Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomised controlled trial
2018
Background Selenium, an essential trace element, is incorporated into selenoproteins with a wide range of
health effects. Selenoproteins may reach repletion at a plasma selenium concentration of ~125
μg/L, at which point the concentration of selenoprotein P reaches a plateau; whether sustained
concentrations higher than this are beneficial, or indeed detrimental, is unknown. Objective In a population of relatively low selenium status, we aimed to determine the effect on
mortality of long-term selenium supplementation at different dose levels. Design The Denmark PRECISE study was a single-centre, randomised, double-blinded, placebocontrolled,
multi-arm, parallel clinical trial with four groups. Participants were 491 male and
female volunteers aged 60-74 years, recruited at Odense University Hospital, Denmark. The
trial was initially designed as a 6-month pilot study, but supplemental funding allowed for
extension of the study and mortality assessment. Participants were randomly assigned to
treatment with 100, 200, or 300 μg selenium/d as selenium-enriched-yeast or placebo-yeast
for 5 years from randomization in 1998–1999 and were followed up for mortality for a further
10 years (through March 31, 2015). Results During 6,871 person-years of follow-up, 158 deaths occurred. In an intention-to-treat
analysis, the hazard ratio (95% confidence interval) for all-cause mortality comparing 300 μg
selenium/d to placebo was 1.62 (0.66, 3.96) after 5 years of treatment and 1.59 (1.02, 2.46)
over the entire follow-up period. The 100 and 200 μg/d doses showed non-significant
decreases in mortality during the intervention period that disappeared after treatment cessation. Although we lacked power for endpoints other than all-cause mortality, the effects
on cancer and cardiovascular mortality appeared similar. Conclusions A 300 μg/d dose of selenium taken for 5 years in a country with moderately-low selenium
status increased all-cause mortality 10 years later. While our study was not initially designed
to evaluate mortality and the sample size was limited, our findings indicate that total selenium
intake over 300 μg/d and high-dose selenium supplements should be avoided.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
44
References
75
Citations
NaN
KQI