Supplements may raise high-grade prostate cancer risk

High-dose supplementation with both selenium and vitamin E increases the risk of high-grade prostate cancer, according to a recent multicenter study. This risk depends upon a man’s selenium status before taking the supplements.

The findings, published online in the Journal of the National Cancer Institute (Feb. 22, 2014), are based on data from the Selenium and Vitamin E Cancer Prevention Trial (SELECT), a randomized, placebo-controlled trial conducted by the SWOG cancer research cooperative group that involved more than 35,000 men. The study sought to determine whether taking high-dose vitamin E (400 IU/day) and/or selenium (200 mcg/day) supplements could protect men from prostate cancer.

SELECT, which began in 2001 and was designed to last 12 years, was stopped early, in 2008, because it found no protective effect from selenium and there was a suggestion that vitamin E increased risk.

While use of the study supplements stopped, men were still followed and after an additional 2 years, the men who took vitamin E had a statistically significant 17% increased risk of prostate cancer.

When the study started, there was some evidence that selenium supplementation would not benefit men who already had an adequate intake of the nutrient. For that reason, researchers measured the concentration of selenium in participants’ toenails and planned to test whether selenium supplementation would benefit only the subset of men with low selenium status at baseline. Instead, they found that taking selenium supplements increased the risk of high-grade cancer by 91% among men with high selenium status at baseline. When selenium supplements were taken by men who had high selenium status to begin with, the levels of selenium became toxic.

The study also found that only a subgroup of men was at increased risk of prostate cancer from taking vitamin E. Among men with low selenium status at baseline, vitamin E supplementation increased their total risk of prostate cancer by 63% and increased the risk of high-grade cancer by 111%. This explained one of the original SELECT findings, which was that only men who received vitamin E plus a placebo pill, and not those who received both vitamin E and selenium, had an increased prostate cancer risk. Selenium, whether from dietary sources or supplements, protected men from the harmful effects of vitamin E.

“Many people think that dietary supplements are helpful or at the least innocuous. This is not true,” said first author Alan Kristal, DrPH, of Fred Hutchinson Cancer Center, Seattle. “We know from several other studies that some high-dose dietary supplements-that is, supplements that provide far more than the daily recommended intakes of micronutrients-increase cancer risk. We knew this based on randomized, controlled, double-blinded studies for folate and beta carotene, and now we know it for vitamin E and selenium.”

The data for the current analysis compared the effect of selenium and vitamin E, taken either alone or combined, on prostate cancer risk among 1,739 men who were diagnosed with prostate cancer and, for comparison purposes, a random sample of 3,117 men without prostate cancer who were matched to the cases by race and age.

The study, which was funded by the National Cancer Institute, showed no benefits to any men from either selenium or vitamin E supplements, and for significant proportions of men in the study these supplements were harmful.

“Men using these supplements should stop, period,” Dr. Kristal said. “Neither selenium nor vitamin E supplementation confers any known benefits-only risks. While there appear to be no risks from taking a standard multivitamin, the effects of high-dose single supplements are unpredictable, complex, and often harmful. Taking a broad view of the recent scientific studies, there is an emerging consistency about how we think about optimal intake of micronutrients. There are optimal levels, and these are often the levels obtained from a healthful diet, but either below or above the levels there are risks.”

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