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Chapter 6: Vitamins and Minerals
Introduction
Vitamin and mineral deficiency diseases in the United States were relatively common prior
to World War II. Today, with the fortification of the food supply, classical vitamin deficiency
diseases such as scurvy and rickets are rare outside the setting of specific disease states, drugnutrient interactions, or extreme malnutrition due to poverty in the U.S.. On a global basis, vitamin
deficiencies still occur in many large countries such as India and China in both rural and urban
populations. What can be classified as suboptimal intake of some vitamins such as vitamin D in
areas of low sun exposure is a more recently discovered and important area of vitamin deficiency
where supplementation is being recommended by authorities in the field.
Surveys, Recommendations and State of the Art
Health and Nutrition Examination Surveys (HANES) are periodic surveys of the
American population that are conducted by the National Center for Health Statistics (NCHS) of
the Centers for Disease Control and Prevention. Data are obtained through personal interviews
and health examinations, and represent some of the best data sets of their kind in the world.
NHANES data are used to estimate the prevalence of selected diseases and health risk factors
in the U.S. population including the prevalence of overweight, high blood pressure, and elevated
serum lipids. National reference values for nutrition and health parameters including food
energy and nutrient intakes from dietary sources, nutritional biochemistry values, and body
measurement data are produced from NHANES data. NHANES data are also used to examine
secular trends in the prevalences of diseases and health risk factors, and to study the etiology
of chronic and infectious diseases in the U.S. population.
Three national HANES (termed “NHANES”) were completed between 1971 and 1994:
NHANES I (1971-75); NHANES II (1976-80); NHANES III (1988-94). Hispanic HANES, a
special survey of three Hispanic subgroups, was conducted from 1982-84 to provide
comprehensive health and nutrition data on three major Hispanic subgroups living in the United
States: Mexican Americans living in the southwest U.S., Cuban Americans in Dade County, FL,
and Puerto Ricans in the New York City metropolitan area. The most recent survey, NHANES
III, 1988-94, was conducted in two phases. Each three-year phase, as well as the entire 6 years
constituted a national sample.
The last such survey was conducted between 1976 and 1980, and the NHANES III ran
from 1988 to 1994. The 1976 to 1980 survey indicated that the most common vitamin deficiencies
in the U.S. population in good health were iron and calcium, in women only. The intake of most B
vitamins, vitamin C, D, E and others were at or above the Recommended Dietary Allowances
(RDA*).
(*The RDA are normally issued every ten years by the National Academy of Science Food
and Nutrition Board to help guide healthy individuals and help in planning various national nutrition
programs for infant feeding and school nutrition. The RDA levels are normally set above the
threshold needed to prevent deficiency diseases, but in some cases the levels are below those
some experts would like to see for the prevention of disease. In fact, in 1980 the guidelines were
not issued due to a philosophical difference of opinion among the expert members of the group as
to whether the RDA should be raised to encourage intake of Vitamin A (carotenoid)-rich and
Vitamin C rich foods such as fruits and vegetables. The controversy was finally settled with the
issuance of the 1989 guidelines which reverted to the original aim of averting nutritional deficiency
states through public policy recommendations.)
The following discussion deals specifically with nutrient deficiencies and only alludes briefly
to the preventive potential of micronutrients including carotenoids, vitamin C, vitamin E and folate.
Recent data on the requirements for Vitamin D and how to assess status are included based on
recent findings. Despite the uncommon occurrence of vitamin deficiencies sufficient to cause acute
disease in healthy individuals, a familiarity with the roles of the various common vitamins and
minerals points to directions of research on suboptimal intakes of vitamins and minerals relevant to
the reduction of the risk of common age-related chronjc diseases.
The Fat Soluble Vitamins A,D, E, and K
Vitamin A
Night blindness was well-recognized in ancient Egypt where it was treated with juice from
cooked liver or by including liver in the diet. The active agent, vitamin A, was discovered as a fatsoluble growth factor necessary for the rat in 1914 and structurally analyzed in 1930 (1). The
parent compound of the vitamin A family is all-trans retinol. Its aldehyde and acid forms are retinal
and retinoic acid. The active form of vitamin A for vision is 11-cis retinal. The most common clinical
manifestations of vitamin A deficiency are night blindness and xerophthalmia (a thickening of the
conjunctiva of the eye). In young children, Bitot's spots (foamy white accumulations of sloughed
cells on the conjunctiva) can be useful in diagnosing vitamin A deficiency. A second active function
for vitamin A is cellular differentiation. The recent discovery of four retinoic acid receptors (termed
RAR-alpha through RAR-gamma) in the nucleus of cells has begun to elucidate the molecular
mechanisms by which vitamin A induces differentiation of many types of cells (2). A number of
retinoids or synthetic vitamin A analogs (the best known is 13-cis retinoic acid or Accutane) are
used to treat acne and have been studied for their differentiating activities in the prevention and
treatment of premalignant lesions of the mouth, trachea, and cervix (3). Retinol, retinal and retinoic
acid are bound to specific retinol-binding proteins in plasma. Tissue cells contain a retinol binding
protein (CRBP, types I and II, the latter an intestinal form) and a retinoic acid binding protein
(CRABP) (4). In the eye, retinol is bound by interphotoreceptor interstitial-binding protein (IRBP)
(5). All of these proteins have been sequenced and cloned, and much is known about their
structure and ligand binding sites.
Given the importance of vitamin A, it is fortunate that it can be formed from provitamin A
carotenoids found in carrots, yellow squash, dark-green leafy vegetables, corn, tomatoes, papaya,
and oranges. Preformed vitamin A is found as retinyl palmitate in liver, various dairy products
including milk, cheese, butter, and ice cream, and fish such as herring, sardines, and tuna. In the
U.S., about 75% of vitamin A is obtained from preformed dietary sources and 25% from provitamin
A carotenoids (6).
Low plasma concentrations of retinol (<0.35 umol/L) are associated with clinical symptoms
of vitamin A deficiency (7). The Recommended Dietary Allowance for vitamin A is 5000 IU (800 to
1000 mcg retinol equivalents, or RE) per day, and toxicity has been reported at intakes of 25,000
IU per day. This makes vitamin A one of the most toxic vitamins known. The plasma levels of
vitamin A can be used to assess status as follows (8):
Vitamin A
Deficient
<0.35 umol/L
Marginal
0.35-0.70
Satisfactory
0.70-1.75
Excessive
1.75-3.5
Toxic
>3.5
Vitamin D
Vitamin D is formed from 7-dehydrocholesterol via the action of sunlight in the skin or is
taken in from dietary sources, primarily in dairy products. Since dairy products have been fortified
with vitamins A and D, dietary rickets has become rare in the U.S. Vitamin D acts to enhance
calcium absorption from the intestine and has been shown to have differentiating effects on a
number of different cell types including white blood cells and prostate cancer cells. The active form
of vitamin D is 1,25 dihydroxyvitamin D formed from 25-hydroxyvitamin D in the kidneys. 25hydroxyvitamin D is a large inactive pool formed and stored in the liver. The kidney also has an
inactivation enzyme (24 hydroxylase) which converts 25 (OH) D to inactive 24,25 dihydroxyvitamin
D. When 1,25 dihydroxyvitamin D acts at the nucleus it turns on the genes necessary to produce
the 24 hydroxylase enzyme. Whenever there is such a branch point in the body, there is additional
protection from toxicity and it indicates a substance with important metabolic roles (e.g. thyroid
hormones).
As people age, the skin becomes less effective in forming vitamin D and people are
advised to use sunscreens and avoid sun exposure to prevent skin cancer. Vitamin D3 as a
supplement is preferable to D2 (found In plants) since D2 is more rapidly cleared and is less
biologically active than D3. Taking doses of 800 IU to 2000 IU per day are clearly not t toxic since it
translates into small increases in 25OHD levels. For exampole 800 IU results in an increase of
only 8 ng/ml (see below, desirable blood levels of vitamin D)
Vitamin D beyond vitamin deficiency, rickets, and osteomalacia
Vitamin D is not just a vitamin but a hormone that travels to the nucleus to program the
transcription of specific proteins. Research over the last three decades has brought to light
many additional functions of vitamin D and redefined what is considered optimal Vitamin D
nutrition. It is now estimated that approximately 1 billion people worldwide have blood
concentrations of vitamin D that are considered suboptimal. Low vitamin D serum
concentrations are linked to several types of cancers, cardiovascular disease, diabetes, upper
respiratory tract infections, and all-cause mortality.
Several observational studies and a few prospectively randomized controlled trials have
demonstrated that adequate levels of vitamin D can decrease the risk and improve survival
rates for several types of cancers including breast, rectum, ovary, prostate, stomach, bladder,
esophagus, kidney, lung, pancreas, uterus, non-Hodgkin lymphoma, and multiple myeloma.
Individuals with serum vitamin D concentrations less than 20 ng/mL are considered most at risk,
whereas those who achieve levels of 32 to 100 ng/mL are considered to have sufficient serum
vitamin D concentrations. Vitamin D can be obtained from exposure to the sun, through dietary
intake, and via supplementation. Obtaining a total of approximately 4000 IU/d of vitamin D3 from
all sources has been shown to achieve serum concentrations considered to be in the sufficient
range. Most individuals will require a dietary supplement of 2000 IU/d of vitamin D3 to achieve
sufficient levels as up to 10 000 IU/d is considered safe. Vitamin D3 is available as an over-thecounter product at most pharmacies and is relatively inexpensive, especially when compared
with the demonstrated benefits.
Serum 25-Hydroxyvitamin D Concentrations by Category
Category
Deficiency
Insufficiency
Sufficiency
Excess
25-Hydroxyvitamin D Concentrations, ng/mL (nmol/L)
<20 (<50)
20-32 (50-80)
32-100 (80-250)
>100 (> 250)
Intoxication
>150 (>325)
An individual's 25-hydroxyvitamin D level is determined by many variables, including the
amount of solar ultraviolet B (UVB) radiation (determined by the time of day, season, latitude,
skin pigmentation, use of sunscreen, and age), dietary habits, and body fat with obese
individuals having lower levels than lean indivduals. UVB radiation penetrates the skin and
converts vitamin D precursors to vitamin D3. Vitamin D obtained from the skin and diet is
metabolized to 25-hydroxyvitamin D. This determines the measured serum level of vitamin D.
25-hydroxyvitamin D is then further metabolized in the kidneys to its active form, 1,25hydroxyvitamin D. Most tissues and cells in the body possess a vitamin D receptor, and many
have the ability to convert 25-hydroxyvitamin D to 1,25-hydroxyvitamin D. This discovery is
thought to be the reason such a broad range of diseases and conditions, including cancer, have
benefited from vitamin D supplementation.
Vitamin E
A group of fat-soluble substances, the tocopherols and tocotrienols are referred to as
vitamin E. There a four forms of tocopherols and tocotrienols called alpha, beta, gamma and delta
making a total of eight forms of vitamin E. There is a specific protein for carrying tocopherols to the
liver called alpha tocopherol transfer protein (alpha-TTP) A neurological disease called Friedrich’s
Ataxia occurs in individuals with a genetic absence of functioning alpha-TTP indicating that it has
some important function in the body that is as yet poorly understood. The tocotrienols have oneseventh the affinity for alpha-TTP as alpha tocopherol. The gamma-tocopherol is carried on
triglycerides in the blood to the various tissues in the body.
Vitamin E was discovered in 1922 by Herbert Evans and isolated from green leafy
vegetables as a fertility factor in rats. Vitamin E was synthesized in 1938 and alpha-D-tocopherol
was found to be is biologically active in rodents where a Vitamin E deficiency can cause infertility.
This deficiency has never been demonstrated in humans, but an RDA value was set for humans
based on the data in rodents. The tocotrienols were isolated in 1964 at the University of Wisconsin
from wheat germ oil, but are also found in palm oil, rice bran oil, barley oil, and oat bran. The
refined forms of rice and oats do not contain tocotrienols. Gamma tocotrienol has been found to be
the most protective against radiation, and both gamma and delta tocotrienols inhibit the rate limiting
enzyme in cholesterol synthesis. Alpha tocotrienol is present in the blood at concentrations ten
times less than alpha tocopherol and so has been ignored by researchers until recent work
demonstrating that in animal models alpha-tocotrienol can reduce the amount of brain tissue
destroyed after blocking a blood vessel to recreate the damage that would occur with a stroke.
Alpha-tocotrienol prevents nerve cell death in test tube experiments and gets into the brain
independent of alpha-TTP. Recently a tocotrienol-rich fraction of palm oil obtained GRAS
(Generally Recognized as Safe Status) from the US Food and Drug Administration. Toctotrienol
supplements are sold commercially as extracts of palm oil. The emerging science on tocotrienols is
growing rapidly.
The Recommended Dietary Allowance for vitamin E is between 8 and 12 mcg retinol
equivalents per day to prevent vitamin E deficiency (infertility seen only in animals), but many
individuals take 400 to 800 IU supplements without ill effects. A recent analysis of multiple studies
found that above 330 IU per day there was a 5 percent increase in overall mortality from
cardiovascular disease. These results remain highly controversial. One of the effects of taking
alpha tocoperol is to reduce the amounts of gamma tocopherol in the blood. In the laboratory
gamma tocopherol is a more potent antioxidant than alpha-tocopherol.
Tocopherols have antioxidant properties protecting tissues and substances from the effects
of oxygen. For example, these compounds can prevent oxidation of cholesterol, polyunsaturated
fats, and other membrane lipids and proteins. The antioxidant effects of vitamin E have been
demonstrated only at doses that cannot be derived from usual diets but can only be achieved using
supplement capsules. The use of vitamin E supplements has been associated with lower
cardiovascular disease risk in males, and has also been used effectively to retard the oxygeninduced damage to the eye in infants given 100% oxygen known as retrolental fibroplasia. There is
increased interest in using vitamin E as an antioxidant for prevention of cardiovascular disease and
common forms of cancer.
Vitamin K
Vitamin K is a fat-soluble vitamin. The "K" is derived from the German word
"koagulation". Coagulation refers to blood clotting, because vitamin K is essential for the
functioning of several proteins involved in blood clotting. A deficiency of this vitamin in newborn
babies results in hemorrhagic disease, as well as postoperative bleeding and hematuria while
muscle hematomas and inter-cranial hemorrhages have been reported. A shortage of this
vitamin may manifest itself in nosebleeds or internal hemorrhaging. Individuals taking
coumadin® (warfarin) must regulate their vitamin K intake since taking in large amounts of
vitamin K from foods or supplements will affect the ability of this blood thinning drug to work.
The small amounts of vitamin K found in some multivitamins are not a problem (around 100
micrograms) and may even smooth out variations in blood clotting due to minor changes in
dietary vitamin K consumption. Patients taking blood thinners are given a list of foods to avoid
which are rich in vitamin K and include spinach, green leafy vegetables, cabbage, potatoes,
cereals, and liver. Half of vitamin K comes from the diet, and the other half is synthesized from
precursors by intestinal bacteria .Since vitamin K is found in so many foods and is also formed by
intestinal bacteria, deficiency is rare. Individuals receiving prolonged antibiotic therapy destroying
intestinal bacteria, and individuals with fat malabsorption are at risk for vitamin K deficiency. The
Recommended Dietary Allowance for adults ranges between 45 and 80 micrograms per day.
There are two naturally occurring forms of vitamin K. Plants synthesize phylloquinone,
also known as vitamin K1. Bacteria synthesize a range of vitamin K forms, using repeating 5carbon units in the side chain of the molecule. These forms of vitamin K are designated
menaquinone-n (MK-n), where n stands for the number of 5-carbon units. MK-n are collectively
referred to as vitamin K2. MK-4 is not produced in significant amounts by bacteria, but appears
to be synthesized by animals (including humans) from phylloquinone. MK-4 is found in a
number of organs other than the liver at higher concentrations than phylloquinone. This fact,
along with the existence of a unique pathway for its synthesis, suggests there is some unique
function of MK-4 that is yet to be discovered.
Vitamin K deficiency has been shown to be a risk factor for hip fracture in the elderly and
vitamin K2 supplementation increases serum levels of osteocalcin ( a bone forming hormone) and
has a modest effect on bone mineral density.
The Water Soluble Vitamins
Unlike fat-soluble vitamins which can be stored after a single administration for long periods of
time, water soluble vitamins need to be supplied in foods and supplements on a regular basis to
avoid deficiency. Industrialized societies have few cases of water-soluble vitamin deficiency except
in homeless or alcoholic individuals. The recent increase in obesity surgeries which lead to
malabsorption of vitamin B12 by bypassing the stomach have led to a new group of individuals at
risk of vitamin deficiencies. Strict vegans, individuals with food intolerances, and raw food
enthusiasts can also develop vitamin deficiencies if their choices of foods are narrowed
significantly.
Vitamin B1 (Thiamin)
Thiamin deficiency disease, still seen today in alcoholics, is known as beriberi (9). This
disease, which damages the nervous and cardiovascular systems, is found in two forms, wet
beriberi with edema and congestive heart failure, and dry beriberi characterized by muscle atrophy
due to nerve damage. In alcoholics, Wernicke-Korsakoff syndrome, characterized by mental
confusion, memory disturbances, ataxia, opthalmoplegia, and nystagmus, can be fatal if not treated
with intravenous thiamin (10). The dietary vitamin is phosphorylated to form thiamin pyrophosphate
in the intestine. Its primary function is to act as a coenzyme for the oxidative decarboxylation of
alpha-keto-acids to carboxylic acids (e.g. pyruvate to acetyl CoA) and the transketolase reaction of
the pentose phosphate shunt. The latter pathway is important for nucleic acid synthesis and the
formation of NADPH for fatty acid synthesis and other reactions. Decreased transketolase activity
in red cells can be detected early in the course of thiamin deficiency.
The Recommended Dietary Allowance of thiamin is 0.5 mg/1000 kcal and this is four times
the intake at which deficiency signs are observed.
Vitamin B2 (riboflavin)
Riboflavin is a yellow fluorescent compound found throughout the animal and plant
kingdoms. Humans and other mammals cannot synthesize these compounds which function in
numerous enzyme complexes (including flavin mononucleotide and flavin adenine dinucleotide)
involved in electron transport oxidation-reduction reactions (11). Flavins are transported in the
blood by albumin and by immunoglobulins. Uncomplicated riboflavin deficiency is uncommon, but
dietary lack of the vitamin can lead to a deficit, not only in flavin coenzyme functions, but also in the
conversion of vitamin B-6 to pyridoxal phosphate. The recommended dietary allowance for
riboflavin ranges between 1.2 and 1.8 mg per day for adults.
Vitamin B6 (Pyridoxine)
The active form of vitamin B6 is pyridoxal 5'- phosphate (PLP), and this coenzyme is
involved in over 60 different enzymatic reactions in the body including such common reactions as
decarboxylation and aminotransferase reactions (12). Isolated deficiencies of vitamin B-6 are rare,
and it is most common to see deficiencies of multiple B vitamins. The best measure of vitamin B-6
status is plasma PLP which can be measured by HPLC. An intake of 2 mg per day is
recommended in the RDA, and doses greater than 1 mg must be given to change PLP levels. At
intakes of greater than 25 mg, PLP levels do not change further with the excess vitamin B-6
excreted in the urine as pyridoxal and pyridoxic acid. Very large doses (e.g. 500 mg/day) can
cause peripheral neuropathy by inducing a conditioned deficiency of other B-vitamins catabolized
in a manner similar to the excess vitamin B-6 ingested.
Niacin
Niacin refers to both nicotinic acid and nicotinamide which are converted to the
Nicotinamide Adenine Dinucleotide cofactors (NAD and NADH) esssential for a number of
enzymatic reactions. The deficiency disease, pellagra, was observed to occur in populations
consuming a maize-based diet deficient in the amino acid tryptophan, which is the precursor for
endogenous niacin formation. Large doses of nicotinic acid (1.5 to 3 gm/day) but not nicotinamide
will lower cholesterol and triglyceride levels and raise HDL levels in subgroups of
hypercholesterolemic individuals. However, long-acting forms of niacin in large doses have been
associated with liver damage, facial flushing and worsening of hyperglycemia in diabetics. The
recommended dietary allowance for niacin ranges between 13 and 20 mg per day for adults.
Folic Acid
Folate is a micronutrient which frequently is deficient in American diets since it is derived
from dark green, leafy vegetables. Folic acid acts in cell maturation and differentiates epithelial
tissues. In the lung and the cervical epithelium pro-differentiation effects have been demonstrated.
Folic acid has also been associated with the prevention of neural tube defects such as spina bifida.
It is included in all prenatal vitamins at an enhanced level. It is restricted by law to 400 mcg per
tablet in over the counter vitamins. Folate given to patients with pernicious anemia can lead to
subacute combined spinal degeneration.
Vitamin B12
Vitamin B12 is needed to make all red blood cells and is necessary for the synthesis of
nerve sheaths, fatty acids, and DNA. Since this vitamin is stored in the liver, nutritional deficiency
usually takes years to develop. It is much more common to see metabolic deficiencies. Most
commonly an anemia due to B12 deficiency results from an autoimmune disease which destroys
the cells in the stomach that make a binding protein (intrinsic factor) necessary for B12 absorption.
The individuals most at risk of a dietary vitamin B12 deficiency are vegetarians, since there is no
B12 in any plant product. There is also a decreased capability for absorption in the elderly. Vitamin
B12 levels need to measured in individuals at risk, since folate administered to an individual with
B12 deficiency will result in subacute combined degeneration of the spine and paralysis. The
Recommended Dietary Allowance for adults is only 2 to 2.6 micrograms per day.
Vitamin C
Vitamin C is an antioxidant and a vitamin necessary for the synthesis of collagen. In scurvy
there is a failure in collagen synthesis leading to the loss of teeth, and poor wound healing. Since
vitamin C is found in fruits, scurvy is rare today except in alcoholics who take in no natural sources
of vitamin C. It enhances the absorption of iron from the gastrointestinal tract, and has been
proposed as an effective means of increasing absorption of iron from supplements in areas of
endemic iron deficiency such as Egypt. The body stores of vitamin C approximate 1500 mg. and
3% per day is excreted leading to an calculated requirement of 45 mg for the prevention of scurvy.
The current Recommended Dietary Allowance for adults is between 50 and 95 mg/day. However,
there are many Americans who take 500 mg. or more of this vitamin. It has been estimated that
paleolithic man ate enough fruit to provide about 500 mg. per day, and that the ability to synthesize
vitamin C was not essential to ancient man. This amount of vitamin C can be obtained by eating
five servings/day of fruits and vegetables or through vitamin supplementation. Vitamin C exists
both as ascorbate and in a reduced form as dihydroascorbate. There are ongoing studies of
vitamin C as an antioxidant, and it has been implicated in the prevention of gastric cancer through
its inhibition of nitrosamine formation.
Minerals
Macro-Minerals
The macro-minerals are inorganic substances derived from soil and water and incorporated
into our diet in significant amounts. Those that are required in large amounts in the diet are called
macro-minerals and include calcium, magnesium, and phosphorus.
Calcium
Calcium is vital component of a healthy diet The blood levels of calcium are carefully
regulated by a number of hormones since elevated levels of calcium in the blood could lead to
kidney malfunction and decreased absorption of other minerals. On the other hand, loss of body
calcium can lead to decreased bone health and dental health as calcium together with
phosphate as the mineral hydroxyapatite is the mineral supporting the function of bones and
teeth. Therefore, calcium is essential for the normal growth and maintenance of bones and
teeth, and calcium requirements must be met throughout life. Vitamin D is also needed to
absorb calcium. Supplementation of calcium with vitamin D is recommended at a level of 1500
milligrams per day from food and supplements for postmenopausal women and at a level of
1000 milligrams per day for women before menopause and for men. Vitamin D supplementation
has been increasing in recent years as the functions of vitamin D beyond bone health have
been discovered.
Dairy products, especially in the U.S. and Europe are the primary dietary source of calcium
often in forms fortified with vitamins A and D. This fortification which became common in the
1950’s accounts for the decrease in bone diseases observed in the U.S. and Europe by
comparison to the early part of the twentieth century. There are many good sources of calcium
beyond dairy products. These include seaweeds such as kelp, wakame and hijiki; nuts and
seeds (like almonds and sesame); blackstrap molasses; beans; oranges; amaranth; collard
greens; okra; rutabaga; broccoli; dandelion leaves; kale; sardines; and fortified products such
as orange juice and soy milk. Individuals throughout the world are allergic to dairy products
and even more people, particularly those of non Indo-European descent, are lactose-intolerant,
leaving them unable to consume dairy products. Moreover, strict vegans avoid dairy products
for ethical and health reasons.
Magnesium
Magnesium ions are essential to the basic DNA chemistry of life, and thus are essential
to all cells of all known living organisms. Many enzymes require the presence of magnesium
ions for their catalytic action, especially enzymes utilizing ATP,
or those which use other
nucleotides to synthesize DNA and RNA.
Magnesium is a vital component of a healthy human diet and deficiency has been
implicated in a number of human diseases. Magnesium is readily available in many common
foods but studies indicate that many Americans are magnesium deficient. Supplemental
magnesium is readily available and it is also difficult to overdose on magnesium. General failure
of the kidneys may also lead to magnesium imbalance.
Magnesium deficiency in humans was first described in the medical literature in 1934.
The adult human daily nutritional requirement, which is affected by various factors including
gender, weight and size, is 300-400 mg/day. Inadequate magnesium intake frequently causes
muscle spasms, and has been associated with cardiovascular disease, diabetes, high blood
pressure,
anxiety
disorders,
migraines
and
osteoporosis.
Acute
deficiency
(called
hypomagnesemia) is rare, and is more common as a drug side effect (such as chronic alcohol
or diuretic use) than from low food intake per se, but it can also occur within people are fed
intravenously for extended periods of time. The incidence of chronic deficiency resulting in less
than optimal health is debated.
The DRI upper tolerated limit for supplemental magnesium is 350 mg/day calculated as
mg of Mg elemental in the salt. The best dietary source is Brazil nuts which have 150 mg in one
ounce followed by pumpkin seeds, fortified bran cereals, halibut, spinach, almonds, soy nuts,
and other seeds and nuts. Magnesium is widely distributed in plant foods so that vegetarian-like
diets are rarely deficient in Magnesium. Dietary deficiencies are only seen in extreme situations
as with homeless people on restricted diets or alcoholics.
Supplements based on Amino Acid Chelates, Glycinate, Lysinate etc. are much better
tolerated by the digestive system and do not have the side effects of the older compounds used.
The most common symptom of excess oral magnesium intake is diarrhea. Since the kidneys of
adult humans excrete excess magnesium efficiently, oral magnesium poisoning in adults with
normal renal function is very rare. Infants, which have less ability to excrete excess magnesium
even when healthy, should not be given magnesium supplements, except under a physician's
care.
Phosphorus
Phosphorus is an essential mineral that is found inside cells where it plays a key role in
maintaining the energy needed by cells. It is linked to adenosine by a high energy bond so that
as the number of phosphates linked to adenosine is reduced from three to two (i.e. ATP going to
ADP or adenosine triphosphate to adenosine diphosphate) chemical energy is released in the
cell that can be used to drive the production of proteins, carbohydrates, and lipids to be used in
the structure of the cell or as intermediates in various chemical reactions essential to cell
function. Similarly, when ADP goes to ATP, energy has been stored for future use. In the cell
the ratio of ATP to ADP is a marker of the energy status of the cell and these compounds
recycle back and forth at a very high rate.
Phosphorus is also utilized when glucose or fructose sugars enter cells. The first step in
their chemical processing for energy is the addition of a phosphate to either glucose or fructose
which then leads to other modifications. In all, there are over 5000 different proteins in the cell
involved in phosphate chemistry.
Despite the important intracellular roles of phosphates, on a weight basis, 85% of the
body's phosphorus is found in bone as calcium phosphate or hydroxyapatite. Phospholipids
(e.g., phosphatidylcholine) are major structural components of cell membranes. All energy
production and storage are dependent on phosphorylated compounds, such as adenosine
triphosphate (ATP) and creatine phosphate. Nucleic acids (DNA and RNA), which are
responsible for the storage and transmission of genetic information, are long chains of
phosphate-containing molecules.
Phosphorus is absorbed in the small intestine, and excess phosphorus is excreted by
the kidneys. The blood levels of phosphorus are regulated together with blood calcium by
parathyroid hormone (PTH) and vitamin D. PTH causes decreased urinary excretion of calcium
and increased urinary excretion of phosphorus. In turn high levels of phosphate in the blood
suppress conversion of vitamin D to its active form in the kidneys serving as a control on
calcium absorption. Increased intakes of phosphates in the diet result from the phosphoric acid
in soft drinks and phosphate additives in a number of commercially prepared foods such as
instant puddings. As long as calcium intake is adequate, increased phosphate intake does
decrease bone density. However, reducing the intake of milk and other calcium rich foods often
coincides with an increased in soft drink consumption and this decrease in calcium intake
without supplementation can lead to decreases in bone density and bone health.
All cells in plant and animal food sources containg phosphorus, so that dietary
phosphorus deficiency is only seen in cases of near-total starvation as can occur in patients with
eating disorders such as anorexia nervosa. Refeeding patients in prison camps has led to
phosphorus deficiency as glucose going into cells rapidly depletes body phosphorus in already
deficient individuals further. There are specific methods for providing minerals and vitamins
together with gradual refeeding in starved patients to avoid this condition.
Trace Minerals
There are also a number of trace minerals which serve critical roles in body metabolism but
are required in much smaller amounts. These trace minerals and their roles include:
Iron: Iron is needed for red cell formation and is also a pro-oxidant used in catalase and
other peroxidase-type enzymes. The use of oral iron cannot lead to overload but parenteral iron
can be toxic. Iron is commonly deficient in menstruating females, and should be replaced when
anemia is identified, or as a preventive in individuals with low range hematocrits. The
Recommended Dietary Allowance for iron is between 10 and 15 mg per day.
Selenium: This is a structural component of enzymes including glutathione peroxidase and
type I iodothyronine monodeiodinase. The Recommended Dietary Allowance is between 40 and 70
micrograms per day in adults.
Zinc: Zinc is an essential component of many different enzymes and is necessary for a
variety of metabolic processes. Zinc deficiency was first observed in adolescent boys in Egypt who
were eating unleavened whole grain bread containing phytate which bound to zinc in the intestinal
tract preventing its absorption. The boys demonstrated growth retardation and delayed puberty.
Zinc supplements have been marketed as a cure for impotence without any substantiation of that
claim. The daily requirements are comparable to those for iron and range between 12 and 15 mg
per day in adults. The major sites of potential losses are in semen and from the gastrointestinal
tract with severe diarrhea or fistula. Zinc should not be administered in the absence of any copper
and should not be consumed as a separate supplement except in individuals with a demonstrated
zinc deficiency.
Copper: The elevation of serum copper seen in Wilson's Disease is due to a deficiency of
ceruloplasmin, the copper-binding protein. This leads to a syndrome of hepatolenticular
degeneration. As mentioned above a copper deficiency can be induced with megadoses of zinc.
There is no Recommended Dietary Allowance for copper but an Estimated Safe and Adequate
Dietary Daily Intake of 3 mg per day in adults was issued by the National Research Council of the
National Academy of Sciences in 1980.
Iodine: The only major role of iodine is to serve as an essential part of the basic structure of
thyroid hormones. Iodine deficiency in areas away from sea water (e.g. highlands around Mexico
City, inland areas of Southeast Asia) can lead to goiter formation. Since the late 1950's iodine has
been used as a bleaching agent for white flour and iodine deficiency in this country is rare. It is not
unusual for individuals immigrating to the U.S. to develop thyroid disease due to the increase in
dietary iodine compared to their country of origin. Iodine supplementation in areas that are normally
iodine deficient has led to an increase in various types of thyroid diseases including Grave's
Disease, Hashimoto's Thyroiditis, and thyroid nodules. It is possible for susceptible individuals to
develop thyroid nodules after taking kelp tablets which are rich in iodine.
Chromium : Chromium is also called glucose tolerance factor, but its effectiveness in
enhancing glucose tolerance is unproven. A recent study demonstrated enhanced lifespan in
small number of rats given chromium picolinate. The increased interest in this trace mineral based
on this small study is probably not justified. A natural source of chromium is brewer's yeast. There
is no evidence that it enhances muscle building or fat loss in humans. There is no Recommended
Dietary Allowance for humans.
Many other trace minerals including arsenic, cobalt, manganese, molybdenum, nickel,
silicon, tin, and vanadium have a variety of metabolic functions. Some of these are not yet well
understood. The combination of taking a multimineral/multivitamin containing these trace minerals
and eating fruits and vegetables will likely provide adequate amounts of these trace elements.
Taking individual supplements of arsenic is not recommended since this is a poison at higher
doses and required as an essential trace element in very low amounts.
Nutritional Adequacy
Despite the epidemic of overnutrition in the United States today, there are still some groups
at risk for nutritional deficiencies. These groups include: 1) pregnant women 2) the elderly, 3)
individuals who smoke, drink excess amounts of alcohol, or abuse drugs. The laboratory
assessment of possible deficiencies in these groups is summarized in Table 2.
Nutritional Optimization - Future Directions
While classical vitamin deficiency diseases are rare today in the U.S. except in certain high
risk groups (e.g. alcoholics, pregnant teenagers, institutionalized elderly), there are a variety of
individuals whose dietary intake is inadequate to maintain optimal health. For instance, it is
recommended that Americans eat 25 grams of fiber per day, but the average intake is only about
10 grams. In California, only about one in five people consumes five servings a day of fruits and
vegetables as recommended by the US Department of Agriculture. As a result there are a number
of micronutrient vitamins and minerals which are deficient but not at levels that would cause
disease. Examples include: carotenoids, vitamin E, vitamin C, folate, and selenium. While it is
established what nutrient levels constitute deficiency, there is little information on what is
suboptimal or what types of responses can be expected following nutritional intervention. It is also
unclear why there are individual variations in the absorption of a beta-carotene oral load, the
effects of dietary fiber eaten at the same time, or the effects of various fats in the diet on
absorption.
TABLE ONE
Recommended Dietary Allowances, Revised 1989
National Academy of Sciences Food and Nutrition Board
for Fat-Soluble Vitamins
Group
Vit A
Vit D
Vit E
Vit K
(mcg RE)
(mcg)
(mg)
(mcg)
Infants 0-6m
375
7.5
3
5
6mo-1yr
375
10
4
10
Children 1-3
400
10
6
15
4-6
500
10
7
20
7-10
700
10
7
30
Males 11-14
1000
10
10
45
15-18
1000
10
10
65
19-24
1000
10
10
70
25-50
1000
5
10
80
51 +
1000
5
10
80
11-14
800
10
8
45
15-18
800
10
8
55
19-24
800
10
8
60
25-50
800
5
8
65
51 +
800
5
8
65
800
10
10
65
1st 6mo
1,300
10
12
65
2nd 6mo
1,200
10
11
65
Females
Pregnant
Lactating
TABLE ONE (CONT'D.)
Recommended Dietary Allowances, Revised 1989
for Water Soluble Vitamins
Group
Vit C
(mg)
Thiamine
(mg)
Riboflavin
(mg)
Niacin
(mg)
B6
(mg)
Folate
(mcg)
B12
(mcg)
Infants
0-6m
6mo-1yr
30
35
0.3
0.4
0.4
0.5
5
6
0.3
0.6
25
35
0.3
0.5
Children
1-3
4-6
7-10
40
45
45
0.7
0.9
1.0
0.8
1.1
1.2
9
12
13
1.0
1.1
1.4
50
75
100
0.7
1.0
1.4
Males
11-14
15-18
19-24
25-50
51 +
50
60
60
60
60
1.3
1.5
1.5
1.5
1.2
1.5
1.8
1.7
1.7
1.4
17
20
19
19
15
1.7
2.0
2.0
2.0
2.0
150
200
200
200
200
2.0
2.0
2.0
2.0
2.0
Females
11-14
15-18
19-24
25-50
51 +
50
60
60
60
60
1.1
1.1
1.1
1.1
1.0
1.3
1.3
1.3
1.3
1.2
15
15
15
15
13
1.4
1.5
1.6
1.6
1.6
150
180
180
180
180
2.0
2.0
2.0
2.0
2.0
70
1.5
1.6
17
2.2
400
2.2
95
90
1.6
1.6
1.8
1.7
20
20
2.1
2.1
280
260
2.6
2.6
Pregnant
Lactating
1st 6mo
2nd 6mo
17
TABLE ONE (CONT'D.)
Recommended Dietary Allowances, Revised 1989
for Minerals
Group
Calcium
(mg)
Phosph
(mg)
Magnesium
(mg)
Iron
(mg)
Zinc
(mg)
Iodine Selenium
(mcg) (mcg)
Infants
0-6m
6mo-1yr
400
600
300
500
40
60
6
10
5
5
40
50
10
15
Children
1-3
4-6
7-10
800
800
800
800
800
800
80
120
170
10
10
10
10
10
10
70
90
120
20
20
30
Males
11-14
15-18
19-24
25-50
51 +
1200
1200
1200
800
800
1200
1200
1200
800
800
270
400
350
350
350
12
12
10
10
10
15
15
15
15
15
150
150
150
150
150
40
50
70
70
70
Females
11-14
15-18
19-24
25-50
51 +
1200
1200
1200
800
800
1200
1200
1200
800
800
280
300
280
280
280
15
15
15
15
15
12
12
12
12
12
150
150
150
150
150
45
50
55
55
55
1200
1200
320
30
15
175
65
1200
1200
1200
1200
355
340
15
15
19
16
200
200
75
75
Pregnant
Lactating
1st 6 mo
2nd 6mo
18
TABLE TWO
LABORATORY ASSESSMENT OF VITAMIN-MINERAL NUTRITURE
Nutrient
Population at Risk
Pregnant Women
Elderly
Smokers/Alcohol Abusers
Vitamins
folate
thiamin
vitamin B6
vitamin B12
vitamin A
vitamin C
vitamin E
Carotenoids Panel
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Minerals
iron
calcium
zinc
Other
transferrin
albumin
prealbumin
19
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