title: Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Antioxidants, such as vitamin A, C and E, selenium and β-carotene, have been proposed as possible agents in the chemoprevention of colorectal cancer and have been the subject of recent trials and reviews. This review aimed to assess the present evidence on the effect of antioxidants on the incidence of colorectal neoplasms in the general population.
  
  
  METHODS
  A systematic review of randomized controlled trials was undertaken comparing antioxidants alone or in combination with other agents vs placebo. The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers. Studies were quality appraised and extracted. Meta-analysis was performed.
  
  
  RESULTS
  Twelve studies were identified as relevant. In the nine comparing antioxidants with no antioxidants (n=148 922), there was no difference in the incidence of colorectal cancer [relative risk (RR) 1.00, 95% confidence interval (CI) 0.88-1.13]. One study assessed the effect of antioxidants on adenoma formation (n=15 538) and did not demonstrate a statistically significant effect (RR 1.47, 95% CI 0.97-2.23). Of 14 discrete analyses for different combinations of antioxidants, only one reported a statistically significant increase in relative risk of adenoma formation in participants receiving vitamin E (RR 1.74, 95% CI 1.09-1.79, P=0.02) or vitamin E plus β-carotene (RR 1.63, 95% CI 1.01-2.63, P=0.04). Effectiveness did not seem to differ between healthy populations, participants with cardiovascular risk factors or populations exposed to smoking or asbestos.
  
  
  CONCLUSIONS
  The review demonstrates that antioxidants (vitamin A, C and E, selenium and β-carotene), as single agents, in combination with other antioxidants or in combination with other agents, are not effective in the chemoprevention of colorectal neoplasia in the general population. This questions their involvement in future randomized controlled trials of chemoprevention in colorectal cancer.
authors.affiliation: Health Economics and Decision Science (HEDS), School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UK. d.papaioannou@sheffield.ac.uk
authors.forename: D
authors.initials: D
authors.lastname: Papaioannou
authors.forename: K L
authors.initials: KL
authors.lastname: Cooper
authors.forename: C
authors.initials: C
authors.lastname: Carroll
authors.forename: D
authors.initials: D
authors.lastname: Hind
authors.forename: H
authors.initials: H
authors.lastname: Squires
authors.forename: P
authors.initials: P
authors.lastname: Tappenden
authors.forename: R F
authors.initials: RF
authors.lastname: Logan
mesh_terms: D000236:Adenoma / Q000517:prevention & control*; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D006801:Humans; D012643:Selenium / Q000627:therapeutic use; D014801:Vitamin A / Q000627:therapeutic use; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D019207:beta Carotene; D014801:Vitamin A; D014810:Vitamin E; D012643:Selenium; D001205:Ascorbic Acid