Multivitamins Do Not Prevent Cardiovascular Events

Abstract & Commentary

By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco

Source: Sesso HD, et al. Multivitamins in the prevention of cardiovascular disease in men: The Physicians’ Health Study II randomized controlled trial. JAMA 2012;308:1751-1760.

Billions of dollars are spent annually in the United States on Multivitamins in the hope they will improve health. The Physicians’ Health Study II is a large, prospective, randomized, controlled trial that studied the effects of vitamins on the health of males aged 50 years or older. In a 2 × 2 × 2 × 2 factorial design, 14,641 men were randomized to multivitamins, vitamin E, vitamin C, and beta-carotene vs respective placebos. The authors have previously published that vitamins E and C had no effect on cardiovascular disease (CVD) incidence or mortality. In this paper, they present the data on multivitamins and CVD.

The baseline characteristics were similar between multivitamin and placebo groups; mean age was 64 years, 42% had hypertension, 6% diabetes, 3.6% were smokers, and 77% were taking aspirin (probably because of participation in the Physicians’ Health Study I, which studied aspirin and cardiovascular disease), 5% had pre-existing cardiovascular disease, and 9% had pre-existing cancer. The median follow-up was 11 years. The rates of major cardiovascular events were 11.0 per 1000 person-years in the multivitamin group and 10.8 per 1000 person-years in the placebo group. Men taking a daily multivitamin experienced no benefit for the primary endpoint of major cardiovascular events (hazard ratio [HR] 1.01; P = 0.91). There was a similar lack of significant benefit for the secondary endpoints of total myocardial infarction [MI] (3.9 and 4.2 events per 1000 person-years for multivitamin and placebo, respectively; HR 0.93; P = 0.39) and total stroke (4.1 and 3.9 events per 1000 person-years; HR 1.06; P = 0.48) compared with men taking placebo. Secondary endpoint analyses showed no difference in the incidence of heart failure, angina, revascularization, or sub-types of stroke, although the authors did find a reduction in MI death (HR 0.61; P = 0.048). The effect of a daily multivitamin on total MI, total stroke, and other cardiovascular endpoints did not differ between men with and without baseline CVD. The authors conclude that among this population of u.S. male physicians, taking a daily multivitamin did not reduce major cardiovascular events, MI, stroke, and CVD mortality after more than a decade of treatment and follow-up.


This study is a very large, well-conducted study that is consistent with prior literature showing no benefit of multivitamin supplementation on cardiovascular outcomes. With high statistical power, they showed no impact on the incidence of any CVD, and they showed no difference in event rates in those with pre-existing CVD. The size and rigorous design strengthen the conclusions that can be drawn from this study. Placing these data in context with the literature, it appears that multivitamins do not affect the incidence of CVD in the populations studied. It should be noted, however, that this was a study of generally healthy physicians, and there was not likely to be any major dietary vitamin deficiencies. In addition, the population of this study was entirely male, so the results may not be generalizable to women or those with dietary deficiencies. At the end of the paper, the authors hint that there may be a reduction in risk of cancer with multivitamins, but these data will be presented in a subsequent manuscript. For now, there is no reason to recommend multivitamins for patients for primary or secondary prevention of CVD events.