Selenium and Immune Function and DNA Repair

Selenium is a trace element essential for for DNA repair, for  good immune function, and for reduced mortality risk.

DNA double helix
Cell studies, animal models, and human clinical trials suggest that an optimal supply of selenium is required to enhance the process of DNA damage repair.

The Micronutrient Information Center maintained by staff members at the Linus Pauling Institute of the Oregon State University provides reliable information about the vitamins and minerals and trace elements used in nutritional supplements.

Today, I want to summarize the information that the Center provides about selenium and supplement that information with the latest scientific research.

An Introduction to Selenium and Selenoproteins

Selenium is a trace element that is essential that humans need for the proper functioning of selenium-dependent selenoproteins. Free selenium is rare in the body. Instead, the selenium in the body is typically a component of selenomethionine, selenocysteine, and methyl-selenocysteine.

Definition: Trace elements are chemical elements that are available in very small quantities. Selenium is the chemical element with the atomic number 34. That means there are 34 protons and 34 electrons in selenium’s atomic structure.

It is the amino acid selenocysteine that is incorporated into selenoproteins. Researchers have now identified 25 selenoproteins in humans.

Here are some of the important selenoproteins, listed with an indication of their most important physiological function:

  • The selenoprotein P: transport of selenium to the tissues
  • The glutathione peroxidases: antioxidant activity
  • The thioredoxin reductases: antioxidant activity
  • The iodothyronine deiodinases: regulation of thyroid hormone production
  • The selenoprotein S: regulation of inflammation
  • The selenoprotein W: antioxidant activity
  • The 15 kDa selenoprotein: highly expressed in prostate, kidney, testes, liver, and brain tissues
Diseases Associated with Selenium Deficiency

Keshan disease and Kashin-Beck disease are proof that selenium deficiency can cause serious disease.

Keshan disease

In selenium-deficient regions of China, researchers have described and identified Keshan disease, an endemic disease of the heart muscle that causes cardiac insufficiency and that is closely associated with very low dietary intakes of selenium. The cause of Keshan disease seems to be the combination of low selenium status and exposure to an infectious virus, e.g., Coxsackie virus B3. The selenium deficiency in the host may lead to increased virulence of the invading virus, and the virus infection then causes inflammation of the heart muscle [Harthill 2011].

Selenium supplementation seems to protect individuals from developing Keshan disease but has not been shown to reverse the damage to the heart muscle damage [Delage 2014].

Kashin-Beck disease

In selenium-deficiency regions of China, North Korea, Siberia, and Tibet, Kashin-Beck disease causes osteoarthritis resulting in joint deformities. The cause of the Kashin-Beck disease seems to involve various factors in association with the selenium deficiency: exposure to fungal toxins, iodine deficiency, and drinking contaminated water have been suggested.

Improving selenium status in children living in endemic areas may reduce the incidence of Kashin-Beck disease [Zou 2009].

Selenium Supplementation for Disease Prevention

A 2016 meta-analysis of 69 studies (26 case-control studies, 14 cohort studies, 19 nested case-control studies, 5 case-cohort studies, 5 randomized controlled trials) has shown that higher serum/plasma selenium status is associated with a protective effect on cancer risk. The higher selenium exposure decreased the risk of breast cancer, esophageal cancer, gastric cancer, lung cancer, and prostate cancer. Higher selenium exposure was not associated with bladder cancer, colorectal cancer, or skin cancer [Cai 2016].

A 2020 meta-analysis of 37 population-based observational or interventional studies with a prospective design revealed a significant inverse relationship between selenium intake and overall cancer risk, adjusted for the effects of age, body mass index, and smoking. The researchers concluded that selenium protects against cancer and that the protective effects vary according to the type of cancer [Kuria 2020].

Cardiovascular disease

A 2021 meta-analysis of 13 observational studies and randomized controlled trials showed reduced risk of heart disease incidence and mortality in individuals with higher selenium status compared to lower selenium status. The collected data showed a 15% reduced risk of the incidence of cardiovascular disease for every 10 mcg increment of selenium in the blood [Kuria 2021].

Selenium Supplementation for Disease Treatment
Immune System Dysfunction

A survey of the available research literature shows that selenium deficiency is associated with immune dysfunction and chronic inflammation, including evidence that shows that selenium and selenoproteins play a role in the mitigation of dysfunctional inflammatory responses [Delage 2014].

Infectious Diseases

A few randomized controlled trials have shown that selenium supplementation of HIV-infected individuals is associated with significantly reduced rates of hospital admissions, with improved CD4 lymphocyte T-cell counts, and with the delay or prevention of any progression of the HIV viral load [Delage 2014].

A 2021 review of epidemiological and animal studies suggests that selenium status affects the host response to RNA viruses. The researchers conclude that selenium status influences the human response to Covid-19, particularly in regions in which the selenium intake is low [Bermano 2021].

Autoimmune thyroid diseases

Three randomized controlled trials have shown that selenium supplementation is associated with reduced levels of auto-antibodies in the blood circulation [Delage 2014].

As of this writing (winter 2022), we are awaiting the publication of the results from two randomized controlled trials — the CATALYST Study of hypothyroidism patients and the GRASS Trial of patients with Graves’ disease [Watt 2013; Winther 2104].

Conclusion: Optimizing Intakes of the trace element selenium for DNA Repair and for good immune function

This is a complex issue, and more research is needed. The following is a summary of what is known to date (winter 2022):

  1. There seems to be a U-shaped relationship between serum/plasma selenium status and health/disease. Rayman estimates the optimal serum/plasma selenium status to be in the neighborhood of 125 mcg/L [Winther 2020, figure 3]. Selenium status considerably below or above 125 mcg/L is associated with increased risk of disease.
  2. A 2020 study of selenium status in heart failure patients has revealed that patients with a selenium status below 100 mcg/L had worse New York Heart Association functional class, more severe heart failure symptoms and signs, poorer exercise capacity, and poorer quality of life [Bomer 2020].
  3. A 2010 study of healthy adults in the UK, aged 50-64 years, with an average pre-intervention selenium status of 95 mcg/L, found that average dietary and supplementation intakes of 105 mcg/day were necessary to enable the attainment of 125 mcg/L, the optimal plasma concentration of selenoprotein P, the primary transporter of selenium in the blood and a useful bio-marker of selenium status [Hurst 2010].
  4. Whether one should take zero selenium supplement or 50 mcg/day or 100 mcg/day depends in great part on the region in which one lives. The following regions are regions in which the estimated daily dietary intake of selenium is below 105 mcg/day: much of Scandinavia and northern Europe and the UK and Ireland, New Zealand and Australia. The USA, Canada, Japan, and Greenland, for the most part, have selenium-rich soils and foodstuffs sufficient to raise the average dietary intake above the 105 mcg/day recommendation. China, a land of contrasts, has regions both selenium-poor and selenium-rich [Winther 2020].
  5. Perhaps the best thing to do is to have one’s serum selenium concentration tested.

Bermano G, Méplan C, Mercer DK, Hesketh JE. Selenium and viral infection: are there lessons for COVID-19? Br J Nutr. 2021 Mar 28;125(6):618-627.

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.

Cai X, Wang C, Yu W, Fan W, Wang S, Shen N, Wu P, Li X, Wang F. Selenium exposure and cancer risk: an updated meta-analysis and meta-regression. Sci Rep. 2016 Jan 20;6:19213.

Delage B. Selenium. Micronutrient Information Center. Linus Pauling Institute. Oregon State University. 2014.

Harthill M. Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 2011;143(3):1325-1336.

Hurst R, Armah CN, Dainty JR, et al. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2010;91(4):923-931.

Kuria A, Fang X, Li M, Han H, He J, Aaseth JO, Cao Y. Does dietary intake of selenium protect against cancer? A systematic review and meta-analysis of population-based prospective studies. Crit Rev Food Sci Nutr. 2020;60(4):684-694.

Kuria A, Tian H, Li M, Wang Y, Aaseth JO, Zang J, Cao Y. Selenium status in the body and cardiovascular disease: a systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2021;61(21):3616-3625.

Watt T, Cramon P, Bjorner JB, et al. Selenium supplementation for patients with Graves’ hyperthyroidism (the GRASS trial): study protocol for a randomized controlled trial. Trials. 2013;14:119.

Winther KH, Watt T, Bjorner JB, et al. The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial. Trials. 2014;15:115.

Winther KH, Rayman MP, Bonnema SJ, Hegedüs L. Selenium in thyroid disorders – essential knowledge for clinicians. Nat Rev Endocrinol. 2020 Mar;16(3):165-176.

Zou K, Liu G, Wu T, Du L. Selenium for preventing Kashin-Beck osteoarthropathy in children: a meta-analysis. Osteoarthritis Cartilage. 2009;17(2):144-151.

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

28 February 2022

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