first_pagesettings Order Article Reprints Open AccessArticleSerum CD5L Responds Positively to Selenium and Coenzyme Q10 Supplementation with Relation to Thyroid Hormones, Mortality, and Health-Related Quality-of-Life—A Sub-Analysis of a Double-Blind Randomised Placebo-Controlled Trial in Elderly Low in Seleniumby Urban Alehagen 1,*, Jan O. Aaseth 2,3 , Trine B. Opstad 4,5, Anders Larsson 6 , Sabrina Asaad 7, Lutz Schomburg 7  and Jan Alexander 8   1Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, 581 85 Linköping, Sweden2Department of Research, Innlandet Hospital Trust, 2380 Brumunddal, Norway3Faculty of Health and Social Sciences, University of Inland Norway, 2605 Lillehammer, Norway4Oslo Center for Clinical Heart Research—Laboratory, Department of Cardiology, Oslo University Hospital Ullevål, 0450 Oslo, Norway5Faculty of Medicine, University of Oslo, 0372 Oslo, Norway6Department of Medical Sciences, Uppsala University, 751 85 Uppsala, Sweden7Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany8Norwegian Institute of Public Health, 0213 Oslo, Norway*Author to whom correspondence should be addressed.Antioxidants 2025, 14(3), 366; https://doi.org/10.3390/antiox14030366Submission received: 8 February 2025 / Revised: 12 March 2025 / Accepted: 12 March 2025 / Published: 20 March 2025(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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AbstractThe Cluster of Differentiation 5-like protein (CD5L) is produced by tissue-resident macrophages. It is an innate immune mediator protein with a multitude of functions, such as binding of invading microorganisms and oxidised LDL, and it is associated with clinical conditions, i.e., atherosclerosis and inflammation. The circulating CD5L level has been reported to correlate to selenium status and thyroid hormone activity. In order to test this hypothesis, we analysed CD5L in serum samples from a randomized controlled trial (RCT) with selenium and coenzyme Q10 supplementation and examined associations between CD5L and thyroid hormones, health-related quality-of-life (Hr-QoL), and mortality in an elderly population low in selenium. Circulating levels of CD5L and thyroid hormones were determined in 359 elderly community-living individuals enrolled in an RCT at inclusion and after 48 months of supplementation (179 received selenium and coenzyme Q10, and 180 placebo). Hr-QoL was recorded at both time-points using Short Form 36. Pre-intervention plasma selenium was low, mean 67 µg/L. CD5L correlated positively to free tri-iodothyronine (fT3) and showed an inverse relation with thyroid stimulating hormone (TSH). Low CD5L concentrations at inclusion in the placebo group were associated with increased cardiovascular mortality during 10 years of follow-up, and impaired Hr-QoL at 48 months. Selenium and coenzyme Q10 supplementation significantly increased CD5L and fT3 levels, in association with a better health outcome. The data indicate that circulating CD5L positively responds to selenium and coenzyme Q10 supplementation, correlates with thyroid hormone status, and associates with positive health indices. The observed effect may be due to increased selenium-dependent deiodinase isozyme expression that converts thyroxine (T4) to T3 locally and supports thyroid hormone activities. Whether the observed associations with Hr-QoL and cardiovascular mortality are a direct effect of circulating CD5L or local thyroid hormone activity is unclear and should be further investigated.