A meta-analysis that included 78 randomized clinical trials was conducted to determine the relationship of oral antioxidant supplementation (beta-carotene, vitamin A, vitamin C, vitamin E, and selenium) and mortality. Mean duration of supplementation was 3 years. When all of the trials were combined, and the analysis that is typically used when similarity is present was conducted (fixed-effect model), antioxidant use did slightly increase mortality. When the trials with low risks of bias were considered, the patients consuming the antioxidants had a 4% higher risk of death compared to those taking placebo or no intervention (relative risk [RR]=1.04). The increased risk of mortality was significantly associated with use of beta-carotene (death rate: 13.8% on supplement vs 11.1% on placebo; RR=1.05) and vitamin E (12.0% vs 10.3%; RR=1.03) and possibly vitamin A, though the relationship was not significant with a 14.0% death rate among those taking vitamin A compared to a 13.6% death rate among placebo subjects. The current evidence does not support the use of these antioxidant supplements in the general population or in patients with various diseases. (101)
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