Randomized trials of dietary antioxidants in cardiovascular disease prevention and treatment.

The hypothesis that antioxidant vitamins might reduce cardiovascular disease risk is based on a large body of basic and human epidemiologic research. Basic research provides a plausible mechanism by which antioxidants might reduce the risk of atherosclerosis. A large number of descriptive, case-control and cohort studies provide data suggesting that consumption of antioxidant vitamins is associated with reduced risks of cardiovascular disease. These data raise the question of a role of antioxidants, such as vitamins C and E, and beta-carotene, in the primary prevention of cardiovascular disease, but do not provide a definitive answer. Randomized trial data will be essential in establishing whether or not there is a causal effect of antioxidants in reducing the risk of cardiovascular disease. For many hypotheses randomized trials are neither necessary nor desirable; however, when searching for small to moderate effects, large-scale randomized trials of adequate dose and duration, in which investigators allocate subjects at random to either active treatment or placebo will provide valuable information about whether there is a causal relationship, and provide reliable estimates of effect size. Results from several large-scale randomized trials of antioxidants are summarized in this paper. At present, there is not sufficient data available to define clearly the role of antioxidants in primary or secondary prevention of cardiovascular disease. Additional trial data should be forthcoming in the near future which will aid in individual clinical decision-making and in the establishment of guidelines for the general public.