Mark Whitacre Research Review: Selenium and a Healthy Immune System

The immune system functions to keep us healthy by fighting off various bacterial and viral infections, while at the same time -- quite miraculously -- not attacking the body’s own cells. Put another way, the immune system functions to protect self (what should be in the body, such as the cells that make up the human body) from non-self (what shouldn’t be in the body such as various microorganisms that can cause illness and as well as cancer cells, which no one wants in their body). Our amazing immune system gets rid of bugs and cancers cells daily in an effort to keep us healthy. Although there are many factors required to keep our immune system functioning smoothly, one of the most important is the essential micro mineral, selenium.

July-Research-Review-blog-1Selenium is essential to a healthy immune system although the details of how it works are quite complex. Suffice it to say that many of the selenium-containing proteins, referred to as selenoproteins, including glutathione reductase (GPx), thioredoxin reductase and selenoprotein P, to name just a few of the 25 selenoproteins in the human body, are essential for a healthy immune system. They play a role in both the humoral (ie, antibody producing) immune cells as well as those of the innate or cellular immunity, which are our first line of defense against viruses and cancer (Sun et al, 2018). Consequently when there is a selenium deficiency, viruses can mutate and become even more virulent (Steinbrenner et al, 2015).

Selenium is particulary intriguing and has been well studied with respect to cancer. Those with low selenium levels were found to have a 45% increase risk of dying from cancer (Bleys et al, 2008), while another study found that low plasma selenium levels was associated with a 79% increase in cancer mortality (Akbaraly et al, 2005). Selenium may also have  a preventive role. Individuals predisposed to skin cancer who ingested 200 micrograms (mcg or μg) of selenium daily from SelenoExcell® (a high-selenium yeast) for 4.5 yrs experienced a 50% reduction in cancer deaths along with the following reductions in cancer incidence:

  • 46% reduction in incidence of lung cancer
  • 58% decrease in colorectal cancer
  • 63% reduction in prostate cancer (Clark et al, 1996).

It is worth pointing out that the beneficial effects of selenium supplementation typically are in line wit the degree of selenium deficiency, as those with the lowest selenium levels at the beginning of the study experienced a 92% reduction in prostate cancer.

One of the key ways that selenium helps with a robust healthy immune system is by maintaining glutathione levels. Glutathione (GSH) is one of the key pillars of a healthy immune system. If GSH levels are high, the immune system tends to function the way it should, but if low, then immune function suffers. There are some interesting links between low GSH and children with autistic spectrum disorders as well as patients with HIV. IN fact, there is no better example than HIV infected individuals where poor immune function is closely associated with significantly reduced GSH levels, with more than 50% of these subjects being deficient in this essential micro mineral (Shivakoti et al, 2016).

Lower GSH is also commonly seen in aging as well as in Alzheimer's patients, which is why some have referred to Alzheimer's as an immune disorder. Fortunately, the higher one's blood levels of selenium, the higher blood GSH levels, as the two are highly correlated (r=0.7; p<0.001; El-Bayoumy et al, 2002). This significant correlation between selenium and GSH levels appears to be due to a higher activity in the rate-limiting enzyme in GSH synthesis, known as gamma-glutamyl cysteine synthetase, now referred to as glutamate cysteine ligase (Richie Jr et al, 2011).

July-Research-Review-blogSelenium is also involved in reducing inflammation and since inflammation is the common underlying disorder of nearly all chronic diseases, this is no small matter.  One recent 2018 publication not only found that those with higher than the mean serum selenium levels had a 34% reduction in overall mortality over a 10 yr time period, but they also found that these same individuals also had a 27% lower inflammation as reflected by C-Reactive Protein (CRP) (Giovannini et al, 2018).

Selenium also supports the immune system by counteracting the negative effects that heavy metals (such as mercury, cadmium, and lead) can have on the immune system.  Selenium does this by directly binding to and helping eliminating these heavy metals (Everson et al, 2017).

It is worth pointing out that when it comes to supplementing one’s diet with selenium, form does matter.  For example, it was supplementation with SelenoExcell® that produced the significant health benefits described above in the Clark (et al, 1996) study, while in another similar study, which involved supplementing another form of organic selenium, selenomethionine, the study found no such benefits (Lippman et al, 2009). 

One explanation might be gene expression. For example, supplementation with high-selenium yeast was shown to have a much more robust effect on gene expression of key proteins when given to mice than not only inorganic selenium, such as sodium selenite, which is not too surprising. But even interesting, the gene expression difference was even greater between high slenium yeast and selenomethionine (Barger et al, 2012), and even though selenomethionine makes up ~60-70% of the selenium in high-selenium yeast. This study, along with others, clearly demonstrates that there are significant differences between these two forms of supplemental selenium.  In fact, in the 2012 animal study, selenomethionine did produce the highest blood levels, yet affected gene expression the least, which again supports the significant difference between the two forms of selenium, while also raising questions around whether higher bioavailability is always associated with improved bioefficacy.

In summary, selenium is essential to a healthy immune system and low levels are leaving many people at risk for infections and chronic health problems. Supplementing selenium with a high-selenium yeast like SelenoExcell® is an important way to address this growing public health problem.


  • Akbaraly NT, Arnaud J, Hininger-Favier I et al.  Selenium and mortality in the elderly: results from the EVA study.  Clin Chem  2005;51:2117-23.
  • Barger JL, Kayo T, Pugh TD et al.  Gene expression profiling reveals differential effects of sodium selenit, selenomethionine, and yeast derived selenium in the mouse.  Genes Nutr  2012;7:155-65.
  • Bleys J, Navas-Acien A, Guallar E.  Serum selenium levels and all-cause, cancer, and cardiovascular mortality among US adults.  Arch Intern Med  2008;168:404-10.Clark LC, Combs Jr GF, Turnbull BW et al.  Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin.  JAMA  1996;276:1957-63.
  • El-Bayoumy K, Richie jr JP, Boyiri T et al.  Influence of selenium-enriched yeast supplementation on biomarkers of Everson TM, Kappil M, Hao K et al.  Maternal exposure to selenium and cadmium, fetal growth, and placental expression of steroidogenic and apoptotic genes.  Environ Res  2017;158:233-44.oxidative damage and hormone status in healthy adult males: a clinical pilot study.  Canc Epidemiol Biomark Prev.
  • Giovannini S, Onder G, Lattanzio F et al.  Selenium concentrations and mortality among community-dwelling older adults: results from Ilsirente study.  J Nutr Health Aging  2018;22:608-12.2002;11:1459-65.
  • Huang Z, Rose AH, Hoffmann PR.  The role of selenium in inflammation and immunity: from molecular mechanism to therapeutic opportunities.  Antioxid Redox Signal  2012;16:705-43.
  • Lippman SM, Klein EA, Goodman PJ et al.  Effect of selenium and vitamin E on risk of prostate cancer and other cancers.  JAMA  2009;301-39-51.
  • Liu H, Wang H, Shenvi S et al.  Glutathione metabolism during aging and in Alzheimer disease.  Ann NY Acad Sci  2004;1019:346-9.
  • Raymond LJ, Deth RC, Ralston NVC.  Potential role selenoenzymes and antioxidant metabolism in relation to autism etiology and pathology.  Autism Res Treat  2014.
  • Richie Jr Jp, Muscat JE, Ellison I et al.  Association of selenium status blood glutathione concentrations in blacks and whites.  Nutr Cancer  2011;63:367-75.
  • Samiec PS, Drews-Botsch C, Flagg EW et al.  Glutathione in human plasma: decline in association with aging, age-related macular degeneration, and diabetes.  Free Radic Biol Med  1998;24:699-704.
  • Shivakoti R, Christian P, Yang W-T et al.  Prevalence and risk factors of micronutrient deficiencies pre- and post-antiretroviral therapy (ART) among a diverse multicountry cohort of HIV-infected adults.  Clin Nutr  2016;35:183-9.
  • Steinbrenner H, Al-Quraishy S, Dkhil MA et al.  Dietary selenium in adjuvant therapy of viral and bacterial infections.  Adv Nutr  2015;6:73-81.
  • Sun Z, Xu Z, Wang D et al.  Selenium deficiency inhibits differentiation and immune function and imbalances the Th1/Th2 of dendritic cells.  Metallomics  2018;10:759-67.


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 These statements have not been evaluated by the Food and Drug Administration.These products are not intended to diagnose, treat, cure or prevent any disease.


Cypress-Dr-Mark-WhitcareAuthor Dr. Mark Whitacre is the Chief Science Officer at Cypress Systems. Dr. Whitacre has nearly two decades of executive management experience in both Fortune 500 and entrepreneurial companies, including broad international experience. Much of his career has been in the area of biotechnology and microbiol fermentation. Dr. Whitacre earned a Ph.D. in Nutritional Biochemistry from Cornell University where he studied under a world-renowned selenium scientist, Dr. G.F. Combs, Jr.  






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