Multivitamin

Multivitamins contain multiple micronutrients, such as vitamins and dietary minerals.

A multivitamin is a preparation intended to supplement a human diet with vitamins, dietary minerals, and other nutritional elements. Such preparations are available in the form of tablets, capsules, pastilles, powders, liquids, and injectable formulations. Other than injectable formulations, which are only available and administered under medical supervision, multivitamins are recognized by the Codex Alimentarius Commission (the United Nations' authority on food standards) as a category of food.^[1] Multivitamin supplements are commonly provided in combination with dietary minerals. A multivitamin/mineral supplement is defined in the United States as a supplement containing 3 or more vitamins and minerals that does not include herbs, hormones, or drugs, where each vitamin and mineral is included at a dose below the tolerable upper level, as determined by the Food and Drug Board, and does not present a risk of adverse health effects.^[2] The terms multivitamin and multimineral are often used interchangeably. There is no scientific definition for either.^[3]

History

In the mid-1930s multivitamins became available in pharmacies and grocery stores. In 1934 Nutrilite Company introduced the first multivitamin-multimineral tablets. These supplements were made from natural dried and compressed vegetable and fruit concentrates. In the early 1940s other brands started to produce synthetic tablets.^[4][5]

Products and components

Many multivitamins are formulated or labeled to differentiate consumer sectors, such as prenatal, children, mature or 50+, men's, women's, diabetic, or stress. Consumer multivitamin formulas are available as tablets, capsules, bulk powder, or liquid. Most multivitamins are intended to be taken once or twice per day, although some formulations are designed for consumption 3–7 or more times per day.

Compositional variation amongst brands and lines allows substantial consumer choices. Modern multivitamin products roughly classify into RDA (recommended dietary allowance) centric multivitamins with or without iron, RDA centric multivitamin/multimineral formulas with or without iron, higher potency formulas with mostly above RDA components with or without iron, and more specialized formulas by condition, such as for diabetics or by less common components, such as diversified antioxidants, herbal extracts, or premium^{[clarification needed]} vitamin and mineral forms. Legally, the United States Food and Drug Administration allows a multivitamin to be called "high potency" if at least two-thirds of its nutrients have at least 100 percent of the DV. In practice, "high potency" usually means substantially increased vitamins C and B, with some other enhanced vitamin and mineral levels, though some minerals may still be much less than DV.

Some components are typically much lower than RDA amounts, often for cost reasons. For example, biotin, usually the most expensive vitamin component, at over $4000 per active pound, is typically added in at only 5%-30% of RDA in many one per day formulations. Biotin is required to be present at 100% of the value of the B-vitamins for them to be absorbed by the body. Any B-vitamins that cannot be absorbed due to a lack of biotin are eliminated by the body. Likewise, boron and magnesium are considered essential for the bioavailability and absorption of Vitamin D and calcium. Sometimes low content composition is for population subgroups, where the RDA would be inappropriate. Iron is needed in larger amounts by menstruating women, but some percentage of HFE variant gene bearing males are at risk for hemochromatosis. Normal dietary intakes also vary by population, indicating different levels of supplementation.

Basic commercial multivitamin supplement products often contain the following ingredients: vitamin C, B₁, B₂, B₃, B₆, folic acid (B₉), B₁₂, B₅ (pantothenate), H (biotin), A, E, D₃, K₁, potassium iodide, cupric (sulfate anhydrous, picolinate, sulfate monohydrate, trioxide), selenomethionine, borate(s), zinc, calcium, magnesium, chromium, manganese, molybdenum, betacarotene, and iron. Other formulas may include additional ingredients such as other carotenes (e.g. lutein, lycopene), higher than RDA amounts of B, C or E vitamins including gamma-tocopherol, "near" B vitamins (inositol, choline, PABA), trimethylglycine (anhydrous betaine), betaine hydrochloride, vitamin K₂ as menaquinone-7, lecithin, citrus bioflavinoids or nutrient forms variously described as more easily absorbed.

Uses

By supplementing the diet with additional vitamins and minerals, multivitamins can be a valuable tool for those with dietary imbalances or different nutritional needs.^[6] People with dietary imbalances may include those on restrictive diets and those who cannot or will not eat a nutritious diet. Pregnant women and elderly adults have different nutritional needs than other adults, and a multivitamin may be indicated by a physician.

In the 1999–2000 National Health and Nutrition Examination Survey, 52% of adults in the United States reported taking at least one dietary supplement in the last month and 35% reported regular use of multivitamin-multimineral supplements. Women versus men, older adults versus younger adults, non-Hispanic whites versus non-Hispanic blacks, and those with higher education levels versus lower education levels (among other categories) were more likely to take multivitamins. Individuals who use dietary supplements (including multivitamins) generally report higher dietary nutrient intakes and healthier diets. Additionally, adults with a history of prostate and breast cancers were more likely to use dietary and multivitamin supplements.^[7]

Precautions

While multivitamins can be a valuable tool to correct dietary imbalances, some risk exists. Various medications may adversely interact with multivitamins, and many people with medical conditions have special dietary needs. In particular, pregnant women should generally consult their doctors before taking any multivitamins: for example, either an excess or deficiency of vitamin A can cause birth defects.^[8] Long-term use of beta-carotene, vitamin A, and vitamin E supplements may shorten life,^[9][10] with the additional risk being particularly large in smokers.^{[citation needed]} Many common brand supplements in the United States contain levels above the DRI/RDA amounts for some vitamins or minerals.

Severe vitamin and mineral deficiencies require medical treatment and can be very difficult to treat with common over-the-counter multivitamins. In such situations, special vitamin or mineral forms with much higher potencies are available, either as individual components or as specialized formulations, sometimes requiring a prescription.^{[citation needed]}

Vitamins follow a biphasic dose-response curve. The curve is a bell curve, with the area in the middle being the safe-intake range and the edges representing deficiency and toxicity.^[11] For example, the Food and Drug Administration recommends that adults on a 2,000 calorie diet get between 60 and 90 milligrams of vitamin C per day.^[12] This is the middle of the bell curve. The upper limit is 2,000 milligrams per day for adults, which is considered potentially dangerous.^[13]

Multivitamins in large quantities may pose a risk of an acute overdose due to the toxicity of some components, principally iron. However, in contrast to iron tablets, which can be lethal to children^[14], toxicity from overdoses of multivitamins are very rare.^[15] There appears to be little risk to supplement users of experiencing acute side effects due to excessive intakes of micronutrients.^[16] There also are strict limits on the retinol content for vitamin A during pregnancies that are specifically addressed by prenatal formulas.

Scientific assessment

Evidence of benefits

In 2002, a paper by Robert H. Fletcher and Kathleen M. Fairfield from the Harvard School of Medicine, in the Journal of the American Medical Association stated that "it appears prudent for all adults to take vitamin supplements." In this article, which examined the clinical applications of vitamins for the prevention of chronic diseases in adults examined English-language articles about vitamins in relation to chronic diseases published between 1966 and 2002, and concluded that inadequate intake of several vitamins has been linked to the development of diseases including coronary heart disease, cancer, and osteoporosis.^[17]

Similarly, the April 9, 1998 issue of the New England Journal of Medicine featured an editorial entitled "Eat Right and Take a Multivitamin" that was based on studies that showed health benefits resulting from the consumption of supplemental folate to prevent birth defects and possibly decrease the incidence of cardiovascular disease.^[18]

A 2007 UC Berkeley School of Public Health study in collaboration with Shaklee Corporation determined that long-term vitamin and mineral supplement users showed markedly better health than people who took no supplements. "After adjustment for age, gender, income, education and body mass index, greater degree of supplement use was associated with more favorable concentrations of serum homocysteine, C-reactive protein, high-density lipoprotein cholesterol, and triglycerides, as well as lower risk of prevalent elevated blood pressure and diabetes."^[19]

There is a new gravitation in the United States towards the Mediterranean diet. This diet is based on the Mediterranean Diet Pyramid, created by Walter Willett in 1995.^[20] In 2008, the Harvard School of Public Health updated Willett’s pyramid in a Nutrition Source article called “Food Pyramids: What Should You Really Eat?”. Included in this new pyramid, and the original pyramid, is a daily multivitamin. The Harvard article states that “A daily multivitamin, multi-mineral supplement offers a kind of nutritional backup, especially when it includes some extra vitamin D. While a multivitamin can't in any way replace healthy eating, or make up for unhealthy eating, it can fill in the nutrient holes that may sometimes affect even the most careful eaters.”^[21]

A 2009 study published in The American Journal of Clinical Nutrition reports that multivitamin use is associated with longer telomere length in women. Longer telomeres have recently been associated with longer life, and therefore multivitamins could have an anti-aging effect. However, this is the first study on this topic, so more studies must be done to confirm this effect.^[22]

In response to a 2009 study^[23] stating the uselessness of multivitamins, the Linus Pauling Institute published an article refuting the study’s legitimacy and claims. According to the Linus Pauling Institute, the 2009 study was an observational study, not a randomized controlled trial. “Every epidemiologist will tell you that observational studies cannot establish cause-and-effect relationships; they only can observe associations.” Additionally, 41.5 percent of the female participants took multivitamins and were overall healthier in all their habits . This makes it difficult to separate their healthy habits from their multivitamin use. Perhaps they used multivitamins because they already had healthy habits and were therefore healthier overall. The Linus Pauling article concludes with this statement: “Even Dr. JoAnn Manson, a principal investigator of the Women's Health Initiative and co-author of the study, acknowledges that ‘the research doesn't mean multivitamins are useless. Multivitamins may still be useful as a form of [health] insurance for people with poor eating habits.’ And let's not fool ourselves, that's the large majority of the people in this country!”.^[24]

Bruce Ames, professor of Biochemistry and Molecular Biology at the University of California, Berkeley, and a senior scientist at Children's Hospital Oakland Research Institute (CHORI), suggests that "to maximize human health and lifespan, scientists must abandon outdated models of micronutrients" and that "a metabolic tune-up through an improved supply of micronutrients is likely to have great health benefits."^[25]

Evidence of little or no benefit (neutral)

In 2006 the National Institutes of Health convened an expert panel to examine the available evidence on nutrient supplements.^[4][5] This review concluded that "Most of the studies we examined do not provide strong evidence for beneficial health-related effects of supplements taken singly, in pairs, or in combinations of three or more." They noted that multivitamins could provide health benefits to some groups of people, such as postmenopausal women, but that there was "disturbing evidence of risk" in other groups, such as smokers. The panel's report concluded that the "present evidence is insufficient to recommend either for or against the use of Multivitamin/Mineral Supplements by the American public to prevent chronic disease."

Prenatal vitamins contain higher levels of iron and folic acid, compared with typical multivitamins

Similarly, a 2006 report for the United States Department of Health and Human Services concluded that "regular supplementation with a single nutrient or a mixture of nutrients for years has no significant benefits in the primary prevention of cancer, cardiovascular disease, cataract, age-related macular degeneration or cognitive decline."^[26] However, the report noted that multivitamins have beneficial effects in people with poor nutritional status, vitamin D and calcium can help prevent fractures in older people, and that zinc and antioxidants can help prevent age-related macular degeneration in people at a high risk of developing this disease.

In 2007 the United Kingdom Food Standards Agency published an updated set of recommendations for eating a healthy diet.^[27] The recommendations stated that pregnant women should take extra folic acid and iron and that older people might need extra vitamin D and iron. However, the report advised that "Vitamin and mineral supplements are not a replacement for good eating habits" and stated that supplements are unnecessary for healthy adults who eat a balanced diet.

One study from 2008 found that multivitamin use had no effect on prevention of lung cancer. Participants in this observational study had been taking multivitamin supplements for an average of 10 years, and this use appeared to have no effect on the prevention of lung cancer.^[28]

In February 2009, a study conducted in 161,808 postmenopausal women from the Women's Health Initiative clinical trials concluded that after 8 years of follow-up "multivitamin use has little or no influence on the risk of common cancers, cardiovascular disease, or total mortality".^[29]

Another 2010 study in the Journal of Clinical Oncology suggested that multivitamin use during chemotherapy for stage III colon cancer had no effect on the outcomes of treatment. The study observed over 1,000 men in treatment for colon cancer and recorded their multivitamin use. About half the men in the study used multivitamins, and it appeared to have no effect on the outcomes of their treatment.^[30]

Evidence of potential harm

A 2008 study found that multivitamin use increased the mean breast density in premenopausal women. Increased breast density is associated with a higher risk for breast cancer. The study surveyed premenopausal and postmenopausal women about their multivitamin use, and found that multivitamin use was associated with higher mean breast density in premenopausal women but not postmenopausal women. The length of time that the women had been taking multivitamins did not seem to affect their mean breast densities.^[31]

In 2010, a Swedish study published in The American Journal of Clinical Nutrition found that multivitamin use may be associated with increased risk of breast cancer among women. The study followed 35,329 women between 1997 and 2009. At the end of the study, 974 women had been diagnosed with breast cancer, suggesting an increased risk of breast cancer relating to multivitamin use.^[32]

However, two larger subsequent studies both published in 2011 reported that there is no increased risk of breast cancer associated with multivitamin/mineral usage (although there was no proven benefit or reduced risk either):

"To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users."^[33]

The second was "a meta-analysis of cohort and case-control studies to evaluate multivitamin intake and its relationship with breast cancer risk." "RESULTS: Eight of 27 studies that included 355,080 subjects were available for analysis. The total duration of multivitamin use in these trials ranged from 3 to 10 years. The frequency of current use in these studies ranged from 2 to 6 times/week. In analyses by duration of use 10 years or longer or 3 years or longer and by frequency 7 or more times/week that were reported in these studies, multivitamin use was not significantly associated with the risk of breast cancer. Only 1 recent Swedish cohort study concluded that multivitamin use is associated with an increased risk of breast cancer. The results of a meta-analysis that pooled data from 5 cohort studies and 3 case-control studies indicated that the overall multivariable relative risk and odds ratio were 0.10 (95% CI 0.60 to 1.63; p = 0.98) and 1.00 (95% CI 0.51 to 1.00; p = 1.00), respectively. The association was not statistically significant. CONCLUSIONS: Multivitamin use is likely not associated with a significant increased or decreased risk of breast cancer, but these results highlight the need for more case-control studies or randomized controlled clinical trials to further examine this relationship."^[34]

Multivitamins and Children

It is not yet clear whether or not multivitamins should be used by children, and if so, what dosages are appropriate. Several studies have been done to determine the efficacy of multivitamins against different conditions.

One study done in 2002 followed 5-to-7-year old girls to determine the influence of their mothers on their multivitamin intake. About 200 mother and daughter pairs participated in this observational study. It was found that mothers who used multivitamin supplements were more likely to give them to their daughters. Daughters’ multivitamin supplement use was predicted by mothers’ beliefs, attitudes, perceptions, and practices regarding mothers’ own eating and child feeding practices, rather than by daughters’ diet quality. In the discussion, the study's authors recommended that mothers foster healthier patterns of food intake in daughters, rather than providing multivitamin supplements, because the daughters' vitamin and mineral intakes during the study exceeded recommendations.^[35]

Another study done in 2009 found that multivitamin use among eight year-old children does not decrease risk for development of allergies. However, it seemed that multivitamin use in the first few years of life decreased the risk of allergies in the children. This study observed over 2,000 children from birth to age 8, and evaluated their multivitamin use in relation to their development of allergic disease.^[36]

According to a study published in The American Journal of Clinical Nutrition in 2007, Tanzanian children born to parents who received multivitamin supplements during pregnancy had a reduced risk of anemia, compared to the control group who received placebo supplements.^[37] However, a 2009 study published in the same journal found that iron and folic acid supplements were just as good at preventing anemia in children as multivitamin supplements were.^[38] Therefore, it is unclear at this time if multivitamin supplements are helpful in treatment and prevention of anemia in children.

Regulations by governmental agencies

United States

Because of their categorization as a dietary supplement by the Food and Drug Administration (FDA), most multivitamins sold in the U.S. are not required to undergo the testing procedures typical of pharmaceutical drugs.

However, some multivitamins contain very high doses of one or several vitamins or minerals, or are specifically intended to treat, cure, or prevent disease, and therefore require a prescription or medicinal license in the U.S. Since such drugs contain no new substances, they do not require the same testing as would be required by a New Drug Application, but were allowed on the market as drugs due to the Drug Efficacy Study Implementation program.^[39]

See also

• Bodybuilding supplement
• Dietary supplement
• Essential nutrient
• Food supplements
• Food additive
• Food fortification
• Functional food
• Food processing
• Health food
• Megavitamin therapy
• Orthomolecular medicine
• Naturopathic medicine
• Nutraceutical
• Nutrification (a.k.a. food enrichment).

References

1. ^ Codex Guidelines for Vitamin and Mineral Food Supplements Accessed 27 December 2007
2. ^ National Institutes of Health State-of-the-Science Panel. National Institutes of Health State-of-the-Science Conference Statement: multivitamin/mineral supplements and chronic disease prevention. Am J Clin Nutr 2007;85:257S-64S
3. ^ [1] Accessed 21 July 2009
4. ^ ^{a b} "NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention". NIH Consens State Sci Statements 23 (2): 1–30. 2006. PMID 17332802. http://consensus.nih.gov/2006/2006MultivitaminMineralSOS028main.htm. 
5. ^ ^{a b} Huang HY, Caballero B, Chang S, et al. (September 2006). "The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference". Ann. Intern. Med. 145 (5): 372–85. doi:10.1001/archinte.145.2.372. PMID 16880453. http://www.annals.org/cgi/pmidlookup?view=reprint&pmid=16880453. 
6. ^ Dietary supplements: Using vitamin and mineral supplements wisely, Mayo Clinic
7. ^ Cheryl L Rock. (2007). Multivitamin-multimineral supplements: who uses them?. American Journal of Clinical Nutrition, 85(1), 277S-279S. http://www.ajcn.org/content/85/1/277S.full
8. ^ Collins MD, Mao GE (1999). "Teratology of retinoids". Annu. Rev. Pharmacol. Toxicol. 39: 399–430. doi:10.1146/annurev.pharmtox.39.1.399. PMID 10331090. 
9. ^ Randerson J. "Vitamin supplements may increase risk of death", The Guardian, April 16, 2008. Cochrane Collaboration author, Goran Bjelakovic's opinion: The bottom line is, current evidence does not support the use of antioxidant supplements in the general healthy population or in patients with certain diseases.
10. ^ Bjelakovic, G.; D. Nikolova, LL Gluud, RG Simonetti, and C. Gluud (2008-04). Bjelakovic, Goran. ed. "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". Cochrane Database of Systematic Reviews 2008 (2): CD007176. doi:10.1002/14651858.CD007176. PMID 18425980. 
11. ^ Combs, Jr., G. F.(1998). The vitamins: Fundamental aspects in nutrition and health. Academic Press: San Diego, CA.
12. ^ "Council for Responsible Nutrition". Crnusa.org. http://www.crnusa.org/about_recs4.html. Retrieved 2011-03-30.
13. ^ MedlinePlus. (2010). "Vitamin C (Ascorbic acid)". http://www.nlm.nih.gov/medlineplus/druginfo/natural/1001.html
14. ^ Cheney K, Gumbiner C, Benson B, Tenenbein M (1995). "Survival after a severe iron poisoning treated with intermittent infusions of deferoxamine". J. Toxicol. Clin. Toxicol. 33 (1): 61–6. doi:10.3109/15563659509020217. PMID 7837315. 
15. ^ Linakis JG, Lacouture PG, Woolf A (December 1992). "Iron absorption from chewable vitamins with iron versus iron tablets: implications for toxicity". Pediatr Emerg Care 8 (6): 321–4. doi:10.1097/00006565-199212000-00003. PMID 1454637. 
16. ^ Kiely M, Flynn A, Harrington KE, et al. (October 2001). "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 4 (5A): 1089–97. doi:10.1079/PHN2001190. PMID 11820922. 
17. ^ Fletcher RH, Fairfield KM (June 2002). "Vitamins for chronic disease prevention in adults: clinical applications". JAMA 287 (23): 3127–9. doi:10.1001/jama.287.23.3127. PMID 12069676. 
18. ^ Eat Right and Take a Multivitamin NEJM, Volume 338:1060-1061, April 9, 1998, Number 15. Published 9 April 1998. Accessed 27 Dec 2007.
19. ^ Block G, Jensen CD, Norkus EP, et al. (2007). "Usage patterns, health, and nutritional status of long-term multiple dietary supplement users: a cross-sectional study". Nutr J 6: 30. doi:10.1186/1475-2891-6-30. PMC 2164946. PMID 17958896. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2164946. 
20. ^ Willet W. C., Sacks F., Trichopoulou A., Drescher G., Ferro-Luzzi A., Helsing E., Trichopoulos D. (1995). "Mediterranean diet pyramid: A cultural model for healthy eating". The American Journal of Clinical Nutrition 61 (6): 14025–14065. PMID 7754995. 
21. ^ Harvard School of Public Health (2008). Food pyramids: What should you really eat?. Retrieved from http://www.hsph.harvard.edu/nutritionsource
22. ^ Xu Q, Parks CG, DeRoo LA, Cawthon RM, Sandler DP, Chen H (June 2009). "Multivitamin use and telomere length in women". Am. J. Clin. Nutr. 89 (6): 1857–63. doi:10.3945/ajcn.2008.26986. PMC 2714373. PMID 19279081. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2714373. 
23. ^ Neuhouser ML, Wassertheil-Smoller S, Thomson C, et al. (February 2009). "Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts". Arch. Intern. Med. 169 (3): 294–304. doi:10.1001/archinternmed.2008.540. PMID 19204221. 
24. ^ Linus Pauling Institute (2009). Are multivitamins useless? A response by the Linus Pauling Institute to an article published in the February 2009 issue of the Archives of Internal Medicine. Retrieved from http://lpi.oregonstate.edu
25. ^ Ames BN (July 2005). "Increasing longevity by tuning up metabolism. To maximize human health and lifespan, scientists must abandon outdated models of micronutrients". EMBO Rep. 6 Spec No: S20–4. doi:10.1038/sj.embor.7400426. PMC 1369274. PMID 15995656. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1369274. 
26. ^ Huang HY, Caballero B, Chang S, et al. (May 2006). "Multivitamin/mineral supplements and prevention of chronic disease" (PDF). Evid Rep Technol Assess (Full Rep) (139): 1–117. PMID 17764205. http://www.ahrq.gov/downloads/pub/evidence/pdf/multivit/multivit.pdf. 
27. ^ The Balance of Good Health Food Standards Agency, Accessed 31 May 2008
28. ^ Slatore C. G., Littman A. J., Au D. H., Satia J. A., White E. (2008). "Long-term use of supplemental multivitamins, vitamin C, vitamin E, and folate does not decrease the risk of lung cancer". American Journal of Respiratory and Critical Care Medicine 177 (5): 524–530. doi:10.1164/rccm.200709-1398OC. PMC 2258445. PMID 17989343. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2258445. 
29. ^ Neuhouser ML, Wassertheil-Smoller S, Thomson C et al. (2009). "Multivitamin use and risk of cancer and cardiovascular disease in the Women's Health Initiative cohorts". Arch Intern Med 169 (3): 294–304. doi:10.1001/archinternmed.2008.540. PMID 19204221. 
30. ^ Ng K, Meyerhardt JA, Chan JA, et al. (October 2010). "Multivitamin use is not associated with cancer recurrence or survival in patients with stage III colon cancer: findings from CALGB 89803". J. Clin. Oncol. 28 (28): 4354–63. doi:10.1200/JCO.2010.28.0362. PMID 20805450. 
31. ^ Bérubé S, Diorio C, Brisson J (May 2008). "Multivitamin-multimineral supplement use and mammographic breast density". Am. J. Clin. Nutr. 87 (5): 1400–4. PMID 18469264. 
32. ^ Larsson SC, Akesson A, Bergkvist L, Wolk A (May 2010). "Multivitamin use and breast cancer incidence in a prospective cohort of Swedish women". Am. J. Clin. Nutr. 91 (5): 1268–72. doi:10.3945/ajcn.2009.28837. PMID 20335555. 
33. ^ Park SY, Murphy SP, Wilkens LR, Henderson BE, Kolonel LN (April 2011). "Multivitamin use and the risk of mortality and cancer incidence: the multiethnic cohort study". Am. J. Epidemiol. 173 (8): 906–14. doi:10.1093/aje/kwq447. PMID 21343248. 
34. ^ Chan AL, Leung HW, Wang SF (April 2011). "Multivitamin supplement use and risk of breast cancer: a meta-analysis". Ann Pharmacother 45 (4): 476–84. doi:10.1345/aph.1P445. PMID 21487086. 
35. ^ Lee Y, Mitchell DC, Smiciklas-Wright H, Birch LL (March 2002). "Maternal influences on 5- to 7-year-old girls' intake of multivitamin-mineral supplements". Pediatrics 109 (3): E46. PMC 2530934. PMID 11875174. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2530934. 
36. ^ Marmsjo K., Rosenlund H., Kull I., Hakansson N., Wickman M., Pershagen G., Bergstrom A. (2009). "Use of multivitamin supplements in relation to allergic disease in 8-y-old children". The American Journal of Clinical Nutrition 90 (6): 1693–1698. doi:10.3945/ajcn.2009.27963. PMID 19864411. 
37. ^ Fawzi W. F., Msamanga G., Kupka R., Spiegelman D., Villamor E., Mugusi F., Wei R., Hunter D. (2007). "Multivitamin supplementation improves hematologic status in HIV-infected women and their children in Tanzania". The American Journal of Clinical Nutrition 85 (5): 1335–1343. PMID 17490971. 
38. ^ Bhutta Z., Klemm R., Shahid F., Rizvi A., Rah J. H., Christian P. (2009). "Treatment response to iron and folic acid alone is the same as with multivitamins and/or anthelminthics in severely anemic 6-to-24 month old children". The Journal of Nutrition 139 (8): 1568–1574. doi:10.3945/jn.108.103507. PMID 19535425. 
39. ^ See 36 Fed. Reg. 6843 (Apr. 9, 1971).

External links

• Safe upper levels for vitamins and minerals - Report of the UK Food Standards Agency Expert Group on Vitamins and Minerals
• Dietary Supplements: Health Information Office of Dietary Supplements, National Institutes of Health
• The Landmark Dietary Supplement Study School of Public Health at UC Berkeley, published in Nutrition Journal