Influence of selenium-enriched yeast supplementation on biomarkers of oxidative damage and hormone status in healthy adult males: a clinical pilot study.

The mechanisms responsible for the protective role of selenium against the development of prostate cancer remain to be determined (L. C. Clark et al., J. Am. Med. Assoc., 276: 1957-1963, 1996). In the present study, we tested the hypothesis that selenium supplementation reduces oxidative stress. A secondary aim was to determine whether selenium-induced changes in testosterone (T) metabolism may also be involved. To this end, we conducted a double-blind, randomized, placebo-controlled trial of 247 micro g selenium/day administered p.o. in the form of Se-enriched yeast. Study subjects were 36 healthy adult males, 11 blacks and 25 whites, 19-43 years of age. Supplementation occurred over the first 9 months, after which all subjects were placed on placebo for an additional 3 months. Blood and urine were collected at baseline and after 3, 9, and 12 months. In the selenium group, plasma selenium levels were 2-fold higher than baseline values after 3 and 9 months and returned to 136% of baseline after 12 months (P < 0.0001), whereas in the placebo group, levels were unchanged. A 32% increase in blood glutathione (GSH) levels was observed after 9 months in the selenium group only (P < 0.05). This change coincided with a 26% decrease in protein-bound GSH (bGSH) and a 44% decrease in bGSH:GSH ratios (P < 0.05). The changes in GSH and bGSH were highly correlated with changes in plasma selenium concentrations and may reflect a decrease in oxidative stress. No changes were observed in either group for plasma T, dihydrotestosterone (DHT) or DHT:T ratios, suggesting that selenium had no effect on the alpha-reductase involved in the conversion of T to DHT. A small but significant decrease in prostate-specific antigen levels was observed after 3 and 9 months (P < 0.001), and this difference disappeared after 12 months. Future trials will test the above hypothesis in prostate cancer patients and in subjects at high risk for prostate cancer.