title: Efficacy of antioxidant supplementation in reducing primary cancer incidence and mortality: systematic review and meta-analysis.
abstract: OBJECTIVE
  To estimate the association between antioxidant use and primary cancer incidence and mortality and to evaluate these effects across specific antioxidant compounds, target organs, and participant subgroups.
  
  
  METHODS
  Multiple electronic databases (MEDLINE, Cochrane Controlled Clinical Trials Register, EMBASE, Science Citation Index) were searched from their dates of inception until August 2005 to identify eligible randomized clinical trials. Random effects meta-analyses estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) that described the effect of antioxidants vs placebo on cancer incidence and cancer mortality.
  
  
  RESULTS
  Twelve eligible trials, 9 of high methodological quality, were identified (total subject population, 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or mortality (RR, 1.03; 95% CI, 0.92-1.15) or any site-specific cancer incidence. Beta carotene supplementation was associated with an increase in the incidence of cancer among smokers (RR, 1.10; 95% CI, 1.03-1.10) and with a trend toward increased cancer mortality (RR, 1.16; 95% CI, 0.98-1.37). Selenium supplementation was associated with reduced cancer incidence in men (RR, 0.77; 95% CI, 0.64-0.92) but not in women (RR, 1.00; 95% CI, 0.89-1.13, value for interaction, P< .001) and with reduced cancer mortality (RR, 0.78; 95% CI, 0.65-0.94). Vitamin E supplementation had no apparent effect on overall cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or cancer mortality (RR, 1.04; 95% CI, 0.97-1.12).
  
  
  CONCLUSIONS
  Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects in men and thus requires further research.
authors.affiliation: Department of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bardia
authors.forename: Imad M
authors.initials: IM
authors.lastname: Tleyjeh
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Amit K
authors.initials: AK
authors.lastname: Sood
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D009369:Neoplasms / Q000401:mortality* / Q000517:prevention & control*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants