The Swedish KiSel-10 Study provides randomized controlled trial evidence that a daily combination of an organic high-selenium yeast supplement and a pharmaceutical-grade Coenzyme Q10 supplement can reduce cardiovascular mortality, improve heart function, and increase health-related quality of life in senior citizens [Alehagen 2013].
Low blood selenium concentrations and higher risk of heart disease
Professor Urban Alehagen and a team of researchers from Linköping University investigated the blood selenium levels in 688 Swedish senior citizens. The mean blood selenium level was 67.1 micrograms per liter, which is quite low but not surprising, given that Sweden is a country with selenium-low soil and selenium-poor foodstuffs [Alehagen 2016].
When the researchers adjusted for gender, smoking, coronary artery disease, diabetes, chronic obstructive pulmonary disease, and impaired heart function, they found that the quartile of senior citizens with the lowest level of blood selenium had a 43% higher risk of all-cause mortality and a 56% higher risk of cardiovascular mortality [Alehagen 2016].
Rationale for Selenium and Coenzyme Q10 in the KiSel-10 Study
Professor Alehagen hypothesized that selenium supplementation might improve the survival chances of senior citizens with low selenium status.
He knew that there is a special interrelationship between selenium and Coenzyme Q10 such that the cells need selenium in order to activate Coenzyme Q10, which is essential for the process of mitochondrial ATP energy production and is an important fat-soluble antioxidant [Alehagen 2015].
Furthermore, the body’s bio-synthesis of Coenzyme Q10 is known to decline with increasing age in the adult years [Kalen 1989]. Accordingly, the Swedish senior citizens could be expected to have low blood Coenzyme Q10 concentrations as well as low blood selenium concentrations.
The benefits of adjuvant treatment of chronic heart failure patients with Coenzyme Q10 were demonstrated in the Q-Symbio Study, in which patients took 3 times 100 milligrams of a medicine-grade Coenzyme Q10 preparation daily for two years in addition to their conventional medication and had, as a result, significantly improved symptoms and survival [Mortensen 2014].
In addition, the special interrelationship between selenium and Coenzyme Q10 is such that the cells need sufficient Coenzyme Q10 in order to make an optimal quantity of selenoproteins, some of which are the selenium containing enzymes that have antioxidant and other biological functions in the body [Alehagen 2015].
Design of the KiSel-10 Study of Selenium and Coenzyme Q10 and Heart Function
Thus, Professor Alehagen recruited 443 senior citizens aged 70 – 88 years at baseline, average age 78 years, who were still well enough to live at home in the community, and who had low blood selenium and Coenzyme Q10 concentrations.
In the KiSel-10 Study, Professor Alehagen and his team randomly assigned the senior citizens to an active treatment group and a placebo control group.
The active treatment group received a 200-microgram SelenoPrecise® tablet and 200 milligrams of Bio-Quinone Q10 Coenzyme Q10 in divided doses (2 times 100 milligrams together with meals). The placebo group received matching placebos [Alehagen 2013].
Outcomes of the KiSel-10 Study of Selenium and Coenzyme Q10 and Heart Function
There were statistically significant differences between the active treatment group and the placebo control group:
- Senior citizens in the placebo group had a 12.6% cardiovascular mortality rate; senior citizens in the selenium and Coenzyme Q10 group had a 5.9% cardiovascular mortality rate. That absolute difference of 6.7% in the death rate from heart disease means that 60 to 70 senior citizens out of every 1000 can expect to live longer and have better health-related quality of life, which gives more time for the grandchildren or travel or hobbies.
- NT-pro-BNP is a bio-marker for the diagnosis and prognosis of heart failure. The average level of NT-proBNP in the placebo group individuals was 302 nanograms per milliliter; in the selenium and Coenzyme Q10 group, the average level was 214 nanograms per milliliter.
- On echocardiograms, the senior citizens in the selenium and CoQ10 group showed significantly better heart function than did the study participants in the placebo group.
The researchers concluded that the significantly improved cardiovascular mortality rates were achieved by an improvement of the senior citizens’ heart function through the daily use of high-selenium yeast and Coenzyme Q10 supplements [Alehagen 2013].
Follow-up of the KiSel-10 Study of Selenium and CoQ10 and Heart Function
In a ten-year follow-up, the researchers discovered that the risk of dying from heart disease for the senior citizens in the active treatment group was only 51% of the cardiovascular mortality risk for the senior citizens in the placebo group [Alehagen 2015].
Two years later, then, the researchers found that the cardiovascular mortality rate in the remaining study participants was 28.1% in the selenium and Coenzyme Q10 group compared with 45% in the placebo group. That is to say, there was a persistent effect of the combined selenium and Coenzyme Q10 supplementation [Alehagen 2018].
Improved Quality of Life with Selenium and CoQ10 Supplementation
The four-year therapy with high-selenium yeast and Coenzyme Q10 improved not only the survival of the senior citizens in the KiSel-10 study. The therapy also helped to maintain quality of life or at least to reduce the extent of age-related loss of quality of life measured along the following dimensions [Johansson 2015]:
- physical performance
- conative function (= a measure of the will to perform an action)
- nervous system function
- overall quality of life
Mechanisms of Action for Selenium and CoQ10 Supplementation
How does the combination of high-selenium yeast and Coenzyme Q10 improve the survival and quality of life of senior citizens?
Less Cardiac Fibrosis
In a sub-analysis, the researchers found that the supplemented study participants had significantly lower levels of various bio-markers for cardiac fibrosis [Alehagen 2017]. Reduced levels of cardiac fibrosis (the thickening and stiffening of the heart muscle tissue) may be one of the mechanisms by which the selenium and CoQ10 supplementation benefited the senior citizens in the KiSel-10 study.
Changes in microRNA
In another sub-analysis, the researchers found that the two study groups had significant differences in as many as 70 microRNAs. MicroRNAs are involved in the expression or non-expression of genes and, by extension, in the formation of proteins. They can play an important role in heart disease. The influence of the selenium and Coenzyme Q10 treatment on the microRNAs may be a mechanism of action that influences cardiovascular mortality and heart function [Alehagen 2017].
Less Oxidative Stress
Analysis of levels of bio-markers for oxidative stress – the over-production of harmful free radicals – in the two groups showed that the selenium and CoQ10 supplementation had a beneficial effect compared to placebo. The reduced oxidative stress could be one of the explanations for the cardio-protective effect of the combined supplementation [Alehagen 2015].
Lower Levels of Inflammation
In the same way, separate analyses showed reduced levels of various bio-markers for inflammation [Alehagen 2015]. Inflammation has not been proved to be a direct cause of heart disease, but it is quite commonly seen in cases of heart disease and stroke. Its reduction might be another mechanism by which the combined selenium and Coenzyme Q10 supplementation improves heart function and reduces the risk of heart disease.
Summary of the KiSel-10 Study
In a four-year study of combined supplementation with a high-selenium yeast preparation and a patented pharmaceutical-grade Coenzyme Q10 preparation, the active treatment group achieved a 54% reduction in cardiovascular mortality compared to the placebo group. Moreover, the active treatment group achieved significantly better results on echocardiograms compared to the placebo group and had lower blood concentrations of a known bio-marker for heart failure.
These beneficial effects of daily supplementation with 200 micrograms of selenium and 200 milligrams of Coenzyme Q10 in two divided 100-milligram doses persisted through the 10-year and 12-year follow-ups.
Alehagen, U., Johansson, P., Björnstedt, M., Rosén, A., & Dahlström, U. (2013). 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. International Journal of Cardiology, 167(5), 1860-1866.
Alehagen, U., & Aaseth, J. (2015). Selenium and Coenzyme Q10 interrelationship in cardiovascular diseases–A clinician’s point of view. Journal of Trace Elements in Medicine and Biology, 31157-162.
Alehagen, U., Aaseth, J., & Johansson, P. (2015). Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Biofactors (Oxford, England), 41(6), 443-452.
Alehagen, U., Lindahl, T. L., Aaseth, J., Svensson, E., & Johansson, P. (2015). Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial. Plos One, 10(9), e0137680.
Alehagen, U., Aaseth, J., & Johansson, P. (2015). Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens. Plos One, 10(12), e0141641.
Alehagen, U., Johansson, P., Björnstedt, M., Rosén, A., Post, C., & Aaseth, J. (2016). Relatively high mortality risk in elderly Swedish subjects with low selenium status. European Journal of Clinical Nutrition, 70(1), 91-96.
Alehagen, U., Aaseth, J., Alexander, J., Svensson, E., Johansson, P., & Larsson, A. (2017). Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality? Biofactors (Oxford, England), doi:10.1002/biof.1404.
Alehagen, U., Johansson, P., Aaseth, J., Alexander, J., & Wågsäter, D. (2017). Significant changes in circulating microRNA by dietary supplementation of selenium and Coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Plos One, 12(4), e0174880.
Alehagen, U., Aaseth, J., Alexander, J., & Johansson, P. (2018). Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly. Plos One, 13(4), e0193120.
Johansson, P., Dahlström, Ö., Dahlström, U., & Alehagen, U. (2015). Improved Health-Related Quality of Life, and More Days out of Hospital with Supplementation with Selenium and Coenzyme Q10 Combined. Results from a Double Blind, Placebo-Controlled Prospective Study. The Journal of Nutrition, Health & Aging, 19(9), 870-877.
Kalén, A., Appelkvist E.L., Dallner G. (1989). Age-related changes in the lipid compositions of rat and human tissues. Lipids, 24(7):579–584.
Mortensen, S. A., Rosenfeldt, F., Kumar, A., Dolliner, P., Filipiak, K. J., Pella, D., & Littarru, G. P. (2014). The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC. Heart Failure, 2(6), 641-649.
The information presented in this review article is not intended as medical advice and should not be used as such.