Abstract 16: Effect of Long-Term Selenium Supplementation on Mortality: Results From a Multiple-Dose Randomised Controlled Trial

Abstract

Background: Selenium (Se) is an essential trace element that is incorporated into selenoproteins with a wide range of health effects. The concentration of selenoproteins plateaus at plasma Se concentrations ~125 μg/L, however, and it is unclear whether Se supplementation is beneficial above this plateau. Methods: In a double-blind, randomized, controlled trial of Se supplementation and mortality in Denmark, a population of moderately-low Se status, 491 men and women, 60-74 years of age, were treated with 100, 200, or 300 μg Se/d as Se-enriched yeast or placebo-yeast. From 2008-2009, active treatment was provided for 5 years and post-treatment follow-up for 10 additional years. During 6,871 person-years of follow-up, there were 158 deaths (31 during active treatment and 127 after treatment cessation). Results: The hazard ratio (95% confidence interval [CI]) for all-cause mortality comparing 300 μg Se/d to placebo was 1.62 (0.66 to 3.96) after 5 years of treatment and 1.59 (1.02 to 2.46) over the entire follow-up. Se doses of 100 and 200 μg/d non-significantly decreased mortality during the intervention period but their effects vanished after treatment cessation. The effects on cancer and cardiovascular mortality were similar but less precise than on all-cause mortality. Conclusions: A dose of 300 μg/d of Se (as high-Se yeast) taken for five years in a country with moderately-low Se status increased all-cause mortality 10 years later. Lower doses showed a non-significant reduction in mortality which dissipated after treatment discontinuation. Total Se intake (diet plus supplements) over 300 μg/d should be avoided.