Antioxidant supplementation with Vitamins C and E and beta carotene, singly or in combination, does not appear to reduce the risk of cardiovascular events or death in women at high risk for heart disease, according to an article in the August 13 issue of Archives of Internal Medicine.

“Antioxidants scavenge free radicals and limit the damage they can cause,” the authors wrote. “Diets high in fruit and vegetable intake, and thus rich in such antioxidants, have been associated with reduced rates of coronary heart disease and stroke. Vitamins C and E and beta carotene are potential mediators of the apparent protective effect of a plant-based diet on cardiovascular disease.”

Nancy R. Cook, ScD, of Brigham & Women’s Hospital and Harvard Medical School, Boston, and colleagues tested the effects of these compounds in the Women’s Antioxidant Cardiovascular Study, which followed 8,171 women 40 years or older (average, 60.6 years) beginning in 1995-1996.

The women, who either had a history of cardiovascular disease or three or more risk factors, were randomly assigned to take 500 mg ascorbic acid or placebo every day; 600 IU vitamin E or placebo every other day; and 50 mg of beta carotene or placebo every other day.

Participants were followed for occurrence of cardiovascular events (including stroke, myocardial infarction, and bypass surgery) or death through 2005. During the average follow-up of 9.4 years, 1,450 women had one or more cardiovascular events, including 274 myocardial infarctions, 298 strokes, 889 coronary revascularization procedures, and 395 cardiovascular deaths (of a total 995 deaths).

“There was no overall effect of ascorbic acid, vitamin E or beta carotene on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization or cardiovascular disease death,” the authors wrote. “There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes.”

No additional adverse effects were observed for those taking active pills versus placebo, with the exception of a small increase in reports of gastrointestinal upset among those taking active beta carotene.

“Overall, we found no benefit on the primary combined end point for any of the antioxidant agents tested, alone or in combination,” the authors concluded. “We also found no evidence for harm. While additional research into combinations of agents, particularly for stroke, may be of interest, widespread use of these individual agents for cardiovascular protection does not appear warranted.”