In the KiSel-10 project, our research group has reported that daily supplementation of elderly community living Swedish citizens with a combination of 200 micrograms of organic Selenium (symbol Se, atomic number 34) is a trace element that is an essential nutrient and an essential component of some of the most important antioxidants in the body, in particular the selenoproteins glutathione peroxidase, thioredoxin reductase, and selenoprotein P. Selenium is involved in the optimal functioning of the immune system. Professor Alehagen has pointed out that there exists a... Read more about this term and 200 milligrams of Coenzyme Q10 molecules are fat-soluble molecules that are both bsynthesized in the body and ingested in the diet and in supplements. Coenzyme Q10 is synthesized in the body in the same biological pathway as cholesterol. Bio-synthesis of Coenzyme Q10 begins to decline once humans reach their adult years. The reduced production of Coenzyme Q10 cannot be compensated in any practical... Read more about this term for four years is associated with the following The outcome of a clinical trial is thought to have statistical significance, or to be statistically significant, if the outcome is likely not caused by chance at a given statistical significance level, typically at the 0.05 level. Statistically significant outcomes may or may not be clinically significant.... Read more about this term heart health outcomes [Alehagen 2013: Johansson 2015]:
- reduced risk of death from heart disease
- reduced blood levels of a protein bio-marker for The Mayo Clinic defines heart failure, also known as congestive heart failure and/or chronic heart failure, as the failure of the heart muscle to pump blood to the body adequately. In other words, heart failure is not a heart attack, and it is not death from heart disease, which its name might seem to imply. Heart failure is a condition... Read more about this term
- improved heart function shown on echocardiograms
- improved health-related quality of life
Possible Mechanisms for the Positive Clinical Outcomes
Thus far, our research group has published sub-analyses from the The KiSel-10 study was a four-year randomized, double-blind, placebo-controlled study of 443 Swedish citizens aged 70 to 88 who received either a combined daily supplementation of high-selenium yeast and Coenzyme Q10 or matching placebos. The elderly Swedish citizens who received the active treatment of selenium and Coenzyme Q10 had significantly reduced risk of death from heart disease, significantly better heart... Read more about this term that illuminate possible mechanisms to explain the positive clinical effects of the combined supplementation:
- reduced plasma levels of two bio-markers for oxidative damage [Alehagen 2015]
- reduced plasma levels of six bio-markers for systemic Inflammation is an immune system response to an injury to cells or tissues. It is the body’s attempt to defend against invaders such as bacteria andviruses and to mend the damage done by invaders. Typically, inflammation manifests itself in the form of fever and swelling, in the swarming of white blood cells and the release of cytokines to fight against... Read more about this term [Alehagen 2015; Alehagen 2019]
- reduced serum levels of eight bio-markers for fibrosis [Alehagen 2018]
- reduced plasma levels of the von Willebrand factor and the plasminogen activator inhibitor-1, both bio-markers for Endothelial dysfunction may be thought of as the failure of the cells lining the inside of arteries and veins to regulate properly blood vessel relaxation and contraction, blood clotting, immune function, and platelet adhesion. Endothelial dysfunction prevents the blood vessels from dilating sufficiently and can lead to increased risk of atherosclerosis, heart attack, and stroke. Coenzyme Q10 supplementation is associated... Read more about this term [Alehagen 2020]
- increased plasma levels of insulin-like growth factor-1, attenuating an age-related decline in IGF-1 concentrations [Alehagen 2017]
Indicators of Endothelial Dysfunction
Elevated von Willebrand factor concentrations are associated with inflammation and with vascular damage; accordingly, von Willebrand factor can be regarded as a marker for endothelial dysfunction.
Note: Endothelial dysfunction is the medical term for the impaired functioning of the The endothelium is the layer of cells that line the surface of the inside of the arteries and veins, the heart, and lymph vessels.The endothelium releases molecules, e.g. nitric oxide, angiotensin II, etc., that help to expand (dilate) or contract (constrict) the blood vessels and thus raise or lower blood pressure. The cells of the endothelium release substances (called factors)... Read more about this term, the thin surface lining of cells on the inside of blood vessels. Endothelial dysfunction is characterized by 1) impaired dilation of blood vessels, 2) sub-optimal levels of nitric oxide, and 3) inflammation and blood clotting. As such, endothelial dysfunction sets the stage for the development of Atherosclerosis is the thickening of the artery walls brought about by the build-up of plaque (plaque is made up of cholesterol and other fatty substances and waste products and calcium and fibrin) and the subsequent slowing of the flow of blood through the clogged arteries. More research is needed into the role of Coenzyme Q10 in the prevention and adjunct... Read more about this term. Fortunately, it is a reversible disorder, and selenium and Coenzyme Q10 appear to improve endothelial function.
Plasminogen activator inhibitor-1 levels are also associated with endothelial dysfunction, including in Ischemic heart disease is heart disease caused by reduced blood flow to the heart. Ischemic heart disease is, in most cases, coronary artery disease. Blockage of the coronary arteries reduces the flow of blood and oxygen to the heart.... Read more about this term and in heart attack.
The finding that the combined selenium and Coenzyme Q10 treatment reduced the blood concentrations of von Willebrand factor and plasminogen activator inhibitor-1 made us look at blood levels of D-dimer as an additional bio-marker for endothelial dysfunction.
D-dimer as a Bio-marker for Endothelial Dysfunction
In our most recent study of the data from the KiSel-10 project, we investigated the levels of D-dimer in plasma in blood samples taken from study participants in the combined selenium and Coenzyme Q10 treatment group and in the placebo group.
- D-dimer is the term for small protein fragments in the plasma that are produced by the fibrinolytic process that the body uses to control the size of blood clots. (Fibrinolysis means the dissolving of fibrin and the breakdown of blood clots.)
- The presence of D-dimer is biomarker of thrombo-embolism (a blood clot blocking blood flow in a blood vessel), increased inflammation, and endothelial dysfunction. As such, elevated D-dimer levels are associated with the risk of ischemic heart disease.
- We measured D-dimer in the plasma of 213 study participants at the start of the KiSel-10 Study and again after 48 months.
- At the end of the 4.9-year follow-up period, we found significantly lower D-dimer concentrations in the active treatment group compared with the placebo group.
- When we controlled for a possible confounding effect of bio-markers for inflammation, we found an independent effect of the selenium and Coenzyme Q10 treatment on D-dimer.
- In a sub-group analysis of KiSel-10 Study participants with Hypertension is abnormally high blood pressure, usually defined as adult systolic blood pressure above 140 mm Hg or adult diastolic blood pressure above 90 mm Hg. Systolic blood pressure is blood pressure measured during the contracting (pumping) of the left ventricle of the heart. Diastolic blood pressure is blood pressure measured during the relaxation of the left ventricle. A meta-analysis... Read more about this term or ischemic heart disease, we found that the combined supplementation resulted in a significantly lower concentration of D-dimer as compared to placebo.
- We concluded that daily selenium and Coenzyme Q10 supplementation of elderly citizens with low selenium status prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group.
- The level of D-dimer in the placebo group increased during the study period; it remained unchanged or was slightly reduced in the active treatment group.
- After 48 months, D-dimer levels were significantly lower in the active treatment group in comparison with the placebo group.
- Our group observed a significantly reduced heart disease mortality in the study participants with a high D-dimer level when they were given selenium and Coenzyme Q10 supplements, compared to study participants given placebos.
- A sub-analysis of study participants with hypertension or ischemic heart disease also demonstrated that a significantly lower concentration of D-dimer was associated with the combined supplementation.
- High D-dimer levels in the elderly populations may reflect age-related inflammatory activity and endothelial dysfunction.
- Elevated D-dimer level independently predicts increased risk of death from heart disease in patients with heart failure symptoms [Alehagen 2004].
D-Dimer and Covid-19
A final word:
A September 2020 meta-analysis of the data from six studies enrolling 1355 patients hospitalized with moderate to critical COVID-19 has shown that D-dimer levels are significantly associated with the risk of mortality in COVID-19 patients [Sakka 2020].
A meta-analysis published in November/September 2020 analyzed data from 18 studies with a total of 3682 Covid-19 patients. The aggregated data showed significantly elevated D-dimer levels in patients who died versus those who survived. The risk of death was four times higher in patients with elevated D-dimer versus low D-dimer, and the risk of developing severe disease was twice as high in patients with elevated D-dimer levels versus low D-dimer. In Covid-19 patients with elevated D-dimer levels, there was a significantly increased risk of severe disease and mortality [Shah 2020].
Alehagen U, Aaseth J, Lindahl TL, Larsson A, Alexander J. Dietary supplementation with selenium and Coenzyme Q10 prevents increase in plasma d-dimer while lowering cardiovascular mortality in an elderly Swedish population. Nutrients. 2021:13:1344.
Alehagen U, Alexander J, Aaseth J, Larsson A, Lindahl TL. The outcome of a clinical trial is thought to have statistical significance, or to be statistically significant, if the outcome is likely not caused by chance at a given statistical significance level, typically at the 0.05 level. Statistically significant outcomes may or may not be clinically significant. ... Read more about this term decrease of von Willebrand factor and plasminogen activator inhibitor-1 by providing supplementation with selenium and coenzyme Q10 to an elderly population with a low selenium status. Eur J Nutr. 2020;59(8):3581-3590.
Alehagen U, Alexander J, Aaseth J, Larsson A. Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a sub-analysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK. J Inflamm (Lond). 2019 Mar 18;16:5.
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 A double-blind study is a study in which neither the investigators nor the study participants know which participants are receiving the active treatment and which participants are receiving the control treatment until the study has been completed and the seal on the code has been broken.... Read more about this term placebo-controlled trial in elderly. PLoS One. 2018 Apr 11;13(4):e0193120.
Alehagen U, Aaseth J, Alexander J, Svensson E, Johansson P, Larsson A. Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10-A mechanism behind reduced cardiovascular mortality? Biofactors. 2018 Mar;44(2):137-147.
Alehagen U, Johansson P, Aaseth J, Alexander J, Brismar K. 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. 2017 Jun 13;12(6):e0178614.
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 trials are research studies in which various treatments, interventions, or tests are investigated for their safety and efficacy when used to detect, prevent, or treat diseases and medical conditions in patients and healthy volunteers. The gold standard for clinical trials are randomized, double-blind, placebo-controlled studies.... Read more about this term. PLoS One. 2016 Jul 1;11(7):e0157541.
Alehagen U, Lindahl TL, Aaseth J, Svensson E, Johansson P. 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 Sep 16;10(9):e0137680.
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 Nov-Dec;41(6):443-52.
Alehagen U, Johansson P, Björnstedt M, Rosén A, Dahlström U. 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. Int J Cardiol. 2013 Sep 1;167(5):1860-6.
Alehagen U, Dahlström U, Lindahl TL. Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure. Thromb Haemost. 2004 Dec;92(6):1250-8.
Johansson P, Dahlström Ö, Dahlström U, Alehagen U. 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. J Nutr Health Aging. 2015 Nov;19(9):870-7.
Sakka M, Connors JM, Hékimian G, Martin-Toutain I, Crichi B , Colmegna I, Bonnefont-Rousselot D, Farge D, Frere C. Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): a systematic review and pooled analysis. JMV-Journal de Médecine Vasculaire. 2020;45(5):268-274.
Shah S, Shah K, Patel SB, Patel FS, Osman M, Velagapudi P, Turagam MK, Lakkireddy D, Garg J. Elevated D-Dimer Levels Are Associated with Increased Risk of Mortality in Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. Cardiol Rev. 2020 Nov/Dec;28(6):295-302.
30 April 2021