Cardiologists at the University of Groningen in The Netherlands have published a comprehensive review of the current knowledge about selenium deficiency and the role of selenoproteins in heart failure patients [Al-Mubarak 2021].
The key points in their review are as follows:
- Selenium is an essential micronutrient. It is incorporated into 25 different selenoproteins that have many biological functions in the body.
- Suboptimal selenium intakes and status lead to the impaired cellular synthesis of these selenoproteins and to the diminished function of selenoproteins, which may aggravate oxidative stress and inflammation, both of which are associated with greater severity of heart failure.
- 70% of patients diagnosed with heart failure have suboptimal serum selenium levels (below 100 micrograms per liter).
- The heart failure patients with suboptimal serum selenium concentrations have lower exercise capacity, lower quality of life, and a worse prognosis than heart failure patients with serum selenium concentrations above 100 mcg/L.
- Clinical trials of the efficacy of selenium supplementation in patients with heart failure have shown improved clinical symptoms such as improvements in NYHA function class, in left ventricular ejection fraction, and in lipid profile.
Selenium Deficiency and Heart Failure
- Selenium deficiency has long been associated with increased incidence of Keshan disease, a form of cardiomyopathy (cardiomyopathy = disease or disorder of the heart muscle). In China, oral selenium supplementation has almost totally eliminated Keshan disease in areas where it was once endemic [Zhou 2018].
- Important selenoproteins such as the glutathione peroxidases and selenoprotein P require a sufficiently high selenium intake to reach plateau levels, generally serum selenium levels from 90 to 125 mcg/L [Hurst 2010].
- In a well-documented heart failure cohort, serum selenium levels below 100 mcg/L have been associated with reduced exercise capacity, poorer quality of life, and a worse prognosis [Bomer 2020].
- The Dutch cardiologists suggest that patients with serum selenium levels below 100 mcg/L should be considered to have suboptimal concentrations [Bomer 2020].
Observational Studies of Selenium Concentration and Heart Failure
Three meta-analyses have provided evidence of a relationship between selenium status and the risk of heart disease:
- Flores-Mateo [2006] showed that higher selenium concentrations are associated with a reduced risk of acute coronary artery disease of 15% in pooled prospective cohort studies and a reduced risk of 57% in pooled case-control studies.
- Zhang [2016] showed that patients with the highest level of selenium status (median 101.5 mcg/L) had a 13% lower risk of developing heart disease compared to the lowest category (median 53.7 mcg/L).
- Kuria [2020] showed that higher selenium status reduces mortality from heart disease by 25% and incidence of heart disease by 20%, compared to low selenium status.
Studies of Selenium Supplementation – the KiSel-10 Study
The most interesting clinical study is the KiSel-10 study in which elderly community living citizens, average age 78 years, with low selenium status (mean baseline status: 67.1 mcg/L), were treated with a combination of 200 mcg of an organic high-selenium yeast preparation and 200 mg of Coenzyme Q10 daily for four years.
- The study data showed that the combined supplementation was significantly associated with a reduction in death from heart disease, with a reduction in NT-proBNP blood levels (a known bio-marker for heart failure), and with better heart function scores on echo-cardiographs [Alehagen 2013].
- A sub-analysis of the data from the study showed that the rate of death from heart disease was significantly higher in the subgroup with the lower serum selenium concentrations below 65 mcg/L in comparison with the subgroup having a selenium concentrations equal to or higher than 85 mcg/L [Alehagen 2016].
- The sub-analysis showed that selenium supplementation was protective of the heart in study participants with a low baseline serum selenium concentration, equal to or below 85 mcg/L [Alehagen 2016].
Studies of Selenium Supplementation and Heart Failure
Two randomized controlled trials conducted with small samples
of heart failure patients are of interest:
- Garakyaraghi [2015] supplemented 32 heart failure patients with
a daily combination of 90 mg of Coenzyme Q10 and 200 mcg selenium for three months. The supplementation was associated with significant improvement of the patients’ NYHA functional class, left ventricular ejection fraction, and myocardial performance index compared to the control group. - Raygan [2018] supplemented 53 congestive heart failure patients with 200 mcg of selenium daily for 12 weeks. The study outcomes showed a significant reduction of LDL-cholesterol levels, insulin levels, and C-reactive protein levels (a bio-marker for inflammation) as well as increased HDL-cholesterol levels.
Take-home Messages: Selenium Status and Heart Disease
- There is some evidence that there may be a U-shaped relationship between selenium status and health outcomes, with the optimal serum/plasma selenium status in the range from 100 – 170 mcg/L [Rayman 2012].
- Most patients with heart failure have serum selenium levels below 100 mcg/L, so supplementation with selenium offers much promise in the treatment of heart failure.
- Selenium in selenoproteins may confer beneficial heart health effects both locally in the heart muscle tissue and systematically.
- Selenoproteins may help to restore heart function through several mechanisms including 1) maintaining healthy mitochondria, 2) reducing oxidative stress, 3) having an anti-inflammatory effect, 4) improving immune system function, and 5) reducing endoplasmic reticulum stress.
- A Penn State University study has shown that supplementation with an organic selenium yeast formulation is associated with significant reductions in biomarkers of oxidative stress whereas a 100% selenomethionine supplement did not show similar reductions, suggesting that selenium species other than selenomethionine account for the decrease in oxidative stress [Richie 2014].
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Alehagen U, Alexander J, Aaseth J. Supplementation with selenium and Coenzyme Q10 reduces cardiovascular mortality in elderly with low selenium status. a secondary analysis of a randomised clinical trial. PLoS One. 2016;11(7):e0157541.
Alehagen U, Johansson P, Bjornstedt M, Rosen A, Dahlstrom U. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Int J Cardiol. 2013;167(5):1860–6.
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The information presented in this review article is not intended as medical advice and should not be used as such.
15 May 2021