Antioxidant vitamins supplementation and mortality: a randomized trial in head and neck cancer patients

Int J Cancer. 2006 Nov 1;119(9):2221-4. doi: 10.1002/ijc.22042.


There has been concern that long-term supplementation with high-dose antioxidant vitamins, especially vitamin E (alpha-tocopherol), may increase all-cause mortality. We conducted a randomized controlled trial with alpha-tocopherol (400 IU/day) and beta-carotene (30 mg/day) supplements among 540 head and neck cancer patients treated by radiation therapy. Supplementation with beta-carotene was discontinued during the trial. The supplements were given during radiation therapy and for 3 additional years. During the follow-up (median 6.5 years), 179 deaths were recorded. All death certificates were obtained. All-cause and cause-specific mortality rates were compared between the 2 arms of the trial by Cox regression. All-cause mortality was significantly increased in the supplement arm: hazard ratio: 1.38, 95% confidence interval 1.03-1.85. Cause-specific mortality rates tended to be higher in the supplement arm than in the placebo arm. Our results concur with previous reports to suggest that high-dose vitamin E could be harmful.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / therapeutic use*
  • Dietary Supplements
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / mortality
  • Humans
  • Placebos
  • Survival Analysis
  • Vitamins / administration & dosage
  • Vitamins / therapeutic use*
  • alpha-Tocopherol / therapeutic use
  • beta Carotene / therapeutic use


  • Antioxidants
  • Placebos
  • Vitamins
  • beta Carotene
  • alpha-Tocopherol