A Chinese study has shown that there is a significant negative association between plasma selenium concentrations and the risk of a first stroke in males but not in females. This is not the first time that sex differences have been reported relative to selenium metabolism. More on that later.
Plasma Selenium Levels and the Risk of a First Stroke
The Chinese researchers analyzed the results from a nested case-control study with 1255 first stroke cases and 1255 matched controls [Hu 2021].
- They found that males (but not females) with plasma selenium concentrations above 94 micrograms per liter had significantly less risk of a first stroke of any kind and significantly less risk of a first ischemic stroke.
- There was also a stronger negative association between plasma selenium levels and first strokes of all kinds — ischemic, hemorrhagic, or unidentified — in males with higher vitamin E levels.
- There was no significant association between plasma selenium levels and first hemorrhagic stroke risk in either males or females.
N.B. In this study, there were many more cases of first ischemic stroke (n=1079) than there are cases of first hemorrhagic stroke (n=171). Five cases were of uncertain origin.
Evidence from Other Studies of Selenium Level and Stroke Risk
The results from studies of selenium level and stroke risk have been somewhat confusing to date:
- A 2019 Chinese case-control study enrolling 1304 cases found that higher plasma selenium levels were significantly associated with a lower risk of hemorrhagic stroke but not ischemic stroke [Xiao 2019].
- A second 2019 Chinese study, a case-control study enrolling 1277 cases, showed that higher plasma selenium levels were associated with a decreased risk of ischemic stroke [Wen 2019].
- The Canadian Health Measures Survey, the US National Health and Nutrition Examination Study, and the Inuit Health Survey have all found inverse associations between whole blood selenium and the prevalence of stroke [Hu 2019, 2017].
Selenium Levels and Risk of Stroke Mortality
The available information re the relationship between selenium status and death from stroke is sparse.
- A Finnish cohort study enrolling males only found that low serum selenium levels (below 45 micrograms/L) in males was associated with a higher risk of stroke mortality [Virtamo 1985].
-A Chinese cohort study including 1103 Chinese participants found no significant association of plasma selenium levels and stroke mortality [Wei 2004].
The results of studies of selenium status and death from stroke remain inconclusive. We need more studies.
Explanations for the Association between Selenium Status and First Stroke
What biochemical mechanisms might explain the inverse relationship between selenium status and risk of stroke [Hu 2021]?
- Selenium incorporated in various selenoproteins has a protective effect against oxidative lipid damage in the brain and modulates neurotoxicity and oxidative stress in the nervous tissue.
- Selenium, again as a component of selenoproteins, has a modulating effect on inflammatory and metabolic signaling.
- Selenium in selenoproteins helps to preserve the functioning of the mitochondria.
From the 2019 Bomer study, we know that selenium deficiency in heart failure patients is associated with impaired exercise tolerance and a higher mortality rate as well as with impaired mitochondrial function in human heart muscle cells in vitro.
Sex Differences in Selenium Metabolism
We know that there are differences. For example, in the French Su.Vi.Max Study, 7.5 years of low-dose antioxidant supplementation including selenium lowered total cancer incidence and all-cause mortality in men but not in women [Hercberg 2004].
The Chinese researchers speculate that the sex differences in their study may be explained by differences in the way that selenium is metabolized in male and female reproductive systems. They point out that the retention of selenium is high in the testes while the female reproductive system does not retain selenium nearly as efficiently.
So, the Chinese researchers ask whether the testes might be competing with the brain for selenium utilization in cases in which selenium status is low. If so, then the male brain might be more susceptible to selenium deficiency and to more oxidative stress than the female brain is.
The Chinese researchers also speculate whether the interaction of selenium with the thyroid might explain the sex differences in selenium metabolism.
be another reason for the differences. Wang et al. [2019] have shown considerable sex differences in the risk and development of hyperthyroidism.
It seems that selenium deficiency is a greater risk factor for hyperthyroidism in males than in females. Because hyperthyroidism is associated with a two- to three-fold increased risk of ischemic and non-ischemic stroke, this relationship could explain why men but not women with low selenium status are at greater risk of a first stroke.
Conclusion: Sufficient Selenium Status to Lower the Risk of Stroke
The Chinese researchers noted a sharp decline in the risk of first stroke when plasma selenium was over 94 micrograms per liter.
Similarly, Bomer et al [2019] have shown that heart failure patients with plasma selenium status above 100 micrograms per liter have better exercise capacity and less risk of death from heart failure.
It is an easy enough matter to have one’s serum selenium levels checked the next time one has a blood test done.
Sources
Bleys J, Navas-Acien A, Guallar E. Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults. Arch Intern Med. 2008; 168: 404-410.
Bomer N, Grote Beverborg N, Hoes MF, Streng KW, Vermeer M, Dokter MM, IJmker J, Anker SD, Cleland JGF, Hillege HL, Lang CC, Ng LL, Samani NJ, Tromp J, van Veldhuisen DJ, Touw DJ, Voors AA, van der Meer P. Selenium and outcome in heart failure. Eur J Heart Fail. 2020 Aug;22(8):1415-1423. doi: 10.1002/ejhf.1644.
Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briançon S. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch Intern Med. 2004 Nov 22;164(21):2335-42.
Hu H, Bi C, Liu L, et al. Sex difference in the association between plasma selenium and first stroke: a community-based nested case-control study. Biology of Sex Differences. 2021. In Review. DOI: 10.21203/rs.3.rs-141452/v1.
Hu XF, Stranges S, Chan LHM. Circulating selenium concentration is inversely associated with the prevalence of stroke: Results From the Canadian Health Measures Survey and the National Health and Nutrition Examination Survey. J Am Heart Assoc. 2019; 8: e012290.
Hu XF, Sharin T, Chan HM. Dietary and blood selenium are inversely associated with the prevalence of stroke among Inuit in Canada. Trace. Elem. Med. Biol. 2017; 44: 322-330.
Virtamo J, Valkeila E, Alfthan G, Punsar S, Huttunen JK, Karvonen MJ. Serum selenium and the risk of coronary heart disease and stroke. Am J Epidemiol. 1985; 122: 276-282.
Wang Y, Zhao F, Rijntjes E, Wu L, Wu Q, Sui J, et al. Role of Selenium Intake for Risk and Development of Hyperthyroidism. J Clin Endocrinol Metab. 2019; 104: 568-580.
Wei WQ, Abnet CC, Qiao YL, Dawsey SM, Dong ZW, Sun XD, et al. Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr. 2004; 79: 80-85.
Wen Y, Huang S, Zhang Y, Zhang H, Zhou L, Li D, et al. Associations of multiple plasma metals with the risk of ischemic stroke: A case-control study. Int. 2019; 125: 125-134.
Xiao Y, Yuan Y, Liu Y, Yu Y, Jia N, Zhou L, et al. Circulating Multiple Metals and Incident Stroke in Chinese Adults. Stroke. 2019; 50: 1661-1668.
The information presented in this review article is not intended as medical advice and should not be construed as such.
30 January 2021