This systematic review investigated the effects of antioxidant supplements on prevention of mortality in adults. The Cochrane Library, MEDLINE, EMBASE, LILACS, the Science Citation Index Expanded, and Conference Proceedings Citation Index- Science were searched. Seventy-eight primary and secondary prevention randomized clinical trials (N = 296,707) on antioxidant supplements versus placebo or no interventions were included. Overall, antioxidant supplements had no significant effect on mortality in a random-effects model but significantly increased mortality in a fixed-effect model. In 56 trials with a low risk of bias, antioxidant supplements significantly increased mortality (RR 1.04; 95% CI 1.01-1.07). Excluding factorial trials with potential confounding, 38 trials with low risk of bias demonstrated a significant increase in mortality (RR 1.10; 95% CI 1.05-1.15). In trials with low risk of bias, beta-carotene (26 trials; RR 1.05; 95% CI 1.01-1.09) and vitamin E (46 trials; RR 1.03; 95% CI 1.00-1.05) significantly increased mortality, whereas vitamin A (12 trials; RR 1.07; 95% CI 0.97-1.18), vitamin C (29 trials; RR 1.02; 95% CI 0.98-1.07), and selenium (17 trials; RR 0.97; 95% CI 0.91-1.03) did not significantly affect mortality. Dose of vitamin A was associated with increased mortality (P = 0.002). Cochrane Database Syst Rev. 2012 Mar 14;3:CD007176. PMID: 22419320
