REVIEW Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention Systematic Review and Meta-analysis

OXIDATIVE STRESS IS IMPLI-cated in most human dis-eases.1,2 Antioxidants maydecrease the oxidative damage and its alleged harmful ef-fects.3-6 Many people are taking anti-oxidant supplements, believing to im-prove their health and prevent diseases.7-10 Whether antioxidant supplements are beneficial or harmful is uncertain.11-15 Many primary or sec-ondary prevention trials of antioxi-dant supplements have been con-ducted to prevent several diseases. We found that antioxidant supple-ments, with the potential exception of selenium, were without significant effects on gastrointestinal cancers and increased all-cause mortality.14,15 We did not examine the effect of antioxidant supplements on all-cause mortality in all randomized preven-tion trials.16 Our aim with the pres-ent systematic review was to analyze the effects of antioxidant supple-ments (beta carotene, vitamins A and E, vitamin C [ascorbic acid], and selenium) on all-cause mortality of adults included in primary and sec-ondary prevention trials. METHODS The present review follows the Coch-raneCollaborationmethod17 and isbased on the principles of our peer-reviewed protocol and review on antioxidant supplements for gastrointestinal cancer prevention.14,15,18,19 We included all pri-mary and secondary prevention trials in adults randomized to receive beta caro