Download Phar 722 Pharmacy Practice III

Phar 722
Pharmacy Practice III
VitaminsIntroduction
(Nutrition Science
Versus
Nutrition Policy)
Spring 2006
STUDY GUIDE FOR THE UNIT ON
VITAMINS-INTRODUCTION
1.
Understand the different philosophies between nutrition science and
nutrition policies.
2.
Be able to explain how nutrient deficiencies can develop and how nutritional
requirements are determined.
3.
Know the following items associated with the DRIs.
A. For each type of DRI know
(1) their definition.
(2) how they are determined generally.
(3) which ones can be used for diet planning.
B.
The adult male and female range and units used for the RDA (the AI
when a vitamin does not have a RDA) for each vitamin.
4.
Know the definition or characteristics of a vitamin.
5.
Know the source of the Daily Values versus the Dietary Reference Intakes.
6.
Know the items mentioned under each of the vitamins. (There will be a set of
learning objectives with each vitamin.)
Should we recommend vitamins?
Nutrition Science versus Nutrition Policy-1
• Nutrition Science
– The emphasis is on science which uses the scientific
method to reach conclusions. This requires a hypothesis,
proper experimental design, and conclusions based on the
experimental results. Among other things, nutrition science
will
• 1. determine the dose to prevent a nutritional deficiency.
• 2. determine the dose to cause a toxic response.
• Unfortunately, the experiments required to obtain the
necessary information for proper dosing of nutrients
can be a long, expensive process. Thus there is a lot
of extrapolation. In the case of the Dietary
Reference Intakes (DRI), the doses are based on
retrospective studies, animal models and surveys.
More will be stated on this later.
Nutrition Science versus Nutrition Policy-2
B. Nutrition Policy
– This is the approach used to determine the dose
required to maintain well being.
– It has become a very political process, particularly
with ascorbic acid (Vitamin C) and α-tocopherol
(Vitamin E).
• These two vitamins are hypothesized to provide some
protection against certain malignancies and
artereosclerosis.
• Thus, some believe that the RDAs should be greater than
that required to prevent a nutritional deficiency.
– This controversy so split that panel that was charged with
developing the 1985 RDAs that it had to be disbanded.
– In other words, nutrition policy can become very
political.
Causes of Nutrient Deficiencies-1
• Inadequate ingestion usually from a poor diet.
– economic deprivation;
– self-imposed reducing diets;
• A 1,200 Calorie diet professionally selected from the four
major food groups (dairy, fruits and vegetables, grains,
and meat) containing no fried food nor added sugar has
been considered the least amount of food not requiring a
vitamin supplement.
– chronic disease.
• This usually is due to loss of appetite from such
conditions as cancer chemotherapy, depression and
eating disorders.
Causes of Nutrient Deficiencies-2
• Inadequate absorption
– Diseased intestinal tract such as chronic inflammatory
conditions (Crohn’s Disease) and parasites.
– Lipase inhibitors (Xenicol®, Alli®; orlistat)
• The undigested triglycerides in the small intestine can
disolve the oil-soluble vitamins (retinol (A),
cholecalciferol/ergocalciferol (D), α-tocopherol (E),
phytonadione( K) from food where they will be excreted
with the feces.
– Ion exchange resins (colestipol, colestyramine, wellchol)
• These cholesterol lowering drugs complex with the bile
salts and can interfere with the absorption of the oil
soluble vitamins. A vitamin supplement can be taken
one hour before or two hours after taking the resin.
Causes of Nutrient Deficiencies-3
• Inadequate absorption-continued
– Cystic fibrosis
• This genetic disease can cause fat
malabsorption (steatorrhea) due to inadequate
production or secretion of pancreatic lipases.
This can lead to malabsorption of the fat
soluble vitamins: retinol (A), cholecalciferol
(D3), α-tocopherol (E), and phytonadione (K1).
– Gastric Bypass
• Decreased absorption of cyanocobalamin (B12)
possibly requiring nasal or parenteral dosage
forms.
Causes of Nutrient Deficiencies-4
• Inadequate utilization
– genetic disease
• Examples include variants of maple syrup urine disease
which will respond to thiamine (B1) supplements and
homocystinuria which will respond to pyridoxine (B6).
– drug antagonists and interactions
• Isoniazid and pyridoxine (B6) (covalent chemical
combination)
• Phenobarbital and cholecalciferol (D3) (possibly induce
metabolism)
• Methotrexate and folic acid (inhibit conversion to the
coenzyme form)
• Phenytoin and folic acid (inhibit folate uptake)
• Warfarin (coumadin) and phytonadione (K) (inhibit reconversion to coenzyme form)
Causes of Nutrient Deficiencies-5
• Increased requirements
– Strenuous exercise
– Disease
• Examples include recovery from a debilitating
illness, severe burn injuries, cancer, etc.
Nutritional assessments are becoming a more
common part of medical treatment.
• Chronic alcoholism
– Interferes with the uptake of some vitamins —
folic acid, thiamine (B1) — or, due to liver disease,
proper processing and/or storage of vitamins.
Determination of Nutritional Requirements
• Vitamin Dose Response Curve
Outcome
Optimum Dosing
Marginal toxicities
Marginal deficiency
symptoms
Deficiency
Toxicity
Death
Death
Dose
Dietary Reference Intakes
try to address marginal
deficiencies.
Toxicities and possibly
death require high doses
over long time periods.
Methods for Obtaining a Dose Response Curve-1
• Extrapolate from animal studies.
– This will be dependent on the species. The
vitamin requirements differ among the common
laboratory animals.
• Ascorbic acid (C) is not a vitamin in most animals.
• α-Tocopherol (E), biotin, and pantothenic acid cause
definitive deficiency syndromes not seen in humans.
• Metabolic balance studies in humans.
– This usually involves a seven day period on a
defined diet in which the urine and feces are
monitored.
• The problem is that corrections have to be made for the
vitamins are stored.
• The pharmacokinetics of most vitamins have not been
carefully determined.
Methods for Obtaining a Dose Response Curve-2
•
Compare nutrient intake in areas with and without the deficiency
disease.
– First, not all vitamin deficiencies lead to a defined deficiency state.
– Second, rarely does one find an area deficient in only one nutrient.
• Most common deficiencies are due to inadequate diet which means
several nutrient deficiencies will result.
• Poor sanitation is usually coordinated with a poor economy. This
leads to intestinal disease and its malabsorption of nutrients.
•
Saturation of biochemical function.
– A reliable biochemical indicator is required.
• Niacin: Which NAD+ or NADP+ containing enzyme should be
selected?
• Pyridoxine (B6): Which transaminase will be the indicator?
• Retinol (A): Is vision in the rods or cell differentiation a reliable
measure?
•
Serum levels
– This probably is the most reliable, but it does require very
sensitive assay methods for those vitamins required in μg (10-6)
amounts.
Dietary Reference Intakes (DRI)
compared with
Recommended Dietary Allowances (RDA)
• The last official set of reference values were
the 1989 Recommended Dietary Allowances
(RDAs) for the United States and 1990
Recommended Nutrient Intakes for Canada.
• The DRIs are published by the Food and
Nutrition Board of the National Academy of
Sciences National Research Council.
Dietary Reference Intakes (DRI)
• How do the DRIs differ from RDAs?
• There is one set of reference values for both Canada and the
United States.
– There will be clear documentation on how reference values are
selected.
– A goal will the "the promotion of nutrient function and biologicphysical well-being” based on peer reviewed science.
– Evidence concerning the prevention of disease and developmental
disorders will be examined in addition to the traditional of how
much nutrient is needed to prevent a deficiency symptom.
– Data supporting food components that, up to this time, have not
been considered essential nutrient will be examined.
• Anti-oxidants
• Omega-3 fatty acids
– There will be recommendations for future research.
Uses of Dietary Reference Intakes-1
• Uses of Dietary Reference Intakes
– The DRIs consist of four components.
•
•
•
•
Estimated Average Requirement (EAR)
Recommended Dietary Allowance (RDA)
Adequate Intake (AI)
Tolerable Upper Intake Level (UL)
– Each type of reference value is calculated
from daily intakes averaged over time
(usually one or more weeks).
– Nutrition labeling
• Uses the FDA’s Daily Values (DV) on vitamin
and nutrition lables.
Uses of Dietary Reference Intakes-2
• Estimated Average Requirement (EAR)
– The intake that meets the estimated
nutrient need of 50 percent of the
individuals in that group (i.e. infants,
children, adult males, adult females,
pregnant women, nursing women, the
elderly, etc.)
• It is used to evaluate the adequacy of nutrient
intakes of population groups and for planning
intakes for group.
• It can be used in diet planning.
• The EAR is based on a median rather than a
mean.
Uses of Dietary Reference Intakes-3
Uses of Dietary Reference Intakes-4
• Recommended Dietary Allowance (RDA)
– The intake that meets the nutrient need of almost all (97 to
98 percent) individuals in that group.
– They can function as a guide to achieve adequate nutrient
intake.
– By themselves, they are not generally recommended for diet
planning for specific groups of individuals.
– Diet planning must take into account extensive physical
activity, type of body build including lean versus adipose
tissue, general life style, etc.
– If the sampling and end points are well defined, the RDA can
be calculated from the EAR.
– RDA = EAR + 2 SDEAR
– Where
• SDEAR = standard deviation above the EAR
Uses of Dietary Reference Intakes-5
Uses of Dietary Reference Intakes-6
• Adequate Intake (AI)
– Average observed or experimentally
derived intake by a defined population or
subgroup that appears to sustain a defined
nutritional state, such as normal
circulating nutrient values, growth, or
other functional indicators of health.
– It is derived from mean intakes of groups
(rather than individuals).
– The AI is used when a reliable EAR is not
available.
• (vitamins D, K, Biotin, Pantothenic Acid and
infants)
Uses of Dietary Reference Intakes-7
• Tolerable Upper Intake Level (UL)
– The maximum intake by an individual that is
unlikely to pose risks of adverse health effects in
almost all (97 to 98 percent) individuals. It
includes intake of a nutrient from all sources
(food, fortified food, water and supplements).
Water can include fluoride and minerals
depending on the source of water.
– "Tolerable" is used to "avoid implying any
possible beneficial effect." The amount can be
"tolerated.“
• (A, D, E, Niacin, Pyridoxine, Folic Acid)
Uses of Dietary Reference Intakes-8
Outcome
Optimum Dosing
Marginal toxicities
Marginal deficiency
symptoms
Deficiency
Toxicity
Death
Death
Dose
UL
Uses of Dietary Reference Intakes-9
What is a Vitamin?
•
Naturally occurring.
–
•
This does not mean that a synthetic copy will not be as effective.
Essential.
–
What about niacin?
•
•
•
Organic
–
A trace element cannot be a vitamin.
•
•
Cholecalciferol (D3) is found on fish, not a common component of many diets, particularly
those who live inland.
Required in minute amounts.
–
•
Fe, Ca, Mg, Zn, etc are not vitamins.
“Normal” constituent of the diet.
–
•
Produced from tryptophan in most mammals including humans
People living in sunny areas may not need vitamin D supplements.
This is arbitrary but ranges from 2.0 μg (10-6 gm) for cyanocobalamin to 90 mg for ascorbic
acid. Other essential nutrient like amino acids generally are required in larger amounts.
Even ascorbic acid's RDA is about 30 times greater than any other vitamin.
Aids in maintaining the normal activities of the tissues.
–
Most vitamins function either as a hormone/chemical messenger, structural component in
some metabolic process, or a coenzyme.
• Why aren’t these other essential
nutrients classified as vitamins.
• Tradition?
– Discoveries of what we call vitamins was
based on discovering deficiency diseases
mostly in animals caused by defined diets.
– There is more effort on dosing for
vitamins.
– Amino acids and omega-3 acids are
required in large amounts.
• Omega-3 RDAs: 650 mg to 2.22 gm depending
on the omega-3 acid.
Very Brief History-1
• There originally were two vitamins.
– Fat soluble A reported in 1913.
– Water soluble B reported in 1915 by McCollum and Davis
who reported a water-soluble B factor that restored growth
in rats.
• The vitamin B complex, of which thiamine is considered
the first one, generally includes the group of water
soluble vitamins found in rice polishings, bean extracts,
yeast, and liver.
– There are no chemical relationships in the B complex. The
nomenclature is very confusing. The common name
originally implied something about the chemical nature of
the vitamin.
– Even the concept of water soluble is somewhat misleading
as some of the vitamins in this group would be considered
poorly soluble by most pharmaceutical standards.
– The one thing the B complex have in common is that nearly
all function either as a cofactor or a structural component of
a cofactor.
Very Brief History-2
• D was discovered during the search for a cure for
rickets.
• Vitamins E and K were discovered later and by
accident.
– The fat-soluble vitamins have a variety of roles including:
• hormonal (A and D)
• an integral part of a biochemical process (A, D, K)
• general antioxidant (E)
• The term vitamin was coined by Funk who isolated
thiamine from rice polishing and called it vitamine
because chemical analysis indicated an amine was
essential for life. Of course there is no consistent
chemical structure among the many vitamins and
not all are humans.
Few Manufacturers of Raw Materials
• Until late 2002, Roche (Switzerland) has controlled
70% of the free world's bulk vitamin production.
Roche sold its vitamin business to DSM for $2.24
billion. The exception has been cyanocobalamin, the
calciferols, and niacin. DSM is followed by Takeda
(Japan), BASF and Lonza. Rhône-Poulenc is leading
producer of cyanocobalmin.
• A few years ago, European prosecutors convicted
mid-level executives for conspiring to fix prices.
• There are 100s of formulators who take the bulk
vitamins and develop the products. Many
formulators manufacture vitamins under several
labels.
Limits to Vitamin Labeling
• Unfortunately, vitamins fall under the Food portion of the Food
and Drug Cosmetic Act. Therefore, as long as no false medical
claims are made and the product actually contains what is stated
on the label, there is little to stop anyone from getting into the
highly profitable vitamin business.
• Much vitamin labeling is ambiguous.
– Vitamin C with rose hips only implies that there is some rose
hips in the product. There is no requirement that the rose hips
is the source of the vitamin in the tablet.
•
All Natural does not mean that 100% of the vitamin is from natural
sources. There is no legal definition of natural.
– Vitamin C is manufactured from glucose. Therefore it is
natural.
– Natural vitamin E may actually contain both the synthetic and
the vitamin from wheat germ.
• Read vitamin labels carefully, particularly those in the health food
stores or sections of pharmacies.
Daily Values (DV) – Nutrition Labels
Nutrient
DV
RDA/AI
Nutrient
DV
Vit A
1500 μg
700-900 μg
Thiamine
1.5 mg
0.9-1.2 mg
Vit C
60 mg
25-90 mg
Riboflavin
1.7 mg
0.9-1.3 mg
Calcium
1000 mg 800-1200 mg Niacin
20 mg
12-16 mg
Iron
18 mg
10-18 mg
Vit B6
2.0 mg
1-1.7 mg
Vit D
400 IU
200-600 IU
Folate
400 μg
200-400 μg
Vit E
30 mg
7-15 mg
Vit B12
6.0 μg
1.8-2.4 μg
Vit K
80 μg
55-120 μg
Biotin
300 μg
20-30 μg
Pantothenic 10 mg
Acid
RDA/AI
20 mg