Does antioxidant supplementation reduce primary cancer incidence and mortality?: Systematic review and meta analysis.

A159

Background: Antioxidant (beta carotene, vitamin E, selenium) supplementation has been postulated to prevent cancer; however, data from randomized clinical trials remain inconsistent. The aim of this systematic review was to estimate whether antioxidants reduce cancer incidence and cancer mortality. Methods: Randomized clinical trials wherein subjects received supplementation with one or more antioxidants versus placebo were included. Studies were identified by searching relevant electronic databases (MEDLINE, CENTRAL, EMBASE, Science Citation Index) from inception until August 2005 and data from eligible trials was extracted by two independent reviewers. Random effects meta-analyses of associations between antioxidants versus placebo on cancer incidence and cancer mortality were conducted to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results: 12 eligible trials, 10 of high methodological quality, were identified (total subject population: 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (RR=0.99, CI: 0.94, 1.04) or mortality (RR=1.03, CI: 0.92, 1.15) or any site-specific cancer incidence. Beta carotene increased in the incidence of smoking (lung, head and neck, upper gastrointestinal and bladder) related cancer (RR: 1.14, 95% CI: 1.06, 1.24), and cancer mortality (RR=1.13, CI: 0.1.00, 1.28). Selenium reduced cancer incidence in men (RR: 0.70, 95% CI: 0.59, 0.82), but not in women (RR: 1.08, 95% CI: 0.90, 1.30; P interaction <.001), and cancer mortality (RR=0.78, CI: 0.65, 0.94). Vitamin E had no effect on overall cancer incidence (RR=0.99, CI: 0.94,1.04 ;) or cancer mortality (RR=1.04, CI: 0.97,1.12). The results remained similar after we excluded the trials with low quality, trials stopped early for harm, or used the inverse log method to pool results. Conclusion: The best available evidence suggests that and vitamin E supplementation does not have any effect on cancer incidence, but beta carotene may increase the risk of smoking related cancers and cancer mortality. Selenium supplementation might provide some anti-cancer effects, especially among males and further studies are needed to confirm the observed selenium effect.