Randomised controlled trial of the effect of long-term selenium supplementation on plasma cholesterol in an elderly Danish population

Abstract

Although cross-sectional studies have shown a positive association between Se and cholesterol concentrations, a recent randomised controlled trial in 501 elderly UK individuals of relatively low-Se status found that Se supplementation for 6 months lowered total plasma cholesterol. The Danish PRECISE (PREvention of Cancer by Intervention with Selenium) pilot study (ClinicalTrials.gov ID: NCT01819649) was a 5-year randomised, double-blinded, placebo-controlled trial with four groups (allocation ratio 1:1:1:1). Men and women aged 60-74 years (n 491) were randomised to 100 (n 124), 200 (n 122) or 300 (n 119) μg Se-enriched yeast or matching placebo-yeast tablets (n 126) daily for 5 years. A total of 468 participants continued the study for 6 months and 361 participants, equally distributed across treatment groups, continued for 5 years. Plasma samples were analysed for total and HDL-cholesterol and for total Se concentrations at baseline, 6 months and 5 years. The effect of different doses of Se supplementation on plasma lipid and Se concentrations was estimated by using linear mixed models. Plasma Se concentration increased significantly and dose-dependently in the intervention groups after 6 months and 5 years. Total cholesterol decreased significantly both in the intervention groups and in the placebo group after 6 months and 5 years, with small and nonsignificant differences in changes in plasma concentration of total cholesterol, HDL-cholesterol, non-HDL-cholesterol and total:HDL-cholesterol ratio between intervention and placebo groups. The effect of long-term supplementation with Se on plasma cholesterol concentrations or its sub-fractions did not differ significantly from placebo in this elderly population.

Effect of selenium supplementation on changes in HbA1c: Results from a multiple‐dose, randomized controlled trial

“…The Denmark PREvention of Cancer by Intervention with SElenium (PRECISE) pilot study (http://clinicaltrials.gov ID: NCT01819649) was a single‐centre, randomized, double‐blinded, placebo‐controlled, multi‐arm, parallel clinical trial with four groups (allocation ratio 1:1:1:1) run from Odense University Hospital, Denmark . Denmark PRECISE was one of two pilot studies for the proposed international PRECISE trial of Se in cancer prevention; the other was carried out in the UK .…”

“…Randomization was computer‐generated, blocked and non‐stratified . Participating couples living at the same address were allocated to the same intervention.…”

“…Participating couples living at the same address were allocated to the same intervention. Participants, research staff and investigators were blinded to treatment assignment . Participants deemed suitable for inclusion provided blood samples and were given yeast tablets for an open‐label, 4‐week, placebo run‐in phase.…”

“…Those (n = 491) who met the inclusion criteria, displayed good adherence in the placebo run‐in phase, and gave written, informed consent, were randomized to 0 (placebo‐yeast), 100, 200 or 300 μg/d of Se as Se‐enriched yeast (SelenoPrecise © Pharma Nord, Vejle, Denmark) (Figure ). Participant evaluation was carried out at Odense University Hospital at baseline, 6, 12, 18 months, 2, 3 and 5 years, as previously described in detail . The intervention was delivered for 5 years and participants were followed up, post‐treatment, for an additional 10 years for mortality ascertainment.…”

“…For the analysis of randomized groups, all trial participants were assigned to their randomized treatment group, irrespective of compliance (intention‐to‐treat analysis). The effect of 100, 200 and 300 μg/d of Se supplementation on changes in HbA1c after 6 months and 2 years was estimated by using a linear mixed model, with fixed effects for treatment groups, follow‐up times and treatment‐by‐time interactions, and random between‐subject variations in baseline HbA1c levels (intercepts) and HbA1c changes over follow‐up (time slopes). The model is specified in detail in the statistical appendix (see Appendix S1).…”