Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial

Abstract

Epidemiologic and laboratory studies indicate that dietary selenium protects against prostate cancer. Results from clinical trials suggest that selenium-enriched yeast (SY) but not selenomethionine (SeMet) may be effective at reducing prostate cancer risk. Our objectives were to directly compare for the first time the effects of SeMet and SY on prostate cancer relevant biomarkers in men. We performed a randomized double blind, placebo-controlled trial of SY (200 or 285 μg/day) and SeMet (200 μg/day) administered for 9 months in 69 healthy men. Primary endpoints included blood levels of selenium-containing compounds and oxidative stress biomarkers [urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin-F2α (8-iso-PGF2α) and blood glutathione (GSH)]. Secondary endpoints included plasma glucose and PSA levels. Compliance was high in all groups (>95%). Plasma selenium levels were increased 93%, 54%, and 86% after 9 months in SeMet and low- and high-dose SY groups, respectively, and returned to baseline levels after a 3-month washout (P < 0.05). Levels of 8-OHdG and 8-iso-PGF2α were decreased 34% and 28%, respectively, after 9 months in the high-dose SY group (P < 0.05). These decreases were greatest in individuals with low baseline plasma levels of selenium (<127 ng/mL). No changes in serum PSA or blood glucose and GSH were observed. Overall, we showed for the first time, reductions in biomarkers of oxidative stress following supplementation with SY but not SeMet in healthy men. These findings suggest that selenium-containing compounds other than SeMet may account for the decrease in oxidative stress.

Trial registration: ClinicalTrials.gov NCT01112449.

Figure 1

Subject flowchart summarized according to the Consolidated Standards of Reporting Trials.

Figure 2

Effect of supplementation with SeMet or SY on plasma selenium levels in adult men. Subjects were randomized to placebo (n=18), 200 µg/d SY (n=16), 285 µg/d SY (n=15) or 200 µg/d SeMet (n=20). Supplementation continued for 9 months followed by a 3 month washout. Plasma total selenium levels were assessed by atomic absorption spectrophotometry. Symbols and bars represent mean and standard error values, respectively.

Figure 3

Effect of supplementation with SeMet or SY on urinary biomarkers of oxidative stress in healthy men. Subjects were randomized to placebo (n=18), 200 µg/d SY (n=16), 285 µg/d SY (n=15) or 200 µg/d SeMet (n=20). Urinary levels of 8-iso-PGF_2α and 8-OHdG were determined by ELISA and corrected for urinary dilution by dividing by urinary creatinine levels, and plasma selenium, determined by atomic absorption spectrophotometry. A. Urinary levels of 8-iso-PGF_2α (upper panel) and 8-OHdG (lower panel) by treatment arm. Bars represent mean change in biomarker values from baseline after 9 and 12 months with associated standard error values. Baseline values for 8-iso-PGF_2α were 199 ± 96, 180 ± 87, 217 ± 117, and 206 ± 114 mg/mg creatinine for placebo, SY₂₀₀, SY₂₈₅ and SeMet groups, respectively. Baseline values for 8-OHdG were 66.8 ± 22, 72.7 ± 43, 90.1 ± 38, and 70.1 ± 38 mg/mg creatinine for placebo, SY₂₀₀, SY₂₈₅ and SeMet groups, respectively. B. Association of reductions in oxidative stress biomarker levels by SY with baseline selenium levels in plasma. Urinary levels of 8-iso-PGF_2α and 8-OHdG for subjects in the 285 µg/d SY group were examined by baseline plasma selenium tertile. Mean baseline plasma selenium levels by tertile are provided in the top panel. Mean changes in 8-OHdG (middle panel) and 8-iso-PGF_2α (bottom panel) from baseline at 9 months are reported by baseline selenium tertile. Bars represent mean and standard error values. Tertile baseline plasma cutpoints (mg/ml) are 127 and 138.