Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases
Abstract
Background
Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival.
Objectives
To assess the effect of antioxidant supplements on mortality in primary or secondary prevention randomised clinical trials.
Search methods
We searched The Cochrane Library (Issue 3, 2005), MEDLINE (1966 to October 2005), EMBASE (1985 to October 2005), and the Science Citation Index Expanded (1945 to October 2005). We scanned bibliographies of relevant publications and wrote to pharmaceutical companies for additional trials.
Selection criteria
We included all primary and secondary prevention randomised clinical trials on antioxidant supplements (beta‐carotene, vitamin A, vitamin C, vitamin E, and selenium) versus placebo or no intervention. Included participants were either healthy (primary prevention trials) or had any disease (secondary prevention trials).
Data collection and analysis
Three authors extracted data. Trials with adequate randomisation, blinding, and follow‐up were classified as having a low risk of bias. Random‐effects and fixed‐effect meta‐analyses were performed. Random‐effects meta‐regression analyses were performed to assess sources of intertrial heterogeneity.
Main results
Sixty‐seven randomised trials with 232,550 participants were included. Forty‐seven trials including 180,938 participants had low risk of bias. Twenty‐one trials included 164,439 healthy participants. Forty‐six trials included 68111 participants with various diseases (gastrointestinal, cardiovascular, neurological, ocular, dermatological, rheumatoid, renal, endocrinological, or unspecified). Overall, the antioxidant supplements had no significant effect on mortality in a random‐effects meta‐analysis (relative risk [RR] 1.02, 95% confidence interval [CI] 0.99 to 1.06), but significantly increased mortality in a fixed‐effect model (RR 1.04, 95% CI 1.02 to 1.06). In meta‐regression analysis, the risk of bias and type of antioxidant supplement were the only significant predictors of intertrial heterogeneity. In the trials with a low risk of bias, the antioxidant supplements significantly increased mortality (RR 1.05, 95% CI 1.02 to 1.08). When the different antioxidants were assessed separately, analyses including trials with a low risk of bias and excluding selenium trials found significantly increased mortality by vitamin A (RR 1.16, 95% CI 1.10 to 1.24), beta‐carotene (RR 1.07, 95% CI 1.02 to 1.11), and vitamin E (RR 1.04, 95% CI 1.01 to 1.07), but no significant detrimental effect of vitamin C (RR 1.06, 95% CI 0.94 to 1.20). Low‐bias risk trials on selenium found no significant effect on mortality (RR 0.90, 95% CI 0.80 to 1.01).
Authors' conclusions
We found no evidence to support antioxidant supplements for primary or secondary prevention. Vitamin A, beta‐carotene, and vitamin E may increase mortality. Future randomised trials could evaluate the potential effects of vitamin C and selenium for primary and secondary prevention. Such trials should be closely monitored for potential harmful effects. Antioxidant supplements need to be considered medicinal products and should undergo sufficient evaluation before marketing.
PICOs
Plain language summary
No evidence to support antioxidant supplements to prevent mortality in healthy people or patients with various diseases
Previous research on animal and physiological models suggest that antioxidant supplements have beneficial effects that may prolong life. Some observational studies also suggest that antioxidant supplements may prolong life, whereas other observational studies demonstrate neutral or harmful effects. Randomised trials have largely been neutral. We need evidence from randomised trials to decide if antioxidant supplements should be used for prevention.
