Effect of selenium supplementation on changes in glycated haemoglobin (HBA1 C): results from a multiple-dose, randomized controlled trial

Background Information from observational studies and a limited number of clinical trials has raised concerns over the potential adverse effects of long-term selenium supplementation on glucose metabolism and risk of type-2 diabetes in populations with high background selenium status, such as the US. There is limited trial evidence on the effect of selenium supplementation on glucose metabolism in European populations whose selenium status is much lower than that in the US. Objective We aimed to determine the effect of selenium supplementation at different dose levels on changes in HbA 1c after 6 months and 2 years in a population of relatively low selenium status. Design The Denmark PRECISE study was a single-centre, randomized, double-blinded, placebo-controlled, multi-arm, parallel clinical trial with four groups. Four hundred and ninety-one male and female volunteers aged 60–74 years, recruited at Odense University Hospital, Denmark, were randomly assigned to treatment with 100, 200, or 300 μg selenium/d as selenium-enriched-yeast or placebo-yeast. HbA 1c measurements were available for 489 participants at baseline (1998–99), 435 at 6 months, and 369 after 2 years of selenium supplementation. Analyses were performed by intention to treat. Results The mean (SD) age, plasma selenium concentration, and HbA 1c at baseline were 66.1 (4.1) years, 86.5 (16.3) ng/g and 36.6 (7.0) mmol/mol, respectively. During the initial 6-month intervention period, mean HbA 1c levels (95% CIs) decreased by 1.5 (0.2 to 2.8) mmol/mol for 100 μg/d of selenium supplementation and by 0.7 (−0.6 to 2.0) mmol/mol for the 200 and 300 μg/d groups compared with placebo ( P  = 0.16 for homogeneity of changes across the four groups). After 2 years of selenium supplementation, HbA 1c decreased significantly in all four treatment groups, with no difference between active treatment groups and placebo. Compared with placebo, mean HbA 1c levels (95% CIs) changed by −0.9 (−2.7 to 0.9) mmol/mol, 0.1 (−1.7 to 2.0) mmol/mol and −1.0 (−2.8 to 0.8) mmol/mol for 100, 200, and 300 μg/d of selenium supplementation, respectively ( P  = 0.52 for homogeneity of changes across the four groups). Conclusions Selenium supplementation in a European population of elderly individuals of relatively low selenium status did not significantly affect HbA1c levels after two years of supplementation. Our results do not support a beneficial or a harmful effect of selenium supplements on glucose metabolism.