Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study.

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP.

The association between selenium status and global and attention specific cognition in very old adults in The Newcastle 85+ Study: cross-sectional and longitudinal analyses.

BACKGROUND: Selenium has potential safeguarding properties against cognitive decline, due to its role in protecting DNA, proteins, and lipids in the brain from oxidative damage. However, acute and chronic overexposure to selenium can be neurotoxic. OBJECTIVE: The aim of this analysis was to explore the association between selenium status (serum selenium and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity) and cognitive function in 85-year-olds living in Northeast England at baseline and up to 5 years of follow-up. METHODS: Global cognitive performance was assessed in 755 participants from the Newcastle 85+ study using the Standardized Mini-Mental State Examination (SMMSE) and attention-specific cognition was assessed using composite scores derived from the Cognitive Drug Research (CDR) System. Serum selenium, SELENOP and GPx3 activity were measured at baseline by total reflection X-ray fluorescence (TXRF), ELISA and coupled-enzyme reaction, respectively. Regression analyses explored linear and non-linear associations between continuous values and tertiles of selenium status biomarkers, respectively, and cognitive function at baseline. Generalized linear mixed models explored associations between continuous values and tertiles of selenium status biomarkers, and global cognitive decline over 5 years, and attention-specific cognitive decline over 3 years. RESULTS: Over 3 and 5 years, none of the selenium biomarkers were associated with the rate of cognitive decline. At baseline, in fully adjusted models, higher serum selenium was non-linearly associated with global cognition (ß 0.05±0.01, P=0.387 linear, ß 0.04±0.01, P=0.002 non-linear). SELENOP and GPx3 activity were not associated with any cognitive outcomes. CONCLUSIONS: There were no associations between selenium status and cognitive decline. However, serum selenium, but not SELENOP or GPx3 activity, was positively associated non-linearly with global cognition at baseline. Furthermore, these associations were not evident during follow-up, potentially due to residual confounding and reverse causation.

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

BACKGROUND: Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. METHODS: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. RESULTS: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. CONCLUSIONS: The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.