How Selenium, Vitamin E Increase Prostate Cancer Risk

New data from the much publicized Selenium and Vitamin E Cancer Prevention Trial (SELECT), which sought to determine whether these supplements could protect against the development of prostate cancer, confirm that both antioxidants can be risky business for men.

As previously reported, men receive no preventive benefit from either selenium or vitamin E supplements; in fact, for certain men, these supplements actually increased the risk for prostate cancer.

The new study, published online February 22 in the Journal of the National Cancer Institute, explored which men who take these supplements are most at risk for prostate cancer, and why.

However, the ongoing public health message from the trial remains the same, said a trial investigator.

"Men using these supplements should stop, period. Neither selenium nor vitamin E supplementation confer any known [health] benefits — only risks," said lead author Alan Kristal, DrPH, from the Fred Hutchinson Cancer Research Center in Seattle, in a press statement.

"Many people think that dietary supplements are helpful or at the least innocuous. This is not true," he added.

The cohort of 4856 men was culled from SELECT, the larger phase 3 placebo-controlled trial in which more than 35,000 men were randomized to high-dose vitamin E (400 IU/day) and/or selenium (200 µg/day) supplements.

SELECT began in 2001 and was expected to run for 12 years, but it was stopped early, in 2008, after participants had been on the supplements for an average of 5 years. The results demonstrated that there was no protective effect from selenium and suggested that vitamin E increased prostate cancer risk.

Although the use of the supplements stopped, the study actually continued. After 2 years of follow-up, the men who took vitamin E had a statistically significant 17% increased risk for prostate cancer, as previously reported.

Notably, the rate of prostate cancer detection was higher in the groups that received either supplement alone or a combination of the 2 than in the placebo group (but the difference was significant only in the vitamin E group).

Selenium is a nonmetallic trace element found in plant in foods such as rice, wheat, and Brazil nuts, and in seafood and meat. In a previous large skin cancer prevention trial, it was associated with a reduced risk for prostate cancer. According to the National Cancer Institute, it is an antioxidant that might help control cell damage that can lead to cancer.

Vitamin E is found in a wide range of foods, especially vegetables, vegetable oils, nuts, and egg yolks. Like selenium, vitamin E is considered an antioxidant.

Key: Increased Risk Depends on Baseline Selenium
In this new case–cohort study, 1739 men diagnosed with prostate cancer during SELECT were compared with 3117 men who were not.

Dr. Kristal and colleagues found that baseline selenium status alone, in the absence of supplementation, was not associated with prostate cancer risk.

However, they also found that the effects of the supplements differed substantially between men with low levels at baseline and those with high levels.

Specifically, selenium supplementation increased the risk for prostate cancer in men who already had high selenium levels at baseline.

Before SELECT even began, there was evidence that selenium supplementation would not benefit men who already had an adequate intake of the nutrient.

For this reason, at baseline, the investigators measured the concentration of selenium in the toenails of participants. The plan was to test whether supplementation would benefit only the subset of men with low selenium levels at baseline, they explain.

Instead, they found that men with high selenium levels at baseline who took selenium supplements increased their risk for high-grade cancer by 91% (P = .007). In other words, the levels of selenium in these men became toxic.

The investigators also report that vitamin E increased prostate cancer risk in men, but only in those with low selenium levels at baseline.

Specifically, in the men with low levels of selenium randomized to receive vitamin E alone, the total risk for prostate cancer increased by 63% (P = .02) and the risk for high-grade cancer increased by 111% (P = .01).

This might explain why, in the 2008 SELECT results, only the men randomized to receive vitamin E alone, not those who received both vitamin E and selenium, had an increased risk for prostate cancer.

There is some evidence from basic science to support the idea of a meaningful dynamic. "An interaction between vitamin E and selenium has long been hypothesized because of their activities in preventing lipid peroxidation," Dr. Kristal and colleagues write.

Selenium, whether from dietary sources or supplements, might protect men from the harmful effects of vitamin E, they suggest. So selenium, at low levels, is not necessarily harmful to men.

Nevertheless, these new results are consistent with the medical literature on supplements and cancer, the investigators report. The message is that nothing good is gained in healthy people.

The literature "suggests that effects of supplementation are dependent upon the nutrient status of the target population, such that supplementation of populations with adequate nutrient status, leading to supraphysiological exposure, has either no effect or increases cancer risk," they write.