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

There has been concern that long‐term supplementation with high‐dose antioxidant vitamins, especially vitamin E (α‐tocopherol), may increase all‐cause mortality. We conducted a randomized controlled trial with α‐tocopherol (400 IU/day) and β‐carotene (30 mg/day) supplements among 540 head and neck cancer patients treated by radiation therapy. Supplementation with β‐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. © 2006 Wiley‐Liss, Inc.