Selenium and Immunity
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How this trace mineral supports immune system function
Winter is just around the corner – is your immune system up to snuff? (Or sniffles!) The seasonality of infectious diseases is well established,[1],[2] as any of us who have suffered from the flu can attest. All nutrients are required in greater quantity during an infection, and even mild nutritional deficiencies can render us more susceptible to viruses and bacteria looking for a cozy home.[3],[4]
The white blood cells that mount an immune response to an infection – or to a vaccination – need a constant supply of nutrients to do their jobs.
Immunity is a remarkably sophisticated process by which the body seeks out and destroys harmful viruses and bacteria before they can establish a full-blown infection. However, the white blood cells that mount an immune response to an infection – or to a vaccination – need a constant supply of nutrients to do their jobs.[5],[6],[7] Extensive research suggests that the most important immune system nutrients are vitamins A, C, E, and B6, folic acid, zinc, copper, and selenium.[3],[8]
Selenium is considered a cornerstone of the body’s antioxidant defense system. It serves as an essential cofactor for glutathione peroxidase (GPx), an enzyme that utilizes glutathione to clean up reactive oxygen species that damage immune cells.[9],[10],[11] In states of selenium deficiency, the amount of GPx drops to 10% of normal levels;[12] this impairs the immune response and allows viruses to replicate freely.[13],[14],[15],[16] It’s perhaps not surprising, then, that selenium plays a major role in shielding us against viral infections.[17],[18]
Evidence that selenium protects against viral infections
The story of selenium and antiviral immunity began in China in the 1960s.[19] Geologists investigating the soil conditions of the Keshan county in Northeast China discovered that a serious cardiomyopathy (heart disease) was a result of selenium deficiency.[20] The disease in Keshan residents turned out to be similar to white muscle disease, a heart condition seen in sheep grazing on selenium-deficient soils in the region. Moreover, selenium supplementation was shown to prevent the disease in humans and sheep.[21] The human cardiomyopathy linked to selenium deficiency is so endemic to Keshan county that the disease now bears the name of this area.
The seasonal incidence of Keshan disease suggested that an infectious agent might be involved, and researchers succeeded in isolating a strain of Coxsackie virus from those affected with the disease.[22] In a series of studies akin to a forensic investigation, scientists began to unravel the mechanism behind the effect of selenium.[20],[21] They found that the Coxsackie virus caused more cardiac damage when inoculated into selenium-deficient mice than in selenium-adequate mice.[22] The evidence suggested that insufficient selenium levels caused oxidative stress,[23],[24] which in turn enabled otherwise benign Coxsackie virus strains to mutate to highly pathogenic strains capable of causing heart disease.[25],[26]
“What the results seemed to say was that one could be immersed in a sea of benign Coxsackie virus without any apparent ill effects until one suffered a decline in selenium to the point that the virus would exhibit its cardiovirulent properties.”
As noted by the author of one of these investigative studies: “What the results seemed to say was that one could be immersed in a sea of benign Coxsackie virus without any apparent ill effects until one suffered a decline in selenium to the point that the virus would exhibit its cardiovirulent properties.”[20] In other words, selenium supplementation not only boosted antiviral immunity, but blocked the virus from mutating to a pathogenic form.
Selenium, influenza, and other viral infections
The effect of selenium on immune susceptibility is not limited to Coxsackie virus. Selenium deficiency has been shown to increase one’s susceptibility to influenza and other respiratory viruses, as well as to hepatitis B, hepatitis C, poliovirus, West Nile virus, and hantavirus infections.[27],[28],[29],[30],[31],[32]
Low selenium levels also contribute to the emergence of new and virulent flu strains.[31],[33],[34] As might be expected, children with the highly infectious H1N1 subtype of influenza virus were found to have low blood levels of selenium.[35]
Blood selenium levels have also been shown to be significantly lower in hepatitis C virus (HCV)-positive individuals than in healthy controls.[30] Moreover, the HCV viral load has been shown to be inversely related to selenium levels.[30] Low selenium levels also increase the risk of liver cancer in individuals with a hepatitis B or hepatitis C infection.[36]
Finally, inadequate selenium levels are strongly associated with the prevalence and severity of HIV infection, as discussed below.[37],[38]
HIV and AIDS
The most common nutrient deficiency in HIV-positive individuals is selenium. More than half of HIV-affected individuals are deficient in this mineral.
HIV is the virus responsible for AIDS (Acquired Immune Deficiency Syndrome). HIV impairs immunity by destroying vital cells in the human immune system – specifically CD4-positive T cells, also known as CD4 cells or T helper cells.[17],[39] The CD4 count serves as a snapshot of immune system function in people with HIV, and if the CD4 count drops below 200, a person is diagnosed with AIDS.[40]
The most common nutrient deficiency in HIV-positive individuals is selenium. More than half of HIV-affected individuals are deficient in this mineral.[37],[38],[41],[42] Low serum selenium concentrations are associated with low CD4 counts;[43] a more severe course of disease;[44],[45] an increased risk of cardiomyopathy[46] and of opportunistic infections;[47] and a higher mortality rate.[48],[49],[50],[51]
When HIV-positive patients were supplemented with dietary selenium, however, CD4 counts generally improved.[13],[42],[52],[53] In one placebo-controlled study, the benefits were seen after nine months of daily supplementation with selenium-enriched yeast, provided at a dose of 200 mcg per day.[53]
How much selenium is needed for good health?
Thankfully, the powerful effects of selenium can be achieved with only trace amounts, which is why it’s called a micronutrient!
The U.S. Recommended Dietary Allowance (RDA) of selenium, calculated to meet the needs of most adults, is 55 mcg per day.[54] The main dietary sources of selenium are Brazil nuts, seafood, meat, poultry, fish, eggs, and whole-grain bread.[54] The selenium content of foods varies by geographic region and soil quality.[55],[56],[57] Soils in many regions of the world are deficient, much like the county in which Keshan disease was seen.[58] Importantly, vegan, gluten-free, and low-protein diets provide suboptimal amounts of selenium.[59],[60],[61],[62],[63] Individuals with malabsorption or inflammatory bowel disease may also be deficient in this mineral.[64]
Selenium deficiency is generally thought to be rare in the U.S.,[65],[66],[67] yet a study of Caucasian and African-American women living in Southern U.S. states found that the diets of more than 60% of the population were deficient in selenium.[68] Suboptimal intakes of vitamins C and E, copper, and zinc were also noted. The scientists concluded, “All women in this population reported dietary intakes of antioxidant vitamins and minerals below recommended values, conditions that could contribute to subsequent health risks unless nutrient-dense food choices and antioxidant supplementation are considered in their overall nutritional support.”[68]
Supplemental selenium benefits people with low selenium status, but high levels of selenium can be harmful over the long term,[69],[70],[71] including a possible increased risk of diabetes and amyotrophic lateral sclerosis (ALS).[72] Recent studies suggest that total selenium intakes (from diet and supplementation) greater than 300 mcg per day should be avoided.[73]
Summary
Diets do not always provide adequate levels of selenium. In individuals with low dietary selenium intake and other conditions which may predispose them to have inadequate levels, selenium supplementation may help support a healthy immune system ready to tackle infections – not only in the winter, but throughout the year!
Click here to see References
[1] Fisman D. Seasonality of viral infections: mechanisms and unknowns. Clin Microbiol Infect. 2012 Oct;18(10):946-54.
[2] Centers for Disease Control and Prevention (US). The flu season [Internet]. Atlanta (GA): U S Department of Health and Human Services; 2018 [cited October 16, 2018]. Available from: https://www.cdc.gov/flu/about/season/flu-season.htm
[3] Chandra RK. Nutrition and the immune system: an introduction. Am J Clin Nutr. 1997 Aug;66(2):460S-3S.
[4] Percival SS. Nutrition and immunity: balancing diet and immune function. Nutrition Today. 2011 Jan 1;46(1):12-7.
[5] Beck MA, et al. Host nutritional status: the neglected virulence factor. Trends Microbiol. 2004 Sep;12(9):417-23.
[6] Pagmantidis V, et al. Supplementation of healthy volunteers with nutritionally relevant amounts of selenium increases the expression of lymphocyte protein biosynthesis genes. Am J Clin Nutr. 2008 Jan;87(1):181-9.
[7] Steinbrenner H, et al. Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr. 2015 Jan 15;6(1):73-82.
[8] Beck MA. Selenium as an antiviral agent. In: Hatfield DL, ed. Selenium: Its Molecular Biology and Role in Human Health. Boston, MA: Springer; 2001: 235-45.
[9] Nencioni L, et al. Intracellular redox signaling as therapeutic target for novel antiviral strategy. Curr Pharm Des. 2011 Dec;17(35):3898-904.
[10] Khomich OA, et al. Redox biology of respiratory viral infections. Viruses. 2018 Jul 26;10(8).
[11] Heyland DK, et al. Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient. Intensive Care Med. 2004;31:327-37.
[12] Weiss Sachdev S, Sunde RA. Selenium regulation of transcript abundance and translational efficiency of glutathione peroxidase-1 and -4 in rat liver. Biochem J. 2001 Aug 1;357(Pt 3):851-8.
[13] Harthill M. Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res. 2011 Dec;143(3):1325-36.
[14] Reshi ML, et al. RNA viruses: ROS-mediated cell death. Int J Cell Biol. 2014;2014:467452.
[15] Gullberg RC, et al. Oxidative stress influences positive strand RNA virus genome synthesis and capping. Virology. 2015 Jan 15;475:219-29.
[16] Ivanov AV, et al. Oxidative stress during HIV infection: mechanisms and consequences. Oxid Med Cell Longev. 2016;2016:8910396.
[17] Avery JC, Hoffman PR. Selenium, selenoproteins, and immunity. Nutrients. 2018 Sep 1;10(9).
[18] Sgarbanti R, et al. Intracellular redox state as target for anti-influenza therapy: are antioxidants always effective? Curr Top Med Chem. 2014;14(22):2529-41.
[19] Tungsheng L. Selenium [Internet]. Washington (DC): American Chemical Society; 2003 [cited October 16, 2018]. Available from: http://pubs.acs.org/cen/80th/print/selenium.html
[20] Levander OA. The selenium-coxsackievirus connection: chronicle of a collaboration. J Nutr. 2000 Feb;130(2S Suppl):485S-8S.
[21] Chen J. An original discovery: selenium deficiency and Keshan disease (an endemic heart disease). Asia Pac J Clin Nutr. 2012;21(3):320-6.
[22] Bai J. [The combined effect of selenium deficiency and viral infection on the myocardium of mice (preliminary study) (author’s transl)]. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 1980 Mar;2(1):29-31.
[23] Xu J, et al. Selenium deficiency aggravates T-2 toxin-induced injury of primary neonatal rat cardiomyocytes through ER stress. Chem Biol Interact. 2018 Apr 1;285:96-105.
[24] Pei J, et al. Oxidative stress is involved in the pathogenesis of Keshan disease (an endemic dilated cardiomyopathy) in China. Oxid Med Cell Longev. 2013;2013:474203.
[25] Beck MA, et al. Benign human enterovirus becomes virulent in selenium-deficient mice. J Med Virol. 1994 Jun;43(2):166-70.
[26] Beck MA, et al. Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat Med. 1995 May;1(5):433-6.
[27] Yu L, et al. Protection from H1N1 influenza virus infections in mice by supplementation with selenium: a comparison with selenium-deficient mice. Biol Trace Elem Res. 2011 Jun;141(1-3):254-61.
[28] Cheng Z, et al. Sodium selenite suppresses hepatitis B virus transcription and replication in human hepatoma cell lines. J Med Virol. 2016 Apr;88(4):653-63.
[29] Fang LQ, et al. The association between hantavirus infection and selenium deficiency in mainland China. Viruses. 2015 Jan 20;7(1):333-51.
[30] Ko WS, et al. Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. World J Gastroenterol. 2005 Aug 14;11(30):4697-702.
[31] Broome CS, et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr. 2004 Jul;80(1):154-62.
[32] Verma S, et al. In vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity. Virol J. 2008 May 31;5:66.
[33] Nelson HK, et al. Host nutritional selenium status as a driving force for influenza virus mutations. FASEB J. 2001 Aug;15(10):1846-8.
[34] Beck MA, et al. Selenium deficiency increases the pathology of an influenza virus infection. FASEB J. 2001 Jun;15(8):1481-3.
[35] ErkekoÄźlu P, et al. Selenium levels, selenoenzyme activities and oxidant/antioxidant parameters in H1N1-infected children. Turk J Pediatr. 2013 May-Jun;55(3):271-82.
[36] Yu MW, et al. Plasma selenium levels and risk of hepatocellular carcinoma among men with chronic hepatitis virus infection. Am J Epidemiol. 1999 Aug 15;150(4):367-74.
[37] Shivakoti R, 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 Feb;35(1):183-9.
[38] Anyabolu HC, et al. Serum micronutrient status of HAART-naĂŻve, HIV infected children in South Western Nigeria: a case controlled study. AIDS Res Treat. 2014;2014:351043.
[39] Cummins NW, et al. Making sense of how HIV kills infected CD4 T cells: implications for HIV cure. Mol Cell Ther. 2014 Jul 3;2:20.
[40] National Institutes of Health. AIDS case definition [Internet]. Bethesda (MD): U S Department of Health and Human Services; 2018 [cited October 16, 2018]. Available from: https://aidsinfo.nih.gov/understanding-hiv-aids/glossary/2925/aids-case-definition
[41] Dworkin BM. Selenium deficiency in HIV infection and the acquired immunodeficiency syndrome (AIDS). Chem Biol Interact. 1994 Jun;91(2-3):181-6.
[42] Stone CA, et al. Role of selenium in HIV infection. Nutr Rev. 2010 Nov;68(11):671-81.
[43] Shivakoti R, et al. Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial. Clin Nutr. 2018 May 29. [In Press]
[44] Baum MK, Shor-Posner G. Micronutrient status in relationship to mortality in HIV-1 disease. Nutr Rev. 1998 Jan;56(1 Pt 2):S135-9.
[45] Ogunro PS, et al. Plasma selenium concentration and glutathione peroxidase activity in HIV-1/AIDS infected patients: a correlation with the disease progression. Niger Postgrad Med J. 2006 Mar;13(1):1-5.
[46] Twagirumukiza M, et al. Prevalence of dilated cardiomyopathy in HIV-infected African patients not receiving HAART: a multicenter, observational, prospective, cohort study in Rwanda. Curr HIV Res. 2007 Jan;5(1):129-37.
[47] Shor-Posner G, et al. Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2002 Feb 1;29(2):169-73.
[48] Look MP, et al. Serum selenium versus lymphocyte subsets and markers of disease progression and inflammatory response in human immunodeficiency virus-1 infection. Biol Trace Elem Res. 1997 Jan;56(1):31-41.
[49] Baum MK, et al. High risk of HIV-related mortality is associated with selenium deficiency. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Aug 15;15(5):370-4.
[50] Kupka R, et al. Selenium status is associated with accelerated HIV disease progression among HIV-1-infected pregnant women in Tanzania. J Nutr. 2004 Oct;134(10):2556-60.
[51] Stephensen CB, et al. Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults. Am J Clin Nutr. 2007 Jan;85(1):173-81.
[52] Kamwesiga J, et al. Effect of selenium supplementation on CD4+ T-cell recovery, viral suppression and morbidity of HIV-infected patients in Rwanda: a randomized controlled trial. AIDS. 2015 Jun 1;29(9):1045-52.
[53] Hurwitz BE, et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial. Arch Intern Med. 2007 Jan 22;167(2):148-54.
[54] National Institutes of Health, Office of Dietary Supplements. Selenium Fact Sheet for Health Professionals [Internet]. Bethesda (MD): U S Department of Health and Human Services; 2018 [cited October 16, 2018]. Available from: https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
[55] Hirai K, et al. Selenium intake based on representative diets in Japan, 1957 to 1989. Nutrition Research. 1996 Sep 1;16(9):1471-7.
[56] Kipp AP, et al. Revised reference values for selenium intake. J Trace Elem Med Biol. 2015 Oct;32:195-9.
[57] Combs GF Jr. Selenium in global food systems. Br J Nutr. 2001 May;85(5):517-47.
[58] Gupta UC, Gupta SC. Selenium in soils and crops, its deficiencies in livestock and humans: implications for management. Comm Soil Sci Plant Analysis. 2000 Jun 1;31(11-14):1791-807.
[59]G Engel M, et al. Micronutrient gaps in three commercial weight-loss diet plans. Nutrients. 2018 Jan 20;10(1):108.
[60] Turner-McGrievy GM, et al. Changes in nutrient intake and dietary quality among participants with type 2 diabetes following a low-fat vegan diet or a conventional diabetes diet for 22 weeks. J Am Diet Assoc. 2008 Oct;108(10):1636-45.
[61] Rauma AL, et al. Antioxidant status in long-term adherents to a strict uncooked vegan diet. Am J Clin Nutr. 1995 Dec;62(6):1221-7.
[62] Rybicka I, et al. Selenium in gluten-free products. Plant Foods Hum Nutr. 2015 Jun;70(2):128-34.
[63] Sirikonda NS, et al. Ketogenic diet: rapid onset of selenium deficiency-induced cardiac decompensation. Pediatr Cardiol. 2012 Jun;33(5):834-8.
[64] Castro Aguilar-Tablada T, et al. Ulcerative colitis and Crohn’s disease are associated with decreased serum selenium concentrations and increased cardiovascular risk. Nutrients. 2016 Dec 1;8(12):780.
[65] Chun OK, et al. Estimation of antioxidant intakes from diet and supplements in U.S. adults. J Nutr. 2010 Feb;140(2):317-24.
[66] Ervin RB. Dietary intake of selected minerals for the United States population: 1999-2000. Adv Data. 2004 Apr 27;(341):1-5.
[67] Rayman MP. Selenium and human health. Lancet. 2012 Mar 31;379(9822):1256-68.
[68] Lewis SM, et al. Assessment of antioxidant nutrient intake of a population of southern US African-American and Caucasian women of various ages when compared to dietary reference intakes. J Nutr Health Aging. 2003;7(2):121-8.
[69] Waters DJ, Chiang EC. Five threads: how U-shaped thinking weaves together dogs, men, selenium, and prostate cancer risk. Free Radic Biol Med. 2018 Nov 1;127:36-45.
[70] Zhang L, et al. Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity. Free Radic Biol Med. 2018 Nov 1;127:3-13.
[71] Hoffman PR, Berry MJ. The influence of selenium on immune responses. Mol Nutr Food Res. 2008 Nov;52(11):1273-80.
[72] Rayman MP, et al. Effect of long-term selenium supplementation on mortality: Results from a multiple-dose, randomized controlled trial. Free Radic Biol Med. 2018 Nov 1;127:46-54.
[73] Vinceti M, et al. Health risk assessment of environmental selenium: emerging evidence and challenges (review). Mol Med Rep. 2017 May;15(5):3323-35.
The information provided is for educational purposes only. Consult your physician or healthcare provider if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
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Marina MacDonald, MS, PhD
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