Systematic review: primary and secondary prevention of gastrointestinal cancers with antioxidant supplements

Aliment Pharmacol Ther. 2008 Sep 15;28(6):689-703. doi: 10.1111/j.1365-2036.2008.03785.x.


Background: The evidence on whether antioxidant supplements prevent gastrointestinal cancers is contradictory.

Aim: To assess the beneficial and harmful effects of antioxidant supplements in preventing gastrointestinal cancers.

Methods: Using the Cochrane Collaboration methodology, we reviewed the randomized trials comparing antioxidant supplements with placebo or no intervention on the occurrence of gastrointestinal cancers. We searched electronic databases and reference lists until October, 2007. Our outcome measures were gastrointestinal cancers, overall mortality and adverse events. Outcomes were reported as relative risks (RR) with 95% confidence intervals (CI) based on random-effects and fixed-effect models meta-analyses.

Results: We identified 20 randomized trials (211,818 participants) assessing beta-carotene, vitamin A, vitamin C, vitamin E, and selenium. The trial quality was generally high. The antioxidant supplements were without a significant effect on the occurrence of gastrointestinal cancers (RR 0.94, 95% CI 0.83-1.06, I(2) = 54.0%). The heterogeneity seemed to be explained by bias risk (low-bias risk trials RR 1.04, 95% CI 0.96-1.13 compared to high-bias risk trials RR 0.59, 95% CI 0.43-0.80, test of interaction P < 0.0005) and type of antioxidant supplement (beta-carotene potentially increasing and selenium potentially decreasing cancer risk). Antioxidant supplements had no significant effect on mortality in a random-effects model meta-analysis (RR 1.02, 95% CI 0.97-1.07, I(2) = 53.5%) but significantly increased mortality in a fixed-effect model meta-analysis (RR 1.04, 95% CI 1.02-1.07).

Conclusions: We could not find evidence that the studied antioxidant supplements prevented gastrointestinal cancers. On the contrary, they seem to increase overall mortality.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antioxidants / therapeutic use*
  • Ascorbic Acid / therapeutic use
  • Bias
  • Carotenoids / therapeutic use
  • Dietary Supplements*
  • Drug Therapy, Combination
  • Female
  • Gastrointestinal Neoplasms / epidemiology
  • Gastrointestinal Neoplasms / prevention & control*
  • Humans
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Randomized Controlled Trials as Topic
  • Selenium / therapeutic use
  • Vitamin E / therapeutic use
  • Young Adult


  • Antioxidants
  • Vitamin E
  • Carotenoids
  • Selenium
  • Ascorbic Acid