through country-wide iodized salt prophylaxis. Presently on the basis of
scientific studies, salt iodization in India is saving millions of children from neonatal hypothyroidism related
psycho-physical retardation.
Can neonatal TSH screening reflect trends in population iodine intake. Thyroid. 2008 Aug;18(8):883-8. The
distribution of neonatal blood thyroid-stimulating hormone (TSH) concentrations has been used as an index
reflecting population dietary iodine intake, with higher concentrations being indicative of lower iodine intake. We
examined this distribution in neonates born in Ireland, where the pregnant population has shown a recent decline in
urinary iodine (UI) excretion. … Conclusions: These data support a link between fetal thyroid function and a fall in
maternal iodine intake. While the findings of the proportion of blood TSH values >5.0 mIU/L exclude severe
maternal or fetal iodine deficiency, a trend toward increasing TSH may provide an early indication of impending
iodine deficiency. The findings assume greater importance in the context of declining UI reported from many
developed countries even where the proportion of blood TSH values >5.0 mIU/L is <3%, thus excluding severe
maternal and fetal iodine deficiency.
Neurodevelopmental and neurophysiological actions of thyroid hormone. J Neuroendocrinol. 2008 Jun;20(6):784-94
For over 100 years, thyroid hormones have been known to be essential for neonatal neurodevelopment but whether
they are required by the foetal brain remains a matter of controversy. For decades, the prevailing view was that
thyroid hormones are not necessary until after birth because circulating levels in the foetus are very low and the
placenta forms an efficient barrier to their transfer from the mother. … It is now clear that thyroid hormones are
essential for both foetal and post-natal neurodevelopment and for the regulation of neuropsychological function in
children and adults. …
Methods to assess iron and iodine status. Br J Nutr. 2008 Jun;99 Suppl 3:S2-9. Four methods are recommended for
assessment of iodine nutrition: urinary iodine concentration, the goitre rate, and blood concentrations of thyroid
stimulating hormone and thyroglobulin. These indicators are complementary, in that urinary iodine is a sensitive
indicator of recent iodine intake (days) and thyroglobulin shows an intermediate response (weeks to months),
whereas changes in the goitre rate reflect long-term iodine nutrition (months to years). Spot urinary iodine
concentrations are highly variable from day-to-day and should not be used to classify iodine status of individuals.
International reference criteria for thyroid volume in children have recently been published and can be used for
identifying even small goitres using thyroid ultrasound. Recent development of a dried blood spot thyroglobulin
assay makes sample collection practical even in remote areas. Thyroid stimulating hormone is a useful indicator
of iodine nutrition in the newborn, but not in other age groups.
Iodine: deficiency and therapeutic considerations. Altern Med Rev. 2008 Jun;13(2):116-27. … The safety of
therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the
Japanese population that consumes 25 times the median intake of iodine consumption in the United States. …
The many reasons why goiter is seen in old paintings. Thyroid. 2008 Apr;18(4):387-93.
The results of the "tiromobil" epidemiological trial of pregnant women in the Russian Federation. Ter Arkh.
2008;80(2):78-81. CONCLUSION: Most of the pregnant women in the regions studied were at risk of diseases
associated with iodine deficiency. Prevention of iodine deficiency is not adequate.
Analysis of food supplements containing iodine: a survey of Italian market[in Italy]. Clin Toxicol (Phila). 2008
Apr;46(4):282-6. Aim: Compare claimed concentrations of iodine with measured ones in various iodinesupplemented products … Analytical values resembled those declared in the label in fewer than half of the
examples… Labeling of iodine-rich food supplements appears to be unreliable …
Iodine in breast milk of nursing mother in normal and with premature birth. Vopr Pitan. 2008;77(6):75-8. Iodine
content in breast milk depends on the consumption level of iodine. Iodine deficiency in mothers results in
inadequate iodine status of neonates. Iodine supplements at any gestation stage normalized iodine content in breast
milk. [Study done in Russia.]
Naturally occurring iodine in humic substances in drinking water in Denmark is bioavailable and determines
population iodine intake. Br J Nutr. 2008 Feb;99(2):319-25.
Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf). 2008 Oct 6. Thirty six MEDLINE
studies between 1960 – 2007.Conclusions: Adequate concentration of iodine in breast milk is essential to provide for
optimal neonatal thyroid hormone stores and to prevent impaired neurological development in breastfed neonates. In
many countries of the world, low iodine content of the breast milk indicates less than optimum maternal and infant
iodine nutrition. The current WHO/ICCIDD/UNICEF recommendation for daily iodine intake (250 mug for
lactating mothers) has been selected to ensure that iodine deficiency does not occur in the postpartum period and
that the iodine content of the milk is sufficient for the infant's iodine requirement.
Intake of iodine and perchlorate and excretion in human milk. Environ Sci Technol. 2008 Nov 1;42(21):8115-21.
Treating iodine deficiency: long-term effects of iodine repletion on growth and pubertal development in school-age
children. Thyroid. 2008;18(4):449-54.[Azerbaijan] Long-term correction of severe ID leads to sustained improvement
of linear growth accompanied by a normalization of the time of onset of pubertal development for both sexes.
The complex hygienic characteristics preventive iodine deficiency in population of Siberia. Vopr Pitan. 2008;77(2):5963. … The study showed that 58.3-88.1% of examined children … suffer from iodine deficiency. …Preventable iodine
deficiency … is the reason for many illnesses. It is an important and until now an unresolved problem of the
Krasnoyarsk areas.
Status of iodine nutrition of children until 1 year: consequences on the thyroid function. Arch Pediatr. 2008 Aug;15
(8):1276-82. Iodine status is not optimal in French population of hospitalized children in the first year. They also
found no clear relationship between iodine status and thyroid function.
Intake of iodine and perchlorate and excretion in human milk. Environ Sci Technol. 2008 Nov 1;42(21):8115-21.
Iodine prophylaxis using iodized salt and risk of maternal thyroid failure in conditions of mild iodine deficiency. J
Clin Endocrinol Metab. 2008 Apr 15
Transient neonatal hypothyroidism due to amiodarone administration during pregnancy--two cases report and
review of literature. Arq Bras Endocrinol Metabol. 2008 Feb;52:126-30.
Iodine deficiency in pregnant women residing in an area with adequate iodine intake. Nutrition. 2008 May;24(5):45861.Conclusion: This observational study demonstrated that, despite the adequate supplementation of iodine intake,
most pregnant women appear not to be protected against iodine deficiency. If confirmed in larger case studies, this
finding claims the attention of relevant professionals to monitor iodine nutrition during gestation, assuming that
ordinary supplementation of iodine intake seems to be sufficient only in non-gestational conditions.
Establishment of reference range for thyroid hormones in normal pregnant Indian women. BJOG. 2008
Apr;115(5):602-6
Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid from preterm and term human
pregnancies. Reprod Toxicol. 2008 Jan;25(1):129-32.
The influence of gestational stage on urinary iodine excretion in pregnancy. J Clin Endocrinol Metab. 2008
May;93(5):1737-42.
Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and
multivitamin use. Endocr Pract. 2008 Jan-Feb;14(1):33-9.
Hypothyroidism and pregnancy: impact on mother and child health. Ann Biol Clin (Paris). 2008;66(1):43-51.
Amniotic fluid iodine concentrations do not vary in pregnant women with varying iodine intake. Br J Nutr. 2008
21:1-4
2007
Reaching optimal iodine nutrition in pregnant and lactating women and young children: programmatic
recommendations. Public Health Nutr. 2007 Dec;10(12A):1527-9.
Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old:
conclusions and recommendations of the technical consultation. Public Health Nutr. 2007 Dec;10(12A):1606-11
The goitre rate, its association with reproductive failure, and the knowledge of iodine deficiency disorders (idd)
among women in ethiopia: cross-section community based study. BMC Public Health. 2007 Nov 8;7(147):316.
The impact of iodised salt or iodine supplements on iodine status during pregnancy, lactation and infancy. Public
Health Nutr. 2007 Dec;10(12A):1584-95.
Reproductive age in the United States Of America. Public Health Nutr. 2007 Dec;10:1532-9; Discuss 1540-1.
The importanceof iodine nutrition during pregnancy. Public Health Nutr. 2007 Dec;10(12A):1542-6. Conclusions:
Iodine prophylaxis should be given systematically to women during pregnancy. In most public health programmes
dealing with the correction of iodine deficiency disorders, iodised salt has been used as the preferred means to
deliver iodine to households. Iodised salt, however, is not the ideal means of delivering iodine in the specific
instances of pregnancy, breast-feeding and complementary feeding because of the need to limit salt intake during
these periods. In European countries, presently it is proposed that iodine is given to pregnant women and breast-
feeding mothers by systematically administering multivitamin tablets containing iodine in order to reach the
recommended dietary allowance of 250 microg iodine day-1.
Iodine requirements during pregnancy, lactation and the neonatal period and indicators of optimal iodine Nutrition.
Public Health Nutr. 2007;10(12A):1571-80; Discussion 1581-3.Conclusions: Pregnant women and young infants,
but especially the second group, are more sensitive to the effects of an iodine deficiency (ID) than the general
population because their serum thyroid-stimulating hormone (TSH) and thyroxine are increased and decreased,
respectively, for degrees of ID that do not seem to affect thyroid function in the general population. Systematic
neonatal thyroid screening using primary TSH could be the most sensitive indicator to monitor the process of ID
control.
Iodine deficiency and brain development in the first half of pregnancy. public health nutr. 2007;10 (12A): 1554-70. An
inadequate supply of iodine during gestation results in damage to the foetal brain that is irreversible by midgestation unless timely interventions can correct the accompanying maternal hypothyroxinemia. Even mild to
moderate maternal hypothyroxinemia may result in suboptimal neurodevelopment. This review mainly focuses on
iodine and thyroid hormone economy up to mid-gestation, a period during which the mother is the only source for
the developing brain of the foetus. The cerebral cortex of the foetus depends on maternal thyroxine (T4) for the
production of the 3',3,5-tri-iodothyronine (T3) for nuclear receptor-binding and biological effectiveness.Maternal
hypothyroxinemia early in pregnancy is potentially damaging for foetal brain development. Direct evidence has
been obtained from experiments on animals: even a relatively mild and transient hypothyroxinemia during
corticogenesis, which takes place mostly before mid-gestation in humans, affects the migration of radial neurons,
which settle permanently in heterotopic locations within the cortex and hippocampus. Behavioural defects have also
been detected.The conceptus imposes important early changes on maternal thyroid hormone economy that
practically doubles the amount of T4 secreted something that requires a concordant increase in the availability of
iodine, from 150 to 250-300 microg I day- 1. Women who are unable to increase their production of T4 early in
pregnancy constitute a population at risk for having children with neurological disabilities. As a mild to moderate
iodine deficiency is still the most widespread cause of maternal hypothyroxinemia, the birth of many children with
learning disabilities may be prevented by advising women to take iodine supplements as soon as pregnancy starts, or
earlier if possible, in order to ensure that their requirements for iodine are met.
Iodine deficiency, iodine content of salt and knowledge of iodine supplementation in the Dominican Republic.
J Trop Pediatr. 2007 Jun;53(3):214-6.
The declaration of nutrition, health, and intelligence for the child-to-be. Nutr Health. 2007;19:85-102.
Increase in congenital hypothyroidism in new york state and in the United States. Mol Genet Metab. 2007
Jul;91(3):268-77. Mandated screening of newborns for congenital hypothyroidism (CH) in NYS was initiated in
l978. Currently, every newborn screening program in the U.S. includes CH in its panel. Between 1978 and 2005, 7.4
million newborns were screened for CH in NYS. In NYS, between 1978 and 2005, the incidence of CH has
increased by 138%. Nationwide (excluding NYS data), with nearly 58 million infants screened between 1987 and
2002, the incidence has increased 73% between 1987 and 2002. These data and possible reasons for the increases
are discussed, though no definitive causes are identified.
Iodine supplementation during pregnancy: a public health challenge. Trends Endocrinol Metab. 2007 Nov;18(9): 33843. Iodine deficiency remains the most frequent cause worldwide, after starvation, of preventable mental retardation
in children. It causes maternal hypothyroxinemia, which affects pregnant women even in apparently iodinesufficient areas, and often goes unnoticed because L-thyroxine (T4) levels remain within the normal range, and
thyroid-stimulating hormone (TSH) is not increased. Even a mild hypothyroxinemia during pregnancy increases the
risk of neurodevelopmental abnormalities, and experimental data clearly demonstrate that it damages the cortical
cytoarchitecture of the fetal brain. The American Thyroid Association (ATA) recommends a supplement of 150
microg iodine/day during pregnancy and lactation, in addition to the use of iodized salt. We discuss the importance
of iodine supplementation to ensure adequate T4 levels in all women who are considering conception and
throughout pregnancy and lactation.
Evaluating iodine deficiency in pregnant women and young infants-complex physiology with a risk of
misinterpretation. Public Health Nutr. 2007 Dec;10(12A):1547-52; Discussion 1553.
The adverse effects of mild-to-moderate iodine deficiency during pregnancy and childhood: a review. Thyroid. 2007
Sep;17(9):829-35. Iodine is required for the production of thyroid hormones, which are essential for normal brain
development, and the fetus, newborn, and young child are particularly vulnerable to iodine deficiency. The iodine
requirement increases during pregnancy and recommended intakes are in the range of 220-250 microg/day.
Monitoring iodine status during pregnancy is a challenge. New recommendations from World Health Organization
suggest that a median urinary iodine concentration >250 microg/L and <500 microg/L indicates adequate iodine
intake in pregnancy. Based on this range, it appears that many pregnant women in Western Europe have inadequate
intakes. A recent Swiss study has suggested that thyroid-stimulating hormone concentration in the newborn is a
sensitive indicator of mild iodine deficiency in late pregnancy. The potential adverse effects of mild iodine
deficiency during pregnancy are uncertain. Controlled trials of iodine supplementation in mildly iodine-deficient
pregnant women suggest beneficial effects on maternal and newborn serum thyroglobulin and thyroid volume, but
no effects on maternal and newborn total or free thyroid hormone concentrations. There are no long-term data on the
effect of iodine supplementation on birth outcomes or infant development. New data from well-controlled studies
indicate that iodine repletion in moderately iodine-deficient school-age children has clear benefits: it improves
cognitive and motor function; it also increases concentrations of insulin-like growth factor 1 and insulin-like growth
factor-binding protein 3, and improves somatic growth.
National trends in iodine nutrition: is everyone getting enough? Thyroid. 2007 Sep;17(9):823-7. Iodine deficiency is an
important public health problem worldwide. Until the 1920s, endemic iodine deficiency disorders were prevalent in
the Great Lakes, Appalachian, and Northwestern regions of the United States. Iodized salt was responsible for eliminating endemic goiter in the United States & remains the mainstay of iodine deficiency disorder eradication efforts
worldwide. Although urinary iodine values have decreased by 50% since the early 1970s, the USA remains iodine
sufficient. However, U.S. iodine nutrition, particularly among women of childbearing age, may remain an area
worthy of public health concern. There is a wide amount of variation in the iodine content of some common foods,
& the iodine content of foods is not well reflected by package labeling. There needs to be increased awareness of the
importance of adequate iodine nutrition, particularly during pregnancy & lactation, among the U.S. public.
Iodine nutrition in pregnancy and lactation in Iran. Public Health Nutr. 2007 Dec;10(12A):1596-9. The currently
recommended intake of iodine through universal salt iodization may not be adequate for pregnant & lactating
women, & supplementation during pregnancy & lactation should be further considered in light of the latest
recommendations.
Iodine nutrition of pregnant and lactating women in Hong Kong, where intake is of borderline sufficiency. Public
Health Nutr. 2007 Dec;10(12A):1600-1 The currently recommended intake of iodine through universal salt
iodization may not be adequate for pregnant and lactating women, and supplementation during pregnancy and
lactation should be further considered in light of the latest recommendations.
Obstetric management of thyroid disease. Obstet Gynecol Surv. 2007 Oct;62(10):680-8; Quiz 691.
Thyroid disorders in pregnancy and after delivery. Przegl Lek. 2007;64(3):159-64.
Reaching optimal iodine nutrition in pregnant and lactating women and young children: programmatic
recommendations. Public Health Nutr. 2007 Dec;10(12A):1527-9.
Reflections on mental retardation and congenital hypothyroidism: effects of trace mineral deficiencies. Sante. 2007
Jan-Mar;17(1):41-50.
Assessment of intertrimester and seasonal variations of urinary iodine concentration during pregnancy in an iodinereplete area. Clin Endocrinol (Oxf). 2007 Oct;67(4):577-81.
Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal
performance of the rat. Indian J Exp Biol. 2007 Jul;45:603-9.
Thyroid hormones, learning and memory. Genes Brain Behav. 2007 Jun;6 Suppl 1:40-4. Thyroid hormones (THs), T3
& T4, have many physiological actions & are essential for normal behavioral, intellectual & neurological
development. THs have a broad spectrum of effects on the developing brain & mediate important effects within the
CNS throughout life. Insufficient maternal iodine intake during gestation & TH deficiency during human
development are associated to pathological alterations such as cretinism & mental retardation. In adulthood, thyroid
dysfunction is related to neurological & behavioral abnormalities, including memory impairment. Analysis of
different experimental models suggests that most of the effects on cognition as a result of thyroid dysfunction rely
on hippocampal modifications. Insufficiency of THs during development thus alters hippocampal synaptic function
and impairs behavioral performance of hippocampal-dependent learning and memory tasks that persist in euthyroid
adult animals. In the present review, we summarize the current knowledge obtained by clinical observations &
experimental models that shows the importance of THs in learning & mnemonic processes.
Iodine and thyroid hormones during pregnancy and postpartum. Gynecol Endocrinol. 2007 Jul;23:414-28. Iodine is a
trace element essential for synthesis of the thyroid hormones, triiodothyronine & thyroxine. These hormones play a
vital role in the early growth & development stages of most organs, especially the brain. The World Health Organization has declared that, after famine, iodine deficiency is the most avoidable cause of cerebral lesions including
different degrees of mental retardation & cerebral paralysis. The main function of iodine in vertebrates is to interact
with the thyroid hormones. During pregnancy sufficient quantities of iodine are required to prevent the appearance
of hypothyroidism, trophoblastic & embryonic or fetal disorders, neonatal & maternal hypothyroidism, & permanent
sequelae in infants. Thyroid hormone receptors & iodothyronine deiodinases are present in placenta & central
nervous tissue of the fetus. A number of environmental factors influence the epidemiology of thyroid disorders, &
even relatively small abnormalities & differences in the level of iodine intake in a population have profound effects
on the occurrence of thyroid abnormalities. The prevalence of disorders related to iodine deficit during pregnancy &
postpartum has increased. Iodine supplementation is an effective measure in the case of pregnant & lactating
women. However, it is not implemented & the problem is still present even in societies with theoretically advanced
health systems. During pregnancy & postpartum, the WHO recommends iodine intake be increased to at least 200
mcg/day. Side-effects provoked by iodine supplementation are rare during pregnancy at the recommended doses.
Iron deficiency predicts poor maternal thyroid status during pregnancy. J Clin Endocrinol Metab. 2007 Sep;92
(9):3436-40. Pregnant women are often iron deficient, and iron deficiency has adverse effects on thyroid
metabolism. Impaired maternal thyroid function during pregnancy may cause neurodevelopmental delays in the
offspring. Our objective was to investigate whether maternal iron status is a determinant of TSH and/or total T(4)
(TT4) concentrations during pregnancy. …Conclusion: Poor maternal iron status predicts both higher TSH and
lower TT4 concentrations during pregnancy in an area of borderline iodine deficiency.
To correct iodine deficiency in pregnancy: another salutary lesson from Tasmania. Med J Aust. 2007 Jun
4;186(11):574-6.
The diagnostic criteria of graves' disease and especially the thyrotropin receptor antibody; our own experience. Hell
J Nucl Med. 2007 May-Aug;10(2):89-94.
Subclinical hypothyroidism and pregnancy. J Gynecol Obstet Biol Reprod (Paris). 2007 Nov;36(7):688-93.
Iodine supplementation for pregnancy and lactation: United States and Canada: recommendations of the american
thyroid association. Thyroid. 2007 May;17(5):483-4.
Placental tissue iodine level and blood magnesium concentration in pre-eclamptic and normal pregnancy. Int J
Gynaecol Obstet. 2007 Aug;98(2):100-4. Results: Placental tissue iodine levels were lower in women with severe
pre-eclampsia than in healthy pregnant …as were blood magnesium levels ….There was a positive correlation
between placental tissue iodine levels and blood magnesium levels in women with severe pre-eclampsia (r=0.55,
P<0.05), but no such correlation was observed in healthy pregnant women (r=0.23, P=0.41). Conclusion: Mg
assimilation is known to be defective when iodine levels are insufficient. In northeast Anatolia, where iodine
deficiency is common, clinical trials of iodine supplementation should be considered for pre-eclamptic therapy.
Clinical and biological consequences of iodine deficiency during pregnancy. Endocr Dev. 2007;10:62-85. The main
change in thyroid function associated with the pregnant state is the requirement of an increased production of
thyroid hormone that depends directly upon the adequate availability of dietary iodine & integrity of the glandular
machinery. In healthy pregnant women, physiological adaptation takes place when the iodine intake is adequate,
while this is replaced by pathological alterations when there is a deficient iodine intake. Pregnancy acts typically,
therefore, as a revelator of underlying iodine restriction. Iodine deficiency has important repercussions for both the
mother & the fetus, leading to hypothyroxinemia, sustained glandular stimulation & finally goitrogenesis. Furthermore, because severe iodine deficiency may be associated with an impairment in the psychoneurointellectual outcome in the progeny, because both mother & offspring are exposed to iodine deficiency during gestation (& the
postnatal period), & because iodine deficiency is still prevalent today in several large regions of the world, iodine
supplements should be given systematically to pregnant & breastfeeding mothers. Particular attention is required to
ensure that pregnant women receive an adequate iodine supply, in order to reach the ideal recommended nutrient
intake of 250 mcg iodine/day.
Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other
environmental antithyroid agents. J Neurol Sci. 2007 Nov 15;262(1-2):15-26.
Smoking and environmental iodine as risk factors for thyroiditis among parous women. Eur J Epidemiol.
2007;22(7):467-72.
Local blood flow in the dorsal hippocampus and cerebellar cortex in the offspring of iodine-deficient rats. Neurosci
Behav Physiol. 2007 Jun;37(5):495-8.
Short-term changes in maternal and neonatal urinary iodine excretion. Thyroid. 2007 Mar;17(3):219-22.
General background on the hypothalamic-pituitary-thyroid (hpt) axis. Crit Rev Toxicol. 2007;37(1-2):11-53.
Evaluating the roles of follicle-stimulating hormone receptor polymorphisms in gonadal hyperstimulation
associated with severe juvenile primary hypothyroidism. J Clin Endocrinol Metab. 2007 Jun;92(6):2312-7.
Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr. 2007;85(2):614S-620S
Effect of the level of iodine in the diet of pregnant ewes on the concentration of immunoglobulin g in the plasma of
neonatal lambs following the consumption of colostrum. Br J Nutr. 2007 Feb;97:315-20.
Urine iodine measurements, creatinine adjustment, and thyroid deficiency in an Adult United States population. J
Clin Endocrinol Metab. 2007 Mar;92(3):1019-22.Hypothyroidism: From the Desire for Pregnancy to Delivery.
Gynecol Obstet Fertil. 2007 Mar;35(3):240-8.
Maternal smoking and infant feeding: breastfeeding is better and safer. Matern Child Health J. 2007;11(3):287-91.
2006
Urinary iodide assessment of the adult population in Catalonia. Med Clin (Barc). 2006 Nov 18;127:730-3.
Iodine excretion with urine and thyrotrophic hormone concentration in normal and complicated pregnancies in the
industrial region of iodine deficiency. Wiad Lek. 2006;59(9-10):612-7.
Radioiodine therapy for women with graves' disease and the risk of foetal hypothyroidism if they are later found to
be pregnant. Ned Tijdschr Geneeskd. 2006 Dec 30;150(52):2845-8.
Food restriction induced thyroid changes and their reversal after refeeding in female rats and their pups. Acta Biol
Hung. 2006 Dec;57(4):391-402.
Effect of environmental iodine deficiency (eid) on foetal growth in Nigeria. Indian J Med Res.2006;124(5):535-44.
Selenium and goiter prevalence in borderline iodine sufficiency. Eur J Endocrinol. 2006 Dec;155(6):807-12.
Brain MR spectroscopy findings in neonates with hypothyroidism born to mothers living in iodine-deficient areas.
AJNR Am J Neuroradiol. 2006 Nov-Dec;27(10):2083-7.
Status of iodine nutrition n france: prevention of iodine deficiency in pregnant and lactating women. Ann Endocrinol
(Paris). 2006 Sep;67(4):281-6.
Thyroid function and thyroid autoimmunity at the late pregnancy: data from 664 pregnant women. Zhonghua Fu
Chan Ke Za Zhi. 2006 Aug;41(8):529-32.
Effects of nutrients (in food) on the structure and function of the nervous system: Update on dietary requirements
for brain. Part 1: Micronutrients. J Nutr Health Aging. 2006 Sep-Oct;10(5):377-85.
Iodine supplementation for pregnancy and lactation-United States and Canada: Recommendations of the American
Thyroid Association. Thyroid. 2006;16(10):949-51. The fetus is totally dependent in early pregnancy on maternal
thyroxine for normal brain development. Adequate maternal dietary intake of iodine during pregnancy is essential
for maternal thyroxine production & later for thyroid function in the fetus. If iodine insufficiency leads to inadequate
production of thyroid hormones & hypothyroidism during pregnancy, then irreversible fetal brain damage can result.
In the USA, the median urinary iodine (UI) was 168 mcg/L in 2001-2, well within the range of normal established
by the World Health Organization (WHO), but whereas the UI of pregnant women (173 mcg/L ; 95% CI 75-229
mcg/L) was within the range recommended by WHO (150-249 mcg/L), the lower 95% CI was less than 150 mcg/L.
Therefore, until additional physiologic data are available to make a better judgment, the American Thyroid
Association recommends that women receive 150 mcg iodine supplements daily during pregnancy and lactation and
that all prenatal vitamin/mineral preparations contain 150 mcg of iodine.
The function of thyroid gland during the course of pregnancy. Georgian Med News. 2006 Sep;(138):68-70.
Micronutrients in women's reproductive health: II. Minerals and trace elements. Int J Fertil Womens Med. 2006
May-Jun;51(3):116-24.
2005
Thyroid hormones and fetal brain development. Minerva Ginecol. 2005 Aug;57(4):367-78.
Iodine Deficiency Disorders: Goiter
http://motherchildnutrition.org/early-malnutrition-detection/images/goitre.jpg
http://medicine-science.com/wp-content/uploads/2011/09/Iodine-Deficiency.jpg
Iodine Deficiency Disorders:
Vulnerability to thyroid cancer from radioactive iodine exposure:
“The Chernobyl Necklace” … Ukraine is a low iodine region.
Iodine Deficiency Disorders: The American “Goiter Belt”
Map showing spatial correlation between the former "Goiter Belt" in the northern U.S.
and areas where the iodine content of drinking water is naturally low.
www.uwsp.edu/gEo/faculty/ozsvath/images/ goiter_belt.htm
The start of the movement to
iodize salt in America.
You often have to look
Closely to see if salt is
iodized or not.
Some sea salt is iodized
but most is not.
Iodine Deficiency Disorders: Cretinism
Iodine Deficiency is the Number One Cause
of Preventable Mental Retardation in the World.
Sanford Medical Center
Aunt Cathy’s Guide to:
Cathy Breedon PhD, RD,CSP,FADA
Clinical/Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
Nutrition Support
of Iron Deficiency
Iron deficiency can result in:
• Poor ability to deliver oxygen to the body
• Loss of energy
• Poor ability to concentrate
• Impaired growth and mental development in children
• Impaired carnitine production, and many other problems
• Impaired clearance from the body of potentially toxic substances
• Difficulty establishing a pregnancy.
Iron deficiency can be quite common and it can be caused by a
variety of factors. It may be related to:
• Diets that provide poor amounts of iron or iron in forms that are poorly
absorbed, or which are high in substances that impair absorption.
• Abnormal iron losses, such as hemorrhage, heavy menstrual periods, or
losses related to childbirth or surgery.
• Conditions that impair iron absorption, such as Cystic Fibrosis, or
intestinal diseases like Crohn’s disease, Inflammatory Bowel Disease or
Celiac Disease. “Bariatric surgery” for weight loss is also associated with
significant iron deficiency. In many parts of the world, people commonly
have severe iron deficiency because of intestinal parasites.
1
• Conditions that increase requirements, (such as rapid growth of tissues
during pregnancy, infancy or childhood,) can result in inadequacy when the
usually adequate intake of iron is not enough to meet all the increased iron
needs.
A Cautionary Note:
Iron deficiency is NOT ALWAYS the cause of anemia.
There are other situations that affect iron or red blood cell metabolism (such as deficiency of
the nutrients needed as tools for iron metabolism (such as copper, or vitamins C, B6, B12, and folic acid.)
There are conditions that result in a short half-life of red blood cells (such as Sickle Cell
Anemia and Thalassemia ) which can result in low red blood cells but can also result in excessive tissue
accumulation of iron from necessary therapeutic blood transfusions. In these conditions giving additional
dietary or supplemental iron will certainly not solve the anemia problem, and it can actually be
detrimental.
Surprisingly, even a genetic condition that results in excessive iron absorption and iron
overload (hemochromatosis) can result in a low red blood cell level. This is because the treatment for
iron overload is phlebotomy (giving blood, as one does for blood donation.) However, the continued
ability to therapeutically remove iron this way requires that red blood cells must be made, so poor intake
of the nutrients other than iron involved in making red blood cells can result in
• inadequate red blood cell production,
• a state of anemia (low red cell number and the associated symptoms) and
• continuation of the unhealthy high iron stores because it limits the ability to continue
phlebotomy for iron removal.
Chronic diseases like arthritis, and infections can also result in low hemoglobin measurements
that look like iron deficiency anemia in the laboratory but inadequacy of iron is not the problem. This is
called “the anemia of chronic disease.” This kind of anemia will be addressed later in this paper.
Bottom line: inadequate iron intake is a common cause of anemia, and so
that is the first place to investigate. But if providing generous absorbable iron does
not correct it, it will not be helpful to just continue to give more and more iron. More
detective work is in order in this case.
2
Now back to the major focus of this paper:
Solving the problem when iron inadequacy IS the problem
FOODS THAT ARE GENEROUS SOURCES OF
WELL-ABSORBED IRON:
MEATS:
1. “Heme iron” vs “Inorganic iron” issues
Meats of all kinds contain iron in an especially absorbable form called “heme” iron. This is
also called “organic iron.” Absorption of organic iron is not affected by the presence or absence of certain
other substances in foods the way plant iron is. Iron in this form is about 20% absorbed.
Twenty percent absorption does not sound very high, but “inorganic iron” is much less well
absorbed … only 2% absorbed, and often considerably less. That is why this approach alone is
often not very effective. Inorganic iron is the kind in plants and in supplements with the word
“ferrous” or “ferric” in them. Ferrous sulfate and ferrous gluconate are examples you will see on most
iron supplement labels.
An “organic iron” supplement that contains the well-absorbed “heme” form of iron is
available though much less commonly used and it is much more expensive. It is called “heme iron
polypeptide.” However, if iron deficiency is not corrected by the usual inorganic iron supplements or
diet changes, this can be a very helpful nutritional supplement. It is well absorbed, it does not compete
with other substances for absorption, and it is better tolerated by many people than the inorganic iron
supplements. The nature of these inorganic iron “tolerance” issues will be discussed below.
Like other nutrients, supplemental or dietary iron does no good at all if it is not absorbed
into the bloodstream from the intestines. It just passes right out in the stools. Ferrous sulfate, a very
commonly used iron supplement product that is less than 2% absorbed. Some plant forms of iron
in foods like spinach that naturally contain “oxalates” are only 0.025% absorbed! This bit of
information is not well known, however, and very common traditional nutrition advice still commonly
given is to correct iron deficiency anemia by eating spinach. Spinach is a terrific food to include in your
diet for many reasons, but it is NOT a terrific iron source … it contains iron but you don’t get very much
out of the spinach because it s also high in oxalates.
Often at the higher doses used to treat anemia, inorganic iron supplements like ferrous sulfate
can cause stools to turn a black color and they may also contribute to constipation. Neither is an
unmanageable problem – the color is not a problem, and the constipation can be addressed a variety of
ways with certain helpful foods or by using a laxative. However, the reality is that people often
discontinue taking this form of supplement because of these problems. [Iron-poisoning of children is
often because they got into the medicine cabinet and took a handful of the small but high-dose ferrous
sulfate pills that some adult quit taking for just these reasons!] And of course, no iron supplements will
solve an iron deficiency problem if a person doesn’t take them.
3
2. “Meat Protein Factor”
In addition to being a generous source of absorbable iron, meat also has a special property of
causing increased absorption of iron from the inorganic iron sources in the meal. In other words, the
iron in chili beans will be much more easily absorbed if there is meat in the chili. This is called the “Meat
Protein Factor” effect. It is not well understood how it works, but it clearly does increase absorption of
inorganic iron in other foods and supplements, so it helps to further improve recovery from low iron
stores.
3. Meat: Variable AMOUNT of Iron
The total AMOUNT of iron in different kinds of meat varies. Red meat is the highest in
absorbable iron. Poultry and fish have much less iron than red meat, but what they have is still a much
greater amount than what is found in plant foods, and it also much better absorbed than inorganic iron.
Additionally, white meat chicken/turkey has less iron than dark meat. Think of the iron content of meat
as “color-coded” … darkest is highest and the lightest is lowest. But all have the beneficial “Meat
Protein Factor” effect described above, and because it is organic iron, the form of iron is well absorbed.
Of the different types of meat, liver is an extremely generous source of absorbable iron. This
also includes foods made from liver like paté or liverwurst. Not surprisingly, the iron content of blood is
high and it is in an absorbable “heme” form, so things like Scandinavian/ German “blood sausage,” and
“blood pudding” are rich in iron. This is not a universally popular choice, however. (Helpful hint: if you
are trying to eat liver for the iron it can provide, but you don’t LIKE liver, it can be ground up and mixed
in with hamburger to make chili or meatballs or meatloaf. You can add a lot of onions and spices to mask
its presence.)
FOODS THAT INCREASE ABSORPTION
OF (INORGANIC) IRON
Acid Foods
Any acid substance, including vinegar, citric acid and vitamin C (ascorbic acid) can enhance iron
absorption from sources of inorganic iron (the form of iron found in pills or plants, like ferrous sulfate.)
Because of this, people with iron deficiency are often advised to take their iron supplement or iron
fortified cereal with orange juice, or some other acidic beverage. However, the size of the increase in
absorption is not as great as many people think, so that intervention alone is not likely to be that helpful.
For example, as noted earlier, inorganic iron is generally only about 2% (or less) absorbed, with
some forms being much less absorbable than that because of substances in some foods that interfere with
absorption. For that reason, the “take with orange juice” effect is a much less important factor affecting
iron absorption than the highly absorbable and generous heme iron found in meat (especially red meat and
liver.) Acidity and alkalinity do not affect absorption of organic iron, so there is no special ironabsorption benefit associated with eating liver with orange juice or dousing it with ketchup (a vinegarcontaining food), although the latter may make it more palatable to some people.
4
Foods That DECREASE Absorption of (Inorganic) Iron:
As described above, the presence of acid and/or meat will contribute to improved absorption
of inorganic iron. Other food substances can significantly impair absorption of inorganic iron but they
have minimal effect on absorption of organic iron. For example, the organic iron forms like “heme” iron
are about 20% absorbed, which is at least ten times as well absorbed as any inorganic iron. In addition,
the per cent of absorption of inorganic iron is much more likely to be negatively affected by other
substances in a meal.
Dairy foods
Dairy foods are notoriously poor sources of iron that also decrease absorption of the iron in
plants and pills. That means that taking iron supplements with milk, or putting milk on iron-fortified
cereal, or cheese on a sandwich can result in less of the iron present in the pill, cereal or bread being
absorbed. This is one of the issues behind the phenomenon of iron deficiency anemia in infants and
toddlers who have cow or goat milk in place of mother’s milk or iron fortified formulas.
A Bit of History:
When I started working in nutrition this kind of iron deficiency anemia condition was common,
and it was called “cow’s milk anemia.” It is much less common today because the WIC Program
(Women, Infants and Children Supplemental Food Program) came along and it has done a lot to prevent
infants being put on cow’s milk or goat’s milk too early as they often were then because of the relative
cost of iron-fortified infant formula.
An even bigger thing WIC has done that has had a tremendous effect on reducing the incidence of
cow’s milk anemia is that they promote and support breastfeeding. The iron in human milk is in the
form of lactoferrin, and it is extremely well-absorbed. Absorption has been described as between 20-50%
absorption, which is WAY better than the absorption of iron in formula or cereal even if orange juice is
fed at the same time.
Another contributor to “cow’s milk anemia” in toddlers is drinking quite a lot of milk, which
serves to displace other foods that are good sources of iron. This is in addition to the role of cow’smilk
actually impairing iron absorption from those foods. Not surprisingly, this effect is most likely seen in
children who also do not eat much meat (which would be unaffected by milk consumption) and who also
do not take a multivitamin with minerals, which would at least have provided a higher amount of
inorganic iron plus vitamin C in the same tablet.
Tea
Tea contains “tannins,” plant substances that bind iron very well in the intestines and significantly
reduces its absorbability. This effect is so marked that tea is the one food shown to be interfere with iron
absorption enough to be helpful for people who have hemochromatosis, a serious genetic problem of
absorbing way too much iron. And, as seen before, it has the most marked effect in decreasing absorption
of inorganic iron compared with meat (organic) iron.
5
Here is an example of a clinical trial showing the effect of regular tea drinking on absorption of
iron even among people with hemochromatosis which causes dangerously high iron accumulation:
“A significant reduction in iron absorption was observed when the test meal was accompanied by drinks
of tea instead of water. In the tea drinking group, the increase in storage iron was reduced by about one
third compared with that of the control group.” Gut. 1998;43(5):699-704.
Hemochromatosis is a dangerous condition, and it is now known to be much more
common than previously thought. For information on nutrition factors that can be helpful
in this condition that causes excessive iron absorption, please see my paper “Aunt Cathy’s
Guide to Nutrition: Nutrition Support of Hemochromatosis Therapy.”
Bottom line, tea has many other excellent healthful properties, but for people with iron
deficiency anemia it is important to remember that helping to improve iron status is not one of
them.
Leafy greens
Many leafy foods like spinach contain “oxalates” that bind up iron in the intestinal tract and make
it too big a molecule to be absorbed well. This is true even though the iron and vitamin C content are
generous. Some green plants like broccoli do not have oxalates and so their iron is better absorbed. As
noted before, these are extremely nutritious foods and a very important part of a healthy diet. They
provid lutein (a potent antioxidant that is a green phytochemical pigment with a special role in preventing
or slowing the development of macular degeneration … the #2 cause of blindness in America. Dark leafy
greens also provide vitamin K, a nutrient now known to be critical for prevention of osteoporosis and
calcification of arteries but found to be inadequate in the diets of many people, plus many more nutrients.
So DO eat these foods for many reasons .… just don’t rely on the oxalate-containing ones to solve the
problem if a person is iron deficient.
For information on nutrition factors that are provided by dark leafy greens, please see my paper “Aunt Cathy’s
Guide to Nutrition: Vitamin K” and “Aunt Cathy’s Guide to Nutrition: Top Five Recommendations.”
Bran
The bran is the fibrous coating on grains. Bran contains “phytates” which impair iron absorption as
tannins and oxalates do. For that reason, taking a bowl of iron-fortified bran cereal in milk along with a
cup of tea is not the best way to get inorganic iron where you want it to go. Some grains naturally contain
less phytate than others, but it is still an issue.
Eggs
Interestingly, although in the 1950s egg yolk used to be fed to infants as an iron source, the form of iron in
eggs has been found to be poorly absorbed. Eggs are an excellent source of protein (the protein in one
6
egg is like the amount in 1 ounce of meat) and other beneficial nutrients as well such as choline and biotin
in particular. The egg white has most of the protein (6 of the 7 grams) and essentially none of the iron at
all. Nearly all of the iron is in the yolk. So eggs are still a great food, but not a good iron source.
Iron-Fortified Foods
Iron “fortification” involves adding inorganic iron to foods that would not usually have iron,
such as milk-based infant formulas or similar “nutrition beverages” for adults or children. “Fortified” also
can mean that the iron (or another nutrient) was added to achieve a level higher than would naturally be in
the food. “Total”-type cereals are an example: it is fortified to provide 18 mg of inorganic iron per cup
compared with 4.5 mg of inorganic iron in a cup of a similar but unfortified whole wheat cereal like
regular wheat flakes.
“Enrichment” means that a nutrient was removed by processing but then it was added back
to the level it contained before processing. In America, iron is added back to refined grains. The
available iron naturally in the grains is in the “germ” part of the grain that is lost when grains are refined.
Unfortunately, we do not add back any other minerals; only iron and three B vitamins are added back
(B1, B2 and B3.) That is all … no magnesium, no chromium, no vitamin E, etc. This is one of the
reasons why “whole grain” products (containing the germ and bran) are nutritionally superior to
enriched grains.
[In 1998, processed grains products, whole or enriched, began to have the B vitamin “folic acid”
added to improve the folic acid status of Americans. This was food “fortification”… a nutrient was added
that was not there very much naturally.]
The iron content of commercial cereals can be quite variable, depending on the enrichment
or fortification of the product. For example, “Quick” iron-fortified cream-of-wheat has over 15 mg of
(inorganic) iron per cup, but unfortified cream-of-wheat or oatmeal only has about 2 mg. Foods that have
had iron added will indicate that they are fortified or enriched with iron if you check the label. The words
“ferrous” or “ferric” in the ingredient list is an indication of inorganic iron being added.
Some Potentially Useful (and Important) Nutrition Teaching Tools:
The removal of so many of the nutrients in grain when they are “enriched,” and the suggestion
from this term that the grain product is made to be more nutritious than before has caused considerable
confusion. It has also contributed to common nutrition problems in America with major consequences.
These include a poor intake of magnesium and chromium, which contributes to diabetes and several other
serious conditions.
For that reason, I teach my clients to think of “EN-riched” as “UN-riched” because so many
nutrients are removed and not added back, and that we should include more “Baby Plants” in our diets,
[seeds, nuts, legumes (e.g. beans, peas, peanuts and lentils) and the germ part of whole grains.]
For more on this please see my other papers “Aunt Cathy’s Guide to Nutrition: Top Five
Recommendations,” “Aunt Cathy’s Guide to Nutrition: Magnesium” “Aunt Cathy’s Guide to
Nutrition: OTHER Nutrition Issues in Diabetes” and “Aunt Cathy’s Guide to Nutrition: Chromium.”
7
The amount of iron contained naturally in some other foods
Legumes (like lima beans, chili beans, lentils, peas and peanuts) have 5-6 mg of iron per cup, but
vegetables like carrots have only about 1 mg. (But I still want you to eat your carrots for reasons other
than iron content.  )
Prune juice contains quite a lot of iron (over 9 mg per cup compared with about 1 mg per cup of
other fruit juices) and it naturally contains some other substances that help one avoid the constipation
issues. Absorbability of the iron has not been well studied, however.
Iron and Zinc Status and
General Iron and Zinc Content Chart of Food
The chart on the next page shows the iron and zinc content of a number of foods and some factors
described earlier that affect absorption of both minerals.
Two Important Points:
1.
As you can see on the chart, the foods highest in absorbable iron tend
to also be highest in absorbable zinc, and vice versa.
2.
Iron deficiency is the most often recognized nutrient deficiency in
theUSA, but that is generally because it is the only one we actually
look for by easily checking hemoglobin levels.
So unless the person is anemic because of actual blood loss, a person who is found to be iron
deficient and living in our “iron fortified/enriched” world could easily have unrecognized poor zinc
status as well. Happily, zinc inadequacy is similarly best corrected by foods that also are best at
correcting iron deficiency. Zinc status is important in iron deficiency anemia as well because inadequate
zinc can also impair the production of red blood cells, even if there is plenty of iron available to make
hemoglobin.
But zinc is important for much more than that. Zinc is involved in over 200 processes in the
body but it is harder to evaluate with labs than iron is, so it is regularly not identified unless a nutrition
history asking about meat consumption and supplement use, etc. is obtained. That does not happen often
Impaired zinc status will interfere with the production of DNA … the genetic center of every cell
… so adequacy of zinc is critical for growth and wound healing. It is also a key factor in the functioning of
the immune system because production of T-cells is very zinc-dependant. Breaking down alcohol also
requires zinc because it is needed by the enzyme alcohol dehydrogenase. So combinations of alcohol
exposure AND inadequate zinc status can make the all the damaging effects of alcohol abuse even more
severe. For more on this, please see “Aunt Cathy’s Guide to Nutrition: Fetal Alcohol Syndrome.”
8
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition:
Iron and Zinc in Food
Cathy Breedon PhD, RD,CSP,FADA
Clinical/Metabolic Nutrition Specialist
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
(Data Source: Agriculture Handbook No. 8-4 US
Dept. of Agriculture Science & Education Admin.)
9
Sanford Medical Center
Aunt Cathy's Guide To:
The Unsaturated Fat
Families: Mono & Poly
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
Omega 3 family
Omega 6 family
“The Fisher Family”
“The Cornelius Family” “The Olivetti Family”
Plant
forms
Polyunsaturated (more
than one double bond)
Polyunsaturated (more
than one double bond)
Monounsaturated (only one
double bond)
18 carbons
Alpha linolenic (18:3)
Linoleic (18:2)
Gamma Linolenic
(18:3)
Oleic, etc. (18:1)
Essential
Essential
Critter
forms
Polyunsaturated (more
than one double bond)
Polyunsaturated (more
than one double bond)
20 carbons
EPA (EicosaPentaenoic
Acid) (20:5)
ARA (20:4)
(Arachidonic Acid)
(May be essential too)
Omega 9 family
(May be essential too)
Important
New Discovery:
22 carbons
DHA (DocosaHexaenoic
Acid) (22:6)
Many people are now
known to be much less able
to do the conversions
) than we thought, so
EPA, DHA and ARA are
also “essential fats” for
them in addition to linoleic
and linolenic acid.
(
(May be essential too)
What does “omega” mean when talking
about fatty acid carbon chains?
It sounds very scientific, but it just means that you start counting the
carbons in the chain from the very end of the fatty acid chain.
“A to Z” = alpha to omega in the Greek alphabet = “beginning and end”
alpha end
omega end
18-carbons-in-a-chain fats:
9 8 7 6 5 4 3 2 1
18 carbons, 1 double bond (monounsaturated) fatty acid starting after 9 carbons from the “omega” (z) end of
the chain, so it is in the “omega 9” family) 18:1 = (18 carbons, one double bond)
6 5 4 3 2 1
Linoleic
18 carbons, 2 double bond (monounsaturated) fatty acid starting after 6 carbons from the “omega” (z) end of
the chain, so it is in the “omega 6” family) 18:2 = (18 carbons, two double bonds)
3 2 1
Linolenic
18 carbons, 3 double bond (monounsaturated) fatty acid starting after 6 carbons from the “omega” (z) end of
the chain, so it is in the “omega 6” family) 18:3 (18 carbons, three double bonds)
“Essential Fatty Acids” Linoleic and alpha-Linolenic
Linoleic
How to keep them sorted out:
Alpha-Linolenic
The only difference is the second n … write it in script and turn it on its side and it is a 3!
=3
(It’s the omega 3 one. The other one isn’t.)
We can add two more carbons and stick in another double bond to make 20 carbon fatty acids,
and then do it again to make 22 carbon fatty acids. These are “critter-level” fatty acids, not plant
fatty acids like linolenic and linoleic acid. [This process is called “enlongation and desaturation”]
20-carbons-in-a-chain fats:
Omega-3 = EPA Eicosapentaenoic Acid
(Eicosa = 20 carbons Penta = 5 enoic = double bonds)
3 2 1
Omega-6 = Arachidonic Acid
(the name is from an old system and so it is not very helpful. If it were named today it would be
ETA Eicosatetraenoic Acid (Eicosa = 20 carbons Tetra= 4 enoic = double bonds)
6 5 4 3 2 1
------------------------------------------------------------------------------------------------------------
22-carbons-in-a-chain fats:
Omega-3 = DHA Docosahexaenoic Acid
(Docosa = 22 carbons Hexaenoic = 6 double bonds)
3 2 1
Why is this important:
Although these fats can be burned as fuel like any fat,
the big deal with these is that
we make several important things out of them
Prostaglandins
Thromboxanes
The 20-carbon fats are the material from which
one makes prostaglandins … inflammatory
messengers. If one makes a prostaglandin out
of ARA (the omega 6 one) the response is
REALLY INFLAMMATORY! But if one
makes a prostaglandin out of EPA (the omega
3 one) instead, the inflammatory response is
MUCH LESS!
The 20-carbon fats are the material from which
one makes thromboxanes … messengers that
tell your blood to clot. If one makes a
thromboxane out of ARA (the omega 6 one)
the coagulation response is REALLY
CLOTTY! But if one makes a thromboxane
out of EPA (the omega 3 one) instead, much
LESS BLOOD CLOTTING results.
Excessive tendencies to clot blood and inflame the arterial walls increase risk of cardiovascular
disease. Both are increased a lot by making these substances from ARA instead of EPA. Both are
also increased by making them from EPA (because that’s what prostaglandins/thromboxanes do)
but the ones made out of EPA cause a much milder response than the ones made from ARA do.
DHA is a critical fat of the brain and retina, and it has roles in development, maintenance of
cognition as we age, mood and attention, and decreasing risk of macular degeneration. As we
now know that many people are not as able to make these very long chain fats, it is a very good
idea to obtain some “ready made.”
Most Americans get adequate ARA (the omega 6 fat) from meat, but the source of ready made
EPA and DHA (the omega 3 fats) is fatty fish like salmon or mackerel, and many Americans eat
very little of these foods. That is why the American Heart Association recommends that
people eat fatty fish twice weekly or take 1000 mg fish oil capsule daily. For certain health
situations, such as having “high triglycerides,” they suggest that 2-4 capsules daily can be helpful
with a physician’s supervision.
This is why I always say you should think of EPA as “Environmental Protection Agency”
since it protects your internal environment from excessive inflammation and blood clotting …
both of which are very important in cardiovascular disease and other serious health concerns.
And it comes pre-packaged with DHA in ready made form.
The typical “American Diet” (whatever THAT is) is described as having
10-20 omega 6 fattyacids for every one omega 3 fatty acid.
That is, a 10:1 ratio up to a 20:1 ratio.
The “Mediterranean Diet” is a heart-healthy eating pattern also associated with
decreased riskof cancer, and one feature of this diet is a ratio of only
4 omega 6 fatty acids for every omega 3 fatty acid.
That is, a 4:1 ratio.
How to remember this stuff: “6 is always bigger than 3”
Omega 6 fats make more clotty (“aggregatory”) thromboxanes than Omega 3 fats do.
Omega 6 fats make more inflammatory prostaglandins than Omega 3 fats do.
In all the ratios described above, the larger number of the two is ALWAYS the omega 6
Aunt Cathy’s Guide to:
Fatty Acid Chain Length
and GI Absorption Site
Mnemonics
Cathy Breedon PhD, RD, CSP, FADA
Perinatal/Pediatric Nutrition Specialist
Clinical Nutrition Specialist
MeritCare Health Systems, Fargo, ND
and UND School of Medicine
MCT (Medium-Chain Triglyceride) (fatty acids are 10-12 carbons long)
May Cross Through a small port-hole (pass directly into the “Portal” (liver) circulation)
LCT Long-Chain Triglyceride (fatty acids are > 12 carbons long)
Lymph Can Transport after micelles are made (does not pass directly into the “Portal”
(liver) circulation; it must first be solubilized into a micelle and taken into the lymph. It
enters the blood stream when the lymph system dumps it into the superior vena cava.)
SCF Short Chain Fats are smaller than 10 carbons in length.
Synthesized from Colonic Fiber. They serve as Special Colon Food.
Clinical Applications and Issues:
People with bile acid problems (as in cystic fibrosis, certain types of liver disease, or failure to
recycle bile due to a short bowel or prematurity) may benefit from receiving some of their fat calories as
MCT, which does not require bile for absorption.
Note that only LCT will contain essential fatty acids (EFA) because of their chain length, so
providing only MCT for a long time would not be good. Infants on special formulas that provide 15% of
the fat as LCT and the rest as MCT (e.g. “Portagen” by Mead Johnson, which is designed for infants with
conditions like biliary atresia) have been shown to become deficient in essential fatty acids over time. If
LCT simply cannot be absorbed adequately, regular i.v. lipids may be needed to provide EFAs.
Accidental surgical injury to lymph vessels during chest surgery can result in “chylothorax”, in
which the chylomicrons (“Kyle – the lipoprotein importer of fat and cholesterol”) are dumped into the
thoracic cavity instead of the vena cava. This requires a temporary strict avoidance of LCT fat to allow
the injury to heal. Even Portagen has too much LCT at 15%. For this condition in adults or children, use
“ProViMin” (Ross Labs), adding the carbohydrate of your choice and adding only MCT oil as the fat. It
contains protein, vitamins and minerals, and is much cheaper than TPN. Making an individual mixture of
protein (e.g. egg whites), vitamins and minerals for adult use is also possible since it is a short-term
condition. There is no danger of EFA deficiency in this brief period, since (unless emaciated) the person
will have adequate stores of EFAs for many weeks, and the MCT and carbohydrate can be used for fuel.
MCT is quite expensive (e.g. $60/quart), so it is not an appropriate form of fat to use simply to add
calories to a person’s diet unless there is a GI or chylothorax issue that makes it especially beneficial. It
provides 7.7 kcals/cc, compared with 8.8 kcal/cc for LCT.
Short chain fatty acids are usually produced by the action of colonic bacteria on dietary fiber.
Provision of pre-formed SCF may have some benefit in colonic disease because it serves as a fuel source
for the colon cells themselves, and it is being added to some tube-feeding products designed for use with GI
problems. Chronic antibiotic use may also limit access of colonic cells to this fuel source (by killing the
friendly bacteria), as would chronic consumption of a fiber-free or very-low-fiber diet (e.g. chronic use of a
tube feeding without fiber or SFA.)
Sanford Medical Center’s
Aunt Cathy’s
Guide to Nutrition:
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Perinatal/Pediatric Nutrition Specialist
Sanford Medical Center and
UND School of Medicine Dept. of Pediatrics
Fargo, ND
MAGNESIUM
Short Version with Minimal References Included
Usual Recommended Intake for Healthy People:
RDA:
Adult women 320; men 420mg
Pregnancy 350-400 mg
Lactation 320-360 mg
1) This mineral plays a role in over 300 functions in the body, including energy
production, all protein metabolism, nervous system activity, and bone flexibility.
2) Most American adults take in less that 2/3 of the RDA. Large national studies (such
as NHANES by the National Center for Disease Control in Atlanta) have shown that
the majority of Americans have a diet too low in these minerals. This inadequacy
contributes to weight problems, diabetes, heart disease and some neurologic problems
that are too common in our society.
3) Intake of magnesium is hard to estimate except for asking some key questions about a
person’s diet. The actual intake of this mineral cannot be evaluated any other way.
The blood magnesium level can be measured, but it does not necessarily
reflect adequacy of magnesium intake or determine if there is an adequate
amount in the cells of the body. Usually it just indicates that a person’s
kidneys are on the job, since the blood Mg level is regulated by the
kidney.
Estimates are that as many as a third of hospitalized patients have a low
magnesium level in their blood that can complicate their care. Poor
magnesium status upon entering a hospital is a predictor of a less
favorable outcome. So, if one’s blood level is low, it may reflect
inadequate intake, but it also may be due to excessive losses or a number
of other metabolic disturbances (and so a low blood magnesium level is a
very important laboratory finding.)
1
However, a normal blood magnesium level tells us very little about the
adequacy of magnesium inside the body’s cells, where most of the
magnesium-dependent work is trying to be done. Therefore, the best way
to know if people’s intake of magnesium is appropriate is to obtain a
careful history of their usual intake from foods and supplements.
At present a magnesium intake evaluation is rarely done because of lack of
time, lack of information about what are the key magnesium-containing
foods to ask about, and/or a lack of awareness that a person’s magnesium
intake may easily be poor and also contributory to poor health outcomes.
Low magnesium intake is associated with a number of adverse health
conditions. However, as is the case for most minerals, excessive intake
from high-dose supplements is not safe. In most cases, supplemental
magnesium in the neighborhood of the RDA levels is certainly safe even
when taken along with a diet that provides a generous amount. An
important exception to this rule are people with kidney problems that
impair the ability control blood magnesium level.
A Brief Overview of Associations of Poor Magnesium Status
with Adverse Health Conditions:
Diabetes:
High blood sugar contributes to magnesium loss in the urine and at the same time
poor magnesium status can increase insulin resistance because magnesium is required
by the insulin receptors on the cells. Low magnesium intake may also contribute to the
development of diabetes, heart disease and stroke, and to certain complications of
diabetes such as retinopathy and neuropathy. Many studies have shown that people with
diabetes often have poor magnesium status. Improved blood sugar control is associated
with eating a “high fiber diet, ” which also provides a better intake of magnesium and
chromium, both of which play very important roles in blood sugar and lipid metabolism.
For example, recently researchers at Harvard University published the results of a
prospective study at of almost 84,000 women who were followed for 16 years. It was
found that those who ate nuts or peanut butter four times a week or more had 25%
less likelihood of developing Type II diabetes (the adult type) than was found for
women who ate these foods rarely or never. Nuts and peanut butter are especially rich in
magnesium, chromium, vitamin E, monounsaturated fat and omega-3 polyunsaturated
fats. All of these nutrients have the potential to have played a protective role in this study.
Later the data was analyzed differently, it was found that the same pattern existed when
the highest and lowest magnesium intake groups were compared. Magnesium
2
inadequacy also is being implicated as a contributor to the development of Type II
diabetes in young people that is evolving from the epidemic of childhood obesity .
Cardiovascular Disease and Hypertension:
Abnormal magnesium status is common in patients with cardiovascular diseases
for a number of reasons, including poor dietary intake or excessive losses due to use of
diuretics or diabetes. Dietary magnesium inadequacy is an independent risk factor in
predicting the development of hypertension and cardiovascular disease. Some of the
benefits of high fiber diets, legumes (especially peanuts) and nut consumption in
decreasing cardiovascular risk are likely due in part to the magnesium content.
Osteoporosis and Bone Health:
Healthy bone production relies on the implantation of calcium into a flexible core
called the bone “matrix.” Magnesium is crucial for the development of the bone matrix,
and so inadequacy can increase the fragility of bone (because it is less flexible) and it
can impair recovery from bone injury.
It is also important to note that calcium and magnesium also interact in other areas
of the body, such as nervous system function, blood pressure control and blood clotting,
so maintaining an appropriate ratio is extremely important. For example, there is concern
that excessively generous calcium supplementation without attention to the calcium:
magnesium ratio may increase risk of thrombosis and stroke. With so much calcium
fortification and supplementation taking place, we cannot afford to ignore the fact that
many Americans have a poor magnesium intake and/or high magnesium losses.
Pregnancy:
Some researchers feel that prenatal magnesium adequacy has a higher priority
than even iron supplementation because of the over 300 enzyme systems in the body that
depend on magnesium to function properly. Several measures of pregnancy outcome,
such as higher frequency of spontaneous abortions (miscarriage), fetal growth
retardation, birth defects, maternal hospitalizations, preterm delivery, SIDS and
referrals to NICUs have been found to be associated with poor magnesium status in
pregnancy. [These issues are related to general nutrition and are separate from issues
related to the acute therapeutic i.v. magnesium sometimes used in the treatment of preeclampsia or premature labor.]
Other studies have shown a benefit of assuring magnesium adequacy (i.e.
providing the RDA level of magnesium) in the reduction of leg cramps in pregnancy.
Pregnant women with diabetes need special attention to adequacy of magnesium intake
because of the potential for increased losses and the common finding of poor magnesium
status among people with diabetes in particular. In addition, inadequacy of magnesium is
a risk factor for the development of gestational diabetes as well as Type II diabetes.
3
Migraine Headaches:
For some migraine sufferers, assuring adequacy of magnesium intake resolves
migraine problems. For others, it decreases the frequency or intensity of the headaches.
So, while Mg status is certainly not the only factor involved in the development of migraines, this intervention can be helpful, and it is safe and inexpensive, so many experts
in headache treatment regard assuring magnesium adequacy as a primary intervention.
Premenstrual Syndrome (PMS):
Providing magnesium at the RDA level has been shown to improve “affect”
(mood or emotional well-being), and certain tissues of women suffering from PMS have
been shown to be low in magnesium. Brain levels of the neurotransmitter serotonin
appear to be significantly involved in PMS, and medications that adjust serotonin levels
are now being used. Assuring adequacy of magnesium may be a factor (both with and
without other medication) because it also is required for the production and metabolism
of serotonin (and all neurotransmitter metabolism.) In any case, assuring adequacy of
magnesium can only help, and inadequacy could potentially contribute to problems.
Cancer:
In 2005 a population-based prospective study of 61,433 women suggested that a
high magnesium intake may reduce the occurrence of colorectal cancer. Animal studies
have also suggested that a higher dietary intake of magnesium is associated with decreased
risk of colon cancer, possibly related to an effect of the magnesium-containing substance
called chlorophyll protecting against cancer-promoting properties of a structurally similar
substance in red meat called heme (or “haem” in the UK.) In addition, in 2004 it was
reported that a lower magnesium level in drinking water was associated with risk of death
from ovarian cancer.
Kidneys, stone forming, and other renal issues:
Low magnesium intake has a role in the development of kidney stones, and the
kidney has an important role in regulating magnesium in the blood.
Miscellaneous:
Magnesium adequacy has been found to be a factor in the development and/or
management of many chronic conditions, such as asthma, certain thyroid conditions,
alcoholism, pancreatitis, hearing loss, and possibly Tourette’s Syndrome, Raynaud's
phenomenon, pain management, corneal disease, skin problems, attempts to quit
smoking, and certain hyperexcitable states.
4
Magnesium Losses and Safety Issues:
Conditions like chronic diarrhea, high blood sugar, or the regular use of
certain drugs (such as thiazide diuretics) cause magnesium loss. As a rule, drugs for
which patients are advised to eat a high potassium diet or to take potassium supplements
are also likely to cause loss of magnesium. This problem is often unrecognized,
however, and because of an interaction between magnesium and potassium, the failure to
correct magnesium losses along with potassium losses further compromises the body’s
ability to achieve normal potassium status in the cells.
As is the case with potassium, most vitamin/mineral supplements contain little
magnesium or none at all. And also like potassium, there may be a need to take in less
when one has certain kidney problems.
As noted above, excessive intake from supplements or magnesium-containing
medications can also cause problems, so never give nutritional supplements of
magnesium above the level described in the RDA table above unless prescribed by a
doctor. It is also useful to know that magnesium oxide, chloride and diglycinate are the
kinds of magnesium that are usually used as a supplement . . . magnesium sulfate
(Epsom salts) and hydroxide ("milk of magnesia") are less well absorbed and more likely
to cause diarrhea instead (which is why they are used to treat constipation . . . in fact,
magnesium citrate is often used as a pre-coloscopy bowel-cleaning product!) There are a
number of magnesium-containing medications, like some over-the-counter antacid
products. Check with a pharmacist about magnesium in specific products.
Finding Good Food Sources of Magnesium:
1.
When you eat grain products, try to use whole grain
whenever possible.
The “germ” (the part that becomes the baby plant) and the bran (the fibrous coating)
of grains are removed in processing when grains are “refined.” After removing the germ
and bran, four of the nutrients that were lost are added back: vitamins B1, B2, B3 and iron,
and the grain product is called “enriched.” That sounds pretty good, but they do not replace
the parts that would have contributed the most magnesium, chromium, vitamin E, fiber and
many other nutrients. Magnesium and chromium have important roles in using the rest of
the grain (the starchy part) for energy and for avoiding diabetes. So, when you see the
term “enriched” think of it as “UNriched” … because it is actually missing many
important nutrients that the germ and bran would have contributed.
5
However, if one really doesn’t like whole grain bread or other whole grain products,
many of these missing nutrients can be found in nuts and legumes and other foods
described below. For example, putting peanut butter on the bread helps fill the nutrition
gap associated with eating only “enriched” grain products. Also, it is not necessary that
these foods be eaten at the same time … we just need to identify some good magnesium
sources that a person likes and include them regularly.
2. Nuts, seeds, peanuts and dried beans/peas are terrific
nutrient-rich foods because they are essentially the germ of
new plants … the “baby plant.”
For example, in one study from Harvard, eating an ounce of nuts or peanuts four
times a week or more was shown to be related to 25% less likelihood of developing
diabetes. This appears to be associated with the generous magnesium in these foods.
They also have more “satiety value” – you feel like you actually ATE something” -- and
they are terrific nutritious snacks including for people who are watching their weight or
who have diabetes.
[Some references: Regular consumption of nuts is associated with a lower risk of cardiovascular disease in
women with type 2 diabetes. J Nutr. 2009 Jul;139(7):1333-8. Prospective study of nut consumption, long-term
weight change, and obesity risk in women. Am J Clin Nutr. 2009 Jun;89(6):1913-9. Nuts and health outcomes:
new epidemiologic evidence. Am J Clin Nutr. 2009 May;89(5):1643S-1648S. The role of tree nuts and peanuts in
the prevention of coronary heart disease: multiple potential mechanisms. J Nutr. 2008 Sep;138(9):1746S-1751S.]
Although all fats have about 9 calories per gram, the forms of fat in nuts and
Peanuts (mostly “monounsaturated” and “omega-3” fats) are less contributory to
heart disease than many other forms of fat. Also they are rich in nutrient content so
they are not an “empty calorie” food. So, although they do have calories, I think of these
forms of fat as potentially “Dangerous to your butt, but not to your heart!” Additionally,
dried beans and peas are also very low in fat and high in fiber. It looks like that means
chili beans, lima beans, split peas, chick peas, navy beans, lentils, pinto beans, etc., are
“health foods!”
These foods, and assuring adequacy of magnesium (and chromium, another
key mineral in the same foods) in general, are especially beneficial for people who
appear to be genetically (or for whatever reason) at greater risk of developing
diabetes. This includes people who have family members with diabetes, people who are
overweight, and some ethnic groups who appear to be disproportionately at risk.
For example, serious health problems related to diabetes have been found to be
causing much more injury to Native Americans and African Americans than to some
other groups of folks. There are many contributing factors, of course, but assuring
adequacy of magnesium and chromium (another key mineral in the same foods) is one
factor that can be easily corrected if people just hear about it. [Vitamin D is another, as
discussed in my other papers.]
6
Food sources are the best way to safely assure adequacy, with the added benefit
of the other nutrients they provide and the pleasure derived from eating them. Unlike
supplement sources, dietary sources of magnesium do not contribute to diarrhea, and
there is not a concern about potential overdose. Only people with renal failure or another
serious medical conditions may be advised by a physician to limit intake of dietary
magnesium.
As can be seen below, the best sources or magnesium are also foods
recommended as healthy choices by the American Dietetic Association, and by many
professional health associations concerned with cardiovascular health, diabetes and
cancer. And although the nuts and peanut butter do contribute fat and calories, they can
easily be included as a part of a healthy diet when used in place of other high calorie or
high fat foods.
As an added bonus, the form of fat in these foods is rich in monounsaturated fat
and omega-3 fatty acids. They are low in saturated fat and trans fatty acids, have no
cholesterol, and compared with other forms of fat, they are generally found to be
protective against heart disease, diabetes and cancer.
Some of the Best Dietary Sources of Magnesium:
Magnesium (mg per 1/2 cup)
500 mg or more
Peanuts and Peanut butter
100-300mg
Wheat germ*, Bran cereals*,
Wild rice
Lentils, Split peas, Tofu,
Cashews, Almonds
25-90 mg
Fortified breakfast cereals, Oatmeal,
Miso, Spinach,
Milk, Yogurt, Fish,
Brewer's yeast (80 mg/Tblsp),
Cocoa powder (25 mg/Tblsp)
*Note that refining grains removes most of the magnesium and it is not added back as
iron is when grain is “enriched.” The phytate content of the grain is also a factor in the
availability of dietary magnesium.
7
A few more references: [Effects of the regular consumption of wholemeal wheat foods on cardiovascular
risk factors in healthy people. Nutr Metab Cardiovasc Dis. 2009 Jun 5. Am J Epidemiol. 2009 Jun
15;169(12):1437-44. Dietary calcium and magnesium intakes and the risk of type 2 diabetes: the Shanghai
Women's Health Study. Am J Clin Nutr. 2009 Apr;89(4):1059-67. Serum and dietary magnesium and risk
of ischemic stroke: the Atherosclerosis Risk in Communities Study. Am J Epidemiol. 2009 Jun 15;169(12):
1437-44. The efficacy and safety of oral magnesium supplementation in the treatment of depression in the
elderly with type 2 diabetes: a randomized, equivalent trial. Magnes Res. 2008 Dec;21(4):218-23. Dietary
intake of selected minerals for the United States population: 1999-2000. Adv Data. 2004 Apr 27;(341):1-5.
Diabetes mellitus and magnesium. Clin Calcium. 2005 Feb;15(2):203-12. Magnesium and hypertension.
Clin Calcium. 2005 Feb;15(2):255-60. Magnesium in congestive heart failure. Clin Calcium. 2005
Feb;15(2):181-6]
8
Sanford Medical Center
Aunt Cathy’s Guide to Nutrition
Aunt Cathy
Understanding
MCAD Deficiency:
Cathy Breedon PhD, RD, CSP, FADA
Clinical/Metabolic/Pediatric Nutrition Specialist
Sanford Medical Center & UND School of Medicine,
801 N. Broadway, Fargo ND 58122
Office: 701-234-5022 Home: 218-233-4596
Pager: 701-234-2000 and ask for pager 1136
Email: [email protected]
(Medium Chain AcylCoA
Dehydrogenase Deficiency)
2014
What is the basic problem? People with MCADD have a genetic problem with chopping up
chains of fat to a size small enough to go into the “furnace” (in the mitochondria in cells) and be
burned to make energy to run one’s body. It is usually identified by newborn screening, and babies
identified that way who follow a special nutrition program have the potential to live healthy normal
lives.
The chains of fat we use for fuel to make energy are like strings of beads, and the size they
need to be chopped up to is 2 beads long. There are three kinds of fat “choppers*” in the
mitochondria:
(* the real name of any chopper is an “enzyme”)
Those who chop up the longest pieces (14 beads or more) are called Long Chain Choppers
Those who chop up the medium-sized pieces (10-12 beads) are called Medium Chain Choppers
Those who chop up the shortest pieces (8 beads or less) are called Short Chain Choppers
People with MCADD stop here
and can’t use any more of the fat molecule for fuel.
The actual name of a fat chopper of this type is AcylCoA Dehdrogenase.
So, the ones that chop up the medium sized chains are called Medium-Chain-AcylCoADehdrogenase, or MCAD. If a person does not make enough of this type of chopper, he/she
is said to have “MCADD” … or Medium Chain AcylCoA Dehdrogenase Deficiency.
People with MCAD cannot use all the rest of the fat molecule to make fuel, so it is very
important that usable fuel sources like carbohydrate (sugars and starches) should be
provided as an alternative fuel.
Problems with fasting:
During fasting we usually burn fat for fuel, so the person with MCADD may not be able to
fast very well. They could run out of fuel and burn the only thing they have available: their
blood sugar. That could cause a low blood sugar and the person could be very sick or hurt or
he/she could even die. That is why babies with MCADD are not allowed to go more than
three hours without being fed … we don’t trust them to be able to burn fat in order to fast
well enough to go longer than that. Later they will be able to go longer between feedings,
and your baby’s doctor will tell you when and how to increase the interval between feedings
as baby grows. There are ways to be very sure when the baby can safely fast longer.
Problems if people with MCADD get sick and can’t eat:
This person needs to be provided with carbohydrate right away… even Kool-aid or juice or
sugar water, or some sugar tucked into baby’s cheek are very useful and easy-to-get
carbohydrate. Another way to provide a longer-lasting form of carbohydrate is to add raw
cornstarch to foods or liquids.
[It does not matter if the food is not usually regarded as a nutritional or traditional food for
babies … the only thing that matters in this emergency situation is safely giving baby
something to keep her/his blood sugar from dropping too low.] Give this sugary or
starchy food right away and take the baby to the ER because if baby is very sick
he/she may need them to give intravenous glucose. But don’t wait until you get there
…give that baby some carbohydrate all the way to the hospital!
Need for supplemental carnitine:
The person with MCADD will need an extra amount of a substance that people make
called carnitine. It helps to cart the long fat molecule into the chopping area. [Memory
trick: Carnitine = “Cart-It-In”] People with MCADD need more than they can usually
make because they also have to haul the medium-chain-length stumps of the fat BACK OUT
of the mitochondria. Usually one does not need to empty the trash like this.
This picture of a logging truck illustrates
the role of carnitine if you imagine the
long trees as long chains of fat. Carnitine
“trucks” are needed to get them into the
saw mill to cut them up in to small enough
bits to go into the furnace.
The MCADD problem affects the ability to
chop up the fats AFTER they are carried
into the saw mill. MCADD makes one need
more carnitine than other people need
because they also need to take the
unusable stumps of fat back out of the
mitochondria so they do not build up.
The baby’s doctor needs to prescribe carnitine, and the amount needs to be increased as
the person gets bigger. (It is calculated by body size.) The usual amount for infants with
MCADD is in the range of 50-150 mg/kg body weight daily, divided into three doses. This is
approximately 25-75 mg per pound the baby weighs. As a rule-of thumb, some families or
home doctors set up an automatic “bump up” whenever the baby gains another pound.
This works very nicely.
As you can see, the range needed is fairly broad … some need a lot and some need less. They
ALL need SOME. That means that there will likely be adjustments made as we know more
about how much an individual baby needs. If the carnitine prescription is set higher than a
certain baby needs, he/she may send the extra amount out in the form that smells like a little
fish. This is not harmful … just stinky. All that needs to be done is dial back the prescription
in 10% increments until the right amount is provided and the fishy smell goes away.
Carnitine is actually “L-carnitine” and it also comes in forms such as “acetyl-L-carnitine.”
The latter form appears to be absorbed more efficiently. Carnitine can be obtained in a liquid
form for babies as well as capsules for older people. [Please be sure that the prescription, the
pharmacist’s interpretation of the word carnitine, and the substance requested on insurance
forms arecorrect. It is important to check because sometimes people mix up the word
carnitine with beta-carotene just because it is a more familiar word. Beta-carotene is the
orange pigment in carrots and it a very different substance from carnitine.
Insurance companies sometimes initially refuse coverage for carnitine because it is available
“over-the-counter.” However, this use of carnitine is central to the health of a baby with this
unusual metabolic condition, so if coverage is refused the doctors should write a letter to
make it very clear that the carnitine should be covered in this case. So far, we have always
been successful in having it covered for babies with MCADD … but sometimes we have had
to re-submit the request a few times.
Other supplements:
Doctors often prescribe an amino acid called glycine (100-200 mg/kg/day) to help some of
the fats that are not able to be chopped up adequately be excreted in the urine.
They may also prescribe very generous vitamin B2 (“riboflavin”) at 100-200 mg/day for
people with MCADD because it may help the affected enzymes work better.
Vitamin D should be provided at 400 iu/day starting right away as recommended by the
American Academy of Pediatrics. This can be as a vitamin D drop, or as part of a
multivitamin drop. This is important for all babies (not just those with a metabolic disease)
for many reasons including decreasing risk of diabetes, cancer, infections and many other
serious problems that nobody wants. In our clinic we do check a vitamin D level because
many babies here are born with actual vitamin D deficiency. When deficiency is found, we
correct the problem with a higher therapeutic dose of vitamin D, after which we have an
appropriate follow-up plan to assure that the baby continues to have this critical need met.
A fish oil supplement is a good way to assure the availablility of two important fats that are
very important to the development of the eye and the brain. Fish oil contains ready-made
EPA and DHA, which are very long chain fats in any case (20 and 22 carbons long) so the
fuel available from them is among the best utilized in MCADD. However, this fish oil
supplementation is provided because these fats are used to make critical substances in
the body, so their ability to be used as energy is secondary.
It appears that many individuals have difficulty producing these fats, including the general
public, which is why the American Heart Association recommends eating fatty fish twice
weekly or taking a fish oil supplement. I prefer to err on the side of caution and assure
adequacy and not assume it.
When people are known to have a metabolic disease of any type, they may have more than
one system disturbed. In research with patients who have a variety of metabolic diseases,
benefit from fish oil supplementation has been found. Supplementation of some of our own
patients with metabolic conditions have demonstrated improvement in behavioral
measurements at school. What it comes down to is if it were my child, I would give him/her
some ready-made fish oil. In fact, I take it myself and make sure all my family members take
it too. [And I don’t sell anything and I never will!]
Keep an eye on the total amount of fat and a particular form of fat in food:
Fats in foods naturally come in many sizes. People with MCADD should avoid eating fats
that are naturally high in medium-chain sized fat. Coconut oil is one that is especially
high in these fats, and the person with MCADD cannot use this fat for fuel at all. Medium
chain fats are called MCT (Medium Chain Triglycerides) on food labels.
People with MCADD will also benefit from a diet that has fewer of the total calories
provided in the form of (any) fat than usual, since much of it cannot be used, and fasting
should be avoided. Their diet should have the same calories any baby needs … and the baby
with MCADD will communicate that quite well in most cases. What it does mean is that a
lower proportion of calories would come from fat and a higher proportion would come
from carbohydrate than is typical in the usual American baby diet.
[The fish oil supplementation described earlier is not calculated in the “grams of fat goal per
day,” primarily because it is a very small amount, and it is a form of very long-chain fat that
people with MCADD could burn better than other fats if they sent it to the furnace to be
burned for energy. However, the biggest reason to include some is because there are a
number of important construction projects that require these fats (including brain structure)
and I want to assure that they have them on hand. In other words, they are not being given
just for their caloric value as a fuel source.]
Breastfeeding babies with MCADD should be encouraged for many reasons.
Interestingly, mother’s milk has a generous amount of fat in the form of MCT because it is
easy for babies to digest. This does not appear to be primarily related to the forms of fat the
mother eats … she just seems to make them from other fats and ships them off to make milk.
One small adjustment may be helpful: It is reasonable for the mother who is nursing her baby
with MCADD to avoid using coconut oil regularly while she is nursing. It is not known if
this source of MCT would alter the amount in a mother’s milk … since she seems to make
her own MCT for the milk anyway … but it seems reasonable and generally not a huge
problem to simply avoid using coconut oil until baby is weaned.
Special formulas for babies with MCADD are available.
If a baby is going to be fed formula, there are special mixtures that can provide all the
calories and nutrients of regular formula. They can be made to have less total fat and, in
particular, no medium-chain fat. Some mothers choose to mostly breast-feed with a feeding
or two from a special fat-free / higher carbohydrate formula. In this situation, a pediatric
nutritionist needs to be involved to assure that nothing baby needs is left out, and that
nothing baby should not have is accidentally left in.
Include lots of brightly colored fruits and vegetables in the diet of anyone with
MCADD … and also in the diet of anyone without MCADD. 
Anyone with a metabolic disease (like MCAD or diabetes or PKU or many more) has a
higher need for antioxidants to protect against a higher than usual production of potentially
injurious “free radicals.” We all produce free radicals all the time, but altered metabolism
clearly results in a much higher production of them. This higher free radical production can
contribute to a wide variety of health issues, so higher free radical production makes one
need a higher than usual intake of antioxidant substances to protect against injury to cells.
Happily, a generous intake of brightly colored fruits and vegetables will provide terrific and
potent antioxidants, so this goal is not difficult to accomplish. They are also almost always
very low in fat, so they are “freebies” for a person with MCADD. Eating more of these foods
benefits everyone, but helping a person with unusual metabolism to regularly eat these foods
is particularly beneficial. Additionally, the person with MCADD may also have a beneficial
effect on the health of the rest of the family since all will be eating more fruits and veggies!
(“Eat the Rainbow!”)
Miscellaneous things to keep an eye on:
Monitor the baby’s weight, length and head circumference progress (which should all be
in the normal range … there is nothing about MCADD that should result in a growth pattern
different from that expected for others in a family.)
Evaluate if the baby seems to be much hungrier than expected for little people of
his/her age, especially if the hunger is unusual considering the amount of food eaten.
In that situation, the baby may also often be seen to be putting on a lot of extra body fat but
still acting hungry. It may be that the form of calories needs to be adjusted to provide more
as carbohydrate and provide less as fat that can’t be burned and ends up being stored. I call
this the “Baby Fluffiness Index.” 
Bottom Line:
Wherever you live, be sure that you find a team of health care professionals that can serve as
a resource to helping to manage your baby’s diet. MCADD is rare but there are people in
every state who specialize in unusual metabolic problems. If your baby has MCADD, they
will help with all of this every step of the way and be sure that you learn all about it so your
baby will be safe and thrive. If you happen to come to see us here at Sanford Medical Center
in Fargo, ND, please do call or email me if any questions or concerns about your baby’s
special diet arise. All my contact information is in the upper right corner. Don’t be shy …
Sanford Medical Center
Aunt Cathy’s Guide to:
A Temporary
Milk-Free Diet for
Breastfeeding Women
Aunt Cathy
Perinatal/Pediatric Nutrition Specialist
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center and
University of North Dakota School of Medicine
Fargo, ND
This paper was designed primarily for breast-feeding women whose physicians think
that milk protein intolerance may be a factor in a breast-fed baby's gastrointestinal
difficulties. It is intended to be a temporary diet for testing this idea.
It is not useful for infants suspected of having "lactose intolerance" because mother's
milk contains lactose naturally and not in response to lactose in her diet. For this reason, to
avoid unnecessary dietary restriction it is always wise to clarify that the reason for the
mother’s temporary milk-free diet involves milk protein (or other) issues, and not infant
intolerance of the milk sugar lactose.
Where is cow’s milk found in food?
All dairy products are the major sources of milk protein, of course.
This includes any kind of cow’s milk (skim, 2%, whole, chocolate, etc.) any kind of cheese, yogurt,
cream, ice cream, most puddings and cream soups.
Less obvious sources of milk protein are foods that have milk products as an ingredient.
Words on labels that indicate that it may contain milk:
acidophilus milk
cream
butter
dairy
dry milk solids
pudding
yogurt
ice cream
sour cream
casein
whey
cheese
margarines with milk solids or "a touch of butter"
buttermilk salad dressings (like ranch dressing)
creamed anything
milk chocolate
whipping cream
sherbet
caseinate
milk (any kind)
buttermilk
cream soups
ice milk
lactose
Read labels for all commercial products or ask the manufacturer.
Watch for: Many crackers, cookies, cakes, muffins, biscuits and frostings are made with margarine or
butter. Most white bread is made with milk. (French bread and whole wheat breads are usually not, but
check the labels. Sometimes the tops are brushed with butter.) Pancakes, waffles, and French toast made
from mixes or commercially prepared. (If made from scratch with soy milk, rice milk, almond milk or
water instead of milk, they are fine.) Instant mashed potatoes or potato dishes made with milk.
These suspicious-looking words on labels actually are unrelated to milk, so they are fine.
lactalbumin
lactate
lactic acid
Although it can feel overwhelming to think about all the foods like breads and crackers that might
have milk in them, remember that you really only have to know the names of one or two brands that
are milk-free.
It doesn’t matter what any other products out there may contain milk if you only buy the one brand
that you have looked at carefully and that you know is milk-free.
Other Nutrition Issues
While you are following a milk-free diet, it is important to replace the nutrients the milk
would have provided. For breast-feeding mothers this is very important because certain vitamins in her
milk will depend on the adequacy of the mother’s intake.
This is not true for all nutrients, but it is certainly true for B vitamins and vitamin C. Additionally,
a new mother’s body needs to recover from pregnancy and handle the work of making milk, so assuring an
adequate intake of all nutrients is very important for her health as well.
A reasonable approach would be to start with a standard daily “complete type” multivitamin
with minerals. A generic product is just fine.. Most have 200 mg calcium and 400 iu of vitamin D, plus
the vitamin C and B vitamins.
You can use up your prenatal vitamins after pregnancy, but note that many prenatal vitamins
can be surprisingly low in many nutrients. So take a look at the product you are using. Some brands are
like a standard multivitamin with minerals plus some extra folic acid and a higher amount of iron than a
non-prenatal product. This kind is just fine, but if your prenatal product does not contain at least ”regular”
levels of zinc, iodine, magnesium and other nutrients a different product can be very helpful. For
example, get a generic or store-brand “multivitamin with minerals” product that says on the label or sign that
says something like “Compare with Centrum” or “Compare with One-a-Day Complete.”
Add a calcium supplement to provide 1000-1500 mg calcium. Any kind is fine. It can have
vitamin D in it or not, because the vitamin D does not have to be in the pill with the calcium. It’s the
vitamin D already in your body that “pulls in” the calcium as it passes by. Take the calcium at a
different time from the multivitamin.
Vitamin D needs special attention. You should have at least 2000 iu of vitamin D daily. Some people
need more. (See my "Top Five Recommendations" paper for more information about this.) If you have 400 iu
from the multivitamin, you can very safely and easily add a tiny and inexpensive 1000 iu or 2000 iu vitamin D
capsule. Some people have low vitamin D stores (e.g. <30 mg/dL in their blood) so they need more. In that
circumstance, tiny and inexpensive 5,000 iu capsules are also available over the counter as well.
This is generous but 2000-5000 iu is now recognized as being nowhere near too high a dose … in fact,
this level of intake is now regarded as a very good idea for many people, including pregnant and breastfeeding
women. The best thing to do is to get your blood level of vitamin D (25-hydroxyvitamin D) measured to see if
you are looking for a maintenance amount or a vitamin D deficiency replacement amount. But even if you choose
not get a blood level checked, at least 2000 iu of vitamin D is very safe and a very good idea.
Dairy products are also very good sources of protein, so your diet
needs to include enough to make up for that as well.
An ounce of meat or one egg has about the same protein as an ounce of cheese (1 slice) or a cup of
milk (about 7-8 g of protein.) For a mental image of this amount, think of 3 oz of meat as the size of a
deck of cards. It is very easy to make up for the dairy protein if you eat meat or eggs.
However, other generous sources of protein include legumes (dried beans like chili beans,
baked beans, etc. and peanuts) and all tree nuts (e.g. walnut, almond, pecan, cashews, etc.) Two
tablespoons of peanut butter provides the protein of a cup of milk. An ounce of any nuts, or ¾ cup of
cooked beans will also provide that amount.
Soy beverages like “Eden Soy” or “Silk” provide the same protein as milk, and also provide
similar nutrition to milk, oz per oz. (About 100 iu of vitamin D and 300 mg calcium per cup.) However,
some milk-replacement products (like almond milk or rice milk or flax milk) have much less
protein. The range is from 0 to 4 grams of protein per cup.
The word “milk” in this context should be thought of as meaning “white and liquid” but not
necessarily as being milk-like in terms of expected protein. There is no problem using these products as
long as you also eat a good amount of the protein-rich foods as described above. But if you are counting
on those “milks” to meet your protein needs, you will need to add more of some of the other items listed.
--------------------------------This quick description is intended to be only a temporary diet to help to evaluate the cow’s milk
protein tolerance of a breast-fed baby. This cow’s milk protein intolerance is possible because some
intact cow’s milk protein has been found to find its way into the milk of some women. This is not a
problem unless the baby happens to be intolerant of cow’s milk protein.
If the baby’s digestive symptoms remain unchanged while mother has been on a carefully
milk-free diet for two weeks or so, it is unlikely that the cow’s milk in her diet was the culprit. In
that case, a normal diet for a breastfeeding mother should be resumed and other causes of any
gastrointestinal distress in the baby would be evaluated.
Sanford Medical Center
Aunt Cathy’s
Guide to Nutrition:
Nutrition Issues in
Multiple Sclerosis
Aunt Cathy
Cathy Breedon PhD, RD, CSP, FADA
Clinical and Metabolic Nutrition Specialist
Sanford Medical Center and
UND School of Medicine, Fargo, ND
(“With References” Version)
For people with MS, their families
and interested health care professionals
Multiple Sclerosis (MS) is an inflammatory disease of the myelin of the central
nervous system, the origin of which is still unknown. Genetic, infectious, immunological
and environmental factors have all been blamed, but none of these factors on their own
can explain the whole spectrum of this disease.
There Are Two Major Areas of Concern Regarding Nutrition and MS:
Nutrition factors in the development and progression of MS
Nutrition problems resulting from MS and its treatment
Nutrients of interest in the development and progression of MS *
*(Each of these will be discussed in the following pages.)
Vitamin D
Fats (amounts and forms, such as saturated fat, monounsaturated fat, and omega-3
and omega-6 polyunsaturated fats)
Antioxidants (e.g. vitamin E, selenium, alpha-lipoic acid, certain phytochemicals)
B vitamins (B6, B12, folic acid. biotin)
Minerals (magnesium, iron and phosphorus)
Carnitine
Nutrition issues will also interact with other factors:
Individual factors including genetic vulnerabilities, ethnicity, skin pigment and
gender.
Exposure to certain viral agents or other infectious agents during sensitive periods.
Age at which a nutritional contributing factor to MS is experienced.
Geographic variables such as latitude, altitude, soil mineral patterns and proximity to
sea coasts.
For ease of reading, only a few references will be included in the text.
A large number of references will be grouped at the end of each section,
and some annotated references / abstracts will be included at the end of the paper.
Vitamin D
The results of large recent studies supported a protective effect of vitamin D intake on
risk of developing MS. Some intervention trials have demonstrated that supplementation
with vitamin D or its metabolites is able to improve symptoms of multiple sclerosis.
(Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8. Vitamin D and calcium
deficits predispose for multiple chronic diseases. Eur J Clin Invest. 2005. Vitamin D intake and incidence of multiple sclerosis
Neurology.,2004)
Vitamin D inadequacy is related to the ability of the sun’s rays to activate skin
receptors. There is a clear latitude gradient, so that the likelihood of making
inadequate vitamin D in the skin is greater in the north. Living in the north is also a
known risk factor for MS, which is why the northern tier is called the “MS Belt” as
well as the “Rickets Belt.”
The map below is from Tufts Health & Nutrition Newsletter 1996. It shows that sunlight
is too weak for vitamin D synthesis from November through February at the 42nd parallel.
Between the 40th and 42nd, the sunlight is too weak to make vitamin D in January and
February. At that rate, it suggests that for every degree of latitude, there is an additional
month of inadequate vitamin D production. The northern border is the 49th parallel across
much of the USA. Alaskans and Canadians are even farther up there.
Why have we assumed that people, especially those in the northern tier, are
obtaining adequate vitamin D? I think we have missed this because we do not
ordinarily obtain vitamin D levels as part of our regular health care assessment, and most
importantly, because people with vitamin D deficiency do not look funny unless they are
infants (who may develop the bowed legs of rickets, or other apparent bone deformity.)
After childhood, the effects of vitamin D deficiency are often far less visible and
unrecognized. Our nutrition health model has tended to be “If you don‟t look funny, you
must be fine.” Now that vitamin D levels are beginning to be done as part of health
check-ups, it has been noted that there is actually “an unrecognized epidemic of vitamin
D deficiency in the northern tier.” [The vitamin D epidemic and its health consequences. J Nutr. 2005
Nov;135(11):2739S-48S.]
Fracture history and bone loss in patients with MS: MS patients have significantly
reduced bone mass and a high prevalence of abnormal vitamin D status. In one study, in
the absence of major trauma, fractures occurred in only 2% of controls but in 22%
of MS patients. After over two years of prospective follow-up both men and women
with MS lost substantially more bone annually in the spine and in the femoral neck (the
part of the leg bone where it meets the hip) than did the people without MS. Having had
steroid treatment for more than 5 months, and a person‟s ambulatory status (ability to
walk) were both predictors of bone loss as well. (Vitamin D deficiency and reduced bone mineral density in
multiple sclerosis: effect of ambulatory status and functional capacity. J Bone Miner Metab. 2005 Long-term effects of intravenous
high dose methylprednisolone pulses on bone mineral density in patients with multiple sclerosis. Eur J Neurol. 2005 (Fracture history
and bone loss in patients with MS. Neurology. 1998) Reduced bone mass and fat-free mass in women with multiple sclerosis: effects
of ambulatory status and glucocorticoid use. Calcif Tissue Int. 1997)
Nutrition Connection: Bone loss in the spine occurred significantly faster in MS patients
who had low 25-hydroxyvitamin D levels (<20 ng/mL). In those with normal levels,
bone loss was insignificant. At the femoral neck, bone loss was substantial in all MS
patients compared with controls, but was somewhat faster in the group with low vitamin
D. These authors concluded that MS patients have more frequent fractures and lose bone
mass more rapidly than do healthy age- and gender-matched peers, in part related to
insufficient vitamin D. Vitamin D repletion might reduce the rate of bone loss and
decrease osteoporosis-related fractures.
“Vitamin D deficiency and reduced bone mineral density in multiple sclerosis: effect of ambulatory status and functional
capacity. J Bone Miner Metab. 2005;23(4):309-13 …In conclusion, BMD is significantly lower in MS patients than in healthy
controls, vitamin D deficiency is prevalent in MS, and ambulatory status is a determinative factor for osteoporosis in MS. Patients
should be encouraged to have adequate sunlight exposure and to increase their mobility. Specific strengthening exercises for hip and
back muscles in MS patients would have a substantial impact on bone density, osteoporosis, fracture risk, and mobility.”
[CB comment: Since this was published it has become apparent that trying to solve the problem with sunlight exposure alone will be
unsuccessful much of the year if you live up north. In other situations, the sunlight approach may be hampered by intolerance of warm
weather. These and other reasons often make it necessary to approach the problem with supplemental vitamin D, either in milk or in
vitamin pills. More on this later.]
Genetic Defect in Vitamin D Metabolism? 1,25-Dihydroxyvitamin D3 is the hormone
(biologically active) form of vitamin D. It exerts an immuno-suppressive effect and can
completely prevent experimental autoimmune encephalomyelitis (EAE – the mouse
model of MS.) Nataf et al (1996) and Cantorna et al (1996) reported that the nonactivated vitamin D from diet or sunlight has no effect on mice with this condition.
However, providing the 1,25 form of vitamin D resulted in decreased progression of
EAE, and in some mice actual improvement of myelin injury. It is possible that failure to
activate vitamin D may account for some forms of MS. Degrees of impaired activation
may account for the variation seen in the severity of symptoms. And clearly, some people
may have no genetic defect like this at all . . . they just have poor vitamin D intake and
poor production in the skin (e.g. they live up north.)
The active (1,25-dihydroxy vitamin D exerts most of its actions only after it has bound to
its specific receptors in the nucleus of a cell. Fukazawa et al. (1999) found an association
of MS with Vit D Receptor Gene (VDRG) polymorphism. Polymorphism just means
that the receptors on body cells that are looking for vitamin D apparently come in
different forms in different groups of people. In other words, there appears to be variation
in the form of the vitamin D receptor in some people. This may be another genetic trait
involved in the development of MS. [Variation in the vitamin D receptor gene is associated with multiple sclerosis
in an Australian population. J Neurogenet. 2005 Jan-Mar;19(1):25-38. …Our results support a role for the VDR gene increasing the
risk of developing multiple sclerosis, particularly the progressive clinical subtypes of MS. CTLA-4 gene polymorphism may
modulate disease in Japanese multiple sclerosis patients. J Neurol Sci. 1999 Dec 1;171(1):49-55.]
Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety.
Except in those with conditions causing hypersensitivity, there is no evidence of adverse
effects with serum 25(OH)D concentrations <140 nmol/L, which require a total vitamin
D supply of 250 mcg (10000 IU)/d to attain. Published cases of vitamin D toxicity with
hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all
involve intake of > or = 1000 mcg (40000 IU)/d. Because vitamin D is potentially toxic,
intake of >25 mcg (1000 IU)/d has been avoided even though the weight of evidence
shows that the currently accepted “no observed adverse effect limit” of 50 mcg (2000
IU)/d is too low by at least 5-fold. (Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. Critique of
the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr. 2006
Apr;136(4):1117-22.)
Point: Since it now looks like 1000-2000 iu is needed up north just to assure adequate
blood levels of vitamin D (which is important for many reasons,) and since this level is
clearly safe, and since some people with MS are avoiding milk (the major dietary source
of vitamin D,) vitamin D supplementation is a very good idea. It is not invasive or
expensive. Assuring vitamin D adequacy may help to prevent the “excess” cases of MS
seen in northern latitudes. Variations in diet or sun exposure that alter adequacy may
explain some differences in severity and relapsing of symptoms. Some people may have a
defect in activation of vitamin D to the active form, and may need to receive “calcitriol”
(a prescription form of vitamin D that is already activated). A one-time blood test of
1,25 dihydroxy vitamin D level may be useful in identifying this problem if it exists. For
more on vitamin D, please refer to one of my other handouts: “Aunt Cathy’s Guide to
Calcium and Vitamin D Supplements”
As can be seen below, the scientific research in this area is growing incredibly
rapidly in just a short time. I have put some shortened versions of the abstracts of some
recent studies at the end of this paper for those of you who are interested in the actual
studies, including the health care professionals who may be looking at this handout.
(I want to be sure they believe me that I am not making this stuff up!  )
However, the summary of it all is
“Yes . . . Vitamin D adequacy is a really big deal in
MS.” The vitamin D recommendations will be reviewed in the summary at the end of
this paper. In the meantime, here is just a list of some vitamin D / MS References from
2000-2007.
2000- spring 2009 vitamin D and MS references
2009
Diet and nutrition: vitamin D regulates MS gene. Environ Health Perspect. 2009 May;117(5):A196.
Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009 Apr 28.
The relevance of vitamin D receptor gene polymorphisms for vitamin D research in multiple sclerosis. Autoimmun Rev. 2009
Jun;8(7):621-6.
Metabolism of 1alpha,25-dihydroxyvitamin D2 by human CYP24A1. Biochem Biophys Res Commun. 2009 Jun 26;384(2):144-8.
Multiple sclerosis and the major histocompatibility complex. Curr Opin Neurol. 2009 Jun;22(3):219-25.
Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction.
Mult Scler. 2009 May;15(5):563-570.
Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis.
Mult Scler. 2009 Jun;15(6):735-40.
Fok-I vitamin D receptor gene polymorphism (rs10735810) and vitamin D metabolism in multiple sclerosis. J Neuroimmunol. 2009
Feb 15;207(1-2):117-21.
Serum vitamin B12, folate, and homocysteine levels and their association with clinical and electrophysiological parameters in multiple
sclerosis. J Clin Neurosci. 2009 Mar;16(3):399-403.
A salmon based diet protects mice from behavioural changes in the cuprizone model for demyelination. Clin Nutr. 2009;28(1):83-7.
2008
Therapeutic potential of vitamin D for multiple sclerosis. Curr Med Chem. 2008;15(5):499-505.
Vitamin D as an immune modulator in multiple sclerosis, a review. J Neuroimmunol. 2008 Feb;194(1-2):7-17.
Vitamin D and multiple sclerosis: an update. Nutr Rev. 2008 Oct;66(10 Suppl 2):S135-8.
A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Med Hypotheses.
2008;71(1):85-90.
Therapeutic potential of vitamin D for multiple sclerosis. Curr Med Chem. 2008;15(5):499-505.
Coagulation status and biochemical and inflammatory markers in multiple sclerosis. J Clin Neurosci. 2008 Apr;15(4):393-7.
Future research directions in multiple sclerosis therapies. Semin Neurol. 2008 Feb;28(1):121-7.
Epidemiology of multiple sclerosis: from risk factors to prevention. Semin Neurol. 2008 Feb;28(1):17-28.
Ectopic thymic parathyroid adenoma and vitamin D deficiency rickets: a 5-year-follow-up case report and review of literature. Bone.
2008 Apr;42(4):819-24.
Hormonal influences in multiple sclerosis. Curr Top Microbiol Immunol. 2008;318:267-311.
A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and
calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008 Feb;79(2):152-7.
Vitamin D status modulates the immune response to Epstein Barr virus: Synergistic effect of risk factors in multiple sclerosis.
Med Hypotheses. 2008;70(1):66-9.
Vitamin D-dependent rickets as a possible risk factor for multiple sclerosis. Arch Neurol. 2008 Jun;65(6):809-11.
Update on the etiology and pathogenesis of multiple sclerosis and neuromyelitis optica. Nippon Rinsho. 2008 Jun;66(6):1087-91.
The immunology of multiple sclerosis: disease mechanisms and therapeutic targets. Minerva Med. 2008 Apr;99(2):119-40.
Pathways and products for the metabolism of vitamin D3 by cytochrome P450scc. FEBS J. 2008 May;275(10):2585-96.
A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10. Med Hypotheses.
2008;71(1):85-90.
Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology.
2008;30(3):140-6.
Vitamin D(3) in fat tissue. Endocrine. 2008 Feb;33(1):90-4.
Vitamin D and multiple sclerosis: an update. Nutr Rev. 2008 Oct;66(10 Suppl 2):S135-8.
Assessment of vitamin D status and definition of a normal circulating range of 25-hydroxyvitamin D.
Curr Opin Endocrinol Diabetes Obes. 2008 Dec;15(6):489-94.
Monthly ambient sunlight, infections and relapse rates in multiple sclerosis. Neuroepidemiology. 2008;31(4):271-9.
2007
The immunological basis for treatment of multiple sclerosis. Scand J Immunol. 2007 Oct;66(4):374-82.
Novel biomarkers in autoimmune diseases: prolactin, ferritin, vitamin D, and TPA levels in autoimmune diseases. Ann N Y Acad Sci.
2007 Aug;1109:385-400.
1,25-dihydroxyvitamin D3 reverses experimental autoimmune encephalomyelitis by inhibiting chemokine synthesis and monocyte
trafficking. Neurosci Res. 2007 Aug 15;85(11):2480-90.2007
Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18.
2006
Dysfunction of the vitamin D endocrine system as common cause for multiple malignant and other chronic diseases.
Anticancer Res. 2006 Jul-Aug;26(4A):2581-8.
New insights into the mechanisms involved in the pleiotropic actions of 1,25dihydroxyvitamin D3. Ann N Y Acad Sci. 2006;1068:194203.
Epidemiology and natural history of multiple sclerosis: new insights. Curr Opin Neurol. 2006 Jun;19(3):248-54
The role of vitamin D in multiple sclerosis. Ann Pharmacother. 2006 Jun;40(6):1158-61
Vitamin D & autoimmune disease--implications for practice from the MS literature. J Am Diet Assoc. 2006 Mar;106(3):418-24.
Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8.
Vitamin D and its role in immunology: MS, and inflammatory bowel disease. Prog Biophys Mol Biol. 2006 Sep;92(1):60-4
Vitamin D physiology. Prog Biophys Mol Biol. 2006 Sep;92(1):4-8.
1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental allergic
encephalomyelitis. J Neurosci Res. 2006 May 15;83(7):1299-309.
Epidemiology of disease risks in relation to vitamin D insufficiency. Prog Biophys Mol Biol. 2006 Sep;92(1):65-79.
The photobiology of vitamin D--a topic of renewed focus. Tidsskr Nor Laegeforen. 2006 Apr 6;126(8):1048-52.
IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis. J Immunol.
2006 Nov 1;177(9):6030-7.
Vitamin D physiology. Prog Biophys Mol Biol. 2006 Sep;92(1):4-8.
Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr.
2006 Apr;136(4):1117-22.
Vitamin D deficiency is associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006
Dec;14(12):1032-40.]
2005
25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler. 2005 Jun;11(3):266-71.
Why we should offer routine vitamin D supplementation in pregnancy & childhood to prevent MS. Med Hypotheses. 2005;64(3):608-18.
Effects of alfacalcidol therapy on serum cytokine levels in patients w multiple sclerosis. Srp Arh Celok Lek.2005;133 Suppl 2:124-8.
A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry.
2005 Sep;76(9):1294-6.
Vitamin D deficiency & reduced bone mineral density in MS: effect of ambulatory status & functional capacity. J Bone Miner Metab. 2005
Long-term effects of intravenous high dose methylprednisolone pulses on bone mineral density in patients with MS. Eur J Neurol. 2005.
Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest. 2005.
The vitamin D epidemic and its health consequences. J Nutr. 2005 Nov;135(11): 2739S-48S.
Variation in the vitamin D receptor gene is associated with multiple sclerosis in an Australian population. J Neurogenet. 2005;19(1):25-38.
2000-2004
Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J Steroid
Biochem Mol Biol. 2004 May;89-90(1-5):575-9.
Mounting evidence for vit. D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med 2004;229(11):1136-42.
Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr. 2004 Aug;58(8):1095-109.
Vitamin D intake and incidence of multiple sclerosis Neurology. 2004 Jan 13;62(1):60-5.
Dodging MS & RA with vitamin D. Health News. 2004;10 (3):4.
The pleiotropic actions of vitamin D. Bioessays. 2004;26(1):21-8.
D-vitamin: old paradoxes & new perspectives Ugeskr Laeger. 2004; 166(1-2):36-40.
The vitamin D deficit. Science. 2003 12;302(5652):1886-8.
Vitamin D target proteins: function & regulation. J Cell Biochem. 2003; 88(2):238-44.
Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr. 2003.
Ultraviolet radiation & autoimmune disease: insights from epidemiological research. Toxicology. 2002;181-182:71-8.
Vitamins for chronic disease prevention in adults: clinical applications. JAMA. 2002; 287(23):3127-9.
Vitamin D: its role & uses in immunology. FASEB J. 2001;15(14): 2579-85
Vitamin D & autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence?. Proc Soc Experi
Biol Med. 2000.
1,25-dihydroxyvitamin D3 treatment decreases macrophage accumulation in the CNS of mice with experimental autoimmune
encephalomyelitis. J Neuroimmunol. 2000.
Vitamin D: a natural inhibitor of multiple sclerosis. Proc Nutr Soc. 2000.
Total Fat Intake:
The Swank Studies (Swank & Dugan 1990.)
In this famous study, 144 MS patients followed a very low-fat diet for 34 years. Patients
who adhered to the diet (which contained less than 20 g fat/day – a VERY small amount)
showed significantly less deterioration and much lower death rates than did those who ate
more fat. The greatest benefit was seen in those with minimum disability at the start of
the trial. In this group, when those who died from non-MS diseases were excluded from
the analysis, 95% survived and remained physically active. Only 20% who did not
follow the diet survived for the whole the study period. Interpretation Caution: It has
been argued that maybe those for whom the diet appeared to be helpful (that is, people
doing well in terms of their MS) stayed on the diet, and those for whom it appeared to be
unhelpful (those with worsening MS for whatever reason) gave up the diet and quit. So,
maybe it was not the diet that accounted for the difference in outcome. Or maybe it was.
Other observations: Swank (1991) also found that women did better than men, and that
patients treated early did better than when treatment was delayed. “High sensitivity to
fats suggests that saturated animal fats are directly involved in the genesis of multiple
sclerosis.” In addition to the issue of Total Amount of Fat in the diet, the Forms of Fat
may be an important factor. The distinctions between the various forms of dietary fats
being investigated now in this area had not been identified at the time the Swank studies
were undertaken.
Biological effects of fish oils in relation to chronic diseases. Omega-3 marine lipids
(polyunsaturated fish oils) affect the types of substances called eicosanoids produced in
the body. These include important substances like prostaglandins, leukotrienes,
prostacyclins, and thromboxanes. The involvement of prostaglandins and leukotrienes in
immune responses has led to studies on the effects of fish oil on various chronic diseases
associated with abnormalities of the immune system, such as MS. One example of an
early observation was that Greenland Eskimos have a high intake of seal, whale and fish,
(rich sources of Omega-3 marine lipids), and MS is uncommon in Eskimos.
Supplementation of Polyunsaturated Fatty Acids (PUFAs). In 1990, Bates reviewed
published controlled trials of omega-6 PUFAs involving 172 patients with acute remitting
MS and one study with omega-3 PUFAs in a double blind controlled study of 312
patients. A trend was found suggesting that the addition of omega-6 and omega-3
PUFAs to the diet of patients with MS results in a reduction of the severity and frequency
of relapses and in a mild overall benefit in a two year period.
Omega-3 polyunsaturated fatty acids and cytokine production in health and disease.
In 1997, Calder studied eicosanoids made from omega-6 oils because they modulate the
production of pro-inflammatory and immunoregulatory substances called cytokines.
Overproduction of these cytokines is associated with both septic shock and chronic
inflammatory diseases. The omega-3 polyunsaturated fatty acids (PUFAs) called EPA
and DHA are found in fish oils. They suppress the production of the eicosanoids made
from Omega-6 PUFAs. EPA is used for making an alternative family of eicosanoids that
are less inflammatory. So, dietary fats which are rich in omega-3 PUFAs have the
potential to alter cytokine production (Gallai et al. 1995 Endres & von Schacky 1996.) Deficiencies of
PUFAs and replacement by nonessential forms of fat has been reported in the plasma
lipids in multiple sclerosis (Holman et al. 1989.) They found that phospholipids in people with
MS have normal levels of (omega 6) linoleic acid and the next fatty acid in the pathway
to make eicosanoids was elevated. But all the omega 6 fatty acids greater than 18 carbons
long were subnormal in MS. This pattern is an indication of impaired ability to add
carbons to lengthen the carbon chain to make the eicosanoids. All the omega-3 acids
were found to be subnormal in people with MS.
Depression in MS Hibbeln and Salem (1995) reported that decreased omega-3 fatty
acid intake (especially DHA) correlates with increasing rates of depression, and this may
be a factor in depression in MS. Depressed individuals with MS have a worse outcome
than non-depressed individuals. There is now evidence of impaired phospholipid
metabolism and impaired fatty acid-related cell communication processes. Impaired
phospholipid and fatty acid metabolism (e.g. involving DHA – an omega-3 fat that is
critical for brain function) may be a primary cause of depression in many patients and
may explain the interactions with MS and other diseases (Horrobin & Bennett, 1999.) Additionally,
there are depression issues related to (what else?) Vitamin D and folic acid (a B vitamin
discussed later.) Specific MS-related research with omega-3 fats and other
polyunsaturated fats is limited, although the research on benefits of these fats in many
aspects of human health is quite impressive. More information about wider applications
is available in my handouts on line on various types of fats and oils. [Vitamin D deficiency is
associated with low mood and worse cognitive performance in older adults. Am J Geriatr Psychiatry. 2006 Dec;14(12):1032-40.]
Here are some of the most recent reports investigating the role of various forms of fat
specifically in MS:
Polyunsaturated fatty acids and neurological diseases. Mini Rev Med Chem. 2006 Nov;6(11):1201-11. This review summarizes
the knowledge of the role of dietary PUFAs, especially omega-3, on normal brain function. It reports the evidence pointing to
potential mechanisms of omega-3 fatty acids in development of neurological disorders and efficacy of their supplementation in terms
of symptom management.
Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005 Dec;59(12):1347-61. These authors
concluded that “Both dietary antioxidants and PUFAs have the potential to diminish disease symptoms by targeting specific
pathomechanisms and supporting recovery in MS.”
Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot
Essent Fatty Acids. 2005 Nov;73(5):397-404. This study suggests that “a low fat diet supplemented with omega-3 PUFA can have
moderate benefits in RRMS patients on concurrent disease modifying therapies.”
Polyunsaturated fatty acid supplementation in MS. Int MS J. 2005 Nov;12(3):88-93. This article focuses on polyunsaturated fatty
acid (PUFA) supplementation. Small-scale studies have demonstrated trends towards some beneficial effects. PUFA supplementation
is generally well tolerated, although some specific supplements are best avoided and some clinical situations warrant caution. A
review of the efficacy and safety data suggests that PUFA supplementation may be a promising approach. Large-scale trials are
required to confirm the benefits.
Effects of omega-3 fatty acids on cognitive function with aging, dementia, and neurological diseases. Evid Rep Technol Assess
(Summ). 2005 Feb;(114):1-3.
Omega-3 fatty acids in health and disease: part 2--health effects of omega-3 fatty acids in autoimmune diseases, mental health,
and gene expression. J Med Food. 2005 Summer;8(2):133-48.
Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr. 2002 Dec;21(6):495-505. “… There have been a
number of clinical trials assessing the benefits of dietary supplementation with fish oils in several inflammatory and autoimmune
diseases in humans, including rheumatoid arthritis, Crohn's disease, ulcerative colitis, psoriasis, lupus erythematosus, multiple
sclerosis and migraine headaches. Many of the placebo-controlled trials of fish oil in chronic inflammatory diseases reveal significant
benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.”
Antioxidants.
Reactive Oxygen Species (ROS) are byproducts of metabolism that are thought to be
involved in causing or contributing to MS and also to experimental allergic
encephalomyelitis (EAE – the mouse model of MS.) Another common name for ROS is
“free radical.” These substances can cause injury to a person‟s cells if they are not
handled properly (that is “quenched” or “extinguished” by substances called antioxidants.)
Van der Goes et al. (1998) found that phagocytosis of myelin by macrophages triggers
the production of ROS. Free radical action has been suggested as a causal factor in
multiple sclerosis (J Neurol 1999.) For example: malondialdehyde in the blood (a marker
for low vitamin E or other antioxidant protection) was increased by 38% during MS
exacerbations (periods of worsening symptoms.) These changes suggest that there is
increased free radical (ROS) production and consumption of the scavenger molecules
during the active phase of the disease.
Demyelination: the role of reactive oxygen and nitrogen species. Smith et al.(1999)
found that reactive oxygen (ROS) and nitrogen species (RNS) play a role in
demyelination, such as in the inflammatory demyelinating disorders like multiple
sclerosis. The concentrations of reactive oxygen and nitrogen species (e.g. superoxide,
nitric oxide & peroxynitrite) can increase dramatically under conditions such as
inflammation. This can overwhelm the person‟s antioxidant defenses within tissues.
Such oxidative and/or nitrative stress can damage the lipids, proteins and nucleic acids of
cells and mitochondria, potentially causing cell death. The reactive species (ROS and
RNS) may also damage the myelin sheath, promoting its attack by macrophages.
Damage can occur directly by lipid peroxidation, and indirectly by the activation of
proteases and phospholipase A2. The neurological deficit resulting from experimental
autoimmune demyelinating disease has generally been reduced by trial therapies [that is,
antioxidants] that diminish the concentration of reactive oxygen species. However,
therapies aimed at diminishing reactive nitrogen species have had a more variable
outcome, sometimes exacerbating disease.
Selenium Issues: Selenium (Se) is a mineral in the news in many areas of medical
research, such as diabetes, prostate cancer, thyroid disease, immune system function and
multiple sclerosis (Foster HD,1993.) Glutathione peroxidase is a very important antioxidant in
the body and selenium is a key component of it. Mazzella et al., (1983) found that the
Se-dependent glutathione peroxidase activity in the red blood cells was lower in the
MS patients.
In addition, the Se concentration in the diet of MS patients was studied and found to
be less than the minimum values suggested by the US Food and Nutrition Board.
The authors‟ interpretation: “Modified glutathione peroxidase activity found in
erythrocytes [red blood cells] of MS patients is independent from the Se concentration in
blood.” The reported dietary inadequacy was not addressed further.
My observations: It is likely that suboptimal Se intake affects various tissues differently,
and that possibly the blood levels had a “higher priority” for the Se available. In view of
new knowledge about the significant health risks associated with Se inadequacy, it is a
good idea to assure an intake within recommended ranges (60-150 mcg). Studies in the late
„90s have revealed that dietary Se intakes are sub-optimal in diets of many people. This is
especially true in certain geographic regions (such as Phoenix, AZ) where the soil is quite
low in selenium.
It is very hard to estimate a person‟s actual selenium intake because it is so variable in
foods. Selenium is an unusual mineral because the amount in a food depends on where it
was produced, and especially in this country, that can be difficult to determine. Excessive
selenium intake can be toxic however, so the upper limit of safety is set at 600 mcg/day,
and the level regarded as toxic is a regular intake of 800 mcg/day. My handouts on
“Nutrition and Eye Health” and “Nutrition in Prostate Cancer” both contain additional
information, as selenium and the selenium-containing antioxidant glutathione peroxidase
are looking very important in general. It is also being found to be very important in the
operation of the immune system and the thyroid gland.
Other potent antioxidants are also being explored in relation to MS, such as “alphalipoic acid.” This substance is also looking to be potentially very beneficial in diabetes,
most specifically with some of the neurologic problems (neuropathy) experienced by
people with diabetes over time. In general, it appears that any inflammatory or
autoimmune condition results in greater production of free radicals, and so as a
generality, a more generous intake of antioxidants is reasonable.
Alpha-lipoic acid is similar to B vitamins in several ways. It is extremely unlikely to be
toxic ven at high doses. Most studies have shown that about 600 mg/day over time is the
level associated with measurable benefits in diabetes research.
It is also reasonable (and a very good idea) to seek out generous potent dietary
antioxidants (like the brightly colored pigments fruits and vegetables . . . lycopene,
anthocyanins, lutein, etc.) The antioxidant vitamins (C and E) are not nearly as potent as
antioxidants as the plant pigments are. For example, lycopene (the red color in tomatoes)
is 200 times as potent an antioxidant as vitamin E. These substances are not vitamins or
minerals, but they fall into a class called “phytochemicals” which just means “plant
chemicals.”
Not all plant chemicals in the world are safe, of course . . . consider poison ivy and
opium, for example. However, the family of these plant pigments (called carotenoids) are
very safe. The only side effect is that eating lots of beta-carotene in carrots, squash and
sweet potatoes may give your skin a harmless orange-ish glow. [That can pass for a tan
up her in North Dakota! ] The huge health benefits now being recognized is the
reason behind the recent change from the familiar “Five-a-Day” recommendation for
fruits and vegetables in everyone‟s diet to something approximating:
“Eat a whole bunch of brightly colored vegetables and fruits
every day for a whole bunch of reasons!!!!”
Antioxidants and MS:
Here is a list of some research specifically about antioxidants and MS. There is
much more since 2006 but I didn’t get a chance to add it all here.
An annotated set of references / abstracts follows at the end of this paper for people
who want more detail.
2006
Dietary chelators as antioxidant enzyme mimetics: implications for dietary intervention in neurodegenerative diseases.
Behav Pharmacol. 2006 Sep;17(5-6):425-30.
Antioxidants in multiple sclerosis: do they have a role in therapy? CNS Drugs. 2006;20(6):433-41.
Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection
via suppression of glia-mediated inflammation. Curr Pharm Des. 2006;12(27):3521-33.
2005
Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005 Dec;59(12):1347-61.
Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. 2005 Feb;11(1):24-32.
The role of methallothioneins in experimental autoimmune encephalomyelitis and multiple sclerosis. Ann N Y Acad Sci.
2005 Jun;1051:88-96
Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during
experimental autoimmune encephalomyelitis. Neuroscience. 2005;132(4):1135-49.
2004
Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune
encephalomyelitis. J Immunol. 2004 Nov 1;173(9):5794-800.
Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res. 2004 Nov 1;78(3):36270.
Protective effects of caffeic acid phenethyl ester against experimental allergic encephalo-myelitis-induced oxidative stress in
rats. Free Radic Biol Med. 2004 Aug 1;37(3):386-94
The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol.
2004 Mar;251(3):261-8.
Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol.
2004 Mar;148(1-2):146-53.
2003
Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of
oxidative stress in the development of multiple sclerosis. J Neuroimmunol. 2003 Jun;139(1-2):27-35.
2002
Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune
encephalomyelitis. J Neuroimmunol 2002 Oct;131(1-2):104-14.
My comments on all these fat and antioxidant issues:
Different types of fat and the adequacy of antioxidant protection interact with each other.
Clearly there is deranged metabolism of fatty acids in MS. Is it a cause of MS, or the
result of having MS? Can it be manipulated? Future directions of research should include
evaluating these substances together and not just as individual agents. For example, it
would be useful to study:
Comparisons of ratios of omega 3 to omega 6 PUFAs (PolyUnsaturated Fatty Acids), with
attention also paid to the ratios of antioxidants to PUFAs.
Evaluation of fat issues while accounting for oxidation status.
Fish x Fat x Antioxidants Antioxidants inhibit the enzyme lipoxygenase and so inhibits
leukotriene synthesis. The fish oil leads to production of less inflammatory leukotrienes.
Antioxidants also protect the fish oils from oxidation We need to learn which of these factors
can be useful in trying to prevent the development of MS, or slow its progress.
Differentiate in the study between omega-3 and omega-6 PUFAs in terms of the size of the
molecule (shorter vs longer chain length,) because this is now looking like an important
feature to consider in research related to many other health conditions.
Issues involving dietary fat and antioxidants are intimately related. For more detail on
these issues, including food sources and supplement considerations, please see my other
handouts “Aunt Cathy’s Guide to Eye Health” (for more information about
antioxidants) and “Aunt Cathy’s Guide to Omega 3 Fatty Acids.”
Other areas of investigation-- B Vitamins:
Biotin, Vitamin B6, Vitamin B12, and Folic Acid
What the Heck is Biotin? It is a B vitamin involved in many body functions that process
carbohydrates, fats and proteins. The recommended intake is 30-100 mcg (based on
reported dietary intakes in healthy people in the US.) Biotin is not toxic, even at levels as
high as 10,000 mcg/day (1000 times the upper end of the assumed adequacy level.)
Bacteria in the intestine produce biotin and they contribute a significant amount, so
getting an adequate amount is unlikely for any person who chronically uses
antibiotics, unless biotin is supplemented. Symptoms of inadequacy include “tingling
in extremities.”
Biotin is a B vitamin that usually receives little attention, since most people obtain an
adequate amount from the intestinal bacteria. However, it is looking interesting in other
autoimmune diseases such as diabetes. (The effect of chromium picolinate and biotin supplementation on glycemic
control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes
Technol Ther. 2006 Dec;8(6):636-43. Use of chromium picolinate and biotin in the management of type 2 diabetes: an economic
analysis. Dis Manag. 2005 Aug;8(4):265-75.)
There is little activity in the MS research at present. However, Anagnostouli et al.(1999),
looked at concentrations in human cerebral-spinal fluid (CSF) & blood serum. Patients
with common neurologic disorders (including MS) were compared with people who had
no evidence of nutritional or neurologic disorders. They found significantly lower values
for biotin in people with MS (both CSF & serum). They concluded that this low level
could be the result of poor biotin absorption in the intestine caused by the underlying
disease, or related to a biotin-binding immunoglobulin which may be involved in MS
development and progression.
Vitamin B6 (Pyridoxine) It is well known that this vitamin plays a vital role in
many physiological processes, such as nerve communication, processing protein and fats,
and supporting the immune system. Levels higher than the RDA appear to have be of
some benefit in decreasing damage to nerves in other autoimmune conditions such as
diabetes. In many of these activities, vitamin B6 is paired with the mineral magnesium
(more on magnesium later) and it appears that both substances need to be present at the
same time for efficient operation. This is just one more situation in which studying a
single nutrient is unlikely to be as useful as studying them in combination.
Of all the B vitamins, B6 is the most likely to be a problem in very high doses fora pretty
long time . . . such as 200-500 mg/day chronically in the most sensitive individuals. (The
RDA level is only 1-2 mg.) Interestingly, the symptoms associated with the highest
doses, while rare, include some MS-like tingling in the arms. The idea that an
unrecognized inadequacy of vitamin B6 might be a factor in MS comes from just one
study: “Serious dangers to health may be associated with undetected, lingering
subclinical deficiencies . . . This includes induction of and predisposition to diseases such
as atherosclerosis and multiple sclerosis” (Kesel et al. 1999.)
Vitamin B12: Vitamin B12 levels have been low in MS patients in many studies. The
significance of this is unclear. Is it related to poor absorption? Is it poorly utilized or kept
in the wrong compartments in the body? (Goodkin, 1994) Low vitamin B12 status may
increase vulnerability to the viral and immunologic processes which are suspected as
being factors in causing MS. Certainly, adequacy of vitamin B-12 has critical
importance to neurologic health (for everyone).
Some individuals are at special risk of poor vitamin B12 status. Some patients may
be following strict vegetarian diets with inadequate vitamin B12, or using
medications such as Glucophage (also called Metformin) for diabetes. Others take
medications that block production of stomach acid called “proton pump inhibitors,”
such as Prilosec, Prevacid, Protonix, Pepcid AC, and Nexium.
Any of these situations will increase the likelihood of impaired vitamin B-12 availability
and/or absorption. Additionally, as we age, some people simply begin to produce much
less acid in their stomachs. Inadequate stomach acid decreases our ability to absorb
vitamin B12 from food sources. However, the form found in vitamin pills and
fortified cereals is far more reliably absorbed in spite of these problems.
Because of this, 15-30% of the elderly are found to be deficient in this critical
vitamin when their level is actually checked with a sensitive measure. (Waiting and
watching for changes to appear in red blood cell size is not a sensitive measure because it
is a very late-appearing symptom of vitamin B12 deficiency.) Assuring a generous intake
of absorbable vitamin B-12 is not difficult or expensive. For most people simply taking a
multivitamin supplement prevents this problem. In some studies described below,
vitamin B12 administered with other therapeutic agents may have some benefit in MS,
although a straightforward vitamin B12 deficiency is apparently not the reason. For more
information about vitamin B-12 issues, please see my other hand-out “Aunt Cathy’s
Guide to Vitamin B-12.”
Here are some research regarding Vitamin B12 and MS. An annotated /
abstract reference list follows at the end of this paper.
Newer references are available but not in time for this publication
2006
Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006 Nov;5(11):949-60.
Vitamin B12 and methionine synthesis: a critical review. Is nature's most beautiful cofactor misunderstood? Biofactors.
2006;26(1):45-57.
Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):189-92.
2005
Vitamin B12, demyelination, remyelination and repair in multiple sclerosis J Neurol Sci. 2005 Jun 15;233(1-2):93-7.
2004
Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-beta plus vitamin B12:
treatment to modify notch-1/sonic hedgehog balance. J Immunol. 2004 May 15;172(10):6418-26.
2003
Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by
blood and cerebrospinal fluid homocysteine and methylmalonic acid. Mult Scler. 2003 Jun;9(3):239-45.
Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis.
Nutr Neurosci. 2003 Jun;6(3):189-96.
2002
Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical
importance: roles of the locus coeruleus and central noradrenergic systems. Med Hypotheses. 2002 Nov;59(5):594602.
A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the "Cari Loder
regime") in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002 Sep;73(3):246-9
Other B-vitamins and Iron: Regeneration of myelin requires both adequacy of iron and
of B vitamins, especially vitamin B12 and folic acid. This situation is a good illustration
of the problems inherent in evaluating the effects of manipulating or measuring a single
nutrient to detect benefit. Many if not most important nutrient-related effects require the
adequacy of several nutrients working together and so the common type of “singlenutrient research” will often fail to detect and identify important roles of that nutrient.
Hyperhomocysteinemia is associated with cognitive impairment in multiple sclerosis. J Neurol. 2008 Jan;255(1):64-9.
Iron and the folate-vitamin B12-methylation pathway in multiple sclerosis. Metab Brain Dis. 2006 Sep;21(2-3):121-37. Some
subjects with multiple sclerosis (MS) present with low blood iron parameters. Anecdotal reports and a single patient study suggest that
iron supplementation may be beneficial in these subjects. Myelin is regenerated continually, but prerequisites for this process are
iron and a functional folate-vitamin B12-methylation pathway. The aim of this study was to determine iron status, folate and
homocysteine in MS subjects, and to evaluate the effect on MS symptoms if deficiencies were addressed. Results: In relapsingremitting MS subjects, serum iron concentration correlated significantly with age at diagnosis (r=0.49; p=0.008). In Caucasian
female MS subjects, serum iron and ferritin concentrations were significantly lower than in matched controls. In a 6-month
pilot study, 12 subjects taking a regimen of nutritional supplements designed to promote myelin regeneration, improved
significantly neurologically as measured by the Kurzke EDSS (Total Score means 3.50 to 2.45, 29.9%; p=0.021). These were
significantly improved (p=0.002) compared to 6 control group patients taking multivitamins (Kurzke Score increased by
13.9% from 4.83 to 5.50). Both groups had significantly reduced homocysteine concentrations at 6 months, suggesting that
methylation is necessary but not sufficient for myelin regeneration.
Magnesium: Magnesium (Mg) is involved in the activity of over 300 enzymes in the
body, and it is very critical in neurologic health. As mentioned earlier, magnesium and
vitamin B6 very often work together in this role. Stelmasiak et al. (1995), found a
significant decrease of Mg concentration in red blood cells and no changes in blood
plasma of MS patients compared with controls. This suggests the presence of changes
in red blood cells which could be connected with their shorter life and impaired function
in MS. Magnesium is known to be decreased in central nervous system (CNS) tissues of
people with MS. Yasui & Ota (1992) note that with Mg depletion, pathologic changes are
seen especially in white matter, and this may contribute to the development of MS.
Magnesium Adequacy: Inadequate Mg intake is common in the general population.
In fact, a large national survey* of Americans done every ten years by the Center for
Disease Control (the CDC) found that the majority of Americans obtain less than 2/3 of
the Recommended Dietary Allowance for this nutrient. Certainly there is every reason
to assure that the common dietary inadequacy of magnesium does not complicate
problems for individuals with MS, since magnesium has so many important roles in
neurologic function.
(*NHANES – National Health And Nutrition Examination Survey.)
There is little MS-specific magnesium research being reported, but I found three items to
include here:
Importance of magnesium depletion with hypofunction of the biological clock in the
pathophysiology of headhaches with photophobia, sudden infant death and some clinical
forms of multiple sclerosis. Magnes Res. 2004 Dec;17(4):314-26. … MS may be associated with
primary disorders of BC Clinical forms of Mg depletion with hBC in MS present diurnal
exacerbations and relapses during fair seasons….
The multifaceted and widespread pathology of magnesium deficiency. Med Hypotheses. 2001
Feb;56(2):163-70. …The very small probability that all the variables affecting Mg levels will
behave favorably, results in a high probability of a gradually intensifying Mg deficiency. It is
highly regrettable that the deficiency of such an inexpensive, low-toxicity nutrient result in
diseases that cause incalculable suffering and expense throughout the world. The range of
pathologies associated with Mg deficiency is staggering: hypertension (cardiovascular disease,
kidney and liver damage, etc.), peroxynitrite damage (migraine, multiple sclerosis, glaucoma,
Alzheimer's disease, etc.)
The effect of magnesium oral therapy on spasticity in a patient with multiple sclerosis. Eur J
Neurol. 2000 Nov;7(6):741-4. The effects of magnesium glycerophosphate oral therapy on
spasticity was studied in a 35-year-old woman with severe spastic paraplegia resulting from
multiple sclerosis (MS). We found a significant improvement in the spasticity after only 1
week from the onset of the treatment on the modified Ashworth scale, an improvement in the
range of motion and in the measures of angles at resting position in lower limbs. No side-effects
were reported and there was no weakness in the arms during the treatment.
In view of the many roles of Mg (especially in the central nervous system) and the true
likelihood that one‟s diet may in fact provide too little magnesium, it is reasonable to take
steps to assure that Mg intake at least meets RDA levels. Magnesium Food Sources:
Best are nuts, peanuts and other legumes, whole grains, wheat germ and bran. If a person
avoids these foods (e.g. out of concern about the fat content or the calories in nuts or
peanut butter,) realize that a supplement is likely necessary to prevent inadequacy. Most
general multivitamins have only 0-25% of the RDA, so read the label. For more
information about magnesium, please see my other handout “Aunt Cathy’s Guide to
Magnesium.”
One study suggested that phosphate adequacy may be a factor in MS:
Phosphate depletion is the link between growth, stress and diet in the aetiology of MS. Med Hypotheses. 2004;63(2):262-7. . . .
Phosphate depletion results in demyelinization. Phosphate depletion (PD) can lead to neurological complications, which have been
characterized in experimental & clinical studies. Hypophosphataemia, whether acute or chronic, induced by stress from accident,
surgery or burns, by infection and/or undernutrition, is therefore an important etiological factor. Low SP levels have been reported in
MS patients & the hypothesis that PD causes MS is presented here.
Carnitine
Carnitine is a substance made by the body and also found in meats. It is important inside
cells for converting fat into energy. There is currently a lot of interest in carnitine in a
wide variety of medical applications. In MS, the applications have been aimed at helping
with fatigue, as reported in these studies:
Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue. Mult Scler. 2006
Jun;12(3):321-4. Nutritional factors and comedications are among the postulated causes of fatigue, a highly prevalent symptom in the
multiple sclerosis (MS) population, with serious impact on patients' quality of life. Deficiency of carnitine may play a role by reducing
energy production through fatty acid oxidation and numerous MS therapies can induce fatigue syndrome. The aim of this prospective
open-labelled study was to collect and study serum carnitine levels in MS patients with and without disease-modifying treatmentinduced fatigue syndrome. We investigated whether restoration of the carnitine pool might improve treatment-induced fatigue in MS
patients. In our study, there was no statistical difference in fatigue frequency between treated and untreated patients (P=0.5). Matched
to age, gender and treatments, carnitine levels were lower for MS treated patients compared to untreated MS patients (P <0.05) or
controls (P <0.001). Consecutive patients with low plasma carnitine levels who experienced fatigue were substituted. Treatment
consisted of oral levocarnitine, 3-6 g daily. All patients achieved normal plasma carnitine levels. For 63% of patients treated with
immunosuppressive or immunomodulatory therapies, oral levocarnitine adjunction decreased fatigue intensity, especially in
patients treated with cyclophosphamide and interferon beta.
Treatment of multiple sclerosis-related fatigue: pharmacological and non-pharmacological approaches. Neurol Sci. 2006
Sep;27(Supplement 4):s297-s299. Fatigue is a common symptom in multiple sclerosis (MS). As fatigue includes a variety of aspects,
its treatment is best approached in a multidisciplinary fashion that includes nonpharmacological interventions and medications. In
individuals with mild fatigue non-pharmacological treatment including yoga, aerobic exercises, cooling therapy and energy
conservation techniques might be considered. Several pharmacological treatments for patients with significant fatigue have proved to
be effective. Among these agents, amantadine and aminopyridines are the most frequently used. More recently also aspirin and
carnitine have been used to treat MS fatigue but they need to be confirmed in larger studies.
Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a
pilot, randomised, double-blind, crossover trial. J Neurol Sci. 2004 Mar 15;218(1-2):103-8. Treatment with acetyl L-carnitine
(ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome, but there have been no trials on the effect of
ALCAR for treating fatigue in multiple sclerosis (MS)…Statistical analysis showed significant effects of ALCAR compared with
amantadine for the Fatigue Severity Scale (p = 0.039). … The results of this study show that ALCAR is better tolerated and more
effective than amantadine for the treatment of MS-related fatigue.
Nutrition problems due to MS and its treatment
avoidance of “suspect” foods
dysphagia
weight / body composition
pressure ulcers (also called “bed sores”)
bladder infection
drug/nutrient interactions
Avoidance of “suspect” foods.
Many people try a variety of dietary changes in the hope that it will help control the
symptoms of MS. It is especially important in this situation that a knowledgeable person
review the total intake picture to assure that important nutrients are not accidentally
obtained in inadequate or excessive amounts.
Oral flavonoids delay recovery from experimental autoimmune encephalomyelitis in SJL mice. …Our results indicate that oral
flavonoids fail to beneficially influence the course of EAE in mice but, instead, suppress recovery from acute inflammatory damage.
Biochem Pharmacol. 2005 Jul 15;70(2):220-8.
Exacerbation of protracted-relapsing experimental allergic encephalomyelitis in DA rats by gluten-free diet. … Here we study
the effects of a gluten-free diet on the course of protracted-relapsing EAE in DA rats, serving as a preclinical model of human MS.
The data show not only that this nutritional approach failed to ameliorate development of the disease but rather that it exacerbated the
course. APMIS. 2004 Oct;112(10):651-5
Dysphagia
Abnormal swallowing is common in MS although people often do not complained of it. It
is associated with disordered brainstem/cerebellar function, overall disability, depressed
mood and low vital capacity (Thomas & Wiles, 1999.) Assure that any textural manipulations to
facilitate safe eating (such as thickening beverages) do not disrupt nutritional adequacy.
For example, some people actually get a third of their calories just from the starchy
thickeners. This will either result in excessive weight gain if they continue to eat the
same amount of food, or it will contribute to poor nutrient intake if the total food
intake is cut back to avoid weight gain.
The best foods are those which have generous amounts of vitamins, minerals and
beneficial phytochemicals relative to the number of calories they provide. These
desirable foods are said to be “nutrient dense.” Starchy thickeners are not nutrient dense
at all, and if a person must use them for safety of swallowing, appropriate nutrient
supplementation will be even more important than usual. A few commercial thickening
products are available that do contribute some vitamins and minerals, but most do not. If
assuring adequate food/nutrient intake orally becomes a problem, it has been shown that a
percutaneous gastrostomy tube can be very useful and improve quality of life
significantly. (Acta Gastroenterol Latinoam 2004)
Weight / Body Composition:
Many evaluations of nutritional status only look at Body Mass Index (BMI) or some
other weight-related measure. It is important to consider the alterations in body
composition that occur with increasing immobility. As mobility decreases, a person‟s
“Lean Body Mass” will also decrease, resulting in a lower requirement for total calories.
Failure to adjust calories downward can contribute to overweight and increased mobility
for people with MS. However, as described above, when caloric requirements and total
intake decrease, there is an increased risk of missing out on essential nutrients.
Supplementation is reasonable, and it will be necessary in almost all instances.
Pressure Ulcers:
Weight influences on mobility can affect risk of pressure ulcers. However, although
optimal protein and micronutrient nutrition is critical in preventing or healing pressure
ulcers, they are often poorly provided when the calorie intake is low. Immobilization
contributes to both the “pressure” and to the likelihood of inadequate intake of
micronutrients. Again, supplementation will be necessary in almost all instances.
Bladder Infection:
Cranberry juice may be helpful, not because of acidification of urine, but because of the
effects of a natural substance in cranberries that helps make bacteria less likely to adhere
to the bladder lining. A generous intake of fluids is also helpful. However, remember
to watch the calories provided by beverages. For example, “cranberry juice cocktail”
has a lot of sugar added because it is otherwise too tart. The result is a beverage with 20
calories per oz -- the same calories as whole milk! Using artificially sweetened cranberry
juice provides the benefits of cranberry in a very small amount of calories.
Drug/Nutrition Interactions: Chronic use of antibiotics is known to impair folic acid
absorption, and it also stops biotin and vitamin K production by intestinal bacteria.
Several specific interactions were described in the section of vitamin B-12 earlier, and
there are many other interactions of potential importance. Some medications can also
affect appetite, swallowing, mouth dryness, and elimination patterns which indirectly
influence the likelihood of obtaining appropriate nutrition. It is always important to
evaluate the potential for drug/nutrient interactions, so ask your physician,
pharmacist or dietitian if there are any important issues with the particular
medications you are taking.
Reproductive Health Note:
Infant health of mothers with multiple sclerosis. West J Nurs Res. 2004 Oct;26(6):632-49. “Controversy
surrounds whether mothers with multiple sclerosis (MS) who wish to breast-feed their infants should
forego breast-feeding in order to resume immunomodulating therapy following birth even though breastfeeding has not been shown to have deleterious effects on these mothers. … Significantly more non-breastfed than breast-fed infants experienced otitis media, lower respiratory illness, constipation, milk
intolerance, & allergy during the 1st year. Study results support the need to encourage mothers with MS
who wish to breast-feed their infants to do so and to delay immunomodulating therapy until breast-feeding
cessation.”
IN SUMMARY:
My Best Guess (subject to change at any moment based on new
research) about diet/nutrients to decrease risk of MS and/or decrease
the rate of progression:
First: Try not to be Scottish, Irish, female, or to have lived up here in North Dakota
when you were 15. Select your parents and other family members very carefully.
[I realize, of course, that we have no control over these particular factors. However,
recognizing these factors as important may help individuals to evaluate or even take steps
to modify their own personal risk or the risk to others in the family.]
Second: Look Closely to Assure Adequacy of All Nutrients. This is true for everyone,
of course. The diet should be “nutrient dense” (lots of nutrients per calorie, or per
volume) because total food intake is often low. Realize that some people with MS are
avoiding fat, milk and meat, so vitamin D, vitamin B6, calcium, zinc, iron and protein
intake are all likely to be suspect.
Third: Specific Food and Nutrient Risk Issues
Realize that to achieve adequacy of Vitamin D requires 2000 iu for many people up
north – more than the usual RDA level-- and that inadequacy may be a factor in the
development and/or progression of MS. Any people who are covered up, who have
dark skin, who have old skin, who use sunscreen, or who often stay indoors should
certainly aim for this amount of vitamin D from food and/or supplements. Interestingly,
the same goes for people who have none of these risks . . . it may be protective against a
number of serious health problems, and that amount is clearly safe even if one regularly
sunbathes in the nude by the equator!
A multivitamin supplement will provide the RDA level of 400 iu. Milk is the major
dietary source because it has been fortified with vitamin D in an effort to decrease the
problem of rickets / bone deformity in children. One cup (8 oz) provides 100 iu. Until
very recently there was no vitamin D in yogurt, cheese, ice cream, or in the calciumfortified orange juice. Now some brands are beginning to add it. Again, look VERY
closely at this one! Some people are avoiding milk, and they may be injuring themselves
substantially if vitamin D is not provided optimally in some other way. The only other
generous food source is salmon and tuna . . . and as with milk, one would need to eat
them frequently to count on these foods to prevent deficiency. Realize that one does
not “have to” drink milk . . . one must simply recognize that if people drink little or
no milk, they will definitely need some other reliable and generous vitamin D source
. . . like a supplement. Assuring a reasonable calcium intake from non-milk sources will
also be import, of course, but the calcium need not be in the same foods or supplements
as the vitamin D provided. It will be well absorbed as long as the total amount of vitamin
D is adequate, regardless of the timing.
Pending further research, if MS is diagnosed (or if it is especially severe), consider
getting a one-time-only measure of 1,25-dihydroxyvitamin D level to rule out a
metabolic problem converting the vitamin to its active form. If that kind of problem is
found, the individual will need a special prescription form of active vitamin D called
“calcitriol.” This kind of metabolic problem has now been found in at least some people
with MS.
Check that calcium intake is at the recommended level for age (e.g. 1000-1500 mg). This
can be especially difficult to achieve if one is avoiding dairy foods. In this situation (low
dairy or low total calories,) a separate calcium supplement will likely be needed because
most multivitamins with minerals provide only about 200 mg of calcium. A supplement
that provides vitamin D along with the calcium is a very good idea in MS and up
north, even with the 400 iu of vitamin D being provided in a multivitamin.
As a rule of thumb, (for everyone) it is a good idea to assure that the magnesium-tocalcium ratio is near the RDA ratio of 1-to-4. Supplementation of large amounts of
calcium in the absence of adequate magnesium may increase risk of blood clots and
stroke, and also bone fragility. Magnesium is often inadequate in the diets of
Americans, so make sure it isn’t inadequate in yours. A person may need a
supplement beyond a “multi with minerals” to achieve the RDA intake, depending on
food choices. The RDA for Mg is 320 mg for women and 420mg for men. Do not take
more than the RDA in supplement form without consulting your doctor. If a person
does take the RDA amount as a supplement, and then also eats magnesium-rich
foods, there is still no problem.
Selenium can be inadequate in low-protein diets especially, and there are other reasons
(e.g geography) why many people have a poor intake. Low selenium intake has negative
implications for cancer and diabetes as well as MS. An intake at 1-2 times the RDA
seems reasonable for all. For example, a goal might be to provide a multi-vitamin with
minerals that contains selenium (check the label) plus food content, for about 100-150
mcg total intake. As described earlier, the RDA = 60 mcg, the upper chronic intake
limit = 600 mcg , and the toxic level = 800 mcg. If the multivitamin does not provide
selenium, it is easy and inexpensive to simply add a small 50 mcg tablet.
A person who follows a strictly vegetarian diet may have a vitamin B-12 level that is
seriously low. Other factors (such as a person‟s age or using drugs that decrease stomach
acid) can impair absorption of vitamin B12 from food sources. Vitamin B-12
requirements may be higher than normal in MS. It is easy to provide a safe, generous,
inexpensive and absorbable amount, such as the 25 mcg usually included in a “silver”
type multivitamin. The RDA level = 2-3 mcg. The crystalline form of the vitamin
provided in pills does not require stomach acid for absorption the way the form in
food does.
Folic acid availability from foods is also known to be quite variable with measurable
differences in health as a result. The best known and studied example of this is a gene
called the methylenetetrahydrofolate reductase (MTHFR) gene that appears to decrease in
the ability of dietary folate to to its job in preventing birth defects, depression and stroke.
This gene is especially common among people of Irish and Scots heritage (also a
group at higher risk of MS,) and most people who have it are unaware that they do.
However, as with vitamin B12, providing folic acid in the form found in standard
vitamin pills or fortified cereals has been shown to bypass the genetic problem and
make folic acid available to do its job.
This is just one more reason why taking at least a standard multivitamin daily is a very
good idea. (And remember . . . I am NOT selling anything! ) For one thing, the
typically recommended levels of nutrients (RDAs and RDIs, etc.) are based on the
needs of the “healthy” population. They were never intended to address the needs of
people with serious health issues. The idea that a person should “just eat right” is no
longer reasonable based on literally thousands of scientific studies.
In fact, as described above, it is actually potentially harmful advice to discourage a
person from taking a standard multivitamin with minerals. Of course, a vitamin pill
does not make up for a poor diet. Many important nutrients are not even provided by
vitamin pills. A much more scientifically sound position today is: “Eat right AND take
a daily multivitamin with minerals.” These are not mutually exclusive goals.
A generous “B-complex” supplement (e.g. “B-100”) in addition to a “multivitamin with
minerals” may be helpful by raising the intake of vitamins B-6, B-12, folic acid and
biotin in particular. The levels of all B-vitamins are safe at this intake level. Avoid taking
more than one general “multivitamin with minerals” daily because the amount of iron,
zinc and vitamin A (as retinol) may be too high.
Foods to Eat Less Of:
Choose a diet generally low in:
total fat and saturated fat,
dairy products;
meats that are smoked or preserved with nitrites. If you do eat cured meat, eat a
vitamin C-rich food with it to decrease the formation of “nitrosamines” that are
thought to contribute to cancer.
Foods to Eat More Of:
Of the dietary fat consumed, generally choose fats rich in omega-3 fatty acids (flax and
especially fish) and high in PUFAs relative to other animal fat and saturated fat.
Supplemental EPA/DHA fish oil or flax oil capsules may be helpful, especially if fisheating is not desirable. The American Heart Association recommends eating fish twice a
week if one has NO risk of cardiovascular disease . . . no high cholesterol, no diabetes, no
family history, no smoking, etc. However, the higher than usual free radical
production and inflammation associated with MS are certainly cardiovascular risk
factors on their own. For people with some cardiovascular risk, a daily fish oil
capsule is suggested:
Recommendations for Therapeutics and Prevention. Proceedings of a symposium, New York, New
York, USA, May 21, 2005. Am J Clin Nutr. 2006 Jun;83(6 Suppl):1451S-1538S.
AHA Nutrition Committee. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular
disease. Circulation 2002;106:2747-2757
“Supplements that provide about a gram (1000 mg) of omega-3 fat daily can benefit persons
with cardiovascular disease. Higher dose (2–4 grams, or 2000-4000 mg) intakes appear to
greatly improve high triglyceride levels in particular. The higher doses (over 3 grams daily)
should be taken only with physician approval.”
For EVERYONE for MANY Reasons:
Assure a generous antioxidant intake relative to PUFAs. If a person has
MS, an even more generous intake of antioxidants is needed because of increased
free radical production. This increased need for antioxidant protection appears to be the
case in many other autoimmune conditions as well, such as diabetes. Be aware that a
“very low fat” diet naturally provides only minimal vitamin E as well. A good idea for
all: a separate vitamin E supplement providing 200 iu and a vitamin C supplement
that provides 200-500 mg. More may be added with a physician‟s approval. Most
multi-vitamins will provide only the RDA value of 30 iu of vitamin E and 60-100 mg of
vitamin C. Again, the RDA levels, by definition, are based on the presumed needs of the
“healthy population,” so additional consideration of specific health problems associated
with MS often results in some departure from the RDA levels as a goal.
Aim for a generous intake of brightly colored fruits and vegetables.
These foods are rich in nutrients and low in calories. They also provide lots of protective
“phytochemicals” like lutein, lycopene, anthocyanins, carotenes, flavones, etc., which are
very potent antioxidants. Other antioxidants may also be found to be helpful with new
research (e.g. CoQ-10, new B-6 analogs, etc.)
Fourth:
Troubleshooting other nutrition pitfalls for the individual with MS:
Watch for dysphagia problems in MS, and assure that manipulations of food texture do
not disrupt nutritional balance or add excessive calories. If eating becomes too difficult to
maintain nutritional status, consider a percutaneous gastrostomy as a tool.
Good nutrition helps prevent pressure ulcers; but if they develop, treat with aggressive,
supportive nutrition (especially generous protein and zinc, copper, and vitamin C.)
Check for potential nutrition interaction effects of all medications, and make
nutritional adjustments as necessary. This is not just a “take with food / don‟t take with
food” issue.
Remember to consider body composition and activity level changes in assessment of
nutritional status and in making recommendations for calories, etc.:
1) weight:height ratio; 2) lean body mass-to-weight ratio; and 3) activity level..
Fifth:
Stay tuned for new information!
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A COLLECTION OF ANNOTATED REFERENCES AND PARTIAL
ABSTRACTSFOR THOSE WHO ARE INTERESTED:
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Vitamin D (2000-2007; selected annotated references)
2007
Risk assessment for vitamin D. Am J Clin Nutr. 2007 Jan;85(1):6-18. The objective of this review was to apply the risk assessment
methodology used by the Food and Nutrition Board (FNB) to derive a revised safe Tolerable Upper Intake Level (UL) for vitamin D.
New data continue to emerge regarding the health benefits of vitamin D beyond its role in bone. The intakes associated with those
benefits suggest a need for levels of supplementation, food fortification, or both that are higher than current levels. A prevailing
concern exists, however, regarding the potential for toxicity related to excessive vitamin D intakes. The UL established by the FNB
for vitamin D (50 mug, or 2000 IU) is not based on current evidence and is viewed by many as being too restrictive, thus curtailing
research, commercial development, and optimization of nutritional policy. Human clinical trial data published subsequent to the
establishment of the FNB vitamin D UL published in 1997 support a significantly higher UL. We present a risk assessment based on
relevant, well-designed human clinical trials of vitamin D. Collectively, the absence of toxicity in trials conducted in healthy
adults that used vitamin D dose >/=250 mug/d (10 000 IU vitamin D(3)) supports the confident selection of this value as the
UL.
2006
Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006 Dec 20;296(23):2832-8. Prospective, nested casecontrol study among more than 7 million US military personnel who have serum samples stored in the Department of Defense Serum
Repository. Multiple sclerosis cases were identified through Army and Navy physical disability databases for 1992 through 2004, and
diagnoses were confirmed by medical record review. Each case (n = 257) was matched to 2 controls by age, sex, race/ethnicity, and
dates of blood collection. Vitamin D status was estimated by averaging 25-hydroxyvitamin D levels of 2 or more serum samples
collected before the date of initial multiple sclerosis symptoms. Conclusion: The results of our study suggest that high circulating
levels of vitamin D are associated with a lower risk of multiple sclerosis.
IL-10 signaling is essential for 1,25-dihydroxyvitamin D3-mediated inhibition of experimental autoimmune encephalomyelitis.
J Immunol. 2006 Nov 1;177(9):6030-7. Conclusion: Thus, 1,25-(OH)(2)D(3) may be enhancing an anti-inflammatory loop involving
hemopoietic cell-produced IL-10 acting on brain parenchymal cells and vice versa. If this interpretation is correct, and humans have a
similar bidirectional IL-10-dependent loop, then an IL-10-IL-10R pathway defect could abrogate the anti-inflammatory and neuroprotective functions of sunlight and vitamin D(3). In this way, a genetic IL-10-IL-10R pathway defect could interact with an
environmental risk factor, vitamin D(3) insufficiency, to increase MS risk and severity.
Dysfunction of the vitamin D endocrine system as common cause for multiple malignant and other chronic diseases.
Anticancer Res. 2006 Jul-Aug;26(4A):2581-8. Extensive research on the CYP27B1-encoded 25-(OH)D-1alpha-hydroxylase has
contributed much to our understanding about how locally produced 1,25-(OH)2D3 exerts tissue-specific control of cellular growth,
differentiation and function. Because many types of epithelial, mesenchymal and immune cells express the 25-(OH)D-1alphahydroxylase, many organ functions are necessarily affected by changes in the activity of the enzyme. It is hypothesized that this is
likely to occur under conditions of hypovitaminosis D, i.e., at serum 25-(OH)D levels below 30 nM, because extra-renal 25-(OH) D1alpha-hydroxylase activity is critically limited by the availability of its substrate. This can provide an explanation, on a molecular
and cellular basis, for the many observations that significant associations exist between a compromised vitamin D status and
the pathogenesis of frequent chronic diseases. In addition to skeletal disorders, vitamin D insufficiency is a risk factor for
malignancies, particularly of the colon, breast and prostate gland, as well as for chronic inflammatory and autoimmune
diseases (insulin-dependent diabetes mellitus, inflammatory bowel disease, multiple sclerosis, etc.).
New insights into the mechanisms involved in the pleiotropic actions of 1,25dihydroxyvitamin D3.Ann N Y Acad Sci. 2006
Apr;1068:194-203. Vitamin D functions to regulate calcium homeostasis in intestine, kidney, and bone. Vitamin D deficiency during
bone development causes rickets and in adults vitamin D deficiency, which has been shown to be common in the elderly population,
can cause secondary hyperparathyroidism that can result in osteomalacia and increased risk of fracture. Recent evidence has
suggested that vitamin D can have numerous other physiological functions including protection against certain autoimmune
diseases, such as diabetes and multiple sclerosis and inhibition of proliferation of a number of malignant cells including breast
and prostate cancer cells. Exactly how vitamin D affects numerous different systems is a subject of continuing investigation. This
article will review new developments related to the function and regulation of vitamin D target proteins in classic vitamin D target
tissues that have provided novel insight into the mechanism of vitamin D action.
Epidemiology and natural history of multiple sclerosis: new insights. Curr Opin Neurol. 2006 Jun;19(3):248-54.PURPOSE OF
REVIEW: The cause of multiple sclerosis remains elusive. We review recent epidemiological studies of genetic and environmental
factors that influence susceptibility to the disease and its clinical course. RECENT FINDINGS: Genetic advances strengthen the
association of multiple sclerosis with the human leukocyte antigen (HLA)-DRB1 allele and interferon-gamma polymorphisms and
suggest that apolipoprotein E alleles play an important role. In the environmental realm, nested case-control studies show that prior
Epstein-Barr virus exposure is overrepresented in multiple sclerosis. Smoking has been associated with both risk of multiple sclerosis
and progressive disease. Vitamin D deficiency might tie together environmental clues with higher multiple sclerosis prevalence
rates; dietary vitamin supplementation is also associated with reduced multiple sclerosis risk….
The role of vitamin D in multiple sclerosis. Ann Pharmacother. 2006 Jun;40(6):1158-61.OBJECTIVE: To evaluate the literature
about the role of vitamin D in the prevention and treatment of multiple sclerosis (MS). DATA SOURCES: MEDLINE (1966-April
2006) and International Pharmaceutical Abstracts (1970-April 2006) searches were performed. In addition, pertinent references from
identified articles were obtained. Key search terms included vitamin D, 25-hydroxyvitamin D, vitamin D deficiency, and multiple
sclerosis. Data synthesis: Vitamin D supplementation prevented the development and progression of experimental autoimmune
encephalitis, an animal model of MS, in mice. A large, prospective, cohort study found that vitamin D supplementation was
associated with a 40% reduction in the risk of developing MS. Four small, noncontrolled studies suggested that vitamin D
supplementation may decrease exacerbation of MS symptoms. CONCLUSIONS: Vitamin D supplementation may help
prevent the development of MS and may be a useful addition to therapy. However, current studies are in small populations and
are confounded by other variables, such as additional vitamin and mineral supplementation.
Vitamin D and autoimmune disease--implications for practice from the multiple sclerosis literature. J Am Diet Assoc. 2006
Mar;106(3):418-24. Recent studies and commentaries link vitamin D with several autoimmune diseases, including multiple sclerosis
(MS). Adequate vitamin D intake reduces inflammatory cytokines through control of gene expression, thus inadequate vitamin D
intake is suggested as a mechanism that could contribute to inflammation and, consequently, development of MS. Poor vitamin D
status has been associated with increased risk for development of MS, and patients with MS may suffer consequences of vitamin D
deficiency, such as bone loss. Animal studies and very limited human data suggest possible benefit from vitamin D
supplementation in patients with MS. Based on the current state of research, a key principle for practicing dietetics
professionals is to include vitamin D status in nutritional assessment. For those at risk for poor vitamin D status, intake can be
enhanced by food-based advice and, when indicated, vitamin D supplementation.
[CB Note about the conclusion of the above citation – the “food-based advice” means that the vitamin D “should” be obtained
from milk, salmon and some tuna. . . as there are very few other food sources. Interesting to me is the tendency for health
professionals to be unaware of the fact that the vitamin D in milk is ADDED to it. It is not naturally rich in vitamin D. This
kind of advice (that people “should” take their supplemental D preferentially in the form of a liquid dairy product) is not
central to the fact that they simply must get enough vitamin D. Nutrition is not a religion . . . there are many ways to solve a
problem. It is now known that many people require 1000-2000 iu of vitamin D daily to assure adequate levels in their blood.
This is the amount provided by10 -20 cups of milk daily … clearly unreasonable and also poor nutrition as there would be
room for nothing else. .Even if the milk is skim, this is rather a lot of calories (900-1800) especially for people with MS, and it
obliges the displacement of other important foods. Clearly some supplemental vitamin D must be provided in a form other than
“vitamin D added to milk.” A multivitamin provides 400 iu of vitamin D. An additional amount can be obtained from an
inexpensive tablet (it comes in 400 iu, 1000 iu and 2000 iu and likely other strengths will become more common. It may also be
obtained from vitamin D fortified calcium pills (usually 200-400 iu) or as 100 iu per cup of milk. Please see my vitamin D
handout and “Top Five” handout for specific suggestions of many ways to be sure to obtain the right amount.]
The photobiology of vitamin D--a topic of renewed focus. Tidsskr Nor Laegeforen. 2006 Apr 6;126(8):1048-52. The sun is our
most important source of vitamin D. Exposure to solaria, in sub-erythemogenic doses, also gives large amounts of this vitamin. The
ultraviolet radiation in these sources converts 7-dihydrocholesterol to previtamin D3 in the skin. Furthermore, heat isomerization to
vitamin D3 takes place, then transport to the liver and hydroxylation to calcidiol, which is transported to the kidneys and hydroxylated
to the active hormone calcitriol. The vitamin D3 status of the body is supposed to be reliably imaged by calcidiol measurements.
Calcidiol levels above 12.5 nmol/l prevent rickets and osteomalacia, but optimal levels are probably higher, in the range 100-250
nmol/l. A daily food intake of 100-200 microg vitamin D3 (50-100 g cod-liver oil), or a weekly exposure to two minimal erythemal
doses of ultraviolet radiation (20 to 40 minutes whole body exposure to midday midsummer sun in Oslo, Norway), will give this level.
An adequate supply of vitamin D3 seems to reduce the incidence rates or improve the prognosis of several cancer forms,
including prostate, breast and colon cancer, as well as of lymphomas. Several other diseases are related to a low vitamin D3
status: heart diseases, multiple sclerosis, diabetes, and arthritis. The action mechanisms of vitamin D are thought to be mainly
related to its known cell-differentiating and immuno-modulating effects. Even though most of the 250 annual death cases from skin
cancer in Norway are caused by sun exposure, we should, in view of the health effects of ultraviolet radiation, consider modifying our
restrictive attitude towards sun exposure and use of solaria.
[CB note on the last sentence of the above citation: Perhaps a multivitamin would be a bit safer intervention to suggest rather than
ignoring the recognized risk of melanoma from sun exposure. It is also easier to do than the “weekly exposure to two minimal
erythemal doses of ultraviolet radiation (20 to 40 minutes whole body exposure to midday midsummer sun in Oslo, Norway,)”
especially for those of us who are shy about the whole-body exposure part.
Vitamin D physiology. Prog Biophys Mol Biol. 2006 Sep;92(1):4-8 … The active metabolite 1,25(OH)2D has an antiproliferative
effect and downregulates inflammatory markers. Extrarenal synthesis of 1,25(OH)2D occurs under the influence of cytokines and is
important for the paracrine regulation of cell differentiation and function. This may explain that vitamin D deficiency can play a
role in the pathogenesis of auto-immune diseases such as multiple sclerosis and diabetes type 1, and cancer. In conclusion, the
active metabolite 1,25(OH)2D has pleiotropic effects through the vitamin D receptor and vitamin D responsive elements of many
genes and on the other side rapid non-genomic effects through a membrane receptor and second messengers. …
Vitamin D and its role in immunology: multiple sclerosis, and inflammatory bowel disease. Prog Biophys Mol Biol. 2006
Sep;92(1):60-4 Autoimmune diseases like multiple sclerosis (MS) and inflammatory bowel disease (IBD) occur because of an
inappropriate immune-mediated attack against self-tissue. Analyses of genetically identical twins shows that besides genetics there are
important environmental factors that contribute to MS and IBD development. Vitamin D availability due to sunshine exposure or
diet may play a role in the development of MS and IBD. Compelling data in mice show that vitamin D and signaling through
the vitamin D receptor dictate the outcome of experimental MS and IBD. Furthermore, the evidence points to the direct and
indirect regulation of T cell development and function by vitamin D. In the absence of vitamin D and signals delivered through
the vitamin D receptor, auto reactive T cells develop and in the presence of active vitamin D (1,25(OH)(2)D(3) ) and a
functional vitamin D receptor the balance in the T cell response is restored and autoimmunity avoided.
1,25 Dihydroxyvitamin-D3 modulates JAK-STAT pathway in IL-12/IFNgamma axis leading to Th1 response in experimental
allergic encephalomyelitis. J Neurosci Res. 2006 May 15;83(7):1299-309. … These findings highlight the fact that vitamin D
modulates JAK-STAT signaling pathway in IL-12/IFNgamma axis leading to Th1 differentiation and further suggest its use in the
treatment of MS and other Th1 cell-mediated autoimmune diseases.
Epidemiology of disease risks in relation to vitamin D insufficiency. Prog Biophys Mol Biol. 2006 Sep;92(1):65-79. Vitamin D
from ultraviolet-B (UVB) irradiance, food, and supplements is receiving increased attention lately for its role in maintaining optimal
health. Although the calcemic effects of vitamin D have been known for about a century, the non-calcemic effects have been studied
intently only during the past two-three decades. The strongest links to the beneficial roles of UVB and vitamin D to date are for bone
and muscle conditions and diseases. There is also a preponderance of evidence from a variety of studies that vitamin D reduces the
risk of colon cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33 ng/mL (82 nmol/L) associated with a
50% lower incidence of colorectal cancer. There is also reasonable evidence that vitamin D reduces the risk of breast, lung, ovarian,
and prostate cancer and non-Hodgkin's lymphoma. There is weaker, primarily ecologic, evidence for the role of vitamin D in reducing
the risk of an additional dozen types of cancer. There is reasonably strong ecologic and case-control evidence that vitamin D reduces
the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid
arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts its
effect are generally well understood for the various conditions and diseases discussed here.
2005
Effects of alfacalcidol therapy on serum cytokine levels in patients with multiple sclerosis. Srp Arh Celok Lek. 2005 Dec;133
Suppl 2:124-8 The aim of our study was to investigate the immunomodulatory effect of alfacalcidol, a vitamin D analogue, on
cytokine levels in RRMS patients in relapse. … Result: Alfacalcidol therapy in RRMS patients did not provoke any side effects.
Vitamin D and its analogues, such as alfacalcidol, act as immunomodulatory agents, with potential therapeutic effects for
patients with multiple sclerosis.
Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis. Med
Hypotheses. 2005;64(3):608-18.... In areas of high MS prevalence, dietary supplementation of vitamin D in early life may reduce the
incidence of MS. In addition, like folic acid, vitamin D supplementation should also be routinely recommended in pregnancy.
Prevention of MS by modifying an important environmental factor (sunlight exposure and vitamin D level) offers a practical and costeffective way to reduce the burden of the disease in the future generations.
A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis. J Neurol Neurosurg
Psychiatry. 2005 Sep;76(9):1294-6. …Conclusions: Oral calcitriol is safe and well tolerated for up to one year by diet compliant
relapsing-remitting MS patients. Further study of vitamin D related mechanisms is warranted in MS.
25-Hydroxyvitamin D levels in serum at the onset of multiple sclerosis. Mult Scler. 2005 Jun;11(3):266-71.…We conclude that the
vitamin D stores in most MS patients are adequate for their normal bone metabolism. However, lower vitamin D levels during MS
relapses than in remission suggest that vitamin D could be involved in the regulation of the clinical disease activity of MS. The
optimal serum levels of vitamin D for the regulation of immune responses remain to be determined.
2004
Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence. Exp Biol Med
(Maywood). 2004 Dec;229(11):1136-42. Low vitamin D status has been implicated in the etiology of autoimmune diseases such as
multiple sclerosis, rheu-matoid arthritis, insulin-dependent diabetes mellitus, & inflammatory bowel disease. The optimal level of
vitamin D intake required to support optimal immune function is not known but is likely to be at least that required for healthy bones.
Experimentally, vitamin D deficiency results in the increased incidence of autoimmune disease. … This review discusses the
accumulating evidence pointing to a link between vitamin D & autoimmunity. Increased vitamin D intakes might decrease the
incidence & severity of autoimmune diseases and the rate of bone fracture.
Why the optimal requirement for Vitamin D3 is probably much higher than what is officially recommended for adults. J
Steroid Biochem Mol Biol. 2004 May;89-90(1-5):575-9. The physiologic range for circulating 25-hydroxyvitamin D3 [25(OH)D; the
measure of Vit. D nutrient status] concentration in humans & other primates extends to beyond 200 nmol/L (>80 ng/mL). This
biologic "normal" value is greater than current population norms for 25(OH)D. Concentrations of 25-(OH)D that correlate with
desirable effects extend to at least 70 nmol/L, with no obvious threshold. Randomized clinical trials using 20 mcg (800 IU) per day of
Vit. D show that this suppresses parathyroid hormone, preserves bone mineral density, prevents fractures, lowers blood pressure &
improves balance. Calcium absorption from diet correlates with 25(OH)D in the normal range. Health effects of Vita. D beyond
osteoporosis are mostly supported by the circumstantial evidence of epidemiologic studies & laboratory research. These include
prevention of cancer & the auto-immune diseases, insulin-dependent diabetes & multiple sclerosis. One mcg per day of Vit. D(3)
(cholecalciferol) increases circulating 25(OH)D by about 1 nmol/L (0.4 ng/mL). A recommended dietary allowance (RDA) is the
long-term daily intake level that meets the total requirements for the nutrient by nearly all healthy individuals (it would presume no
sunshine). If 70 nmol/L is regarded as a minimum desirable target 25(OH)D concentration, then current recommendations of 15 mcg
per day do not meet the criterion of an RDA.
Multiple sclerosis and vitamin D: an update. Eur J Clin Nutr. 2004 Aug;58(8):1095-109. …The prevalence of MS is highest where
environmental supplies of vitamin D are lowest. … Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary
vitamin D(3) intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly
be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to
obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone
resorption, fractures, and muscle weakness.
Vitamin D intake and incidence of multiple sclerosis Neurology. 2004 Jan 13;62(1):60-5. … Dietary vitamin D intake was
examined directly in relation to risk of MS in two large cohorts of women: the Nurses' Health Study (NHS; 92,253 women followed
from 1980 to 2000) and Nurses' Health Study II (NHS II; 95,310 women followed from 1991 to 2001). ... CONCLUSION: These
results support a protective effect of vitamin D intake on risk of developing MS.
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FATS
Polyunsaturated fatty acids and neurological diseases. Mini Rev Med Chem. 2006 Nov;6(11):1201-11. This review summarizes
the knowledge of the role of dietary PUFAs, especially omega-3, on normal brain function. Furthermore, it reports the evidence
pointing to potential mechanisms of omega-3 fatty acids in development of neurological disorders and efficacy of their
supplementation in terms of symptom management.
Polyunsaturated fatty acid supplementation in MS. Int MS J. 2005 Nov;12(3):88-93. This article focuses on polyunsaturated fatty
acid (PUFA) supplementation, which is a popular form of complementary and alternative therapy among people with MS. Owing to
their popularity, clinicians should be knowledgeable about the PUFA supplements that are widely available, and the efficacy and
safety data from clinical studies. Small-scale studies have demonstrated trends towards some beneficial effects. PUFA
supplementation is generally well tolerated, although some specific supplements are best avoided and some clinical situations warrant
caution. A review of the efficacy and safety data suggests that PUFA supplementation may be a promising approach. Large-scale trials
are required to confirm the benefits.
Low fat dietary intervention with omega-3 fatty acid supplementation in multiple sclerosis patients. Prostaglandins Leukot
Essent Fatty Acids. 2005 Nov;73(5):397-404. OBJECTIVES: To determine whether a low fat diet supplemented with omega-3
positively affects quality of life (QOL) in relapsing-remitting MS (RRMS) patients. In this 1-year long double-blind, randomized trial,
patients were randomized to two dietary interventions: the "Fish Oil" (FO) group received a low fat diet (15% fat) with omega-3 FOs
and the "Olive Oil" (OO) group received the AHA Step I diet (fat 30%) with OO supplements. The primary outcome measure was the
Physical Components Summary Scale (PCS) of the Short Health Status Questionnaire (SF-36). Additional measures using MS specific
QOL questionnaires, neurological status and relapse rate were obtained. RESULTS: 31 RRMS patients were enrolled, with mean
follow up over 9-14 months. Clinical benefits favoring the FO group were observed on PCS/SF-36 and MHI. at 6 months. Reduced
fatigue was seen on the OO diet at 6 months. The relapse rate decreased in both groups relative to the rates during the 1 year
preceding the study: mean change in relapse rate in the FO group: -0.79 +/- SD 1.12 relapses/year vs. -0.69 +/- SD 1.11 in the OO
group. This study suggests that a low fat diet supplemented with omega-3 PUFA can have moderate benefits in RRMS patients
on modifying therapies.
Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005 Dec;59(12):1347-61. Multiple sclerosis
(MS) is a chronic inflammatory disease of the central nervous system (CNS). Oligodendrocyte damage and subsequent axonal
demyelination is a hallmark of this disease. Different pathomechanisms, for example, immune-mediated inflammation, oxidative
stress and excitotoxicity, are involved in the immunopathology of MS. The risk of developing MS is associated with increased dietary
intake of saturated fatty acids. Polyunsaturated fatty acid (PUFA) and antioxidant deficiencies along with decreased cellular
antioxidant defence mechanisms have been observed in MS patients. Furthermore, antioxidant and PUFA treatment in experimental
allergic encephalomyelitis, an animal model of MS, decreased the clinical signs of disease. Low-molecular-weight antioxidants may
support cellular antioxidant defences in various ways, including radical scavenging, interfering with gene transcription, protein
expression, enzyme activity and by metal chelation. PUFAs may not only exert immunosuppressive actions through their
incorporation in immune cells but also may affect cell function within the CNS. Both dietary antioxidants and PUFAs have the
potential to diminish disease symptoms by targeting specific pathomechanisms and supporting therapies.
Antioxidants in multiple sclerosis: do they have a role in therapy? CNS Drugs. 2006;20(6):433-41. Multiple sclerosis (MS) is an
immune-mediated disease, with inflammation and neurodegeneration contributing to neuronal demyelination and axonal injury.
Current therapies for MS are directed toward modulation of the immune response; however, there is increasing evidence that oxidative
stress is an important component in the pathogenesis of MS. The inflammatory environment in demyelinating lesions is conducive to
the generation of reactive oxygen species. When these species are generated in MS and animal models of MS, products such as
peroxynitrite and superoxide are formed that are highly toxic to cells. There are several examples of potential beneficial effects from
various antioxidants in animal models of MS, but the efficacy may vary between different agents and, in some instances, may yield
deleterious effects. Despite these promising results in animal models, there is limited and conflicting evidence of potential therapeutic
effects of antioxidants such as vitamins C and E in treating MS. However, clinical trials in MS patients with more potent
antioxidants, identified in animal studies, have been initiated.
Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via
suppression of glia-mediated inflammation. Curr Pharm Des. 2006;12(27):3521-33. Oxidative stress, in which production of highly
reactive oxygen species (ROS) and reactive nitrogen species (RNS) overwhelms antioxidant defenses, is a feature of many
neurological diseases and neurodegeneration. ROS and RNS generated extracellularly and intracellularly by various processes initiate
and promote neurodegeneration in CNS. ROS and RNS can directly oxidize and damage macromolecules such as DNA, proteins, and
lipids, culminating in neurodegeneration in the CNS. … We propose that combinations of agents which act at sequential steps in
the neurodegenerative process can produce additive neuroprotective effects. A cocktail of multiple antioxidants with antiinflammatory agents may be more beneficial in the prevention of neurodegenerative disease. A clearer appreciation of the
potential therapeutic utility of antioxidants would emerge only when the complexity of their effects on mechanisms that
interact to determine the extent of oxidative damage in vivo are more fully defined and understood.
Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005 Dec;59(12):1347-61. Multiple sclerosis
(MS) is a chronic inflammatory disease of the central nervous system (CNS). Oligodendrocyte damage and subsequent axonal
demyelination is a hallmark of this disease. Different pathomechanisms, for example, immune-mediated inflammation, oxidative
stress and excitotoxicity, are involved in the immunopathology of MS. The risk of developing MS is associated with increased dietary
intake of saturated fatty acids. Polyunsaturated fatty acid (PUFA) and antioxidant deficiencies along with decreased cellular
antioxidant defence mechanisms have been observed in MS patients. Furthermore, antioxidant and PUFA treatment in experimental
allergic encephalomyelitis, an animal model of MS, decreased the clinical signs of disease. Low-molecular-weight antioxidants may
support cellular antioxidant defences in various ways, including radical scavenging, interfering with gene transcription, protein
expression, enzyme activity and by metal chelation. PUFAs may not only exert immunosuppressive actions through their
incorporation in immune cells but also may affect cell function within the CNS. Both dietary antioxidants and PUFAs have the
potential to diminish disease symptoms by targeting specific pathomechanisms and supporting recovery in MS.
Lipoic acid in multiple sclerosis: a pilot study. Mult Scler. 2005 Feb;11(1):24-32. Lipoic acid (LA) is an antioxidant that suppresses
and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. … We conclude that oral LA is
generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating
MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune
encephalomyelitis. J Neuroimmunol 2002 Oct;131(1-2):104-14
Antioxidants and polyunsaturated fatty acids in multiple sclerosis. Eur J Clin Nutr. 2005 Aug 24.…Both dietary antioxidants and
PUFAs have the potential to diminish disease symptoms by targeting specific pathomechanisms and supporting recovery in MS.
The role of methallothioneins in experimental autoimmune encephalomyelitis and multiple sclerosis. Ann N Y Acad Sci. 2005
Jun;1051:88-96. … In this review we summarize recent progress in understanding the regulation and function of methallothioneins
during experimental autoimmune encephalomyelitis and MS. Ann N Y Acad Sci. 2005 Jun;1051:88-96.
Time-course expression of CNS inflammatory, neurodegenerative tissue repair markers and metallothioneins during
experimental autoimmune encephalomyelitis. Neuroscience. 2005;132(4):1135-49. … suggest that metallothionein proteins are
implicated in the clinical recovery of EAE and perhaps these antioxidant proteins may provide therapeutic benefits in MS.
Green tea epigallocatechin-3-gallate mediates T cellular NF-kappa B inhibition and exerts neuroprotection in autoimmune
encephalomyelitis. J Immunol. 2004 Nov 1;173(9):5794-800. … We show that the major green tea constituent, (-)-epigallocatechin3-gallate (EGCG), dramatically suppresses EAE induced by proteolipid protein 139-151. EGCG reduced clinical severity when given
at initiation or after the onset of EAE by both limiting brain inflammation and reducing neuronal damage. …Because its structure
implicates additional antioxidative properties, EGCG was capable of protecting against neuronal injury in living brain tissue induced
by N-methyl-D-aspartate or TRAIL and of directly blocking the formation of neurotoxic reactive oxygen species in neurons. Thus, a
natural green tea constituent may open up a new therapeutic avenue for young disabled adults with inflammatory brain disease by
combining, on one hand, anti-inflammatory and, on the other hand, neuroprotective capacities.
Alpha lipoic acid inhibits human T-cell migration: implications for multiple sclerosis. J Neurosci Res. 2004 Nov 1;78(3):362-70.
We have demonstrated previously the ability of the antioxidant alpha lipoic acid (ALA) to suppress and treat a model of multiple
sclerosis (MS), relapsing experimental autoimmune encephalo-myelitis (EAE). … These data, coupled with its ability to treat
relapsing EAE, suggest that ALA warrants investigation as a therapy for MS.
Protective effects of caffeic acid phenethyl ester against experimental allergic encephalo-myelitis-induced oxidative stress in
rats. Free Radic Biol Med. 2004 Aug 1;37(3):386-94. … Caffeic acid phenethyl ester (CAPE), an active component of honeybee
propolis, has been determined to have antioxidant, anti-inflammatory, antiviral, & anticancer activities. … Treatment with CAPE
significantly inhibited reactive oxygen species (ROS) production induced by EAE, & ameliorated clinical symptoms in rats. These
results suggest that CAPE may exert its anti-inflammatory effect by inhibiting ROS production at the transcriptional level through the
suppression of nuclear factor kappaB activation, & by directly inhibiting the catalytic activity of inducible nitric oxide synthase.
The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol. 2004
Mar;251(3):261-8.Accumulating data indicate that oxidative stress (OS) plays a major role in the pathogenesis of multiple sclerosis
(MS). Reactive oxygen species (ROS), leading to OS, generated in excess primarily by macrophages, have been implicated as
mediators of demyelination and axonal damage in both MS and experimental autoimmune encephalomyelitis (EAE), its animal model.
… treatment with antioxidants might theoretically prevent propagation of tissue damage and improve both survival and neurological
outcome. Indeed, several experimental studies have been performed to see whether dietary intake of several antioxidants prevents or
reduces the progression of EAE. Although a few antioxidants showed some efficacy in these studies, little information is available on
the effect of treatments with such compounds in patients with MS. Well-designed clinical studies using antioxidant intake, as well as
investigations based on larger cohorts studied over a longer periods of time, are needed in order to assess whether antioxidant intake
together with other conventional treatments, might be beneficial in treating MS.
Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol.
2004 Mar;148(1-2):146-53.Alpha-lipoic acid (alpha-LA) is a neuroprotective metabolic antioxidant that has been shown to cross the
blood brain barrier. We tested whether alpha-LA is capable to prevent MOG35-55-induced experimental autoimmune
encephalomyelitis (EAE), an established model of multiple sclerosis (MS). … Our data indicate that alpha-LA can effectively
interfere with the autoimmune reaction associated with EAE through mechanisms other than its antioxidant activity and supports
further studies on the use of alpha-LA as a potential therapy for MS.
Bilirubin as a potent antioxidant suppresses experimental autoimmune encephalomyelitis: implications for the role of
oxidative stress in the development of multiple sclerosis. J Neuroimmunol. 2003 Jun;139(1-2):27-35. Increasing evidence shows
that oxidative stress plays an important role in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental
autoimmune encephalomyelitis (EAE).
Annotated References / Abstracts for Vitamin B12
Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006 Nov;5(11):949-60.
There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate
relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their
overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin
B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to
methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may
have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and
vascular dementia in elderly people.
Vitamin B12 and methionine synthesis: a critical review. Is nature's most beautiful cofactor misunderstood? Biofactors.
2006;26(1):45-57. The mechanism by which Vitamin B12 prevents demyelination of nerve tissue is still not known. The evidence
indicates that the critical site of B12 function in nerve tissue is in the enzyme, methionine synthase, in a system which requires Sadenosylmethionine. In recent years it has been recognized that S-adenosylmethionine gives rise to the deoxyadenosyl radical which
catalyzes many reactions including the rearrangement of lysine to beta-lysine. Evidence is reviewed which suggests that there is an
analogy between the two systems and that S-adenosyl methionine may catalyze a rearrangement of homocysteine on methionine
synthase giving rise to iso- or beta-methionine. The rearranged product is readily degraded to CH3-SH, providing a mechanism for
removing toxic homocysteine.
Plasma homocysteine levels in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006 Feb;77(2):189-92. BACKGROUND: There
is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been
observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased
in MS, and whether they play a role in the disease course. METHODS: We compared plasma levels of homocysteine in 88 patients
with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary
progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12,
tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative
stress). RESULTS: Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls
(10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical
subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and
controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or
TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. CONCLUSIONS: Elevated plasma homocysteine
occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a
deficiency in vitamin B6, vitamin B12, or folate.
Vitamin B12, demyelination, remyelination and repair in multiple sclerosis J Neurol Sci. 2005 Jun 15;233(1-2):93-7. Multiple
Sclerosis (MS) and vitamin B12 deficiency share common inflammatory and neurodegenerative pathophysiological characteristics.
Due to similarities in the clinical presentations and MRI findings, the differential diagnosis between vitamin B12 deficiency and MS
may be difficult. Additionally, low or decreased levels of vitamin B12 have been demonstrated in MS patients. Moreover, recent
studies suggest that vitamin B12, in addition to its known role as a co-factor in myelin formation, has important immunomodulatory
and neurotrophic effects. These observations raise the questions of possible causal relationship between the two disorders, and
suggest further studies of the need to close monitoring of vitamin B12 levels as well as the potential requirement for
supplementation of vitamin B12 alone or in combination with the immunotherapies for MS patients.
Attenuation of experimental autoimmune encephalomyelitis and nonimmune demyelination by IFN-beta plus vitamin B12:
treatment to modify notch-1/sonic hedgehog balance. J Immunol. 2004;172(10):6418-26. Interferon-beta is a mainstay therapy of
demyelinating diseases, but its effects are incomplete in human multiple sclerosis & several of its animal models. In this study, we
demonstrate dramatic improvements of clinical, histological, & laboratory parameters in in vivo mouse models of demyelinating
disease through combination therapy with IFN-beta plus vitamin B(12) cyanocobalamin (B(12)CN) in nonautoimmune
primary demyelinating ND4 (DM20) transgenics, and in acute and chronic experimental autoimmune encephalomyelitis in
SJL mice. Clinical improvement (p values <0.0001) was paralleled by near normal motor function, reduced astrocytosis, and reduced
demyelination. IFN-beta plus B(12)CN enhanced in vivo and in vitro oligodendrocyte maturation. In vivo & in vitro altered
expression patterns of reduced Notch-1 & enhanced expression of sonic hedgehog & its receptor were consistent with oligodendrocyte
maturation & remyelination. IFN-beta-B(12)CN combination therapy may be promising for the treatment of multiple sclerosis.
Increased plasma homocysteine levels without signs of vitamin B12 deficiency in patients with multiple sclerosis assessed by
blood and cerebrospinal fluid homocysteine and methylmalonic acid. Mult Scler. 2003 Jun;9(3):239-45. Objective: The aim of
this study was to evaluate if multiple sclerosis (MS) is associated with vitamin B12 (cobalamin) deficiency. Methods: We measured
serum vitamin B12, plasma folate, serum methylmalonic acid (MMA), plasma homocysteine (tHcy) and also cerebrospinal fluid
(CSF) MMA and tHcy in 72 patients with MS and 23 controls. Results: The mean plasma tHcy level was significantly increased in
MS patients (11.6 micromol/L) compared with controls (7.4 micromol/L) (P = 0.002). Seven patients showed low serum vitamin B12
levels but only one of them had concomitant high plasma tHcy. None of them showed high serum MMA. Plasma or blood folate levels
did not differ between MS patients and controls. We found no significant differences in mean values or frequency of pathological tests
of serum B12, serum MMA, mean corpuscular volume (MCV), haemoglobin concentration, CSF tHcy or CSF MMA between patients
and healthy subjects. There were no correlations between CSF and serum/plasma levels of MMA or tHcy. Serum vitamin B12, serum
MMA, plasma tHcy, CSF Hcy or CSF MMA were not correlated to disability status, activity of disease, duration of disease or age.
Conclusions: The relevance of the increased mean value of plasma tHcy thus seems uncertain and does not indicate functional vitamin
B12 deficiency. We can not, however, exclude the possibility of a genetically induced dysfunction of the homocysteine metabolism
relevant for the development of neuroinflammation/degeneration. Our findings indicate that, regardless of a significant increase in
plasma tHcy in MS patients, the MS disease is not generally associated with vitamin B12 deficiency since we did not find any other
factors indicating vitamin B12 deficiency. Analysis of CSF MMA and CSF tHcy, which probably reflects the brain vitamin B12 status
better than serum, are not warranted in MS. We conclude that B12 deficiency, in general, is not associated with MS.
Lipoprotein oxidation, plasma total antioxidant capacity and homocysteine level in patients with multiple sclerosis. Nutr
Neurosci. 2003 Jun;6(3):189-96. Free radical-mediated peroxidation of biological molecules, especially of lipids, is implicated in the
pathogenesis of a number of diseases like multiple sclerosis. Low concentration of antioxidant vitamins: beta carotene, retinol,
alpha tocopherol and ascorbic acid have been observed in serum or cerebrospinal fluid of multiple sclerosis patients. On the
basis of these observations, we studied the potential lipoprotein oxidation and total antioxidant capacity in the pathogenesis of
multiple sclerosis. Lipoprotein oxidizability for plasma in vitro, serum levels of autoantibodies against oxidized low-density
lipoproteins, plasma total homocysteine levels with vitamin B12 and folate, and plasma total antioxidant capacity were measured in
twenty four patients with multiple sclerosis and twenty four healthy sex- and age-matched person as control. In multiple sclerosis
patients during an attack, a significant increase in both in vitro lipid oxidizability for plasma and in the levels of autoantibodies against
oxidized low-density lipoproteins, and a strong decrease in plasma total antioxidant capacity were detected. Plasma total
homocysteine levels were significantly higher in multiple sclerosis patients whose plasma vitamin B12 and folate levels were
lower but not statistically significant, than controls. The present study indicates that lipoprotein oxidation may be important
factor in the course of multiple sclerosis and in vitro measurements of plasma oxidation kinetics as an indication for
lipoprotein oxidation might be useful as an additional tool for the clinical diagnosis of multiple sclerosis.
Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical
importance: roles of the locus coeruleus and central noradrenergic systems. Med Hypotheses. 2002 Nov;59(5):594-602. In a
randomized, placebo-controlled double-blind trial a combination of lofepramine, phenylalanine and vitamin B(12) was found to
be effective in relieving the symptoms of multiple sclerosis (MS). The effect occurred within 2-4 weeks, and improved all types of
symptoms in all types of MS. The combination was also effective in relieving symptoms in patients with chronic pain and chronic
fatigue. We hypothesize that the action of this combined therapy may relate to activation of the noradrenergic locus coeruleus/lateral
tegmentum (LC/LT) system which has the potential to influence the functioning of large areas of the brain and spinal cord.
A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the "Cari Loder
regime") in the treatment of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2002 Sep;73(3):246-9 OBJECTIVE: To determine
whether combination therapy with lofepramine, L-phenylalanine, and intramuscular vitamin B-12 (the "Cari Loder regime") reduces
disability in patients with multiple sclerosis. METHODS: A placebo controlled, double blind, randomised study carried out in five
United Kingdom centres on outpatients with clinically definite multiple sclerosis, measurable disability on Guy's neurological
disability scale (GNDS), no relapse in the preceding six months, and not on antidepressant drugs. Over 24 weeks all patients received
vitamin B-12, 1 mg intramuscularly weekly, and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily, or matching
placebo tablets. Outcome was assessed using the GNDS, the Kurtzke expanded disability status scale; the Beck depression inventory,
the Chalder fatigue scale, and the Gulick MS specific symptom scale. RESULTS: 138 patients were entered, and two were lost from
each group. There was no statistically significant difference between the groups at entry or at follow up. Analysis of covariance
suggested that treated patients had better outcomes on four of the five scales used. Both groups showed a reduction of 2 GNDS points
within the first two weeks, and when data from all time points were considered, the treated group had a significant improvement of 0.6
GNDS points from two weeks onwards. CONCLUSIONS: Patients with multiple sclerosis improved by 2 GNDS points after
starting vitamin B-12 injections. The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit. More
research is needed to confirm and explore the significance of this clinically small difference.
UND School of Medicine,
Sanford Medical Center
Aunt Cathy‟s Guide to
Nutrition:
Comments Regarding the
Prader Willi Syndrome
Association‟s Food Guide
Pyramid for Weight
Control
Cathy Breedon PhD, RD, CSP, FADA
Perinatal/Pediatric Nutrition Specialist
Clinical/Metabolic Nutrition Specialist
Sanford Medical Center, Dept. of Pediatrics
University of North Dakota School of
Medicine, Dept. of Pediatrics, Fargo, ND
Children with a genetic condition called Prader Willi Syndrome usually struggle with their weight all
of their lives. They appear to use up fewer calories each day, so just eating “normally” can still cause them to
gain weight extremely fast. Losing weight is extremely difficult. The following is a 2003 Food Guide Pyramid
that was designed for people with PWS, but potentially useful for any people with very low calorie
requirements (such as people whose movement is impaired.) This pyramid has some helpful ideas (especially
the suggestion to place vegetables as the “base” of the pyramid instead of the grains and cereals food group in
the “regular” USDA Food Guide Pyramid.)
In addition to calorie concerns, however, I am very concerned about assuring that
micronutrients (vitamins and minerals) and protein are provided in appropriate amounts in spite of the
decreased total food intake. There are some other serious concerns as well. Unfortunately, there are some
problems in that area in the 2003 Prader Willi Food Guide presented below. As it appears to continue to be
used in practice in spite of these important issues, I have taken the liberty of interjecting my thoughts on this
issue as you look over this otherwise helpful way of adjusting the base of the pyramid.
My comments are clearly delineated from those of the PWS
Pyramid designer (Beverly Ekaitis, DTR, registered dietetic technician)
by brackets [ ] and by bold print.
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Start of Original Article: Prader-Willi Syndrome Association (USA)
A PRADER-WILLI FOOD PYRAMID
by Beverly Ekaitis, DTR, dietetic technician
The Children's Institute of Pittsburgh (TRI)
PWSA Editors‟ Note: The USDA’s Food Guide Pyramid provides an appealing graphic tool for thinking
about a day’s food portions, but it simply adds up to too much food for someone on a Prader-Willi diet. We
asked the Children's Institute if they could adapt the new pyramid to the typical PW diet for families that
might wish to use it as an alternative to the Exchange System, the Red-Yellow-Green (Stoplight) Diet, or other
methods of counting calories.
The Institute was glad to oblige but urges those who have been through the Institute’s program to
continue using the Red-Yellow-Green Diet that they learned there. The Prader-Willi Food Pyramid that
follows may not be appropriate for young children or for those on growth hormone therapy, and it should not
be considered substitute for individualized dietary guidance. Dietary guidance preferably should come from a
nutritionist who is familiar with PWS.
The Food Pyramid Guide to Daily Food Choices, designed by the U.S. Department of Agriculture for
adults who need 1,600 to 2,800 calories a day, represents the relative portions of foods to eat each day to
maintain a healthy weight and body. To make the Food Pyramid usable for people with Prader-Willi
Syndrome, a few changes have to be made.
The first change needed is to adjust the number of daily servings for each food group in order to
reduce the total calorie level to 800 to 1,200 a day. These lower levels will provide for weight loss or PWS.
[CB note:
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It is potentially useful for others with very low caloric requirements as well, with the same
caveats described below.] Actual calorie goals for PWS and non-PWS individuals will vary
considerably. Also, when establishing such a low calorie goal, consider that the daily values and other
guidelines are usually based on a 2000 calorie diet. It is important to remember that such low calorie
levels will invariably be inadequate in a number of nutrients unless careful supplementation is done.
Failure to replace these nutrients is not benign.]
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Second, although the five main food groups — bread, vegetable, fruit, meat, and milk — remain the
same, the positions of two of the groups need to be changed on the pyramid to reflect a change in the
recommended number of servings. Each group has a specific number of servings that determines its position
on the pyramid.
The Food Groups
The first USDA Food Pyramid (which had horizontal lines) has a base of the Bread group, which would
provide the highest number of daily servings. The PW Pyramid, on the other hand, has as its base the
Vegetable group, with 6-8 servings a day. For those familiar with the RedYellow-Green Diet, these would
be "GO" foods, i.e., foods low in calories and fat. Making the vegetable group the base of the pyramid and the
bulk of the diet will allow a large volume of food to be eaten without many additional calories.
The Bread group, which includes cereal, pasta, and rice, moves up the pyramid with a decrease in number
of servings to three to five per day. We would also include starchy vegetables like corn, peas, and potatoes in
this group because they have the same amount of calories per serving as breads.
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[CB note: Try to use whole grains and foods that are naturally high in fiber whenever able to
improve the micronutrient content of the diet (especially magnesium, chromium and natural forms