Margaret P. Rayman, DPhil; Saverio Stranges, MD, PhD; Bruce A. Griffin, PhD; Roberto Pastor-Barriuso, PhD; Eliseo Guallar, MD, DrPH
Rayman MP, Stranges S, Griffin BA, Pastor-Barriuso R, Guallar E. Effect of Supplementation With High-Selenium Yeast on Plasma Lipids: A Randomized Trial. Ann Intern Med. 2011;154:656-665. doi: 10.7326/0003-4819-154-10-201105170-00005
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Published: Ann Intern Med. 2011;154(10):656-665.
High selenium status has been linked to elevated blood cholesterol levels in cross-sectional studies.
To investigate the effect of selenium supplementation on plasma lipids.
Randomized, placebo-controlled, parallel-group study stratified by age and sex. Participants, research nurses, and persons assessing outcomes were blinded to treatment assignment. (International Standard Randomised Controlled Trial Number Register registration number: ISRCTN25193534)
4 general practices in the United Kingdom.
501 volunteers aged 60 to 74 years.
Participants received selenium, 100 mcg/d (n = 127), 200 mcg/d (n = 127), or 300 mcg/d (n = 126), as high-selenium yeast or a yeast-based placebo (n = 121) for 6 months.
Total and high-density lipoprotein (HDL) cholesterol concentrations were measured in nonfasting plasma samples stored from participants in the UK PRECISE (United Kingdom PREvention of Cancer by Intervention with SElenium) Pilot Study at baseline (n = 454) and at 6 months (n = 394). Non-HDL cholesterol levels were calculated.
Mean plasma selenium concentration was 88.8 ng/g (SD, 19.2) at baseline and increased statistically significantly in the treatment groups. The adjusted difference in change in total cholesterol levels for selenium compared with placebo was −0.22 mmol/L (−8.5 mg/dL) (95% CI, −0.42 to −0.03 mmol/L [−16.2 to −1.2 mg/dL]; P = 0.02) for 100 mcg of selenium per day, −0.25 mmol/L (−9.7 mg/dL) (CI, −0.44 to −0.07 mmol/L [−17.0 to −2.7 mg/dL]; P = 0.008) for 200 mcg of selenium per day, and −0.07 mmol/L (−2.7 mg/dL) (CI, −0.26 to 0.12 mmol/L [−10.1 to 4.6 mg/dL]; P = 0.46) for 300 mcg of selenium per day. Similar reductions were observed for non-HDL cholesterol levels. There was no apparent difference in change in HDL cholesterol levels with 100 and 200 mcg of selenium per day, but the difference was an adjusted 0.06 mmol/L (2.3 mg/dL) (CI, 0.00 to 0.11 mmol/L [0.0 to 4.3 mg/dL]; P = 0.045) with 300 mcg of selenium per day. The total–HDL cholesterol ratio decreased progressively with increasing selenium dose (overall P = 0.01).
The duration of supplementation was limited, as was the age range of the participants.
Selenium supplementation seemed to have modestly beneficial effects on plasma lipid levels in this sample of persons with relatively low selenium status. The clinical significance of the findings is unclear and should not be used to justify the use of selenium supplementation as additional or alternative therapy for dyslipidemia. This is particularly true for persons with higher selenium status, given the limitations of the trial and the potential additional risk in other metabolic dimensions.
The Cancer Research Campaign (now Cancer Research UK) and the University of Surrey.
Observational studies of selenium status offer conflicting evidence that deficiency is associated with heart disease, whereas nondeficiency is associated with dyslipidemia.
In this randomized trial, selenium supplementation was associated with modest reductions in total and non–high-density lipoprotein cholesterol levels. At higher doses, selenium supplementation was associated with increases in high-density lipoprotein cholesterol levels.
The trial lasted only 6 months and enrolled only older patients.
Selenium supplementation modestly improves lipid profiles. The findings more definitively identify the effects of selenium on lipids because they are trial-based. However, the findings do not justify the use of selenium for dyslipidemia because the clinical significance of the changes is unknown and selenium supplementation may have other side effects.
Curves represent mean baseline lipid concentrations (solid line) and their 95% CIs (dashed line) based on restricted quadratic splines for baseline selenium concentrations, with knots at the 5th, 50th, and 95th percentiles (61.0, 87.8, and 119.0 ng/g, respectively). Results were obtained from linear mixed models with random between-participant variations in baseline lipid levels and adjusted for age, sex, center, smoking status, body mass index, and use of lipid-lowering medications (Appendix). To convert cholesterol values to mg/dL, divide by 0.02586. Scatterplots represent adjusted baseline concentrations of selenium and lipids. HDL = high-density lipoprotein.
Curves represent mean changes in lipid concentrations from baseline to 6 months (solid line) and their 95% CIs (dashed line) based on restricted quadratic splines for within-participant changes in selenium concentration, with knots at the 5th, 50th, and 95th percentiles (−8.0, 74.0, and 173.9 ng/g, respectively). Results were obtained from linear mixed models with random between-participant variations in both baseline lipid levels and lipid changes over time and adjusted for baseline selenium concentration, age, sex, center, smoking status, body mass index, and use of lipid-lowering medications (Appendix). Scatterplots represent adjusted changes in selenium and lipid concentrations over time for participants randomly assigned to receive placebo (gray dots) or 100 mcg (blue dots), 200 mcg (green dots), or 300 mcg (red dots) of selenium per day. To convert cholesterol values to mg/dL, divide by 0.02586. HDL = high-density lipoprotein.
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Cardiology, Dyslipidemia, Coronary Risk Factors.
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