Vitamins E and C in the Prevention of Prostate and Total Cancer in Men The Physicians' Health Study II Randomized Controlled Trial

Context Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large- scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. Objective To evaluate whether long- term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. Design, Setting, and Participants The Physicians' Health Study II is a randomized, double- blind, placebo- controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14 641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. Intervention Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. Main Outcome Measures Prostate and total cancer. Results During a mean follow- up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer ( active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person- years; hazard ratio [ HR], 0.97; 95% confidence interval [ CI], 0.85- 1.09; P=. 58) or total cancer ( active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person- years; HR, 1.04; 95% CI, 0.95- 1.13; P=. 41). There was also no significant effect of vitamin C on total cancer ( active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person- years; HR, 1.01; 95% CI, 0.92- 1.10; P=. 86) or prostate cancer ( active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person- years; HR, 1.02; 95% CI, 0.90- 1.15; P=. 80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site- specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow- up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. Conclusions In this large, long- term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle- aged and older men. Trial Registration clinicaltrials. gov Identifier: NCT00270647.