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No Role for Vitamin E or Vitamin C in the Prevention of Cardiovascular Disease in Men

Findings from a large randomized trial confirm that supplementation confers no benefit and suggest that vitamin E might increase risk for hemorrhagic stroke.

Although laboratory research suggests that antioxidants, including vitamins E and C, might be of value in reducing incident cardiovascular disease, observational and clinical studies have produced conflicting results. To assess whether long-term vitamin supplementation decreases the risk for major cardiovascular events in men, investigators for the Physicians’ Health Study II used a factorial design to randomize 14,641 male physicians in the U.S. to 400 IU of vitamin E every other day, 500 mg of vitamin C daily, both, or placebo. The primary study outcome was a composite of major cardiovascular events including nonfatal MI, nonfatal stroke, and cardiovascular death.

During a mean follow-up of 8 years, >1200 major cardiovascular events occurred among the subjects. Compared with placebo, assignment to vitamin E or C had no significant effect on the incidence of the primary outcome or of the individual secondary outcomes of nonfatal MI and cardiovascular death. Interestingly, men in the vitamin E–alone group had an increased risk for hemorrhagic stroke compared with those in the placebo group (hazard ratio, 1.74; P=0.04).

Comment: In this large, randomized, double-blind, placebo-controlled, factorial trial of male physicians, neither vitamin E nor vitamin C supplementation was associated with reductions in cardiovascular events. In fact, an increase in hemorrhagic stroke was associated with the use of vitamin E. These data do not support the use of either vitamin C or E in the prevention of cardiovascular disease in middle-aged or older men.

— JoAnne M. Foody, MD

Published in Journal Watch Cardiology November 12, 2008

Citation(s):

Sesso HD et al. Vitamins E and C in the prevention of cardiovascular disease in men: The Physicians’ Health Study II randomized controlled trial. JAMA 2008 Nov 12; 300:2123.

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