Multivitamins and Cancer Prevention: Using the Data

Best Evidence Review of Multivitamins in the Prevention of Cancer

The Study

Gaziano JM, Sesso HD, Christen WG, et al. Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA. 2012;308:1871-1880.

The Physicians' Health Study (PHS) II was the first large-scale, randomized, placebo-controlled trial to test the long-term effects of a daily multivitamin on the prevention of cancer. The results -- an 8% decrease in total cancer incidence among men taking a daily multivitamin -- have generated significant attention in the popular press. But is the evidence strong enough to recommend a change in clinical practice? How should physicians best use the results of this study?

Background

Epidemiologic studies have consistently found that a diet rich in fruits and vegetables is associated with reduced risk for cancer.^[1,2] However, it remains unclear whether daily multivitamins -- which are purported to mimic a healthier diet -- can result in a similar benefit.

To be certain, substantial indicates evidence that specific vitamins might mitigate cancer risk at the biochemical level. Folate, for example, is an essential factor in DNA synthesis and repair, and folate deficiency has been shown to increase the risk for tumor development in vitro.^[3] Similarly, research has shown that antioxidants, such as beta-carotene, vitamin E, and vitamin C, can prevent cancer cell proliferation in vitro.^[4]

The nutritional supplement industry often cites such studies in their advertising, and sales of multivitamins and dietary supplements now total over $28 billion annually.^[5] Multivitamin use is widespread among adults in the United States, with nearly one half of all Americans taking some form of dietary supplement and one third taking a daily multivitamin.^[6]

Despite the popular belief that daily multivitamins protect against cancer, there is little evidence to support such claims in human trials. Several large-scale observational studies have found no association between multivitamin use and cancer,^[7,8] and some have even reported increased mortality among patients taking multivitamins.^[9,10]

Randomized controlled trials have done little to clarify the debate. To date, such trials have been few and far between,^[11] and the results have often contradicted one another. In most cases, these RCTs have tested specific vitamins -- such as selenium, vitamin E, or beta-carotene -- in high doses and specific combinations that differ significantly from the contents of the more commonly used multivitamin. The results have ranged from decreased cancer incidence^[12] to increased cancer incidence^[13,14] or no effect.^[15,16]

Not surprisingly, this maelstrom of conflicting evidence has led to the lackluster conclusion that more research is needed. A 2006 systematic review of the use of multivitamins and mineral supplements to prevent cancer, funded by the National Institutes of Health, found insufficient evidence to prove the presence or absence of benefits.^[17] More pointedly, a 2012 Cochrane systematic review found no evidence of benefit, but further cautioned that "beta-carotene and vitamin E seem to increase mortality, and so may higher doses of vitamin A. Antioxidant supplements need to be considered as medicinal products and should undergo sufficient evaluation before marketing."^[18]

In light of the inconclusive and often contradictory evidence to date, the PHS II provides an important addition to the literature. It is the first large-scale, randomized, placebo-controlled trial to test a multivitamin -- rather than selected vitamins or minerals -- in the primary prevention of cancer.^[11]