Vitamin and mineral supplements: do we really need them?

In the United States, 40 - 50% of the men and women 50 years of age or older regularly use multivitamin/mineral (MVM) supplements, making the annual sales of these supplements over $11 billion. However, the question remains whether using MVM supplements is beneficial to health. This article reviews the results of randomized studies of MVM supplements and individual vitamins/mineral supplements in relation to overall mortality and incidence of chronic diseases, particularly cancer and ischemic heart disease. The results of large-scale randomized trials show that, for the majority of the population, there is no overall benefit from taking MVM supplements. Indeed, some studies have shown increased risk of cancers in relation to using certain vitamins.

INTRODUCTION

Multivitamin / mineral (MVM) supplements certainly sell well in the United States. According to the National Health and Nutrition Examination Survey (NHANES) data, collected between 2003 and 2006, 40 – 50% of the men and women 50 years of age or older regularly consume MVM 0supplements.[1] In 2009, the total sale of nutritional supplements in the United States was approximately $27 billion,[2] and in 2010, despite the economic downturn, this number grew by 4.4% to over $28 billion.[3] Of this, over $11 billion was the sales of MVM or MVM-containing supplements.[23] However, do healthy individuals really need MVM supplements? Are they beneficial in reducing the risk of chronic diseases such as ischemic heart disease, cancer, and stroke? The answer is most likely NO. The results of large-scale randomized trials in the past two decades have shown that for the majority of the population, MVM supplements are not only ineffective, but they may be deleterious to health.

When the Alpha-Tocopherol Beta-Carotene Cancer Prevention (ATBC) study presented the first strong evidence for a harmful effect of vitamins in 1994,[4] health scientists were caught by surprise. The results of this large-scale 2 × 2 factorial design trial, which randomized over 29,000 middle-aged Finnish smoker men to receive α-tocopherol (a form of vitamin E), beta-carotene (a precursor of vitamin A), both, or neither, showed that β-carotene statistically significantly increased lung cancer incidence by 18% and total mortality by 8%, mainly due to increased deaths from lung cancer and ischemic cardiac disease.[4] α-tocopherol did not materially change the risk of lung cancer or total deaths. Despite the strong design of this trial and its large sample size, the results were met with skepticism. The results were deemed to be inconsistent with several of the previously published observational studies, based on which the trial had been designed to reduce the risk of lung cancer.[56] Several of the accompanying letters of correspondence, published in the New England Journal of Medicine, pointed to the potential shortcomings of this study, such as short duration of the study (i.e., a median follow-up of six years). Nevertheless, results of most of the subsequent trials, using other forms of vitamins and supplements, conducted in different populations and with different durations of use, have confirmed no benefit or even harm from the use of such vitamin supplements [Table 1].[47-17] The most recent notable one was the Selenium and Vitamin E Cancer Prevention Trial (SELECT Trial), the extended results of which showed that vitamin E supplements could increase the risk of prostate cancer among healthy men.[17] One exception to these null or deleterious effects was the result of the General Population Nutrition Intervention Trial conducted in Linxian, China,[718] which tested four combinations of vitamins and supplements (namely, factors A, B, C, and D). Factor D (a combination of selenium, α-tocopherol, and β-carotene) reduced overall mortality by approximately 10%. However, this trial was conducted in an area where micronutrient intake was quite poor, and thus supplements might have had a beneficial role. Even in this nutrition-deficient population, results of the trial showed no benefit for two of the other MVM supplements (factors B and C; see Table 1), and extended follow-up showed adverse results for one of the supplements (factor A containing zinc and vitamin A).[18]

Table 1

Randomized, double-blind, placebo-controlled, primary prevention trials designed to reduce risk of major chronic diseases

Thus far, several meta-analyses, authoritative reviews, and expert panel reports have been published on the use of MVMs in preventing chronic diseases in healthy individuals. Almost all have found no overall benefit. For example, a systematic review and meta-analysis, published in the Journal of the American Medical Association (JAMA), in 2007, concluded that, “Treatment with β-carotene, vitamin A, and vitamin E may increase mortality. The potential roles of vitamin C and selenium on mortality need further study”.[19] Another more recent meta-analysis concluded that, “Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within five years on cardiovascular events or on overall cancer or mortality in the populations studied” .[20] A recent re-analysis of the Women's Health Initiative, which was published along with the meta-analysis of the available literature, concluded that calcium supplements with or without vitamin D increased the risk of the cardiovascular events, particularly myocardial infarction.[21] An expert panel meeting at the National Institutes of Health, in 2006, concluded that there was ‘insufficient evidence’ to recommend for or against the use of MVMs by the American public to prevent chronic diseases.[22] The World Cancer Research Fund and the American Institute for Cancer Research has recommended against the use of dietary supplements by the public, for cancer prevention.[23] These expert panel reports appeared prior to the publication of the recent results from the SELECT Trial or those from the Women's Health Initiative, which bolstered the ‘no benefit or even harm’ conclusion.

We would like to emphasize that these conclusions are for the general population, and for prevention of chronic diseases such as cancer and cardiovascular disease. In special cases, individuals may need vitamins or supplements. For example, periconceptional folate supplements substantially reduce the risk of neural tube defects.[24] Likewise, iron supplements during pregnancy can substantially reduce the risk of anemia and perinatal complications in mothers.[25] Physician-recommended treatment of disorders such as osteoporosis,[26] as well as other diseases, may require use of MVMs or individual vitamins or minerals, but these are not the subject of this article. In addition, these conclusions do not negate the potential health benefits of eating fresh fruits and vegetables.

One might ask then, given substantial evidence for lack of any health benefit from MVM use for the majority of the adult population, why are these products so widely marketed in the United States and elsewhere? Or why would over 40% of the older population of the United States regularly use them? The answer is perhaps multifactorial. First, the belief in the use of vitamins has deep roots. The immense beneficial effects of vitamins in preventing pellagra, rickets, and scurvy at a period when overt nutritional deficiencies were common, gave the halo of a magical effect to these drugs. Before the 1990s, some eminent scientists strongly advocated the use of vitamins and supplements. Most notably, Linus Pauling, a two-time Nobel Laureate and a towering figure in chemistry, believed that vitamin C could prevent cancer and increase the life expectancy of cancer patients.[27] Pauling and Cameron supplemented 100 terminal cancer patients with vitamin C and compared them with 1000 similar patients who did not receive such supplementation and concluded that the lives of those receiving vitamin C were prolonged by one year.[28] However, this study was not randomized, and two subsequent double-blind randomized trials sponsored by the National Cancer Institute and conducted in the Mayo Clinic, did not find any benefit from oral supplementation with vitamin C.[2930] Despite such negative results, the effect of Pauling's and other scientists’ highly publicized comments still linger in the media and in people's minds.

Second, in the United States, unlike the case for drugs, human research is not required to prove that supplements are safe or effective.[31] Only if the Food and Drug Administration (FDA) finds that supplements are unsafe, can they stop the distribution of the products.[31] Third, there exists substantial inaccurate or misleading advertising in the media, which might be expected, given the annual $27 billion business. For example, a TV commercial has advertised the use of a certain brand of MVMs based on the results of a ‘Harvard Study,’ which had shown that lycopene use may reduce risk of prostate cancer. Although a Harvard Study’ has indeed shown an inverse association between dietary lycopene intake and prostate cancer risk,[32] the inference that one must use MVMs is incorrect for various reasons: (a) MVMs contain many vitamins and elements other than lycopene; (b) the results had come from an observational study and not a randomized trial, hence the results are subject to confounding factors; (c) prostate cancer is not the only meaningful health outcome, and the overall effect of MVMs on health needs to be considered. Fourth, many believe that MVMs, if not useful, will not harm. As the results of ATBC have shown, such a belief may be false. Fifth, many people want to take an active role in improving their health and increasing their longevity. Avoiding tasty, but unhealthy food, may be difficult, but taking a pill once a day is relatively easy. As others have discussed, prescription is more convenient than proscription.[533]

In summary, although in the long run MVMs may slightly increase the risk of cancer and cardiovascular diseases, in the short run they produce little harm or no harm, and thus negative consequences will not be discernible by individuals taking them. MVM sales benefit from misleading commercials, and people are pleased by the well-known placebo effects. Therefore, Americans who have been using MVMs since the early 1940s,[22] will most likely continue to use them in the foreseeable future, and the rest of the world will follow.