Study: Vitamin E and Selenium Increased Prostate Cancer Risk

New data from the long-term SELECT trial shows that men given high-dose supplementation of both selenium and vitamin E had a higher risk of developing high-grade prostate cancer.

New data from the long-term Selenium and Vitamin E Cancer Prevention Trial (SELECT) shows that men given high-dose supplementation of both selenium and vitamin E had a higher risk of developing high-grade prostate cancer. The study shows that the higher risk depends on the level of selenium already present in the body prior to starting the supplementation. No benefit of supplementation with either selenium or vitamin E was seen in any subgroups. These new results are published in the March issue of the Journal of the National Cancer Institute.

The SELECT trial, a placebo-controlled randomized trial that started in 2001, involved 35,000 men and studied whether a relatively high-dose of daily vitamin E (400 IU per day) and/or selenium (200 mcg per day) would protect men from prostate cancer. Although scheduled to go on until 2013, the trial was stopped early in 2008 when analyses showed no benefit from selenium on prostate cancer risk. Men in the study had received supplements for an average of 5 years. A 2-year follow-up after the men had stopped taking the supplements suggested that the supplemental vitamin E increased prostate cancer risk by 17%.

Recently, study results have questioned the health benefits of a daily multi-vitamin for the average person. This study now shows that specific high-dose supplements of vitamins may even be harmful. "Many people think that dietary supplements are helpful or at the least innocuous. This is not true," said Alan Kristal, DrPH, a faculty member in the Public Health Sciences Division of Fred Hutch and lead author of the study in a press release. "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."

At the start of the study in 2001, researchers measured the amount of selenium using toenail samples from the participants and set out to test whether those men with low selenium levels at baseline would benefit from selenium supplementation. Instead, the new analysis found that selenium supplementation increased the risk of high-grade prostate cancer by 91% (P = .007) in men with higher baseline selenium levels. No effect of the selenium supplementation on prostate cancer risk was found in men who started out with low selenium levels.

Vitamin E supplements did not affect those men who started out with high selenium levels (greater than the 40th percentile of selenium as measured using toenail samples) but it did increase low- and high-grade prostate cancer in those who had lower selenium levels. Men with low levels of selenium at baseline who received vitamin E supplementation had an increased risk of prostate cancer of 63% (P = .02). The increase of high-grade prostate cancer increased by 111% (P = .01).

Selenium status at baseline alone was not linked with risk of prostate cancer.

The new analysis of the case-cohort study included 1,739 men diagnosed with prostate cancer (including 489 diagnosed with high-grade disease) and 3,117 not diagnosed.

Most of the men with prostate cancer (92.7%) were diagnosed with prostate cancer prior to the discontinuation of the supplements on the trial.

In their discussion, the authors note that there is not likely to be another trial to test high-dose selenium or vitamin E supplements for the primary prevention of prostate cancer.

"Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confers any known benefits-only risks," Kristal said, in a statement.

"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."