How to grow older and still maintain good health with CoQ10 and Selenium
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% with Coenzyme Q10 and Selenium
Leading Swedish cardiologists have published a sensational study showing how easily they were able to reduce cardiovascular disease mortality by over 50% among a large group of town villagers.
Medical history is being written these days in a community called Kinda not far from the university city 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 with CoQ10 and Selenium 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: A new cornerstone in CoQ10 and Selenium research
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 Kinda community, 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.
At the start of the study, the mean serum selenium concentration was 67.1 μg/L (SD 16.8). After 48 months, the concentration of selenium in the active treatment group was 210.3 μg/L (SD 59.4).
Regarding the concentration of CoQ10, the pre-intervention concentration in the population was 0.82 mg/L (SD 0.31), and the concentration in the active treatment group after 48 months was 2.17 mg/L (SD 1.33).
To date, spring 2023, the researchers have published 24 papers detailing the results of the analysis of the data from the KiSel-10 study.
Following are the citations and summaries of the 24 published journal articles.
1. Relatively high cardiovascular disease mortality risk in elderly Swedish subjects with low selenium status
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.
Ref 1: Alehagen U, Johansson P, Björnstedt M, Rosén A. Relatively high mortality risk in elderly Swedish subjects with low selenium status. Eur J Clin Nutr. 2016;70:91-6.
2. Reduced cardiovascular disease mortality after combined selenium and CoQ10 supplementation
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 CoQ10 and selenium, and the echocardiograms of the study participants receiving the active treatment showed significantly better heart function.
Ref 2: Alehagen U, Johansson P, Björnstedt M, Rosén A. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: A 5-year prospective randomized double-blind placebo-controlled trial. Int J Cardiol. 2013;167:1860-1866.
3. Effect of selenium and CoQ10 on the cardiac biomarker proBNP
The purpose of the KiSel-10 study was to investigate whether four years of supplementation with a combination of CoQ10 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 (proBNP) at baseline and again after four years of supplementation showed that individuals in the middle three quintiles – quintiles two through four, representing individuals with mild to moderate heart function impairment – benefited most from the supplementation.
Ref 3: Johansson P, Dahlstrom O, Dahlstrom U, Alehagen U. Effect of selenium and Q10 on the cardiac biomarker NT-proBNP. Scand Cardiovasc J. 2013;47:281-8.
4. CoQ10 and Selenium combined decreased levels of CRP and sP-selectin
The KiSel-10 researchers also evaluated the effect of the combination supplementation of CoQ10 and Selenium 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 group receiving CoQ10 and Selenium. 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.
Ref 4: Alehagen U, Lindahl TL, Aaseth J, Svensson E. 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. 2015;10:e0137680.
5. Combined intervention with selenium and CoQ10 improved biomarkers of oxidative stress
Both CoQ10 (in its reduced ubiquinol 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 (MR-proADM).
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 (MR-proADM) in the active CoQ10 and selenium 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.
Ref 5: Alehagen U, Aaseth J, Johansson P. 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. 2015;41:443-52.
6. Improved quality of life, and more days out of hospital with supplementation with selenium and CoQ10
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.
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 proBNP, the researchers found that the average number of days hospitalized was significantly lower in the CoQ10 and Selenium 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.
Ref 6: Johansson P, Dahlstrom O, Dahlstrom U, Alehagen U. Improved health-related quality of life, and more days out of hospital with supplementation with selenium and coenzyme Q10 combined. J Nutr Health Aging. 2015;19:870-7.
7. Reduced cardiovascular disease mortality 10 years after supplementation with selenium and CoQ10
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 CoQ10 and selenium combination. Sub-group analysis of the data showed that the effect persisted in both males and females.
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.
Ref 7: Alehagen U, Aaseth J, Johansson P. 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. PLoS One. 2015; 10(12):e0141641.
8. The role of Selenium and coenzyme Q10 in cardiovascular diseases – A clinician s point of view
Insufficient intakes of selenium can prevent the cells from getting adequate concentrations of CoQ10. Moreover, the cells need adequate CoQ10 levels in order to achieve optimal selenium function.
Professor Alehagen (Sweden) and Professor Aaseth (Norway) explained the clinical significance of the combination supplementation with CoQ10 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 CoQ10, itself a fat-soluble anti-oxidant in its reduced form.
Ref 8: Alehagen U, Aaseth J. Selenium and coenzyme Q10 interrelationship in cardiovascular diseases – A clinician s point of view. J Trace Elem Med Biol. 2015;31:157-62.
9. Supplementation with selenium and CoQ10 reduces cardiovascular disease mortality in elderly with low selenium status
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.
Ref 9: 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:e0157541.
10. Significant changes in circulating microRNA by dietary supplementation of selenium and CoQ10 in healthy elderly males
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 CoQ10 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 CoQ10 and high-selenium yeast reduced significantly the risk of death from heart disease and reduced the extent of inflammation in the elderly Swedish citizens.
Ref 10: Alehagen U, Johansson P, Aaseth J, Alexander J. Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males: A subgroup analysis. PLoS One. 2017;12:e0174880.
11. Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and CoQ10
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 CoQ10 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 CoQ10 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.
Ref 11: Alehagen U, Johansson P, Aaseth J, Alexander J. Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. PLoS One. 2017;12:e0178614.
12. Less fibrosis in elderly subjects supplemented with selenium and CoQ10: A mechanism behind reduced cardiovascular disease mortality?
Professor Alehagen and his research colleagues investigated the effect of supplementation with Coenzyme Q10 and high-selenium yeast on eight bio-markers of fibrogenic activity in healthy elderly Swedish citizens, aged 70 – 88 years. They analyzed the blood concentrations of the various bio-markers at the six-month mark and the 42-month mark in the study. The data showed that there were significantly reduced blood concentrations of seven of the eight bio-markers in the active CoQ10 and selenium group after 42 months of supplementation as compared with the placebo group. The reduced fibrogenic activity seems to be a consequence of the daily intervention with CoQ10 and high-selenium supplements. There appears to be an association between the supplementation and the reduction in the bio-markers of fibrosis and the statistically significant reduction in the risk of death from cardiovascular disease among the elderly study participants.
Note: Cardiac fibrosis – the development of excess fibrous tissue depositions in the heart muscle or heart valves – can increase the risk of heart failure.
Ref 12: Alehagen U, Aaseth J, Alexander J, Svensson E. Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10: A mechanism behind reduced cardiovascular mortality? Biofactors. 2018;44:137-147.
13. Still reduced cardiovascular disease mortality 12 years after supplementation with selenium and CoQ10 for four years
Even as long as 12 years after the supplementation with Coenzyme Q10 and high selenium yeast, elderly Swedish citizens who got the active treatment rather than the placebo treatment showed significantly lower risk of death from heart disease. Moreover, the reduced risk in the active treatment group was seen in such subgroups of patients as those with diabetes, hypertension, ischemic heart disease, and impaired functional capacity. Professor Alehagen and his team of researchers have not determined all of the mechanisms of the protective action of the CoQ10 and selenium supplements, but they point to the documented effects of the supplement combination on heart function, oxidative stress, fibrosis, and inflammation.
Ref 13: Alehagen U, Aaseth J, Alexander J, Johansson P. 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 controlled trial. PLoS One. 2018;13:e0193120.
14. Decrease in inflammatory biomarker concentration by intervention with selenium and CoQ10
In a secondary analysis of a sub-group of 219 individuals from the larger KiSel-10 study of 443 senior citizens aged 70 to 88 years at baseline, Professor Alehagen and his colleagues examined the effect of daily supplementation with 200 micrograms of high-selenium yeast and 200 milligrams of ubiquinone Coenzyme Q10 on plasma bio-markers of inflammation after 6 months and after 42 months. The results showed significantly lower concentrations of the following bio-markers for inflammation: osteopontin, osteoprotegerin, sTNF receptor 1, and sTNF receptor 2. Only the tumor necrosis factor-like weak inducer of apoptosis called TWEAK did not show a significant reduction associated with the selenium yeast and CoQ10 supplementation.
These results follow the earlier report that daily supplementation with selenium yeast and CoQ10 in the KiSel-10 study was associated with significant positive changes in the inflammatory bio-markers C-reactive protein and sP-selectin, reflecting important effects on inflammation and atherosclerosis in the individuals who took the combined selenium yeast and CoQ10 treatment as compared to the individuals who took the matching placebos.
These results indicating a significant decrease in inflammation could be one of the mechanisms by which the combined selenium yeast and Coenzyme Q10 supplementation reduced cardiovascular mortality and improved heart function in senior citizens. In an earlier publication, Professor Alehagen and his colleagues presented evidence that the four-year combined supplementation was associated with significantly reduced levels of oxidative stress.
One possible conclusion is that the combined supplementation improved the senior citizens’ anti-oxidative and anti-inflammatory defenses to an extent that resulted in reduced cardiovascular mortality, improved heart function, and improved health-related quality of life.
Ref 14: Alehagen U, Alexander J, Aaseth J, Larsson A. Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK. J Inflamm (Lond). 2019;16:5.
15. Significant changes in metabolic profiles after intervention with selenium and coenzyme Q10 in an elderly population
In this sub-analysis, Professor Alehagen reported clear differences in the metabolic profiles in plasma from elderly men who took 200 micrograms of selenium and 2 x 100 milligrams of CoQ10 daily for at least 18 months as compared to the metabolic profiles of elderly men who took matching placebos. The researchers found major differences in such biological pathways as the pentose phosphate pathway, the mevalonate pathway, and the beta-oxidation pathway. They concluded that these effects of the combined selenium and CoQ10 supplementation, together with the reduced levels of oxidative stress, inflammation, and fibrosis associated with the combined supplementation, help to explain that four years of supplementation with selenium and CoQ10 is associated with significantly reduced cardiovascular disease mortality, improved heart function, and improved health-related quality of life in senior citizens.
Ref 15: Alehagen U, Johansson P, Aaseth J, Alexander J. Significant changes in metabolic profiles after intervention with selenium and coenzyme Q10 in an elderly population. Biomolecules. 2019;10:E553.
16. Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and Coenzyme Q10 to an elderly population
The elderly KiSel-10 Study participants (age range: 70 – 88 years) were given 200 milligrams of Coenzyme Q10 (2 times 100 milligrams at different times) and 200 micrograms of organic selenium yeast or matching placebos daily for four years. One of the main results from the study was a significant reduction in cardiovascular mortality. In this sub-analysis, Professor Alehagen and his team of researchers found significantly lower levels of von Willebrand factor and plasminogen activator inhibitor-1 in the active treatment group as compared to the placebo group. They interpreted these outcomes as an indication that the intervention had improved endothelial function. The better endothelial function may be one of the mechanisms by which the combination of selenium and CoQ10 supplements results in significantly reduced cardiovascular mortality.
Increased concentrations of the von Willebrand factor have been linked to increased risk of cardiovascular disease and heart attack. The von Willebrand factor is a plasma glycoprotein that is important for hemostasis and coagulation (the first stage of wound healing). The von Willebrand factor is produced and stored in the endothelial cells and platelets. However, increased concentrations of the von Willebrand factor are regarded as a sign of vascular dysfunction.
Plasminogen activator inhibitor-1 is secreted from endothelial cells and liver cells. It is also synthesized and stored in platelets. Higher levels of plasminogen activator inhibitor-1 have been associated with increased risk of ischemia and coronary artery disease and with the development of diabetes and insulin resistance.
In this sub-study of the KiSel-10 Study, the concentration of both von Willebrand factor and plasminogen activator inhibitor-1 were significantly lower after 36 months of supplementation with selenium and CoQ10.
Ref 16: Alehagen U, Alexander J, Aaseth J, Larsson A. Significant decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and Coenzyme Q10 to an elderly population. European Journal of Nutrition. 2020;59:3581-3590.
17. Supplemental selenium and CoQ10 reduce glycation along with cardiovascular disease mortality in an elderly population with low selenium status
In this sub-study of the KiSel-10 Study of heart disease mortality, Professor Alehagen determined the fructosamine plasma concentrations after six and 42 months of intervention in 219 study participants supplemented with selenium yeast (200 μg/day) and Coenzyme Q10 (200 mg/ day) (n = 118 of whom 20 had diabetes at inclusion) or matching placebos (n = 101 of whom 18 had diabetes at inclusion).
Fructosamine is a marker for long-term glycemic control in diabetic patients. It is positively associated with risk of cardiovascular diseases both in diabetics and non-diabetics.
In this sub-study, the intervention with selenium and Q10 was associated with a significant decrease in plasma fructosamine concentration. The decrease was observed in both males and females, in both the middle-aged and in the elderly, and in the non-diabetic group. Study participants with a lower pre-intervention level of selenium had a more pronounced decrease in plasma fructosamine concentrations.
Professor Alehagen suggested that the decrease in plasma fructosamine levels may have contributed to the reduced cardiac mortality associated with the selenium and CoQ10 intervention and might reflect the lower levels of bio-markers of inflammation and oxidative stress that have been associated with the combination supplementation.
Ref 17: Alehagen U, Aaseth J, Alexander J, Johansson P. Supplemental selenium and coenzyme Q10 reduce glycation along with cardiovascular mortality in an elderly population with low selenium status. Journal of Trace Elements in Medicine and Biology. 2020;61:126541.
18. Selenium and CoQ10 supplementation improves renal function in elderly deficient in selenium
In a sub-analysis of the KiSel-10 data, Professor Alehagen searched for a possible association between selenium and renal function in an elderly population low in selenium and coenzyme Q10 and investigated the impact of intervention with selenium and CoQ10 on the renal function. In individuals with a deficiency of selenium and CoQ10, low selenium status was found to be related to impaired renal function, and supplementation with selenium and CoQ10 resulted in significantly improved renal function as seen from creatinine levels and cystatin-C levels and through the use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) algorithm.
Ref 19: Alehagen U, Brismar K, Alexander J, Aaseth J. Selenium and Coenzyme Q10 supplementation improves renal function in elderly deficient in selenium: observational results and results from a subgroup analysis of a randomised placebo controlled trial. Nutrients. 2020;12(12):3780.
19. Dietary supplementation with selenium and Coenzyme Q10 prevents increase in plasma D-dimer while lowering cardiovascular disease mortality in an elderly Swedish population
Fibrinolysis is the body’s process of breaking down no longer needed blood clots. D-dimers are leftover fragments of the fibrinolysis process. The presence of d-dimers above a certain level in the blood plasma is a bio-marker for a possible major blood clot such as a deep vein thrombosis and, by extension, for increased risk of death in ischemic heart disease. Moreover, high D-dimer levels in an elderly population may reflect age-related inflammatory activity and age-related endothelial dysfunction.
In this sub-study based on an analysis of data from elderly Swedish citizens enrolled in the KiSel-10 Study, Professor Alehagen and a team of researchers found a significantly lower plasma D-dimer concentration in study participants in the active treatment group receiving 200 mg of CoQ10 and 200 micrograms of organic selenium daily as compared to study participants in the placebo group.
In study participants with a D-dimer level above median at baseline, the combined CoQ10 and selenium supplementation was associated with significantly lower cardiovascular mortality compared to the placebo administration.
Ref 19: Alehagen U, Aaseth J, Lindahl TL, Alexander J. Dietary supplementation with selenium and CoQ10 prevents increase in plasma D-dimer while lowering cardiovascular mortality in an elderly Swedish population. Nutrients. 2021;13:1344.
20. Improved cardiovascular health by supplementation with selenium and coenzyme Q10
The main findings of the KiSel-10 randomized double-blind placebo-controlled intervention with selenium and CoQ10 in elderly Swedes low in selenium and coenzyme Q10 were 1) a significantly increased systolic heart function, 2) a reduced myocardial wall tension, and 3) a reduced cardiovascular mortality. A series of secondary analyses of the KiSel-10 data showed some of the underlying mechanisms for the positive clinical results.
Prof. Alehagen and the research team used Structural Equation Modelling (SEM) techniques to investigate the statistical inter-relationships between biomarkers related to inflammation, oxidative stress, insulin-like growth factor 1, expression of microRNA, fibrosis, and endothelial dysfunction and their impact on the clinical outcomes.
Their SEM analysis showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress that influenced the factors fibrosis and myocardium (heart muscle tissue). According to the SEM model, the combined selenium and CoQ10 intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced cardiovascular mortality.
Ref 20: Alehagen U, Johansson P, Svensson E, Aaseth J, Alexander J. Improved cardiovascular health by supplementation with selenium and coenzyme Q10: applying structural equation modelling (SEM) to clinical outcomes and biomarkers to explore underlying mechanisms in a prospective
randomized double‑blind placebo‑controlled intervention project in Sweden. Eur J Nutr. 2022; https://doi.org/10.1007/s00394-022-02876-1.
21. Decreased concentration of Fibroblast Growth Factor 23 (FGF-23) as a result of supplementation with selenium and Coenzyme Q10 in an elderly Swedish population
The KiSel-10 research team evaluated the effect of 48-month supplementation with selenium and Coenzyme Q10 on the Fibroblast Growth Factor 23 concentrations in senior citizens with low concentrations of both selenium and CoQ10 in whom the supplementation had improved cardiac function and reduced cardiovascular disease mortality.
Compared to placebo, the supplementation with selenium and CoQ10 was associated with a significantly lower level of Fibroblast Growth Factor 23.
Moreover, after 10 years of follow-up, the study participants who later died a cardiovascular death were seen to have had a significantly higher FGF-23 concentration compared with study participants who survived. Also, the study participants who had normal kidney function had significantly lower Fibroblast Growth Factor 23 concentrations than the study participants with impaired renal function.
Ref 21: Alehagen U, Aaseth J, Larsson A, Alexander J. Decreased concentration of Fibroblast Growth Factor 23 (FGF-23) as a result of supplementation with selenium and CoQ10 in an elderly Swedish population: A sub-analysis. Cells. 2022 Feb 1;11(3):509.
22. Selenium and CoQ10 intervention prevents telomere attrition, with association to reduced cardiovascular disease mortality
In this KiSel-10 sub-study, Prof Alehagen and the KiSel-10 research team investigated whether 42 months of combined selenium and Coenzyme Q10 supplementation prevented telomere shortening and further cardiovascular
mortality. They quantified leukocyte telomere length at baseline and after 42 months. They found that less shortening of the leukocyte telomere length was observed after active treatment compared with placebo.
Moreover, study participants who suffered future death were seen to have significantly shorter leukocyte telomere length at 42 months than survivors did. The KiSel-10 researchers concluded that the preservation of leukocyte telomere length after 42 months of combined selenium and CoQ10 supplementation is associated with reduced cardiovascular mortality.
Ref 22: Opstad TB, Alexander J, Aaseth JO, Larsson A, Seljeflot I, Alehagen, U. Selenium and Coenzyme Q10 intervention prevents telomere attrition, with association to reduced cardiovascular mortality—sub-study of a randomized clinical trial. Nutrients. 2022;14:3346.
23. Increased SIRT1 concentration following four years of selenium and q10 intervention associated with reduced cardiovascular mortality at 10-year follow-up—sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial.
A 2023 follow-up analysis of blood samples from the KiSel-10 Study show that daily supplementation of elderly individuals with Coenzyme Q10 and selenium for four years significantly increased serum Sirtuin1 (SIRT1) concentrations. Individuals who suffered cardiovascular disease deaths during a 10-year follow-up had significantly lower baseline SIRT1 concentrations compared to the survivors. The increased SIRT1 concentration after the combined CoQ10 and selenium intervention was associated with reduced cardiovascular disease mortality. SIRT1 appears to be an additional mediator of the CoQ10 and selenium intervention, reducing cardiovascular mortality and preventing vascular ageing.
Ref 23: Opstad TB, Alexander J, Aaseth J, Larsson A, Seljeflot I, Alehagen U. Increased SIRT1 concentration following four years of selenium and q10 intervention associated with reduced cardiovascular mortality at 10-year follow-up—sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial. Antioxidants 2023, 12, 759.
24. Selenium and coenzyme Q10 improve the systemic redox status while reducing cardiovascular mortality in elderly population-based individuals.
The concentration level of circulating free thiols in serum is a recognized biomarker of intracellular oxidative stress. Lower levels of level of free thiols in the blood circulation are a sign of systemic oxidative stress. Serum free thiol levels are associated with significantly increased risk of cardiovascular disease events and with all-cause mortality. Higher levels of serum free thiol concentrations are associated with lower risk of heart failure and with favorable disease outcome.
After 48 months of daily combined supplementation with selenium and Coenzyme Q10 in the KiSel-10 study, elderly study participants in the active treatment group showed significantly increased levels of serum free thiols compared to placebo. The Ki-Sel-10 researchers concluded that combined supplementation with selenium and Coenzyme Q10 of elderly community-dwelling individuals with low status of both substances significantly improved serum free thiol levels and effectively reduced systemic oxidative stress.
Note: Thiols are sulfur-containing organic compounds with the formula R-SH where R stands for any hydrocarbon group.
Ref. 24: Dunning BJ, Bourgonje AR, Bulthuis ML, Alexander J, Aaseth JO, Larsson A, van Goor H, Alehagen U. Selenium and coenzyme Q10 improve the systemic redox status while reducing cardiovascular mortality in elderly population-based individuals. Free Radical Biology and Medicine. 2023;204:207-214.
As more studies based on the KiSel-10 data are published, we will summarize them here for you.
Read more about KiSel-10: Swedish scientists behind amazing discovery
In addition to publishing journal articles based on the data from the KiSel-10 clinical trial, Professor Alehagen has co-authored papers on the following topics together with Professor Jan Aaseth and Professor Jan Alexander.
Alehagen U, Opstad TB, Alexander J, Larsson A, Aaseth J. Impact of selenium on biomarkers and clinical aspects related to ageing. A review. Biomolecules 2021;11:1478.
Aaseth J, Alexander J, Alehagen U, Tinkov A, Skalny A, Larsson A, Crisponi G, Nurchi VM. The Aging Kidney-as influenced by heavy metal exposure and selenium supplementation. Biomolecules. 2021 Jul 22;11(8):1078.
Aaseth J, Alexander J, Alehagen U. Coenzyme Q10 supplementation – In ageing and disease. Mech Ageing Dev. 2021 Jul;197:111521.
Aaseth J, Ellefsen S, Alehagen U, Sundfør TM, Alexander J. Diets and drugs for weight loss and health in obesity – An update. Biomed Pharmacother. 2021 Aug;140:111789.
Alexander J, Alehagen U, Aaseth JO. Selenium – a trace element of clinical significance. Tidsskr Nor Laegeforen. 2020 Nov 23;140(17).
Alexander J, Tinkov A, Strand TA, Alehagen U, Skalny A, Aaseth J. Early nutritional interventions with zinc, selenium and vitamin d for raising anti-viral resistance against progressive COVID-19. Nutrients. 2020 Aug 7;12(8):2358.
Aaseth J, Alexander J, Bjørklund G, Hestad K, Dusek P, Roos PM, Alehagen U. Treatment strategies in Alzheimer’s disease: a review with focus on selenium supplementation. Biometals. 2016 Oct;29(5):827-39.
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