Klein EA, Thompson IM Jr, Tangen CM, et al.
What is the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men?
A total of 35,533 men from 427 study sites in the United States, Canada, and Puerto Rico were randomized between August 22, 2001, and June 24, 2004, in the SELECT study (Selenium and Vitamin E Cancer Prevention Trial). Eligibility criteria included a prostate-specific antigen (PSA) of 4.0 ng/ml or less, a digital rectal examination not suspicious for prostate cancer, and age 50 years or older for black men and 55 years or older for all others. The primary analysis included 34,887 men who were randomly assigned to one of four treatment groups: 8,752 to receive selenium; 8,737 vitamin E; 8,702 both agents; and 8,696 placebo. With a median follow-up of 5.5 years, there was no benefit from either antioxidant or combination, but there was a signal for increased prostate cancer. This analysis reflects the final data collected by the study sites on their participants, with extension through July 5, 2011.
This report includes 54,464 additional person-years of follow-up (median 7 years) and 521 additional cases of prostate cancer since the primary report. Compared with the placebo (referent group) in which 529 men developed prostate cancer, 620 men in the vitamin E group developed prostate cancer (hazard ratio [HR], 1.17; 99% confidence interval [CI], 1.004-1.36; p = 0.008); as did 575 in the selenium group (HR, 1.09; 99% CI, 0.93-1.27; p = 0.18), and 555 in the selenium plus vitamin E group (HR, 1.05; 99% CI, 0.89-1.22; p = 0.46). Compared with placebo, the absolute increase in risk of prostate cancer per 1,000 person-years was 1.6 for vitamin E, 0.8 for selenium, and 0.4 for the combination.
The authors concluded that dietary supplementation with vitamin E significantly increased the risk of prostate cancer among healthy men.
The antioxidant supplement story continues to evolve with no evidence of benefit for cancer or cardiovascular disease risk reduction from beta carotene, folate, vitamin E, selenium, or vitamin C, and increased risk of lung cancer with high-dose beta carotene and risk of polyps with high-dose folate. Yet so many patients take large doses, some of which is prescribed by well-intended physicians including specialists in aging/dementia, ophthalmology, and urology. The authors concluded with the following message for providers and the public: ‘The lack of benefit from dietary supplementation with vitamin E or other agents with respect to preventing common health conditions and cancers or improving overall survival, and their potential harm, underscore the need for consumers to be skeptical of health claims for unregulated over-the-counter products in the absence of strong evidence of benefit demonstrated in clinical trials.’ Clearly, long-term implications of taking nutraceuticals and dietary supplements are not known and very hard to assess.
Melvyn Rubenfire, M.D., F.A.C.C. (Disclosure)
POSTED BY DAVID CRAGG, MD