The randomized controlled clinical trial known as the KiSel-10 study documented that daily supplementation of healthy elderly adults (men and women aged 70 – 88 years) with 200 milligrams of Coenzyme Q10 and 200 micrograms of a high-selenium yeast preparation yields significant health benefits as compared with placebo supplementation:
- reduced heart disease mortality
- better heart function
- fewer signs of chronic low-grade inflammation
- fewer signs of oxidative stress (cell damage caused by harmful free radicals)
These research findings were/are encouraging for middle-aged adults and for senior citizens, no doubt about it.
The KiSel-10 study of selenium and Coenzyme Q10 treatment
Professor Alehagen and the team of bio-medical researchers in Linköping, Sweden, knew that selenium intakes and selenium status are low in Sweden generally. They knew, moreover, that the human body’s bio-synthesis of Coenzyme Q10 declines with increasing age to the extent that, typically, an 80-year-old body produces about one half of the Coenzyme Q10 that a 25-year-old body produces.
443 healthy elderly citizens taking selenium and Coenzyme Q10 daily
The Swedish researchers recruited 443 healthy elderly study participants and randomly assigned them:
- to a control group receiving placebo preparations
- to an active treatment group receiving daily supplements of high-selenium yeast tablets and Coenzyme Q10 capsules
Four-year treatment period, ten-year follow-up period
The daily supplementation continued for a period of four years. After 5.2 years of follow-up, and then again after 10 years of follow-up, the researchers documented significantly reduced risk of death from heart disease in both the male and the female participants assigned to the active selenium and Coenzyme Q10 treatment group [Alehagen 2015].
Mechanism underlying the treatment effects of selenium and Coenzyme Q10
Naturally, Dr. Alehagen and his colleagues wondered how the selenium and Coenzyme Q10 treatment helped to maintain good heart function in elderly people. They knew the reason why: elderly people in Sweden had low selenium intakes in their diets, and their bodies were producing less and less Coenzyme Q10 with each passing year.
But, what was the biological mechanism underlying the remarkably beneficial clinical effects of supplementation with selenium and Coenzyme Q10? That was the 64-thousand-dollar question.
Selenium and Coenzyme Q10 provide anti-oxidant and anti-inflammation protection
Part of the explanation for the health effects has to be that selenium, a key component of antioxidant selenoproteins, and Coenzyme Q10 are needed for defense mechanisms against oxidative damage (toxic effects of free radicals) and against chronic low-grade inflammation.
Selenium and Coenzyme Q10 provide improved endothelial function
Part of the explanation has to be the positive effect of the selenium-dependent enzymes and Coenzyme Q10 on endothelial function (the proper functioning of the cells in the inner lining of blood vessels)[Brigelius-Flohé].
Link between low selenium status and the expression of microRNAs?
But, another possible explanation for the beneficial health outcomes in the KiSel-10 study is that the selenium supplementation affected the expression of more than 100 different microRNAs [Alehagen 2017].
Professor Alehagen and his team randomly selected 25 male participants from the KiSel-10 study’s treatment group and 25 male participants from the KiSel-10 study’s placebo group. They evaluated and found that the pre-treatment levels of expression of microRNAs did not differ between the two groups.
The post-treatment comparison of microRNA levels in the active treatment group and in the placebo control group revealed that 70 microRNAs exhibited significant changes [Alehagen 2017].
What are microRNAs?
Let’s start first with RNA. RNA, the abbreviation for ribonucleic acid, is a nucleic acid that is found in all living cells. Primarily, RNA acts as a messenger carrying the DNA instructions for the synthesis of proteins. But RNA has other non-coding functions as well.
MicroRNAs are non-coding RNA molecules involved in the regulation of gene expression. That is to say, microRNAs are a factor in the regulation of the genes that encode for proteins. They can inhibit (or promote?) the expression of genes. Several hundred microRNAs have been identified, and they play a significant role in the development of cancer and heart disease and diabetes [Clancy].
Most microRNAs are found in the cells. But some microRNAs circulate in the bloodstream and can be measured in the blood circulation and may be useful as bio-markers for various forms of heart disease. It is these extracellular circulating microRNAs that the Alehagen team investigated.
MicroRNAs different in normal hearts and diseased hearts
It is known that the levels of expression of specific microRNAs are changed in diseased human hearts from the levels of expression in healthy human hearts. The levels of expression of microRNAs seem to vary according to the level of selenium status.
Professor Alehagen has documented cardio-protective effects for the changed expression of microRNAs resulting from the supplementation with selenium and Coenzyme Q10.
- A 2.2-fold increase in the expression of microRNAs that are known to be associated with the health of the myocardium, the protective tissue around the heart
- A 2-fold increase in the expression of microRNAs that are known to be poorly expressed in patients with acute heart failure
- A 3-fold increase in the expression of microRNAs that are known to be poorly expressed in patients suffering from ischemic stroke
- Decreased expression of microRNAs whose increased expression has been observed in cases of myocardial hypertrophy (thickening of the heart muscle)
- Decreased expression of microRNAs whose increased expression has been observed in cases of pulmonary hypertension (high blood pressure that affects the arteries in the lungs and affects the right side of the heart)
Professor Alehagen wrote in his report that the changes in the expression of microRNAs that resulted from the treatment with selenium and Coenzyme Q10 may explain the mechanism for the protection of the heart muscle. The beneficial effects of the daily supplementation with selenium and Coenzyme Q10 may take place at the molecular level via the changes in the expression of microRNAs.
Changes in microRNA levels in the selenium supplemented group
More research is needed to understand the underlying biological mechanisms, but outcomes of the supplementation of healthy elderly adults with selenium and Coenzyme Q10 are impressive:
- reduced risk of death from heart disease
- better functioning of the heart muscle later in life
- fewer signs of inflammation
- fewer signs of oxidative damage to DNA, proteins, and lipids
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. doi:10.1016/j.ijcard.2012.04.156
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. doi:10.1371/journal.pone.0141641
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. https://doi.org/10.1371/journal.pone.0174880
Brigelius-Flohé, R., Banning, A., & Schnurr, K. (2003). Selenium-dependent enzymes in endothelial cell function. Antioxidants & Redox Signaling, 5(2), 205-215.
Clancy, S. (2008) RNA functions. Nature Education 1(1):102.
Creemers, E.E., Tijsen, A.J., Pinto, Y.M. & van Rooij, E. (2012). Circulating microRNAs. Circulation Research, 110:483-495. https://doi.org/10.1161/CIRCRESAHA.111.247452
Disclaimer: the information presented in this review article is not intended as medical advice and should not be construed as such.