Influence of Selenium-enriched Yeast Supplementation on Biomarkers of Oxidative Damage and Hormone Status in Healthy Adult Males: A Clinical Pilot Study 1 Karam El-Bayoumy, 2 John P. Richie, Jr., Telih Boyiri, Despina Komninou, Bogdan Prokopczyk, Neil Trushin, Wayne Kleinman, Julie Cox, Brian Pittman, and Steven Colosimo American Health Foundation, Valhalla, New York 10595 Abstract 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 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 -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. Introduction Several epidemiological studies, experimental research, and a recent clinical intervention trial supported the hypothesis that enhanced selenium status reduces the risk of cancer, including that of cancer of the prostate (1–12). One of the most exciting clinical trials in the United States supported the protective effect of selenium-enriched yeast against cancer of the prostate (13, 14). This protective effect was confirmed in a recent follow-up investigation of this trial (15). However, the mech- anisms responsible for the protective effect remain largely unknown. The outcome of this trial prompted two new clinical trials: Prevention of Cancers by Intervention with Selenium Trial (PRECISE), in three European countries and the Selenium and Vitamin E Cancer Prevention Trial (SELECT) in the United States (16 –18). Prostate cancer presents a major clinical and public health challenge in the United States. Adenocarcinoma of the prostate is now the most frequently diagnosed malignancy in adult males and the second most frequent cause of death due to cancer in males; it is estimated that 189,000 new cases of prostate cancer will be diagnosed in the year 2002 and that 30,200 men will die from this disease (19). Earlier estimates indicate that a 50-year-old American male has a 40% chance of developing prostate cancer during his lifetime, a 10% chance of being diagnosed with it, and a 2–3% chance of dying from this disease (20). Today the probability of developing invasive cancer of the prostate by age group is as follows: birth to 39 years, less than 1 in 10,000; 40 –59 years, 2.08 or 1 in 48; 60 –79 years, 12.5 or 1 in 8; and overall (birth to death), 16.67 or 1 in 6 (19). Although the etiology of prostate cancer remains poorly understood, a number of hypotheses have been put forth. The most commonly considered risk factors are briefly mentioned here. Studies in migrant populations pointed to the role of environmental factors in the development of prostate cancer (21–23). The role of Western diet, especially fat, has been suggested, but its role in prostate cancer development has not been consistent in the literature (24 –28). Available data suggest the protective role of dietary components (such as fruits, veg- etables, whole grains, and soy) against the development of prostate cancer (29 –31). The involvement of genetic factors (family component) has been suggested (32–35). Androgen metabolism may be implicated because the androgen receptor gene is highly poly- morphic in humans (36). An association between increased Received 4/18/02; revised 8/6/02; accepted 8/14/01. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 1 Supported in part by a grant from the Cancer Treatment Research Foundation and supported by National Cancer Institute Grant P30 17613, the American Health Foundation Cancer Center Support Grant. 2 To whom requests for reprints should be addressed, at American Health Foun- dation, 1 Dana Road, Valhalla, NY 10595. Phone: (914) 789-7176. 1459 Vol. 11, 1459 –1465, November 2002 Cancer Epidemiology, Biomarkers & Prevention on January 22, 2022. © 2002 American Association for Cancer Research. cebp.aacrjournals.org Downloaded from