Antioxidants. Several selenoproteins play important roles as antioxidant enzymes in the protection of the cells and the mitochondria against the oxidative damage caused by harmful free radicals. Prominent among the antioxidant seleno-enzymes are the glutathione peroxidases and the thioredoxin reductases [Alehagen 2022].
Note: Oxidative stress is the bio-medical term for an imbalance in the relationship of 1) harmful free radicals, mostly of the reactive oxygen species, and 2) protective antioxidants, which should neutralize the harmful free radicals.
In many regions of the world, notably in much of Europe and the Middle East, there is selenium-poor soil and selenium-poor foodstuffs. In Sweden, for example, the average daily intake of selenium among senior citizens
is approximately 35 mcg/day, well below the amounts (110–150 mcg/day) needed for an optimal expression of the selenoprotein antioxidants [Alehagen 2022].
Selenium Supplementation of Senior Citizens Low on Selenium
In the KiSel-10 Study, Prof. Alehagen and a team of researchers administered a combination treatment of 200 mcg/day of selenium and 2 x 100 mg Coenzyme Q10 or matching placebos to community living senior citizens (average age: 78 years) in Sweden. The study participants had low selenium status and low CoQ10 status [Alehagen 2013].
Selenium-poor soil and selenium-poor foodstuffs in Sweden were the reason for the low mean baseline selenium status in the KiSel-10 study participants 67.1 mcg/L. The plasma/serum selenium status needs to be about 120 – 150 mcg/L for the various seleno-enzymes to be at an optimal level, i.e., fully expressed [Alehagen 2022].
Selenium – Coenzyme Q10 Interrelationship in the Body
The participants in the Kisel-10 Study were also somewhat low on Coenzyme Q10: 0.82 mg/L.The best estimate for a therapeutic effect of Coenzyme Q10 is above 2.0 mg/L [Langsjoen 2014].
About Coenzyme Q10, it is known that the endogenous synthesis declines with increasing age in the adult years to the extent that the CoQ10 production in the heart muscle cells is reduced to about half at the age of 80 years [Kalén 1989]; CoQ10 supplementation of elderly individuals, especially of individuals living in regions with low selenium content in the soil, is important [Alehagen 2022].
Prof. Alehagen notes that Coenzyme Q10 needs sufficient presence of selenium for the reduction of the oxidized form, ubiquinone, to the reduced form, ubiquinol, which is the antioxidant form.
Coenzyme Q10 in its reduced form is an important antioxidant in lipid structures in the body — membranes and lipoproteins. In its oxidized form, Coenzyme Q10 is especially important for crucial ATP energy generation in the mitochondrial respiratory chain. In the extramitochondrial space, the seleno-enzyme thioredoxin reductase-1 is a main reducing enzyme that regenerates the antioxidant form ubiquinol from ubiquinone [Alehagen 2022].
Beneficial Outcomes of the Combined Selenium and CoQ10 Supplementation
The KiSel-10 Study researchers found that the selenium + Coenzyme Q10 combination was associated with following statistically significant outcomes, compared to placebo treatment [Alehagen 2013]:
- improved heart function
- less cardiac wall tension
- reduced cardiovascular mortality
The researchers also noted that the significantly reduced cardiovascular
mortality persisted after five, 10, and 12 years of follow-up, from the beginning of the combined supplementation, again, compared to placebo treatment [Alehagen 2015: Alehagen 2018].
Physiological Mechanisms Explaining the Reduced Cardiovascular Mortality
In the years following the reporting of the KiSel-10 Study health outcomes, Prof Alehagen and the research team conducted sub-analyses of the study data in an effort to understand the physiological mechanisms that could explain the beneficial health outcomes.
They found that the combined selenium and Coenzyme Q10 treatment, compared to the placebo treatment, was significantly associated with improvements in the following bio-markers [Alehagen 2022]:
- reduced plasma levels of two bio-markers for oxidative damage
- reduced plasma levels of six bio-markers for systemic inflammation
- reduced serum levels of eight bio-markers for fibrosis
- reduced plasma levels of the von Willebrand factor and the plasminogen activator inhibitor-1, both bio-markers for endothelial dysfunction
- increased plasma levels of insulin-like growth factor-1, attenuating an age-related decline in IGF-1 concentrations
- reduced fructosamine concentration; increased fructosamine concentrations are positively associated with incidence of diabetes and increased blood glucose level
- improved renal function bio-markers
- inhibited increase in D-dimer levels, which are associated with increased risk of thrombotic disorders
Validation of the KiSel-10 Study Health Outcomes
To validate the above clinical results and to explore further the possible mechanisms behind the clinical results, the KiSel-10 research team conducted a secondary analysis using a technique called Structural Equation Modelling (SEM). The analysis showed the following relationships [Alehagen 2022]:
- the lower the selenium concentration of the individual, the higher the extent of inflammatory activity and the higher the level of bio-markers of oxidative stress
- suboptimal selenium status accompanied by a higher level of fibrosis and by increased myocardial wall tension (indicating a higher risk of cardiovascular mortality)
Conclusion: Antioxidant and Anti-Inflammatory Protection
The SEM model showed that, in individuals with low selenium and CoQ10
concentrations, combined supplementation with the two substances significantly reduces the extent of chronic systemic inflammation, oxidative stress, fibrosis and cardiovascular mortality risk [Alehagen 2022]. The combined supplementation was associated with beneficial antioxidant and anti-inflammatory activity.
Note: A 2014 comparative study conducted by Richie et al has shown that supplementation with a selenium yeast product, but not with a 100% selenomethionine product, is associated with reductions in biomarkers of oxidative stress. These findings suggest that selenium-containing compounds in the selenium yeast other than selenomethionine may account for the antioxidant effect of the selenium [Richie 2014].
Alehagen U, Johansson P, Bjornstedt M, Rosen A, Dahlstrom 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;167:1860–1866.
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 in elderly citizens. PLoS One. 2015;10:e0141641.
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 double-blind placebo-controlled trial in elderly. PLoS One. 2018;13:e0193120.
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 Apr 6. doi: 10.1007/s00394-022-02876-1. Epub ahead of print.
Kalén A, Appelkvist EL, Dallner G. Age-related changes in the lipid compositions of rat and human tissues. Lipids. 1989;24:579–584.
Langsjoen PH, Langsjoen AM. Comparison study of plasma coenzyme Q10 levels in healthy subjects supplemented with ubiquinol versus ubiquinone. Clin Pharmacol Drug Dev. 2014 Jan;3(1):13-7.
Richie JP Jr, Das A, Calcagnotto AM, Sinha R, Neidig W, Liao J, Lengerich EJ, Berg A, Hartman TJ, Ciccarella A, Baker A, Kaag MG, Goodin S, DiPaola RS, El-Bayoumy K. Comparative effects of two different forms of selenium on oxidative stress biomarkers in healthy men: a randomized clinical trial. Cancer Prev Res (Phila). 2014 Aug;7(8):796-804.
The information presented in this review article is not intended as medical advice and should not be used as such.
30 April 2022