Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials

Methods: We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. Results: Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96-1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97-1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83-1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06-2.17) in a subgroup meta-analysis of four trials. Conclusions: The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.