Vitamin E May Raise Prostate Cancer Risk

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Eric A. Klein, MD
Eric A. Klein, MD

Men who take vitamin E supplements may be at increased risk of prostate cancer (PCa), new findings show.

Analysis of longer follow-up data from participants in the Selenium and Vitamin E Cancer Prevention Trial (SELECT)—a double-blind, placebo-controlled study that enrolled 35,533 men in the United States, Canada, and Puerto Rico—revealed that subjects who took vitamin E alone had a statistically significant 17% increased risk of PCa compared with those who took placebo.

Put another way, 76 cases of PCa were diagnosed in every 1,000 men who took vitamin E; 65 cases were diagnosed in every 1,000 who took placebo, according to lead investigator Eric A. Klein, MD, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic.

Earlier findings from SELECT showed that men who took vitamin E and selenium or both substances together experienced no significant change in their PCa risk.

Previous preclinical and epidemiological studies suggested that vitamin E and selenium may decrease PCa risk, so the finding of no benefit—and even potential harm with vitamin E—was unexpected. “Almost all of the data going into the design of SELECT suggested that these agents would be beneficial,” Dr. Klein said.

The SELECT findings should serve to educate the public. “We tend to think of vitamins and nutritional supplements as innocuous substances, but they're not. They're really part of our biology, and too much of them can be harmful,” Dr. Klein said.

Dr. Klein and his collaborators published their findings in the Journal of the American Medical Association (2011;306:1549-1556), where they concluded: “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.”

In SELECT, investigators randomly assigned men to receive selenium alone, vitamin E alone, a combination of the two supplements, or placebo. After a median 5.5 years of follow-up, researchers observed no significant reduction in PCa risk with either selenium, vitamin E, or both selenium and vitamin E compared with placebo. The trial was stopped, and men stopped taking the supplements. Researchers observed the 17% increased risk after another 18 months of follow-up  (seven years total follow-up).

The absence of a significantly increased PCa risk the vitamin E and selenium combination arm suggests that “selenium may have a protective effect by dampening the increased risk associated with vitamin E alone,” the authors observed.

Researchers do not have a biological explanation for why vitamin E raises PCa risk, Dr. Klein said. He pointed out that SELECT included a large biorepository of blood, DNA, and toenails (for measuring selenium levels), “and we've opened that biorepository to the wide scientific community to propose hypotheses that might explain the findings.”

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