Antioxidants in the chemoprevention of colorectal cancer and colorectal adenomas in the general population: a systematic review and meta-analysis

Aim Antioxidants, such as vitamin A, C and E, selenium and beta-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. Method 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 The following databases were searched for published and unpublished literature: Cochrane Library, MEDLINE, PreMEDLINE, CINAHL, EMBASE, Web of Science, and Biological Abstracts and Research Registers.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 beta-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. Conclusion The review demonstrates that antioxidants (vitamin A, C and E, selenium and beta-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.