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

Urban Alehagen, Peter Johansson, Erland Svensson, Jan Aaseth, Jan Alexander, Urban Alehagen, Peter Johansson, Erland Svensson, Jan Aaseth, Jan Alexander

Abstract

Purpose: Selenium and coenzyme Q10 have synergistic antioxidant functions. In a four-year supplemental trial in elderly Swedes with a low selenium status, we found improved cardiac function, less cardiac wall tension and reduced cardiovascular mortality up to 12 years of follow-up. Here we briefly review the main results, including those from studies on biomarkers related to cardiovascular risk that were subsequently conducted. In an effort, to explain underlying mechanisms, we conducted a structured analysis of the inter-relationship between biomarkers.

Methods: Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/ day), or placebo was given to 443 elderly community-living persons, for 48 months. Structural Equation Modelling (SEM) was used 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 effects. The main study was registered at Clinicaltrials.gov at 30th of September 2011, and has the identifier NCT01443780.

Results: In addition to positive clinical effects, the intervention with selenium and coenzyme Q10 was also associated with favourable effects on biomarkers of cardiovascular risk. Using these results in the SEM model, we showed that the weights of the first-order factors inflammation and oxidative stress were high, together forming a second-order factor inflammation/oxidative stress influencing the factors, fibrosis (β = 0.74; p < 0.001) and myocardium (β = 0.65; p < 0.001). According to the model, the intervention impacted fibrosis and myocardium through these factors, resulting in improved cardiac function and reduced CV mortality.

Conclusion: Selenium reduced inflammation and oxidative stress. According to the SEM analysis, these effects reduced fibrosis and improved myocardial function pointing to the importance of supplementation in those low on selenium and coenzyme Q10.

Keywords: Coenzyme Q10; Elderly; Mechanisms; Mortality; SEM; Selenium.

Conflict of interest statement

The authors declare no conflicts of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Plasma concentration of fructosamine in those with active treatment compared with placebo after six and 42 months
Fig. 2
Fig. 2
Plasma concentration of copeptin in the active treatment group, compared with placebo at inclusion and after 48 months
Fig. 3
Fig. 3
Structural equation model of the relations between Selenium (Selenium/age), the second-order factor Infl/Oxid. Stress, Fibrosis and Myocardium. Ellipses depict latent variables or factors and squares manifest or measured variables. All effects (Beta-values italicized) and factor loadings are significant (p < .001). Model fit: Chi-square = 56.43, df = 57, p = 0.497, RMSEA = 0.000, CFI = 0.99
Fig. 4
Fig. 4
The obtained changes in factor weights between the factors “Inflammation” before and after intervention with selenium and coenzyme Q10
Fig. 5
Fig. 5
A linear regression smoothing plane optimizing the fit of data points in a three-dimensional space. The figure is based on the regression equation predicting ”CV age” from logarithmized values of NT-proBNP and Selenium. X = LogNT-proBNP, Y = ”CV age”, and Z = logselenium

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