Strong associations of serum selenoprotein P with all-cause mortality and mortality due to cancer, cardiovascular, respiratory and gastrointestinal diseases in older German adults

Abstract

Background Selenium is an essential trace mineral. The main function of selenoprotein P (SELENOP) is to transport selenium but it has also been ascribed anti-oxidative effects. Methods To assess the association of repeated measurements of serum SELENOP concentration with all-cause and cause-specific mortality serum SELENOP was measured at baseline and 5-year follow-up in 7,186 and 4,164 participants of the ESTHER study, a German population-based cohort aged 50–74 years at baseline. Results During 17.3 years of follow-up, 2,126 study participants (30%) died. The relationship of serum SELENOP concentration with all-cause mortality was L-shaped, with mortality being significantly higher at SELENOP concentrations < 4.1 mg/L, which is near the bottom tertile’s cut-off (4.2 mg/L). All-cause mortality of participants in the bottom SELENOP tertile was significantly increased compared to subjects in the top tertile (hazard ratio [95% confidence interval]: 1.35 [1.21–1.50]). SELENOP in the bottom tertile was further associated with increased cardiovascular mortality (1.24 [1.04–1.49]), cancer mortality (1.31 [1.09–1.58]), respiratory disease mortality (2.06 [1.28–3.32]) and gastrointestinal disease mortality (2.04 [1.25–3.32]). The excess risk of all-cause mortality for those in the bottom SELENOP tertile was more than twice as strong in men as in women (interaction of SELENOP and sex; p = 0.008). Conclusions In this large cohort study, serum SELENOP concentration was inversely associated with all-cause and cause-specific mortality. Consistent inverse associations with multiple mortality outcomes might be explained by an impaired selenium transport and selenium deficiency in multiple organs. Trials testing the efficacy of selenium supplements in subjects with low baseline SELENOP concentration are needed. Trial registration Retrospectively registered in the German Clinical Trials Register on Feb 14, 2018 (ID: DRKS00014028).

Selenoprotein P in a Rodent Model of Exercise; Theorizing Its Interaction with Brain Reward Dysregulation, Addictive Behavior, and Aging

“…AD has also been linked to selenium deficiency [23]. Dietary selenium supplementation has been shown in numerous studies to have multiple beneficial effects on the alleviation of disease symptoms [37][38][39].…”

“…In humans, low levels of SEPP1 are strongly associated with all-cause mortality and mortality due to cancer, cardiovascular, respiratory, and gastrointestinal diseases [22,23]. Selenium deficiency may contribute to multiple neurodegenerative disorders and neurological deficits, such as Alzheimer's disease (AD), PD, and Huntington's disease, as well as multiple sclerosis [24].…”

Selenoprotein P – die Drehscheibe im Selenstoffwechsel

“…Diese Schlussfolgerung wurde gerade in einer großen longitudinalen Studie des Deutschen Krebsforschungszentrums (DKFZ), Heidelberg, und der Charité, Berlin, eindrucksvoll belegt [44] (▶ abb. 3).…”

“…Die tatsächlichen Todesursachen erstreckten sich über viele der oben benannten Risiken, also kardiovaskulär, onkologisch und metabolisch, wodurch wiederum die breite Bedeutung der Selenoproteine für die unterschiedlichen Organsysteme und Pathomechanismen unterstrichen wird [44]. Der gesundheitsrelevante Mangel umfasste knapp ⅓ der gesamten Studienpopulation und lag damit in einer ähnlichen Größenordnung, wie wir es vom Vitamin-D-Status in Deutschland kennen [45].…”