A 2025 review summarizes the biological activities and health functions of important selenoproteins. The selenoproteins play a role in antioxidant and anti-inflammation defense, cancer prevention, cardiovascular health, fertility, immune system regulation, and defense against viral infections including COVID-19 [Shahidin 2025].
Selenium deficiency leads to insufficient synthesis of the selenoproteins. Generally, selenium researchers regard serum selenium concentrations under 70 mcg/L as deficiency levels. Serum selenium concentrations below 45 mcg/L indicate severe selenium deficiency [Winther 2020; Schomburg 2021].
The point is that selenium deficiency and insufficient selenoprotein synthesis can impair antioxidant and anti-inflammation defense, weaken immune function, and disturb thyroid hormone metabolism. Likewise, selenium deficiency can contribute to neurological and endocrine disorders. Selenium deficiency can have a detrimental effect on cardiovascular health. Selenium deficiency is associated with increased incidence of Keshan disease and Kashin–Beck disease [Shahidin 2025].
The Key Selenoproteins and Their Biological Functions
Selenoprotein P (SELENOP)
SELENOP is synthesized in the liver. It is the primary transporter of selenium from the blood to key tissues. It delivers selenium in a hierarchical manner, favoring some tissues and organs over others. For example, even in times of low selenium intake, top-priority delivery of selenium goes to the brain and the endocrine glands. The hierarchical delivery system tries to maintain brain and the endocrine gland selenium concentrations at optimal levels [Schomburg 2022].
Glutathione Peroxidases (GPx’s)
The GPx’s comprise eight members of the GPx family. They are designated GPx1 to GPx8. Notably, GPx1-GPx4 and GPx6 are prominent in mammals. GPx4 is known for its ability to reduce directly and eliminate lipid hydroperoxides. All GPx enzymes are antioxidant enzymes with an ability to reduce hydroperoxides using thiols [Shahidin 2025].
Thioredoxin Reductases (TrxR)
The TrxR’s are antioxidant enzymes that reduce thioredoxin. Thioredoxin is a protein that is an electron donor. Together, thioredoxin and the TrxR’s help maintain cellular redox balance and help protect cells against oxidative damage. Note that TrxR1 is found in the nucleus and the cytoplasm of cells, TrxR2 is found in mitochondria, and TrxR3 is found in the testes [Shahidin 2025].
Iodothyronine Deiodinases (DIO’s)
The DIO’s help regulate thyroid hormone levels and metabolism. There are three types of DIOs: DIO1, DIO2, and DIO3 [Shahidin 2025].
In Table 1 of their review article, Shahidin et al list the known selenoproteins, their abbreviations, their effect on organs, and their functions [Shahidin 2025].
Health Roles of Selenium and Selenoproteins
Antioxidant Properties
The element selenium does not act independently as an antioxidant. It is the incorporation of selenium into antioxidant selenoproteins that helps protect cells and tissues from oxidative damage. Shahidin et al [2025] estimate that nearly half of the known 25 selenoproteins are involved in antioxidant defense against harmful free radicals.
Anticancer Activity
Shahidin et al [2025] assert a significant role for selenium in cancer prevention. In this respect, selenium is involved in antiangiogenic effects, apoptosis induction, selective cytotoxicity, and modulation of cell cycle progression. The researchers point to chemopreventive mechanisms of selenium and selenoproteins. Some of these mechanisms are well-established, they say. Other are under investigation.
Cardiovascular Diseases
In populations with low levels of selenium and SELENOP, e.g., in northern Europe, there is an increased risk of developing cardiovascular disease. The outcomes of the KiSel-10 clinical trial underscores the importance of supplementary selenium and its associated selenoproteins in cardiovascular health [Shahidin 2025; Alehagen 2016].
At baseline in the KiSel-10 study, there was a low mean serum selenium concentration, 67 mcg/L. At the study end, the researchers made two important observations [Alehagen 2016]:
- Cardiovascular mortality was higher in the subgroup with the lower serum selenium concentrations below 65 mcg/L compared to the subgroup having serum selenium concentrations greater than 85 mcg/L.
- Supplementation was cardio-protective in the study participants with a serum selenium concentration equal to or less than 85 mcg/L at the start of the study.
Immune System Enhancement
The biological function of selenium and selenoproteins in the immune system has been researched extensively. The level of dietary and supplementary selenium intake is central to immune system function.
Sufficient selenium intake enhances the synthesis of selenoproteins that play a role in the functioning of innate immune cells, e.g., monocytes, macrophages, granulocytes, and natural killer cells [Shahidin 2025].
An example of this is the role that the deiodinase enzymes play in converting thyroid hormones to their active or inactive forms. In this way, the DIOs influence both the innate and the adaptive immune response during infection. Thyroid hormones modulate immune cell signaling pathways. The thyroid hormone activity helps maintain immune system homeostasis and promotes adequate response to pathogens [Shahidin 2025]
Promotion of Male Fertility
The body needs sufficient selenium for the synthesis of testosterone and
for the development of spermatozoa. The GPx1 and GPx3 selenoproteins are active in the male reproductive system. They protect the developing sperm and the surrounding tissues against oxidative damage. The selenoprotein GPx4 is especially notable for safeguarding sperm cells from oxidative stress. Basically, men with lower sperm GPx activity have sub-optimal sperm viability and motility [Shahidin 2025].
Protection Against Viral Infections
Selenium through the action of its selenoproteins neutralizes harmful free radicals and lessens the extent of oxidative damage during viral infections.
Selenium in selenoproteins helps alleviate inflammation. As indicated above, selenoproteins modulate immune function [Shahidin 2025]..
With respect to outcomes in COVID-19 patients, a study in China has shown that regions with higher selenium levels had better cure rates and lower death rates than did regions with selenium deficiency [Zhang 2020].
In the same way, a German study has shown that patients who survived COVID-19 had significantly higher serum selenium levels than did the patients who did not survive [Moghaddam 2020].
Safety of Selenium Supplementation
The no observed adverse effect level (NOAEL) for selenium intakes is 2.9 mcg/kg of body weight per day (around 200 mcg/day). Below this level, no adverse effects and no increased mortality have been observed [Shahidin 2025].
For adult men and women (including pregnant and lactating women), EFSA has established an upper intake limit for 255 mcg of selenium per day [EFSA 2023].
Prof. Lutz Schomburg has written that, too often, the possible side effects of selenium supplementation are exaggerated. At the same time, the health risks of insufficient selenium intakes and selenium deficiency are often
neglected. The result is a lack of attention to potential preventive and adjuvant treatment options for the situations of pregnancy, severe illness, and COVID-19. Selenium deficiency is associated with increased risk of autoimmune diseases, with long-lasting health impairments, and with slow recovery from illness [Schomburg 2021].
Conclusions
Humans need adequate selenium intakes to synthesize selenoproteins.
Selenoproteins have numerous important biological functions.
Addressing selenium deficiency and exploring the health benefits of selenium supplementation, e.g., supplement form and dose and duration, are important research areas
Sources
Alehagen U et al. Supplementation with selenium and Coenzyme Q10 reduces cardiovascular mortality in elderly with low selenium status. A secondary analysis of a randomized clinical trial. PLoS One. 2016 Jul 1;11(7):e0157541.
EFSA. Scientific opinion on the tolerable upper intake level for selenium. EFSA Journal. 2023;21(1):e07704.
Moghaddam A et al. Selenium Deficiency is associated with mortality risk from COVID-19. Nutrients. 2020 Jul 16;12(7):2098.
Schomburg L. Selenium deficiency due to diet, pregnancy, severe illness, or Covid-19-a preventable trigger for autoimmune disease. Int J Mol Sci. 2021 Aug 8;22(16):8532.
Schomburg L. Selenoprotein P – Selenium transport protein, enzyme and biomarker of selenium status. Free Radic Biol Med. 2022 Oct;191:150-163.
Shahidin W et al. Selenium and selenoproteins: mechanisms, health functions, and emerging applications. Molecules. 2025 Jan 21;30(3):437.
Winther KH et al. Selenium in thyroid disorders – essential knowledge for clinicians. Nat Rev Endocrinol. 2020 Mar;16(3):165-176.
Zhang J et al. Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr. 2020 Jun 1;111(6):1297-1299.
The information presented in this review article is not intended as medical advice. It should not be used as such.