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Synthetic vs. Natural Vitamin Forms
INTRODUCTION
Our Commitment to Excellence
Pharmanex has always maintained a single goal when developing new products and
improving existing products: to provide the highest quality products that are proven by
science to be safe and effective. Pharmanex has always used a pharmaceutical approach
to research and development activities. All of Pharmanex’s products are supported by
credible, scientific research and, when necessary, are re-substantiated through in-house
trials and clinical studies. These criteria, which form the foundation of our 6S process,
are what guide our decisions as to which raw materials and ingredients to use, as well as
what products to research and develop.
We have employed these same criteria when determining which sources of vitamins and
minerals provide the best benefits and highest quality to customers. Whenever scientific
findings show that one vitamin form is preferable over another, we will always formulate
our products to conform to those findings in order to provide the highest quality and most
effective products possible. When formulating LifePak, Pharmanex reviewed the
available literature and research regarding vitamin, forms, bioavailability, and efficacy.
The remainder of this document provides a summary of those findings along with the
corresponding references.
Use of Multi-vitamin and Mineral Supplements
Large nutrition surveys consistently show that inadequate intakes of essential vitamins
and minerals are common in the U.S. and other industrialized countries (Benton et al
1997, Block et al 1993, Pennington et al 1982, Pennington et al 1996). The Continuing
Survey of Food Intakes by Individuals (CSFII), conducted in 1994-96 by the US
Department of Agriculture (USDA), showed that most people do not meet the
Recommended Dietary Allowances (RDAs) for essential vitamins and minerals (USDA
1996).
It is a well-established fact that multi-vitamin and mineral supplements (MVMS) are
beneficial in those suffering from nutrient deficiencies. A recent study in healthy adults,
however, showed that use of MVMSs is safe and beneficial to healthy individuals as well
(Kiely et al 2001). A recent article published in the Journal of American Medical
Association (JAMA) states that healthy individuals can derive benefit from regular use of
multi-vitamin and mineral supplements and even encourages everyone to use some sort
of MVMS daily (Fletcher and Fairfield 2002). Yet another study concluded that,
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“Supplementation with a multivitamin supplement can improve micronutrient status in
healthy, older Americans to levels above those obtained with a fortified diet” (McKay et
al 2000, italics added).
Natural, Synthetic, and Nature-identical
“Natural” has come to be associated with substances in their native, unaltered state
derived directly from a wide variety of plants, animals, or other organisms. “Synthetic”
substances are produced from basic chemical building blocks by means of chemical
synthesis processes. “Nature-identical” refers to synthetic substances that have the same
chemical structure as its natural counterpart.
There is a proliferating belief that natural substances are inherently superior in function,
efficacy, and safety to synthetic substances. Except for certain specific instances,
however, this belief is not substantiated by scientific research. In addition to the
exorbitant costs associated with natural substances, they are typically less stable and less
conducive to a single-dosage delivery form.
Vitamins with the same structure are recognized and utilized in the same way by the
human body, regardless of their origin. This was reiterated in a recent study performed
by the International Union of Pure and Applied Chemistry (IUPAC). The study states
that the actions of individual substances are determined by their individual chemical
structures and dose, not whether they are of natural or synthetic origin (Topliss et al
2002).
Supplement Bioavailability
A common concern with MVMS use is bioavailability of vitamins and minerals in
supplement form compared to those from foods. A study performed on healthy
individuals showed that increases in serum nutrient levels after taking a supplement are
higher than after eating a comparable meal (Navarro 2003). This indicates that the
bioavailability of nutrients in supplement form is at least equal to, and may even be
greater than, that of nutrients in actual foods. It is also important to point out that the
forms of vitamins and minerals used by the food industry to enrich and fortify foods in
the United States are the same synthetic forms used in many dietary supplements.
WATER-SOLUBLE VITAMINS
Vitamin C:
Studies have shown that there is no difference in bioavailability between synthetic and
natural forms of L-ascorbic acid, or vitamin C (Gregory 1993, Chalmers 1993). Studies
have shown that vitamin C from supplement forms are more readily absorbed and
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produce a greater increase in serum ascorbate levels than that from a variety of fruits and
vegetables (Gregory 1993, Mangels et al 1993). Available literature provides no
evidence that one form of vitamin C is better than another. It has been shown, however,
that certain vitamin C forms which are less acidic help alleviate gastrointestinal distress
that may arise from supplementation. Mineral salts of ascorbic acid are buffered and
therefore less acidic than ascorbic acid. Consequently, some people find them less
irritating to the gastrointestinal tract than ascorbic acid. Sodium and calcium ascorbates
are the most common forms. Both are readily absorbed and bioavailable to the body.
Bioflavonoids are a class of water-soluble plant pigments that are often found in vitamin
C-rich fruits and vegetables, especially citrus fruits. Despite overwhelming evidence of
the antioxidant functions and properties of bioflavonoids, there is little evidence that the
bioflavonoids in most commercial preparations of vitamin C increase the bioavailability
or efficacy of vitamin C (Johnston and Luo 1994).
Ester-C®, a common vitamin C supplement, contains mainly calcium ascorbate. It also
contains small amounts of the vitamin C metabolites dehydroascorbate and calcium
threonate, as well as trace levels of xylonate and lyxonate. Despite the belief that these
metabolites supposedly increase the bioavailability of vitamin C, the only published study
in humans found no difference between Ester-C® and commercially available ascorbic
acid tablets with respect to the absorption and urinary excretion of vitamin C (Johnston
and Luo 1994). Ascorbyl palmitate, a fat-soluble esterified form of ascorbate, is sold and
labelled as a “vitamin C ester”, but has not been shown to have any increase in
bioavailability. It is most likely hydrolyzed to ascorbic acid and palmitic acid in the GI
tract prior to absorption (Austria et al 1997, DeRitter 1951).
LifePak utilizes calcium ascorbate as it is as bioavailable and efficient as other forms of
vitamin C. Additionally, since it is a buffered form, the reduced acidity allows
individuals to ingest it without gastrointestinal irritation that is occasionally experienced.
Vitamin B6:
Natural vitamin B6 in many plant foods is in the form of pyridoxine glucoside. The
bioavailability of pyridoxine glucoside is only about half that of other forms of vitamin
B6. Vitamin B6 in supplements is in the form of pyridoxine hydrochloride (Hendler and
Rorvik 2001). Studies have shown that there is no difference in bioavailability of
synthetic and natural vitamin B6 (Nelson et al 1976, Institute of Medicine 1998). LifePak
uses a nature-identical pyridoxine hydrochloride as its B6 source.
Vitamin B12:
In 1988 the Food and Nutrition Board (FNB) of the Institute of Medicine revised the
Recommended Daily Allowance (RDA) for vitamin B12. Because of the increased risk of
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food-bound vitamin B12 malabsorption in older adults, the FNB recommended that adults
over 50 years of age get most of the RDA from fortified food or vitamin B12-containing
supplements (Institute of Medicine 1998)
Methylcobalamin and 5-deoxyadenosyl cobalamin are the forms of vitamin B12 used in
the human body. The form of cobalamin used in most supplements, cyanocobalamin, is
readily converted to 5-deoxyadenosyl and methylcobalamin (Brody 1999). Because the
chemical structure of B12 is so complex, chemically synthesizing it is not feasible. As
such, a bacterial fermentation process has been found to be efficient in producing
bioavailable and safe B12 in large enough quantities to meet world demand. Studies
revealed that bacterially fermented vitamin B12 supplements are just as bioavailable as
both naturally sourced B12 supplements, as well as B12 ingested from a typical mixed diet
(Navarro 2003, Institute of Medicine 1998). LifePak uses a natural B12 (cyanocobalamin)
which is derived through this bacterial fermentation process. Additionally, we use a
unique, stabilized form that provides even greater bioavailability.
Folate:
Efforts to ensure optimal folate intake are a relatively recent development. In 1992 the
US Public Health Service (PHS) first recommended that pregnant women increase folate
intake by 400 mcg. In 1996, in accordance with the PHS and FDA Food Advisory
Committee’s suggestions, the FDA required that specific flours, breads, and other grains
be fortified with folic acid (Suitor et al 2000, Insitute of Medicine 1998). This was due,
in part, to the discovery that folate from foods is significantly less bioavailable than that
in supplement form.
It is a well-established fact that the bioavailability of folate in a typical mixed diet is
incomplete. A long-term controlled study in humans showed that bioavailability of folate
in a typical mixed diet is no more than 50% of that in a formula diet (Sauberlich et al
1987). Another study in free-living subjects confirmed these results. It found that folic
acid from supplements or folate-fortified foods was significantly more bioavailable than
that in a diet of high-folate foods (Cuskelly et al 1996).
The role of folic acid supplementation in preventing neural-tube defects is well
established. Recently, however, it was shown that folate from food sources readily
absorbed by younger individuals is not absorbed by the elderly. It has been found that
supplementation with folic acid is important in preventing deficiencies in elderly
individuals (Baker et al 1978). Additionally, it was found in another study that synthetic
and natural forms of folic acid have the same bioavailability and are absorbed equally
well by healthy individuals (Nelson et al 1975).
Pharmanex uses synthetic folic acid derived from amino acid building blocks. This form
of folic acid is stable, bioavailable, and chemically identical to natural folic acid.
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Thiamin (B1):
Thiamin mononitrate is the form used by the food industry to enrich and fortify foods.
Human supplementation studies have used thiamin mononitrate as a thiamin source and
have found it to be readily absorbed and utilized by the human body (Levy et al 1994,
van der Beek et al 1994, Moss et al 1994, Baker et al 1975, Suzuki and Itokawa 1996).
In one animal study, thiamin mononitrate was found to have the same bioavailability as
other water-soluble forms of thiamin (Geyer et al 2000). In Mexico, a government study
to determine the best vitamin forms for fortifying grains based on bioavailability,
stability, and cost showed that thiamin mononitrate was preferable over other vitamin B1
forms (Rosado et al 1999). Another study showed that the relative biological values of
thiamin in white and whole wheat breads compared to thiamin mononitrate in supplement
form were 88% and 91% respectively. This indicates superior bioavailability of thiamin
mononitrate in supplement form compared to that in foods (Ranhotra et al 1985).
LifePak uses thiamin mononitrate which is synthetically produced from the natural
thiothiamine.
Riboflavin (B2):
Only two forms of riboflavin are commonly used in dietary supplements, riboflavin and
riboflavin 5’-monophosphate, riboflavin being the most common form (Hendler et al
2001, Institute of Medicine 1998). This is the form found in LifePak. There have been
no studies to suggest that riboflavin 5’-monophosphate is more bioavailable or preferable
over riboflavin, which has substantial evidence validating its easy absorption by humans.
Niacin (B3):
Though niacin is common in many foods, that found in plants, especially mature cereal
grains like corn and wheat, may be bound to sugar molecules in the form of glycosides,
which significantly decrease niacin bioavailability (Gregory 1998). Despite its relative
abundance in different foods, average niacin intake by both men and women in the
United States was found to be significantly lower than the RDA (15% and 25%
respectively) (Institute of Medicine 1998).
Niacin supplements are available as niacinamide or nicotinic acid. Niacinamide is the
form of niacin typically used in nutritional supplements and in food fortification.
Nicotinic acid is available over the counter and with a prescription as a cholesterollowering agent (Hendler and Rorvik 2001, Knopp 2000). Niacinamide has been shown
to be more easily tolerated as a supplement and is utilized as well as any other form of
niacin. Synthetic niacinamide and nicotinic acid have been shown to have no difference
in bioavailability in low doses (20-40 mg). However, high doses of nicotinic acid (2002000 mg), used primarily by doctors to treat high-cholesterol, may produce serious side
effects and, as such, is available by prescription only (Institute of Medicine 1998, Knopp
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2000, Schuna 1997, Sikand et al 1998). In order to mimic niacin content of a normal
diet, Pharmanex uses a blend of nicotinic acid and niacinamide in doses found to be safe
and effective.
Pantothenic Acid:
Many foods contain pantothenic acid. Refining of grains and the freezing and processing
of various food sources, however, can reduce pantothenic acid content by as much as 3575% (Institute of Medicine 1998). Few studies have been devoted to the research of
pantothenic acid and its various forms. Supplements commonly contain either
pantothenol or calcium or sodium D-pantothenate. Pantothenol, an alcohol derivative, is
converted by the human body to pantothenic acid. Calcium and sodium D-pantothenate,
the calcium and sodium salts of pantothenic acid, are available as supplements and are
readily bioavailable to and utilized by the body (Plesofsky 1999). A recent study showed
that pantothenic acid supplementation in the form of D-calcium pantothenate was readily
absorbed and effective preventing nutrient deficiencies in children (Rivera et al 2001).
LifePak provides pantothenic acid in the form of D-calcium pantothenate.
FAT-SOLUBLE VITAMINS
Vitamin A:
The principal forms of preformed vitamin A (retinol) in supplements are retinyl palmitate
and retinyl acetate. Beta-carotene is one of the most common sources of vitamin A in
supplements, and many supplements provide a combination of retinol and beta-carotene
(Hendler and Rorvik 2001). Beta-carotene is one of the few vitamin forms that have
significant research indicating a preference of natural over synthetic. Studies have shown
that a natural beta-carotene mix was significantly more bioavailable than the synthetic
all-trans form (Ben-Amotz and Levy 1996). Later studies supported these findings and
also revealed higher anti-oxidant activity in natural beta-carotene versus synthetic forms
(Ben-Amotz and Fishler 1998, Levin and Mokady 1994). Vitamin A palmitate (retinyl
palmitate) has been shown to be beneficial in those who cannot convert beta-carotene, a
vitamin A precursor, to vitamin A. Retinyl palmitate is the preformed vitamin A that is
found commonly in foods. In accordance with these findings, LifePak provides a blend
of all-natural beta-carotene and vitamin A palmitate to provide individuals with safe,
bioavailable vitamin A source.
Vitamin E:
Vitamin E is another of the few vitamins with substantial research verifying that the
natural form is preferable to the synthetic form. LifePak provides vitamin E derived
entirely from natural soy. The bioavailability of the natural d--tocopheryl acetate and d-tocopherol used in LifePak is approximately twice that of synthetic dl--tocopherol
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used in other leading brand multivitamins (Hendler and Rorvik 2001, Acuff et al 1994,
Burton et al 1998, Ferslew et al 1993, Horwitt et al 1984, Kiyose et al 1997). In addition
to d--tocopherol, LifePak also provides mixed natural tocopherols and tocotrienols. The
level of 300 IU of vitamin E in LifePak is supported by numerous human studies that
show significant health benefits at daily vitamin E intakes between 100 and 400 IU
(Acuff et al 1994, Spencer et al 1999, Stampfer and Rimm 1995, Stephens et al 1996).
Vitamin D:
Ultraviolet radiation from the sun is our main source of vitamin D. Ultraviolet B
radiation at 290-320 nm hits our skin and converts 7-dehydrocholesterol into
precholecalciferol. Precholecalciferol is converted to cholecalciferol via thermal
isomerization. However, many groups are at risk for vitamin D deficiency due to
restricted sun exposure. The US Bureau of the Census estimated 5% of individuals in the
US over the age of 65 (approximately 1 million people) and more than 20% of those over
the age of 85 are in retirement homes with little exposure to the sun. One study at a
Boston hospital showed that 57% of patients admitted for a variety of reasons were
deficient in vitamin D (Thomas 1998). Additionally, restriction of sun exposure
stemming from studies correlating ultraviolet radiation with several skin and cancer
conditions has made vitamin D status in healthy humans more of a concern (Neale et al
2003, Veierod et al 2003, Livingston et al 2003).
Currently, ergocalciferol (D2), a form of vitamin D that is can be either naturally derived
or synthesized, and cholecalciferol (D3) are used in supplements. The body uses and
metabolizes ergocalciferol, which is derived from the plant ester ergosterol, similar to the
natural cholecalciferol (Specker 1994). However, ergocalciferol has been shown to be
less active than cholecalciferol, and it has been shown to lead to severe toxicity problems
when taken in large doses (Takahashi 1993, Albert et al 1988). For these reasons,
Pharmanex uses a nature-identical form of cholecalciferol, the natural form of vitamin D
in our bodies, which has the exact same chemical structure as cholecalciferol derived
from natural sources.
Vitamin K:
The natural form of vitamin K found in nature is phylloqiuinone (K1), or phytonadione. A
synthetic phytonadione is the form used in most dietary supplements and MVMS’s
(Hendler and Rorvik 2001, Institute of Medicine 1998). This form has been shown to be
safe and is even used in infant injections to prevent deficiencies and subsequent bloodclotting abnormalities (Institute of Medicine 1998). Menaquinone (vitamin K2), an active
form of vitamin K, is synthesized by bacteria that normally colonize the large intestine.
Until recently it was thought that up to 50% of the human vitamin K requirement might
be met by bacterial synthesis. Based on recent research, the contribution of bacterial
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synthesis is much lower than previously thought, although the exact contribution has not
been quantified (Suttie 1995). In some studies, it was shown that the bioavailability and
absorption of synthetic vitamin K in supplement form was superior to that of vitamin K
in a variety of foods and green vegetables (Booth et al 1998, 1999). LifePak uses the
nature-identical vitamin K1 (phytonadione).
CONCLUSION
Pharmanex has always placed emphasis on science as the foundation and guideline for
everything that we do. Pharmanex makes every effort to keep consumers informed
concerning the science and research that forms the foundation of Pharmanex’s products
through, among others, our web site, product support teams, and printed materials. This
compilation of studies and references is by no means comprehensive. We encourage all
consumers to be proactive and seek credible sources of information through free, publicaccess resources, focusing on those that cite and make reference to credible scientific
studies.
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References
1.
Acuff, R. V., Thedford, S. S., Hidiroglou, N. N., Papas, A. M., and Odom Jr, T. A. Relative
bioavailability of RRR- and all-rac-a-tocopheryl acetate in humans: studies using deuterated
compounds. Am.J.Clin.Nutr. 60, 397-402. 1994.
2.
Albert DM, Saulenas AM, Cohen SM. Verhoeff's query: is vitamin D effective against retinoblastoma?
Arch Ophthalmol. 1988 Apr;106(4):536-40.
3.
Austria R, Semenzato A, Bettero A. Stability of vitamin C derivatives in solution and topical
formulations. J Pharm Biomed Anal. 1997;15(6):795-801.
4.
Baker H, Frank O, Zetterman RK, Rajan KS, ten Hove W, Leevy CM. Inability of chronic alcoholics
with liver disease to use food as a source of folates, thiamin and vitamin B6.Am J Clin Nutr. 1975
Dec;28(12):1377-80.
5.
Baker H, Jaslow SP, Frank O. Severe impairment of dietary folate utilization in the elderly. J Am
Geriatr Soc. 1978 May;26(5):218-21.
6.
Bendich A, Langseth L. The health effects of vitamin C supplementation: A review. J.Am.Coll.Nutr.
1995;14:124-36.
7.
Ben-Amotz A, Fishler R. Analysis of carotenoids with emphasis on 9-cis b-carotene in vegetables and
fruits commonly consumed in Israel. Food Chem. 1998;62:515-20.
8.
Ben-Amotz A, Levy Y. Bioavailability of a natural isomer mixture compared with synthetic all- trans
beta-carotene in human serum. Am J Clin Nutr 1996;63:729-34.
9.
Benton D, Haller J, Fordy J. The vitamin status of young British adults. Int J Vitam.Nutr Res
1997;67:34-40.
10. Block G, Abrams B. Vitamin and mineral status of women of childbearing potential.
Ann.N.Y.Acad.Sci. 1993;678:244-54.
11. Booth, Sarah L; Maueen E O’Brien-Morse; Gerard E Dallal; Kenneth W Davidson; and Caren M
Gundberg. Response of vitamin K to different intakes and sources of phylloquinone-rich foods:
comparison of younger and older adults. Am J Nutr 1999;70:368-77
12. Booth SL, Suttie JW. Dietary intake and adequacy of vitamin K. J Nutr. 1998;128(5):785-788.
13. Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999.
14. Burton, G. W., Traber, M. G., Acuff, R. V., Walters, D. N., Kayden, H., Hughes, L., and Ingold, K. U.
Human plasma and tissue alpha-tocopherol concentrations in response to supplementation with
deuterated natural and synthetic vitamin E. Am J Clin Nutr 67(4), 669-684. 1998.
15. Chalmers AH. Ascorbic acid bioavailability in foods and supplements (Nutr Rev 1993;51:301-3)
Nutr Rev. 1994 Mar;52(3):110-1.
16. Cuskelly G. J., McNulty H., Scott J. M. Effect of increasing dietary folate on red-cell folate:
implications for prevention of neural tube defects. Lancet 1996;347:657-659
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17. Dawson EB, Evans DR, Conway ME, and McGanity WJ. Vitamin B12 and folate bioavailability from
two prenatal multivitamin/multimineral supplements. Am J Perinatol. 2000; 17(4):193-9
18. DeRitter E. Physiologic availability of dehydro-L-ascorbic acid and palmitoyl-L-ascorbic acid.
Science. 1951;113:628-631.
19. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United
States population. Epidemiology 1992;3:194-202.
20. Ferslew KE, Acuff RV, Daigneault EA, Woolley TW, Stanton PEJ. Pharmacokinetics and
bioavailability of the RRR and all racemic stereoisomers of alpha-tocopherol in humans after single
oral administration. J Clin Pharmacol. 1993;33:84-8.
21. Fletcher RH, Fairfield KM. Vitamins for chronic disease prevention in adults: clinical applications.
JAMA. 2002 Jun 19;287(23):3127-9.
22. Food and Nutrition Board, Institute of Medicine. Biotin. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington,
D.C.: National Academy Press; 1998:374-389.
23. Food and Nutrition Board, Institute of Medicine. Folic Acid. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington,
D.C.: National Academy Press; 1998:193-305.
24. Food and Nutrition Board, Institute of Medicine, National Research Council. Dietary reference
intakes: folate, other B-vitamins and choline. Washington D.C.: National Academy Press, 1998.
25. Food and Nutrition Board, Institute of Medicine. Niacin. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington,
D.C.: National Academy Press; 1998:123-149.
26. Food and Nutrition Board, Institute of Medicine. Pantothenic acid. Dietary Reference Intakes:
Thiamin, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline.
Washington, D.C.: National Academy Press; 1998:357-373.
27. Food and Nutrition Board, Institute of Medicine. Riboflavin. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington
D.C.: National Academy Press; 1998:87-122.
28. Food and Nutrition Board, Institute of Medicine. Thiamin. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington
D.C.: National Academy Press; 1998:58-86.
29. Food and Nutrition Board, Institute of Medicine. Vitamin B 6. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington
D.C.: National Academy Press; 1998:150-195.
30. Food and Nutrition Board, Institute of Medicine. Vitamin B 12. Dietary Reference Intakes: Thiamin,
Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington
D.C.: National Academy Press; 1998:306-356.
Nature  Wisdom  Science™
31. 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.
32. Geyer J, Netzel M, Bitsch I, Frank T, Bitsch R, Kramer K, Hoppe PP. Bioavailability of water- and
lipid-soluble thiamin compounds in broiler chickens. Int J Vitam Nutr Res. 2000 Dec;70(6):311-6.
33. Gregory JF, 3rd. Ascorbic acid bioavailability in foods and supplements. Nutr Rev. 1993;51(10):301303.
34. Gregory JF, 3rd. Nutritional Properties and significance of vitamin glycosides. Annu Rev Nutr.
1998;18:277-296.
35. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics
Company, Inc; 2001.
36. Horwitt, M. K., Elliott, W. H., Kanjananggulpan, P., and Fitch, C. D. Serum concentrations of alphatocopherol after ingestion of various vitamin E preparations. Am J Clin Nutr 40(2), 240-245. 1984.
37. Hunt C, Chakravorty NK, Annan G, Habibzadeh N, Schorah CJ. The clinical effects of vitamin C
supplementation in elderly hospitalised patients with acute respiratory infections. Int J Vitam.Nutr Res
1994;64:212-9.
38. Johnston CS, Luo B. Comparison of the absorption and excretion of three commercially available
sources of vitamin C. J Am Diet Assoc. 1994;94(7):779-781.
39. Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics
Company, Inc; 2001
40. Kiely M, Flynn A, Harrington KE, Robson PJ, O'Connor N, Hannon EM, O'Brien MM, Bell S, Strain
JJ. The efficacy and safety of nutritional supplement use in a representative sample of adults in the
North/South Ireland Food Consumption Survey. Public Health Nutr. 2001 Oct;4(5A):1089-97.
41. Kiyose, C., Muramatsu, R., Kameyama, Y., Ueda, T., and Igarashi, O. Biodiscrimination of atocopherol stereoisomers in humans after oral administration. American Journal of Clinical Nutrition
65(3), 785-789. 1997.
42. Knopp RH. Evaluating niacin in its various forms. Am J Cardiol. 2000;86(12A):51L-56L.
43. Levine M, Conry-Cantilena C, Wang Y et al. Vitamin C pharmacokinetics in healthy volunteers:
evidence for a recommended dietary allowance. Proc Natl.Acad.Sci U S A 1996;93:3704-9.
44. Levin G, Mokady S. Antioxidant activity of 9-cis compared to all-trans beta- carotene in vitro. Free
Radic.Biol.Med. 1994;17:77-82.
45. Levy G, Hewitt RR. Evidence in man for different specialized intestinal transport mechanisms for
riboflavin and thiamin. Am J Clin Nutr. 1971 Apr;24(4):401-4.
46. Livingston PM, White V, Hayman J, Dobbinson S. Sun exposure and sun protection behaviours
among Australian adolescents: trends over time. Prev Med. 2003 Dec;37(6):577-84.
Nature  Wisdom  Science™
47. Mangels, A.R. et al. The bioavailability to humans of ascorbic acid from oranges, orange juice, and
cooked broccoli is similar to that of synthetic ascorbic acid. Journal of Nutrition. 1993; volume 123:
pages 1054-1061.
48. Manson JE, Gaziano JM, Jonas MA, Hennekens CH. Antioxidants and cardiovascular disease: a
review. J Am Coll Nutr 1993;12:426-32.
49. McKay DL, Perrone G, Rasmussen H, Dallal G, Hartman W, Cao G, Prior RL, Roubenoff R,
Blumberg JB. The effects of a multivitamin/mineral supplement on micronutrient status, antioxidant
capacity and cytokine production in healthy older adults consuming a fortified diet. J Am Coll Nutr.
2000 Oct;19(5):613-21.
50. Moss AJ, Levy AS, Kim I, Park YK. 1994. Use of Vitamin and Mineral Supplements in the United
States: Current Users, Types of Products, and Nutrients. Advance Data. Vital and Health Statistics of
the National Center for Health Statistics, No. 174. Hyattsville, MD: National Center for Health
Statistics.
51. Navarro M, Wood RJ. Plasma changes in micronutrients following a multivitamin and mineral
supplement in healthy adults. J Am Coll Nutr. 2003 Apr;22(2):124-32.
52. Neale RE, Purdie JL, Hirst LW, Green AC. Sun exposure as a risk factor for nuclear cataract.
Epidemiology. 2003 Nov;14(6):707-12.
53. Nelson EW, Lane H, and Cerda JJ. Comparative human intestinal bioavailability of vitamin B-6 from
a synthetic and a natural source. J Nutr. 1976 Oct; 106(10): 1433-7
54. Nelson EW, Streiff RR, and Cerda JJ. Comparative bioavailability of folate and vitamin C from a
synthetic and natural source. Am J Clin Nut. 1975 Sep; 28(9): 1014-9
55. [No Authors Listed]. Optimal calcium intake. Sponsored by National Institutes of Health Continuing
Medical Education. Nutrition. 1995 Sep-Oct;11(5):409-17. Review.
56. Pennington JAT, Young BE, Wilson DB. Nutritional elements in U.S. diets: Results from the total diet
study, 1982-86. J.Am.Diet.Assoc. 1989;89:659-64.
57. Pennington JAT. Intakes of minerals from diets and foods: Is there a need for concern? J.Nutr.
1996;126:2304S-8S.
58. Plesofsky-Vig N. Pantothenic acid. In: Shils M, ed. Nutrition in Health and Disease,. 9th ed.
Baltimore: Williams & Wilkins; 1999:423-432.
59. Ranhotra G, Gelroth J, Novak F, Bohannon F. Bioavailability for rats of thiamin in whole wheat and
thiamin-restored white bread. J Nutr. 1985 May;115(5):601-6.
60. Rivera JA, Gonzalez-Cossio T, Flores M, Romero M, Rivera M, Tellez-Rojo MM, Rosado JL, Brown
KH. Multiple micronutrient supplementation increases the growth of Mexican infants.
Am J Clin Nutr. 2001 Nov;74(5):657-63.
61. Rosado JL, Camacho-Solis R, Bourges H. [Addition of vitamins and minerals to corn and wheat flour
in Mexico] Salud Publica Mex. 1999 Mar-Apr;41(2):130-7. Spanish.
62. Sauberlich H. E., Kretsch M. J., Skala J. H., Johnson H. L., Taylor P. C. Folate requirement and
metabolism in nonpregnant women. Am. J. Clin. Nutr. 1987;46:1016-1028
Nature  Wisdom  Science™
63. Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, Bodenham A. Total
vitamin C, ascorbic acid, and dehydroascorbic acid concentrations in plasma of critically ill patients.
Am J Clin Nutr. 1996 May;63(5):760-5.
64. Schuna AA. Safe use of niacin. Am J Health Syst Pharm. 1997 Dec 15;54(24):2803.
65. Sikand G, Kashyap ML, Yang I. Medical nutrition therapy lowers serum cholesterol and saves
medication costs in men with hypercholesterolemia. J Am Diet Assoc. 1998 Aug;98(8):889-94.
66. Specker BL. Do North American women need supplemental vitamin D during pregnancy or lactation?
Am J Clin Nutr. 1994 Feb;59(2 Suppl):484S-490S; discussion 490S-491S. Review.
67. Spencer AP, Carson DS, Crouch MA. Vitamin E and coronary artery disease. Arch Intern.Med
1999;159:1313-20.
68. Stampfer MJ, Rimm EB. Epidemiologic evidence for vitamin E in prevention of cardiovascular
disease. Am.J.Clin.Nutr. 1995;62:1365S-9S.
69. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomised
controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study
(CHAOS). Lancet 1996;347:781-6.
70. Suitor CW, Bailey LB. Dietary folate equivalents: interpretation and application. J Am Diet Assoc.
2000 Jan: 100(1): 88-94
71. Suttie JW. The importance of menaquinones in human nutrition. Annu Rev Nutr. 1995;15:399-417.
72. Suzuki M, Itokawa Y. Effects of thiamine supplementation on exercise-induced fatigue. Metab Brain
Dis. 1996 Mar;11(1):95-106.
73. Takahashi O. A large dose of ergocalciferol does not cause deficient blood coagulation but is
extremely toxic to rats. Toxicol Lett. 1993 Sep;69(3):257-72.
74. Thomas MK, Lloyd-Jones DM, Thadhani RI, et al. Hypovitaminosis D in medical inpatients. N Engl J
Med. 1998; 338:777-83.
75. Topliss JG, Clark AM, Ernst E, Hufford CD, Johnston GAR, Rimoldi JM, Weimann BJ. Natural and
Synthetic Substances Related to Human Health (IUPAC Technical Report). Pure and Applied
Chemistry. 2002: 74(10): 1975-1985.
76. U.S.Department of Agriculture, Agricultural Research Service. Data Tables: Results from USDA's
1996 Continuing Survey of Food Intakes by Individuals and 1996 Diet and Health Knowledge Survey.
ARS Food Surveys Research Group 97. Electronic Citation.
77. Van der Beek EJ, van Dokkum W, Wedel M, Schrikver J, van der Berg H.Thiamin, riboflavin and
vitamin B6: Impact of restricted intake on the physical performance in man. J Am Coll Nutr. 1994;
13:629-640.
78. Veierod MB, Weiderpass E, Thorn M, Hansson J, Lund E, Armstrong B, Adami HO. A prospective
study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women.
J Natl Cancer Inst. 2003 Oct 15;95(20):1530-8.
Nature  Wisdom  Science™
79. Wilson CW, Greene M, Loh HS. The metabolism of supplementary vitamin C during the common
cold. J Clin Pharmacol 1976; 16:19-29.
80. Zempleni J, Mock DM. Biotin biochemistry and human requirements. 1999; volume 10: pages 128138. J Nutr. Biochem. 1999;10:128-138.