The Health Effects of Multivitamin Supplements

Introduction: the Concern

Multivitamins have long been considered an inexpensive nutritional insurance policy. However, with no tangible or immediate way of assessing effect and no go-ahead from the FDA, whose testing determines safety and efficacy, consumers rely on the age old-notion that vitamins are good for us and assume that they will help to prevent or slow the onset of disease. The claims seen on product’s front labels often make it easy to disregard possible doubts:

Are the forms of vitamins used in multivitamin formulations identical to the kind found in natural products? Are there any differences in effects between the two?
Are the “100% of the DV” amounts seen on the Supplement Facts Label always accurate?

The Facts

Supplement formulations and the contents listed on their Supplement Facts label are not regulated by industry entities, namely the Food and Drug Administration (FDA), which only steps in once supplement-related illness has been reported. The catch: there is no easy-to-use or established system for consumer to report either side effects or potential benefits. Supplement related-adverse effects are often reported to the Center for Disease Control (CDC), which does not communicate with the FDA, and to physicians, who can document these effects to the FDA through an online portal. Often times, however, the FDA never hears of dietary supplement-caused illness.

So, how do we know if these multivitamins actually work? One of the most effective ways of assessing the health outcomes of dietary practice is through large, long-term clinical trials. Of course, trials can vary in nature, with large, properly controlled, bias-free experimental designs providing far more reliable information on safety and efficacy than their poorly-designed counterparts.

In this review, we assess the results of the largest known studies on multivitamin supplementation – as well as the nature of the studies themselves – to sort the scientific proof from the hype.

The Studies: a Dive into the Nitty Gritty

Improving Nutrient Intake: A 2007 study examining the effects of multivitamin use on nutrient status assessed large Los Angeles- and Hawaii-based multiethnic cohorts without chronic disease. Nutrient intake from the diet was approximated by a food frequency questionnaire and from multivitamin use by the defaulting to the two most commonly reported multivitamin supplements in each population. In this study, approximately 75% of the 90,771 participants recorded adequate levels of nutrients from food alone, but multivitamin use showed an 8% increase in the number of individuals recording nutrient adequacy. Vitamin A, vitamin E, and zinc saw the greatest improvement after multivitamin use – indicating that these nutrients were the ones most often deficient in regular diet.

However, improving dietary intake of these nutrients in some people also meant exceeding the recommended intake in others. 10-15% of multivitamin users exceeded the recommended intake of Vitamin A, vitamin E, and zinc and 48-61% of users exceeded the recommended intake of niacin (vitamin B3), the effects of which (flushing of the skin, increased heart rate, and nausea) can be felt quickly after exposure. The study concluded that multivitamins “could be better formulated to target public health concerns.”

A separate study, the National Health and Nutrition Examination Survey (NHANES), is designed to “assess the health and nutritional status adults and children in the United States” by combining both interviews and physical examinations. NHANES data highlighted the prevalence of folic acid, the synthetic form of folate (vitamin B9), in the diet of US citizens from 2003-2006. According to the nationally representative, cross-sectional survey, 34.5% of US population reported consuming supplements containing folic acid. Supplementation appeared to improve folic acid status in some individuals. However, 4% of participants exceeded the nutrients Upper Limit (UL), the level at which the risk of significant side-effects increases. 5% of people over the age of 50 exceeded the UL. Alarmingly, of the 28% of children aged 1-13 who took folic-acid containing supplements, more than half exceeded the UL. The risk of toxicity from folic acid is, fortunately, suggested to be low but has been linked to masking a vitamin B12 deficiency, which may cause permanent damage to the nervous system.

Multivitamins & Chronic Disease: The results of scientific analyses here have been mixed, primarily due to differences in experimental design. According to the Office of Dietary Supplements of the National Institutes of Health (NIH), “most of the studies of the potential value of MVMs (multivitamins) to enhance health and prevent disease have been observational, which can only suggest an association but do not prove a cause-effect relationship.”

An observational study, one of the largest of its kind, followed 161,808 postmenopausal women aged 50-79 for a median of 8 years to study the “health and risks for cancer, heart disease, and osteoporosis.” Around 41.5% of these women supplemented with multivitamins. At the study’s end, the research authors concluded there was no association between multivitamin use and the risk of incidence of “common or total cancers, cardiovascular disease, or total mortality.” A separate study, which followed 182,099 men and women aged 45-75 years in Hawaii and California for an average of 11 years, reached similar conclusions regarding disease prevention.

An outline of major studies and their results:

A prospective study following Swedish women found an association, but no cause-effect relationship, between multivitamin supplementation and an increased risk for breast cancer. A separate study, also in Swedish women, concluded that multivitamin use led to a reduced risk of myocardial infarction (heart attack).
A U.S. based study did not find an association between multivitamin use and an increased risk for developing breast cancer, but found the supplementation may reduce the risk of breast cancer in women who consume alcohol.
One large prospective study concluded that men who supplement with multivitamin more than seven times weekly had a higher risk of “advanced and fatal prostate cancers.”
An 18 year study following postmenopausal women in Iowa found that multivitamin supplementation resulted in a “slight but significant” increase in the risk of total mortality when compared against those who did not supplement.

It is widely considered that controlled randomized experiments – where allocation bias is minimized in comparison to other trials – are the gold-standard for assessing the quality and efficacy of a treatment on health outcomes. The Physicians Health Study II, the longest randomized controlled trial following multivitamin effects on disease prevention, followed 14,641 male physicians aged 50 or older who took a daily multivitamin (Centrum Silver) for a median of 11.2 years. The conclusion: multivitamin users did not have fewer cardiovascular-related deaths (myocardial infarctions, strokes, etc.) but did modestly reduce incidence of total cancer by 8%. Importantly, it did not reduce the risk of some specific cancers, such as prostate cancer, and has no effect on cancer mortality.

Another well-known trial, the French Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX), examined the effect of a multivitamin formulation containing certain minerals and antioxidants on the development and progression of disease after 7.5 years of observation. Participants were randomly assigned placebo or a multivitamin supplement containing 120mg vitamin C, 30mg vitamin E, 6mg beta-carotene, 100mch selenium, and 20mg zinc. Study authors concluded that the supplements had no effect on incidence of cardiovascular disease but did lower the risk of cancer and all-cause mortality in men but not women.

Conclusion

Taking a multivitamin may help to improve nutrient intake in those who have poor diets, but it may come at the expense of exceeding not only the nutrient’s recommended dietary allowance but also its upper limit.

It appears that regular diet typically provides adequate amounts of most nutrients. If you recognize in which nutrients you are deficient, a specific vitamin or a more finely-tuned multivitamin might be your best bet to avoid excessive intake and its associated side-effects.

Taken together, data from clinical studies assessing multivitamins effect on chronic disease suggest supplementation doesn’t appear to influence the risk of developing cardiovascular disease but does seem to reduce incidence of cancer in otherwise health men but not (also healthy) women. Multivitamin abuse (supplementing more than seven times weekly) by men may increase incidence of advanced and fatal prostate cancers.

Data for women is more conflicting. Supplementation may reduce the risk of breast cancer in women, particularly in those who consume alcohol, but does not seem to have any effect on cardiovascular disease risk.

In a recent publication from 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 risk for most people.” However, the authors also note that while “a multivitamin provides some insurance against deficiencies…[it] is far less important for health than the healthy food patterns….Choose a diet rich in fruits, vegetables, whole grains, nuts, and healthy oils, and low in red meat and unhealthy fats.”

Note: The Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) establishes RDAs and AIs. RDAs are the average daily intake level of essential nutrients sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people. These values vary by age, gender, and nutrient. The FNB establishes AIs for nutrients for which evidence is insufficient to develop an RDA; the FNB sets AIs at levels that the board’s experts assume will ensure nutritional adequacy and that are high enough to meet or exceed the needs of most “apparently healthy” people. The U.S. Food and Drug Administration (FDA) develops DVs to help consumers compare the nutrient content of products within the context of a total diet. The FDA establishes a single DV for each nutrient for adults and children from age 4 years, and the DV is usually similar to the RDA or AI for that nutrient.

ULs, which the FNB establishes for many nutrients, are the maximum daily intakes unlikely to cause adverse health effects. As intake increases above the UL, the potential risk for adverse effects increases.

Header Image: Andy Simmons (Flickr)
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