Multivitamin

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

A multivitamin is preparation intended to be a dietary supplement 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]

In otherwise healthy people, some scientific evidence indicates that multivitamin supplements do not prevent cancer, heart disease, or other ailments. However, there may be specific groups of people who may benefit from multivitamin supplements (for example, people with poor nutrition or at high risk of macular degeneration).[4][5] According to the Harvard School of Public Health: "Looking at all the evidence, the potential health benefits of taking a standard daily multivitamin seem to outweigh the potential risks for most people."[6]

Contents

Products and components[edit]

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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.[citation needed] 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[edit]

By supplementing the diet with additional vitamins and minerals, multivitamins can be a valuable tool for those with dietary imbalances or different nutritional needs.[7] 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.[8]

Precautions[edit]

The amounts of each vitamin type in multivitamin formulations are generally adapted to correlate with what is believed to result in optimal health effects in large population groups.

Bell curve of intake versus health effect.svg

The health benefit of vitamins generally follows a biphasic dose-response curve, taking the shape of a bell curve, with the area in the middle being the safe-intake range and the edges representing deficiency and toxicity.[9] 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.[10] This is the middle of the bell curve. The upper limit is 2,000 milligrams per day for adults, which is considered potentially dangerous.[11]

However, these standard amounts may not correlate what is optimal in certain subpopulations, such as in children, pregnant women and people with certain medical conditions and medication.

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.[12] Long-term use of beta-carotene, vitamin A, and vitamin E supplements may shorten life,[media 1][13] 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.

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.

As noted in dietary guidelines from Harvard School of Public Health in 2008, multivitamins should not replace healthy eating, or make up for unhealthy eating.[17]

Epidemiological research on multivitamin use and disease[edit]

Provided that proper precautions are taken (such as adjusting the vitamin amounts to what is believed to be appropriate for children, pregnant women or people with certain medical conditions), multivitamin intake is generally safe, but research is still ongoing in regard to what health effects multivitamins have.

Evidence of health effects of multivitamins comes largely from prospective cohort studies which evaluate differences in health parameters between cohorts that take multivitamins versus cohorts that do not. Associations derived from such studies may not result from multivitamins themselves, but may reflect underlying characteristics of multivitamin-takers. For example, it has been suggested that multivitamin-takers may, overall, have more underlying diseases (making multivitamins appear as less beneficial in prospective cohort studies).[18] On the other hand, it has also been suggested that multivitamin users may, overall, be more health-conscious (making multivitamins appear as more beneficial in prospective cohort studies).[19][20] Randomized controlled studies have been encouraged to compensate for such confounders.[21]

Cohort studies[edit]

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".[22] 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.[23] A very large prospective cohort study published in 2011, including more than 180,000 participants, found no significant association between multivitamin use and mortality from all causes. The study also found no impact of multivitamin use on the risk of cardiovascular disease or cancer.[24]

The Physicians' Health Study II Randomized Controlled Trial[edit]

On October 17, 2012, researchers reported on a double-blind study of 14,641 male U.S. physicians initially aged 50 years or older (mean age of 64.3, standard deviation 9.2 years), that began in 1997 with treatment and follow-up through June 1, 2011. They compared total cancer (excluding nonmelanoma skin cancer) for participants taking a daily multivitamin (Centrum Silver by Pfizer) versus placebo. Compared with placebo, men taking a daily multivitamin had a statistically significant reduction in the incidence of total cancer, with a hazard ratio (HR) = 0.92 (95% confidence interval (CI) 0.86-0.998; P = .04). No statistically significant effects were found for any specific cancers or cancer mortality. The 95% CI of the hazard ratio implied a benefit of between 14% and .2% over placebo. In absolute terms the difference was 1.3 cancer diagnoses, per 1000 years of life (18.3-17 events, respectively). The median follow up time was 11.2 years.[25] The paper’s co-principal investigator, Dr. J. Michael Gaziano, a cardiologist, was quoted by the New York Times as saying “it certainly appears there is a modest reduction in the risk of cancer from a typical multivitamin.”[media 2] The study was also featured in a Wall Street Journal article on October 17, 2012.[media 3]

An editorial in the same issue of the Journal of the American Medical Association (JAMA), reflecting the opinion of JAMA, was dismissive of the report on several counts. First, they said, "it seems unlikely that a common characteristic across all diseases included under this wide category of cancer would be a protective effect from multivitamins", suggesting if no specific cancer was effected, why would general cancer risk be so effected. Second, they questioned the study's abilities to deliver on the question of whether a multivitamin would be protective in a well-nourished population (Bayesian probability) stating: "The plausibility of a protective effect is reduced by the absence of a clear path through which 30 different vitamins and minerals would cause a decline in the risk of multiple cancers and, especially, by the negative pattern of prior results." In addition the investigators observed no difference in effect whether the study participants were or were not adherent to the multivitamin intervention, which diminishes the dose–response relationship.[26]

The editorial was critical of the statistical multiplicity (multiple comparisons): the complete planned analysis of the primary and secondary end points in the PHS II study would entail 28 tests of association; each of which has "some possibility of yielding a statistically significant result by chance alone, even when there is no true treatment effect. ... when this finding is considered in the context of the number of already completed and planned analyses of the same study, the strength of the inference is weaker, because the likelihood of a randomly occurring finding ... is much greater." They concluded that any of the conventional P value corrections for multiple comparisons would eliminate the apparent “statistical significance” of the results.[26]

From the same double-blind study, they found that taking a daily multivitamin did not have any effect in reducing heart attacks and other major cardiovascular events, MI, stroke, and CVD mortality.[27]

Meta-analyses[edit]

One major meta-analysis published in 2011, including previous cohort and case-control studies, concluded that multivitamin use was not significantly associated with the risk of breast cancer. It noted that 1 Swedish cohort study has indicated such an effect, but with all studies taken together, the association was not statistically significant.[21] A 2012 meta-analysis of 10 randomized, placebo-controlled trials published in the Journal of Alzheimer's Disease found that a daily multivitamin may improve immediate recall memory, but did not affect any other measure of cognitive function.[28]

Expert bodies[edit]

A 2006 report by the U.S. Agency for Healthcare Research and Quality 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."[4] However, the report noted that multivitamins have beneficial effects for certain sub-populations, such as people with poor nutritional status, that vitamin D and calcium can help prevent fractures in older people, and that zinc and antioxidants can help prevent age-related macular degeneration in high-risk individuals.[4]

The U.S. Office of Dietary Supplements, a branch of the National Institutes of Health, suggests that multivitamin supplements might be helpful for some people with specific health problems (for example, macular degeneration). However, the Office concluded that "most research shows that healthy people who take an MVM [multivitamin] do not have a lower chance of getting any diseases, such as cancer, heart disease, or diabetes. Based on current research, it's not possible to recommend for or against the use of MVMs to stay healthier longer."[5]

The United Kingdom Food Standards Agency recommended in 2007 that pregnant women should take extra folic acid and iron and that older people might need extra vitamin D and iron.[29] However, these recommendations also advised that "Vitamin and mineral supplements are not a replacement for good eating habits."[29]

Multivitamins and children[edit]

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.[30]

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.[31]

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.[32] 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.[33]

Regulations by governmental agencies[edit]

[icon] This section requires expansion. (March 2009)

United States[edit]

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.[34]

See also[edit]

References[edit]

  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 c 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. 
  5. ^ a b "Dietary Supplement Fact Sheet: Multivitamin/mineral Supplements". Office of Dietary Supplements, National Institutes of Health. Retrieved March 2, 2012. 
  6. ^ http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamins/index.html
  7. ^ Dietary supplements: Using vitamin and mineral supplements wisely, Mayo Clinic
  8. ^ 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
  9. ^ Combs, Jr., G. F.(1998). The vitamins: Fundamental aspects in nutrition and health. Academic Press: San Diego, CA.
  10. ^ "Council for Responsible Nutrition". Crnusa.org. http://www.crnusa.org/about_recs4.html. Retrieved 2011-03-30.
  11. ^ MedlinePlus. (2010). "Vitamin C (Ascorbic acid)". http://www.nlm.nih.gov/medlineplus/druginfo/natural/1001.html
  12. ^ 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. 
  13. ^ Bjelakovic, G.; D. Nikolova, LL Gluud, RG Simonetti, and C. Gluud (2008-04). "Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases". In Bjelakovic, Goran. Cochrane Database of Systematic Reviews 2008 (2): CD007176. doi:10.1002/14651858.CD007176. PMID 18425980. 
  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. ^ Harvard School of Public Health (2008). Food pyramids: What should you really eat?. Retrieved from http://www.hsph.harvard.edu/nutritionsource
  18. ^ Li, K.; Kaaks, R.; Linseisen, J.; Rohrmann, S. (2011). "Vitamin/mineral supplementation and cancer, cardiovascular, and all-cause mortality in a German prospective cohort (EPIC-Heidelberg)". European Journal of Nutrition 51 (4): 407–13. doi:10.1007/s00394-011-0224-1. PMID 21779961.  edit
  19. ^ Seddon, J. M.; Christen, W. G.; Manson, J. E.; Lamotte, F. S.; Glynn, R. J.; Buring, J. E.; Hennekens, C. H. (1994). "The use of vitamin supplements and the risk of cataract among US male physicians". American Journal of Public Health 84 (5): 788–792. doi:10.2105/AJPH.84.5.788. PMC 1615060. PMID 8179050.  edit
  20. ^ 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. 
  21. ^ a b 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. 
  22. ^ 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. 
  23. ^ 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. 
  24. ^ 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. 
  25. ^ Gaziano, J. Michael; Sesso, Howard D.; Christen, William G.; Bubes, Vadim; Smith, Joanne P.; MacFadyen, Jean; Schvartz, Miriam; Manson, JoAnn E.; Glynn, Robert J.; Buring, Julie E. (October 17, 2012). "Multivitamins in the Prevention of Cancer in Men - The Physicians' Health Study II Randomized Controlled Trial". JAMA. doi:10.1001/jama.2012.14641. Retrieved October 17, 2012. 
  26. ^ a b Bach, Peter B.; Lewis, Roger, J. (14 November 2012). "Multiplicities in the Assessment of Multiple Vitamins Is It Too Soon to Tell Men That Vitamins Prevent Cancer?". The Journal of the American Medical Association 308 (18): 1916–1917. doi:10.1001/jama.2012.53273. Retrieved 13 December 2012. 
  27. ^ Sesso, Howard D.; Christen, William G.; Bubes, Vadim; Smith, Joanne P.; MacFadyen, Jean; Schvartz, Miriam; Manson, JoAnn E.; Glynn, Robert J.; Buring, Julie E.; Gaziano, J. Michael (November 7, 2012). "Multivitamins in the Prevention of Cardiovascular Disease in Men - The Physicians' Health Study II Randomized Controlled Trial". JAMA. doi:10.1001/jama.2012.14805. Retrieved November 8, 2012. 
  28. ^ The Effects of Multivitamins on Cognitive Performance: A Systematic Review and Meta-Analysis. Journal of Alzheimer's Disease. 10.3233/JAD-2011-111751. Published 13 February 2012. Accessed 2 March 2012.
  29. ^ a b The Balance of Good Health Food Standards Agency, Accessed 31 May 2008
  30. ^ 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. 
  31. ^ 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. 
  32. ^ 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. 
  33. ^ 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. 
  34. ^ See 36 Fed. Reg. 6843 (Apr. 9, 1971).

News media reporting[edit]

  1. ^ 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.
  2. ^ Rabin, Roni Caryn (October 17, 2012). "Daily Multivitamin May Reduce Cancer Risk, Clinical Trial Finds". New York Times. Retrieved October 17, 2012. 
  3. ^ Winslow, Ron (18 October 2012). "Multivitamin Cuts Cancer Risk, Large Study Finds". The Wall Street Journal. Retrieved 13 December 2012. 

External links[edit]

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