Sex Differences in Selenium Metabolism

Sex differences in selenium metabolism played a considerable role in the heart health outcomes of the KiSel-10 study. In that randomized controlled trial, the researchers administered 200 mcg/day selenium and 200 mg/day Coenzyme Q10 or matching placebos to elderly Swedish study participants with low selenium status. The combined supplementation significantly improved heart function and reduced cardiovascular mortality [Alehagen 2013].

Note that, on average,  the baseline selenium status in the KiSel-10 study participants was at a deficiency level, 67.1 mcg/L. The elderly citizens’ CoQ10 level was only borderline satisfactory, 0.82 mg/L at the study start. Prof. Urban Alehagen and the KiSel-10 research team knew that a low selenium intakes and an aging-related decline in CoQ10 bio-synthesis are associated with increased risk of cardiovascular disease [Alehagen 2013; Alehagen 2020].

Now, in a further analysis, Prof. Urban Alehagen and the KiSel-10 research team have reported the following significant sex-related outcomes [Alehagen 2025]:

• 48 months of daily supplementation with selenium and Coenzyme Q10 reduced the risk of cardiovascular mortality to a greater extent in females than males.
• After 48 months of supplementation and then six years of follow-up, the cardiovascular survival rate was significantly higher in females.
• The researchers noted that the improved survival rate began to show itself later in females than in males.

Sex Differences in the KiSel-10 Study of Combined Selenium and CoQ10 Supplementation

Prof. Alehagen et al suggested that the following differences between the sexes at the study start may account for some of the sex-related different outcomes. However, other sexual dimorphism factors in selenium metabolism are most likely also involved [Alehagen 2025].

• At the study start, male study participants had a higher prevalence of diagnosed ischemic heart disease and had more signs of impending heart failure.
• At the study start, males had noticeably higher rates of systemic inflammation and oxidative stress.
• At the study start, male study participants had a higher rate of smoking.

Regarding study participants with diagnosed ischemic heart disease, Prof. Alehagen and the research team observed the following differences:

• The combined supplementation did improve cardiovascular survival in both males and females with ischemic heart disease.
• The combined supplementation was more effective in the elderly citizens with no ischemic heart disease at the study start than it was in elderly citizens with ischemic heart disease.
• The improved health effect in elderly citizens without ischemic heart disease was stronger in females. The beneficial effect was first recorded four years into the follow-up, i.e., four years after the cessation of the 48-month supplement.

Sexual Dimorphism a Known Factor in Selenium Metabolism

In a 2018 review article, Seale et al warned that too often researchers fail to acknowledge physiological sex differences between males and females in their analysis of study results and in their conclusions. For example, researchers need to consider sex differences when they analyze studies involving selenium metabolism, selenoprotein expression and action, and selenium-dependent parameters. They should not assume that a result from an all-male or mostly male trial can be extended to both sexes without verification. In selenium research, there is a need for more female samples and more attention to sexual dimorphism as a variable to be considered during analysis [Seale 2018].

Already in 2004, Waters et al reported that the data from selenium and cancer studies showed that selenium status more profoundly affects cancer risk in men than it does cancer risk in women. There appear to be sex-related differences in selenium metabolism and tissue distribution of selenium. The researchers called for more studies of how selenium can modulate cancer initiation and progression [Waters 2004].

In 2021, Cardoso et al presented an analysis of data from an NHANES cross-sectional study. The study results provided evidence for sex differences in the association between selenium status and cognitive performance in older adults [Cardoso 2021].

Conclusions: Sex Differences and Selenium Metabolism

Sex differences are a variable that can influence the health effects of selenium supplementation.

Analysis of data from the KiSel-10 study show that females benefited more from the combined selenium and CoQ10 supplementation than males did.

Sources

Alehagen U, Johansson P, Bjørnstedt M, Ros A, et al. Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation. Int J Cardiol. 2013;167(5):1860-1866.

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.

Alehagen U, Aaseth JO, Schomburg L, Opstad TB, Larsson A, Alexander J. Selenium and Coenzyme Q10 supplementation and sex differences in cardiovascular mortality results from a prospective randomized double-blind placebo-controlled trial in elderly people low in selenium. Antioxidants. 2025; 14(6):685.

Cardoso B, Hare DJ, Macpherson H. Sex-dependent association between selenium status and cognitive performance in older adults. Eur J Nutr. 2021 Mar;60(2):1153-1159.

Seale LA, Ogawa-Wong AN, Berry MJ. Sexual dimorphism in selenium metabolism and selenoproteins. Free Radic Biol Med. 2018 Nov 1;127:198-205.

Waters DJ, Chiang EC, Cooley DM, Morris JS. Making sense of sex and supplements: differences in the anticarcinogenic effects of selenium in men and women. Mutat Res. 2004 Jul 13;551(1-2):91-107.

The information presented in this review article is not intended as medical advice. It should not be used as such.