The KiSel-10 Study

How to grow older and still maintain good health

Professor Urban Alehagen, Ph.D., M.D., Institute of Medicine and Health, University Hospital of Linköping, Sweden, has been the principal investigator for the KiSel-10 study of the effect of a four-year intervention with selenium and Coenzyme Q10 on cardiovascular mortality and cardiac function in an elderly Swedish population.

As we grow older, our health tends to deteriorate. Our blood vessels clog up, our circulation slows down, our hearts lose strength, we have problems with our joints, and we tend to tire more easily. It’s only natural – but so are the things we can do to prevent this from happening.

How Swedish scientists managed to cut heart deaths by over 50%
Leading Swedish cardiologists have published a sensational study showing how easily they were able to reduce cardiovascular mortality by over 50% among a large group of town villagers.

Medical history is being written these days in a hamlet called Kisa just outside of Linköping in the southeastern region of Sweden. Some of Sweden’s leading cardiologists have conducted a study on 443 of the elderly town villagers and discovered, much to their own surprise, that a novel treatment which has never been tested before reduces the risk of dying from heart disease by over 50 per cent. Considering that cardiovascular disease is the number one killer in Western countries, this discovery is quite a sensation.

The KiSel-10 Study
The KiSel-10 clinical trial was a prospective randomized, double-blind, placebo-controlled study designed and carried out by Professor Urban Alehagen and a team of researchers at Linköping University in Sweden.

The study was an investigation of the effect of a combination of Coenzyme Q10 capsules and high-selenium yeast tablets, as compared with placebo capsules and tablets, on the rate of death from heart disease, the age-related change in heart function as measured by echocardiograms, and the changes in blood concentrations of cardiac natriuretic peptides.

The researchers enrolled, initially, 443 healthy elderly citizens of Kisa, Sweden, both men and women, aged 70 – 87 years.  The study participants received either the active treatment — a combination of 200 milligrams per day of Coenzyme Q10 and 200 micrograms per day of organic selenium yeast — or matching placebos daily for four years.  The study began in 2003 and was completed in 2010.

To date, autumn 2017, the researchers have published eleven papers detailing the results of the analysis of the data from the KiSel-10 study.

Following are the citations and summaries of these eleven published journal articles.

1. 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. doi:10.1038/ejcn.2015.92

The Linköping University researchers knew that the daily dietary intake of selenium is generally quite low in Sweden.  They measured and evaluated the serum selenium levels of 668 elderly citizens of the rural municipality of Kinda.  They established that the serum selenium concentrations of the study participants in this sample was, on average, 67.1 micrograms per liter.  This is a level considerably below the physiological saturation level required for the activation of several important selenoproteins.

The researchers made appropriate adjustments to rule out the effect of such confounding variables as male gender, smoking, diabetes, chronic obstructive pulmonary disease, and impaired heart function and found that individuals in the lowest quartile of serum selenium concentrations were at a 43% greater risk of death from all causes and at a 56% greater risk of death from heart disease.  The researchers concluded that moderate daily supplementation with selenium might improve the overall health of the Swedish population.

2. 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

This 2013 journal article was the first and primary report based on data from the KiSel-10 study.  Professor Alehagen and his colleagues reported that four years of daily supplementation with a combination of Coenzyme Q10 and high-selenium yeast had resulted in a 54% reduction in the risk of dying from heart disease.

Moreover, the data showed significantly lower levels of the N-terminal proBNP peptide – a known biomarker for heart disease – in the blood of the study participants who had received the combination of Coenzyme Q10 and selenium, and the echocardiograms of the study participants receiving the active treatment showed significantly better heart function.

3. Johansson, P., Dahlström, Ö., Dahlström, U., & Alehagen, U. (2013). Effect of selenium and Q10 on the cardiac biomarker NT-proBNP. Scandinavian Cardiovascular Journal: SCJ, 47(5), 281-288. doi:10.3109/14017431.2013.820838

The purpose of the KiSel-10 study was to investigate whether four years of supplementation with a combination of Coenzyme Q10 and high-selenium yeast would slow the age-related decline of heart function in elderly Swedish citizens.  The researchers’ analysis of the data from measurements of the biomarker N-terminal natriuretic peptide at baseline and again after four years of supplementation showed that individuals in the middle three quintiles – quintiles two though four, representing individuals with mild to moderate heart function impairment – benefited most from the supplementation.

4. 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. doi:10.1371/journal.pone.0137680

The KiSel-10 researchers also evaluated the effect of the combination supplementation on the blood concentrations of the C-reactive protein – a known biomarker for inflammation – and of the sP-selectin cell adhesion molecules – known biomarkers for oxidative stress.  Elevated levels of each of these biomarkers may be related to higher risk of atherosclerosis and heart disease.

The study results showed that C-reactive protein levels increased in the placebo group over time but decreased significantly in the active treatment group.  Levels of the sP-selectin molecules increased in both groups but increased very significantly in the placebo group and only slightly in the active treatment group.

5. 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. doi:10.1002/biof.1245

Both Coenzyme Q10 (in its reduced form) and selenium as a component of certain selenoproteins function as antioxidants in the body.  The KiSel-10 researchers evaluated the effect of the combination supplementation on two biomarkers of oxidative stress: copeptin and adrenomedullin.

Over the four-year period of the study, the data showed a significant increase in copeptin levels in the placebo group, as compared to the active treatment group. Similarly, the data showed a lesser increase of adrenomedullin in the active treatment group compared to the placebo group.

And, of course, the KiSel-10 data showed significantly less death from heart disease in the active treatment group.  The same cardioprotective effect of the supplementation was seen again in a follow-up study after 10 years of observation.

6. 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.
doi:10.1007/s12603-015-0509-9

In a sub-analysis of the data from KiSel-10 study participants who were matched for age, gender and baseline cardiac wall tension as measured by NT-proBNP, the researchers found that the average number of days not hospitalized was significantly lower in the active treatment group as compared to the placebo group.

Furthermore, the study participants who received the combination supplementation showed significantly lesser declines in various aspects of health-related quality of life: physical role performance, vitality, cognitive function, nervous system function, and overall quality of life.

The supplementation with Coenzyme Q10 and selenium increased the number of days study participants stayed out of the hospital and slowed the age-related decline in health-related quality of life.

7. 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

Using the information in death certificates and autopsy reports available from the Swedish National Registry of Mortality, the KiSel-10 researchers were able to follow study participants for up to ten years following the initiation of the four-year intervention period.  They reported that no participant was lost to follow-up.

The significantly reduced risk of death from heart disease, first reported in 2013, was seen to persist for the entire ten-year follow-up period in the study participants who had received the Coenzyme Q10 and selenium combination.  Sub-group analysis of the data showed that the effect persisted in both males and females.

8. 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. doi:10.1016/j.jtemb.2014.11.006

Professor Alehagen (Sweden) and Professor Aaseth (Norway) explained the clinical significance of the combination supplementation with Coenzyme Q10 and high-selenium yeast by pointing to the potential role of selenium deficiency in heart disease, with emphasis on the antioxidant role of various selenoproteins, including the glutathione peroxidases and selenoprotein P.

In their explanation, they stressed the special interrelationship between selenium and Coenzyme Q10, itself a fat-soluble anti-oxidant in its reduced form.

Insufficient intakes of selenium can prevent the cells from getting adequate concentrations of Coenzyme Q10.  Moreover, the cells need adequate Coenzyme Q10 levels in order to achieve optimal selenium function.

9. Alehagen, U., Alexander, J., & Aaseth, J. (2016). 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, 11(7), e0157541. doi:10.1371/journal.pone.0157541

The KiSel-10 researchers did a secondary analysis of the available data to determine whether the positive effects of daily supplementation with Coenzyme Q10 and high-selenium yeast for four years are directly associated with the baseline serum selenium levels of study participants.

They reported two important findings from their secondary analysis: 1) the risk of death from heart disease was higher among study participants with baseline serum selenium concentrations lower than 65 micrograms per liter as compared with study participants whose baseline serum selenium concentrations were above 85 micrograms per liter, and 2) the daily supplementation with a combination of Coenzyme Q10 and high-selenium yeast was shown to provide protection against death from heart disease in the study participants with baseline serum selenium levels below 85 micrograms per liter.

10. 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. doi:10.1371/journal.pone.0174880

The KiSel-10 researchers focused in on the data from 50 study participants, all males, 25 of whom had been in the active treatment group and 25 of whom had been in the placebo group.  They isolated RNA from the plasma of these 50 study participants.

Then they analyzed the pre-treatment and post-treatment levels of expression of numerous microRNAs.  At baseline, there were no significant differences between the two groups in terms of microRNA expression levels.  After four years of treatment with either Coenzyme Q10 and high-selenium yeast or placebo, however, the data showed significant differences between the two groups in as many as 70 different microRNAs.  (MicroRNAs are non-coding RNA molecules involved in the regulation of genes that code for proteins.  These microRNAs can inhibit the expression of genes and thus influence the formation of proteins.  MicroRNAs can play a significant role in the development of heart disease and diabetes.)

The researchers concluded that the significant differences between the Coenzyme Q10/high-selenium yeast treatment group and the placebo group in the expression of microRNAs might be one of the biological mechanisms by which the supplementation with Coenzyme Q10 and high-selenium yeast reduced significantly the risk of death from heart disease and reduced the extent of inflammation in the elderly Swedish citizens.

11. Alehagen, U., Johansson, P., Aaseth, J., Alexander, J., & Brismar, K. (2017). Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and Coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens. Plos One, 12(6), e0178614. doi:10.1371/journal.pone.0178614

The KiSel-10 study data show conclusively that daily Coenzyme Q10 and high-selenium yeast supplements provide protection against death from heart disease and from age-related declines in heart function.  The researchers trace these beneficial effects in part to the antioxidant and anti-inflammatory functions of the two substances.

Insulin-like growth factor-1 (abbreviated IGF-1) has many functions in the body such as cell growth and metabolism and also anti-inflammatory and antioxidative effects.  IGF-1 concentrations decrease with age and during periods of inflammation.

The KiSel-10 researchers examined the effects of four years of daily supplementation with Coenzyme Q10 and high-selenium yeast on concentrations of IGF-1 and its binding protein IGFBP-1 in the elderly Swedish study participants.  They found that the individuals in the group taking Coenzyme Q10 and high-selenium yeast supplements had significantly increased IGF-1 and IGF-1 SD scores at the end of the study period while individuals in the placebo group had reduced concentrations.

The researchers suggested that the positive effect of Coenzyme Q10 and high-selenium yeast supplementation on IGF-1 concentrations might be one of the biological mechanisms explaining the positive clinical effects the risk of death from heart disease and on heart function.

As more studies based on the KiSel-10 data are published, we will summarize them here for you.