Researchers warn against broad use of selenium supplementation

Men with high selenium levels and SOD2 genotypes VA and VV were at increased risk for aggressive prostate cancer.

The results of several recently released studies have questioned the widespread use of selenium in men with prostate cancer.

In a new study, published in The Journal of Clinical Oncology, June M. Chan, ScD, and colleagues have concluded that a certain variant of the SOD2 genotype combined with high plasma selenium levels increased risk for aggressive prostate cancer twofold in men already diagnosed with the disease.

However, they also found that a different variant of the SOD2 genotype had a protective effect for about 25% of patients who had the SOD2 genotype and high selenium levels.

Researchers performed a cross-sectional analysis of 489 men with localized or locally advanced prostate cancer. Median PSA was 6.0 ng/mL and median age was 62. Median selenium level for the entire cohort was 121 mcg/L (64 mcg/L-221 mcg/L).

They found that among men with a V allele, those with high selenium levels were at increased risk for aggressive prostate cancer whether they were had the “VV” variant (RR=2.48; 95% CI, 1.07-5.71) or the “VA” variant (RR=1.59; 95% CI, 1.07-2.35). The association between selenium level and aggressive disease was “clearly dependent on SOD2” and the interaction remained constant for men with a V allele through all quintiles of selenium.

“We observed strong support for the hypothesis that plasma selenium levels and SOD2 genotype interact to influence risk of presenting with aggressive prostate cancer at diagnosis in men with localized or locally advanced prostate cancer,” the researchers wrote.

Men with the “AA” genotype who had the highest selenium levels had a 40% decreased risk for aggressive disease that the researchers said was “borderline significant.” They suggested that the AA genotype might be more effective at carrying antioxidants through the mitochondrial membrane, which aids the breakdown of superoxide radicals into hydrogen peroxide.

Selenium’s track record

Researchers have been looking for a protective effect with selenium without success for years. The SELECT trial was stopped in October after initial analysis showed that supplementation with selenium and vitamins E and C did not have a preventive effect in prostate cancer. Further analysis presented at the American Urological Society Annual Meeting in April showed no preventive effect from selenium, vitamin E and soy.

In an accompanying editorial, Elizabeth A. Platz, MD, and Scott M. Lippman, MD, wrote that the results of Chan et al generate two hypotheses: 1) Selenium supplementation does not decrease risk except possibly in selenium-deficient populations and 2) Supplementation possibly increases risk for prostate cancer, especially aggressive disease, in selenium-replete men or men with a particular genotype for antioxidant enzymes.

“These hypotheses . . . suggest the need for personalized risk prediction. At present, we do not know enough to determine how much selenium any man or woman should receive from the diet or a supplement,” they wrote. “This lack of knowledge supports the common public health recommendation of moderation with respect to supplements for men and women.”

Platz and Lippman wrote that the best methods of disease prevention are simple: eat well, exercise, avoid smoking and drink only in moderation. “Unlike the prospect of personalized chemoprevention, this is not new or exciting advice, but it is common sense,” they wrote.

Chan JM. J Clin Oncol. 2009;doi:10.1200/JCO.18.8938.

Platz EA. J Clin Oncol. 2009;doi:10.1200/JCO.22.2117.