Understanding Heterogeneity in Supplementation Effects of Selenium in Men: A Study of Stratification Variables and Human Genetics in a Prospective Sample from New Zealand

Abstract

There is marked controversy on the beneficial levels of selenium (Se) to be used as a dietary supplement. The form of supplemented Se and the baseline plasma or serum Se status among supplemented populations are generally considered as crucial factors in this controversy. However, responses to supplemented Se can further vary with other factors, including health status, lifestyle, demographics and genetics. In the present study, the putative supplementation benefits of Se as 200 µg/day selenised yeast for six months were evaluated among a stratified male population from Auckland, New Zealand. Our study considered changes in surrogate biomarkers for cancer including antioxidant selenoenzymes glutathione peroxidase (GPx) and thioredoxin reductase activity (TR) levels, basal and peroxide-induced DNA damage levels. A total of 569 subjects self-reporting a European ancestry signed in for the study and provided answers to a basic demographic, health and lifestyle questionnaire. The effects of Se supplementation on biomarkers showed significant variability based on age, BMI, health status and seleno-genotypes of SELS rs4965373, GPx1 rs1050450, and SEPP1 rs3877899. The data indicate that the benefits of supplementary Se vary significantly across a population, based on demographics, lifestyle, health conditions and seleno-genotypes. As a contrast to "one-size-fits-all" nutritional interventions, these observations collectively inform rational targeting and personalisation of future Se-based dietary supplementation in regards to cancer chemoprevention strategies. This work also represents a way forward in critically understanding Se requirements in populations.

Selenium Supplementation and Prostate Health in a New Zealand Cohort

“…Our studies have also shown that optimal levels of serum selenium towards minimizing DNA damage are recorded between 116 and 150 ng/mL which also have genetic influences [15]. The influence of age and BMI in influencing serum selenium retention was reported by us previously [16]. We have also shown that a 200 µg/d selenium supplementation benefits by way of DNA damage reduction is achieved dependent on dietary methionine and folate levels and BMI [16,17].…”

“…The influence of age and BMI in influencing serum selenium retention was reported by us previously [16]. We have also shown that a 200 µg/d selenium supplementation benefits by way of DNA damage reduction is achieved dependent on dietary methionine and folate levels and BMI [16,17]. Studies including ours have reported selenium supplementation to lower serum prostate-specific antigen (PSA) levels among men with high-risk for prostate cancer and among middle-aged US men [18,19].…”

“…Meanwhile, New Zealand is known for soil deficiencies in selenium that affects the dietary content of this trace mineral [53]. Our previous studies with New Zealand men have shown that benefits of 200 µg/d selenium supplementation for six months in preserving DNA integrity is achieved only in stratified groups of men [16,45]. We have also shown that DNA integrity benefits vary between serum selenium levels between 116 and 150 ng/mL depending on genetic variation [15].…”

“…A cohort of men (n = 572), self-reported as having no history of cancers (other than non-melanoma skin cancers), and not taking more than 50 µg selenium/day as supplements were recruited to a selenium supplementation study [15,16,45]. Participant recruitment was carried out with informed consent (ethics reference NTY/06/07/060, from the Health and Disability Ethics Committees, Ministry of Health, New Zealand).…”

Prostatic Response to Supranutritional Selenium Supplementation: Comparison of the Target Tissue Potency of Selenomethionine vs. Selenium-Yeast on Markers of Prostatic Homeostasis

“…Whether or not supplementation with SeMet or Se-yeast differentially alters the amount of particular selenium species within the prostate, such as methylselenol or selenoproteins [30,31], could not be determined in our study, because only total selenium concentration was measured. Whether or not host factors, such as age or obesity [32], impact the systemic and intraprostatic concentrations of selenium achievable after supplementation with different selenium forms could not be rigorously interrogated in our dogs due to small sample size, but deserves further evaluation.…”