Phase 3 clinical trial investigating the effect of selenium supplementation in men at high-risk for prostate cancer
ABSTRACT PURPOSE: This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer. METHODS: A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA) >4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity >0.75 ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N = 234), or 400 µg selenium (N = 233) as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model. RESULT: Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (P = 0.18 and P = 0.17, respectively). CONCLUSION: Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention. Prostate © 2012 Wiley Periodicals, Inc.
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ABSTRACT: Prostate cancer (PCa), the most commonly diagnosed cancer and second leading cause of male cancer death in Western societies, is typically androgen-dependent, a characteristic that underlies the rationale of androgen deprivation therapy (ADT). Approximately 90% of patients initially respond to ADT strategies, however many experience side effects including hot flashes, cardiotoxicity, metabolic and musculoskeletal alterations. This review summarizes pre-clinical and clinical studies investigating the ability of dietary supplements to alleviate adverse effects arising from ADT. In particular, we focus on herbal compounds, phytoestrogens, selenium (Se), fatty acids (FA), calcium, and Vitamins D and E. Indeed, there is some evidence that calcium and Vitamin D can prevent the development of osteoporosis during ADT. On the other hand, caution should be taken with the antioxidants Se and Vitamin E until the basis underlying their respective association with type 2 diabetes mellitus and PCa tumor development has been clarified. However, many other promising supplements have not yet been subjected large-scale clinical trials making it difficult to assess their efficacy. Given the demographic trend of increased PCa diagnoses and dependence on ADT as a major therapeutic strategy, further studies are required to objectively evaluate these supplements as adjuvant for PCa patients receiving ADT.Nutrients 10/2014; 6(10):4491-4519. DOI:10.3390/nu6104491 · 3.15 Impact Factor
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ABSTRACT: Epidemiologic studies, particularly randomized controlled trials, have shown a direct relation between dietary and environmental exposure to the metalloid selenium and risk of type 2 diabetes. We investigated the association between baseline toenail selenium levels and diabetes occurrence in a case-control study nested in ORDET, a population-based female cohort in Northern Italy. After a median follow-up of 16 years, we identified 226 cases of type 2 diabetes cases and 395 age-matched control women with available toenail samples at baseline. The multivariate odds ratios of diabetes in increasing a priori defined categories of toenail selenium exposure were 1.09 (95% confidence interval 0.61, 1.96), 0.71 (0.38, 1.34) and 1.14 (0.46, 2.80) compared with the lowest category. The results were not substantially altered when quartile distribution of toenail selenium in controls was used to define exposure categories. Spline regression analysis did not show homogeneous risk trends. Overall, we did not find an association between toenail selenium and subsequent development of diabetes. Since the diabetogenic activity of selenium is strongly supported by experimental studies and some observational investigations, our null results might be explained by the limitations of overall selenium toenail content to assess environmental exposure to selenium species of etiologic relevance in the study population.Journal of Trace Elements in Medicine and Biology 08/2014; DOI:10.1016/j.jtemb.2014.07.017 · 2.49 Impact Factor
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ABSTRACT: The study was designed to determine the differential protein expression of Caco-2 cells treated with different forms of selenium including sodium selenite, selenomethionine (Se-Met), and selenium nanoparticles (nano-Se). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry (MS) were used to identify the differentially expressed proteins. The results indicated that seven protein spots, ubiquitin-conjugating enzyme E2 (E2), glutathione synthetases (GS), triosephosphate isomerase (TSP), T-complex protein 1 subunit zeta (TCPZ), lamin-B1, heterogeneous nuclear ribonucleoprotein F (hnRNP F), and superoxide dismutase [Cu-Zn] (Cu, Zn-SOD) were significantly different among all the groups. According to the order of control, sodium selenite, Se-Met, and Nano-Se, the expression levels of two proteins (E2 and GS) increased and the other differential proteins were reverse. Except for E2, there were no significant differences in other protein expressions between the groups treated with nano-Se and Se-Met.Nanoscale Research Letters 10/2014; 9(1):589. DOI:10.1186/1556-276X-9-589 · 2.52 Impact Factor