KiSel-10
The KiSel-10 Study was a randomized, placebo-controlled, double-blind clinical trial that was first reported in the International Journal of Cardiology in 2013[1]. The full title of the report is “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.”
Purpose
Professor Urban Alehagen and a team of researchers at Linköping University designed and conducted the KiSel-10 study to investigate the effect of a daily combination of Coenzyme Q10 capsules and high-selenium yeast tablets on the extent of chronic heart failure, all-cause mortality, and cardiovascular mortality in senior citizens. The researchers' secondary objective was to determine whether the intervention with Coenzyme Q10 and selenium would influence cardiac function as evaluated by cardiac natriuretic peptides and by echocardiography[1].
Dosage
The KiSel-10 study participants in the active treatment group received a combination of 2 times 100 milligrams per day of Coenzyme Q10 and 200 micrograms per day of an organic high-selenium yeast for 48 months[1]. The study participants in the control group received matching placebos daily.
Study Participants
Professor Alehagen and the KiSel-10 researchers recruited 443 healthy elderly citizens living in the rural community of Kinda in southeastern Sweden.
They recruited both men and women, aged 70 – 88 years with an average age of 78 years at the time of enrollment into the study. The ratio of men to women was close to 1:1[1].
Discussion of the Results
Reduced Cardiovascular Mortality
In their first journal article reporting the results of the 48-month daily supplementation with a combination of a ubiquinone Coenzyme Q10 preparation and an organic high-selenium yeast preparation, Professor Alehagen and his team of researchers reported a 54% reduction in cardiovascular mortality as well as significantly lower blood levels of the N-terminal proBNP peptide – a known bio-marker for heart disease – and significantly better heart function seen on echocardiograms in the senior citizens receiving the active treatment as compared to the placebo treatment[1].
Improved Health-Related Quality of Life
The senior citizens receiving the Coenzyme Q10 and high-selenium yeast supplementation had significantly less decline in health-related quality of life indicators and in overall quality of life. Furthermore, they had significantly less need for hospitalization than did the senior citizens taking the placebo supplements[2].
Persistent Cardio-Protection
Professor Alehagen and the Linköping researchers used data from the records of the Swedish National Registry of Mortality to follow the senior citizens in the KiSel-10 study for 10 and 12 years following the beginning of the four-year intervention period. They were able to follow every participant, no one was lost to follow-up[3].
The follow-up studies showed that the senior Swedish citizens who had received a combination of Coenzyme Q10 and high-selenium yeast continued to have a significantly lower cardiovascular mortality rate. The reduced cardiovascular mortality rate in the active treatment group held in patients with risk factors such as diabetes, hypertension, ischemic heart disease, and impaired functional capacity[4].
Possible Mechanisms of Action
Professor Alehagen and Professor Aaseth explained the beneficial effects of the combination supplementation by pointing to the antioxidant function of both Coenzyme Q10 in its reduced form and numerous selenium containing antioxidant seleno-enzymes.
There exists a special interrelationship between Coenzyme Q10 and selenium such that insufficient bio-availability of selenium can inhibit the cells from synthesizing adequate quantities of Coenzyme Q10 while, at the same time, the cells require adequate Coenzyme Q10 levels to realize optimal selenium function[5].
More specifically, Professor Alehagen documented specific effects of the combination supplementation that might explain the significantly reduced cardiovascular mortality in the senior citizens who received the Coenzyme Q10 and high-selenium yeast supplements:
Reduced levels of inflammation
Early on, the KiSel-10 researchers investigated the effect of the combination supplementation on the known bio-markers for inflammation: C-reactive protein and sP-selectin. The active treatment was associated with significantly decreased levels of C-reactive protein. The levels of the sP-selectin were elevated in both groups but were significantly elevated in the placebo group and only slightly elevated in the active treatment group[6].
In a later secondary analysis, the researchers found that the active treatment was associated with significantly reduced concentrations of the osteopontin, osteoprotegerin, sTNF receptor 1, and sTNF receptor 2 bio-markers for inflammation[7].
Reduced levels of oxidative stress
Professor Alehagen and the research team found that the combination supplementation of senior citizens had a beneficial effect on the levels of two known bio-markers for oxidative stress: copeptin and adrenomedullin[8].
Reduced levels of cardiac fibrosis
The Coenzyme Q10 and high-selenium yeast supplementation was associated with significantly reduced blood levels for seven out of the eight tested bio-markers for cardiac fibrosis[9].
Changed microRNA activity
Between the active treatment group and the placebo control group, there were significant differences in the expression of 70 microRNAs[10].
Increased insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein-1
Senior citizens in the Coenzyme Q10 and high-selenium yeast treatment group had significantly increased IGF-1 levels at the end of the study period. Senior citizens in the placebo group had reduced IGF-1 concentrations[11].
References
- ↑ 1.0 1.1 1.2 1.3 1.4 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.CS1 maint: Multiple names: authors list (link)
- ↑ 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): 880–887.CS1 maint: Multiple names: authors list (link)
- ↑ 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". PlosOne. 10(12): e0141641.CS1 maint: Multiple names: authors list (link)
- ↑ 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". PlosOne. 13(4): , e0193120.CS1 maint: Multiple names: authors list (link)
- ↑ 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. 31: 157–162.CS1 maint: Multiple names: authors list (link)
- ↑ 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". PlosOne. 10(9): e0137680.CS1 maint: Multiple names: authors list (link)
- ↑ Alehagen, U., Alexander, J., Aaseth, J. & Larsson, A. (2019). "Decrease in inflammatory biomarker concentration by intervention with selenium and Coenzyme Q10: a sub-analysis of osteopontin, osteoprotergerin, TNFr1, TNFr2, and TWEAK". Journal of Inflammation. 16(5): 1–9.CS1 maint: Multiple names: authors list (link)
- ↑ 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.CS1 maint: Multiple names: authors list (link)
- ↑ Alehagen, U., Aaseth, J., Johansson, P., & Larsson, A. (2018). "Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality?". Biofactors. 44(2): 137–147.CS1 maint: Multiple names: authors list (link)
- ↑ 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". PlosOne. 12(4): e0174880.CS1 maint: Multiple names: authors list (link)
- ↑ 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". PlosOne. 12(6): e0178614.CS1 maint: Multiple names: authors list (link)
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