In this article, we will examine theeffects of the trace mineral seleniumin the human body. Specifically, we’lltake a look at selenium’s biological

functions, interactions with other nutri-ents, its role in human health, its intakein the U.S. and the rational for seleniumsupplementation. You will also see whyit is important to avoid an excessiveintake of selenium in order to enjoy itsbenefits to human health.

Biological functionsSelenium is essential in small amountsas a trace mineral, but toxic at high lev-els. As selenocysteine, selenium isincorporated into a number of seleno-proteins (selenium-dependent antioxi-dant enzymes).1 It is these selenopro-teins that are responsible for selenium’sbiological functions. These selenopro-teins protect against free radicals andother damaging reactive oxygen

species, help regulate cell growth andviability, help produce biologicallyactive thyroid hormones, support mus-cle metabolism, support protein pro-duction, support sperm formation, andmay be involved in inflammatory andimmune responses.2

Interaction With Other NutrientsIn the form of selenoproteins, seleniumhelps to convert vitamin E3 and vitamin

By Gene Bruno, MS, MHS

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Selenium:Understanding Benefits & Risks

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C4 from their oxidized forms back intotheir non-oxidized/antioxidant forms.Selenium also works with copper andzinc to produce the antioxidant enzymesuperoxide dismutase, and with iron toproduce catalase.5 In addition, asselenoprotein selenium works withiodine in the T4 thyroid hormone to thebiologically active T3 hormone.6

Human HealthThere are a number of areas in whichselenium can make a positive contribu-tion toward human health. In the caseof diabetes, however, the jury is still outregarding potential harm or benefit.Following is a review of the relationshipbetween selenium and diabetes, andwell as other areas of human healthwhere it may make an impact.

Autoimmune Thyroiditis: Auto-immune thyroiditis (Hashimoto's thy-roiditis) is a disease in which the bodysees the thyroid glands and its hor-mones as threats, resulting in the pro-duction of antibodies that target anddestroy thyroid cells. Clinical researchhas demonstrated that three to 12months of treatment with 200 mcg sele-nium daily in combination with themedication levothyroxine significantlyreduces thyroid peroxidase antibodiesby about six to 30 percent more thanplacebo in patients with thyroiditisafter.7-13 Both sodium selenite andselenomethionine were used as sourcesof selenium in the research, but dosesunder 200 mcg daily may not be aseffective.

Cholesterol Levels: In a randomized,double-blind, placebo-controlledstudy14, patients with relatively low sele-nium levels received 100 mcg, 200 mcgand 300 mcg of selenium (as high-sele-nium yeast) daily for six months. Thosereceiving 100-200 mcg experienced sig-nificant reductions in total cholesterol.Patients receiving 300 mcg daily, how-ever, did not. Rather, they experienceda significant decrease in HDL choles-terol (the “good cholesterol”). It is notclear whether selenium supplementa-tion would have the same impact oncholesterol levels in patients with higherselenium levels.

Diabetes: Selenium has been shownto activate key proteins involved in theinsulin-signal cascade.15 Furthermore,one study found that selenium statuswas lower in men with type 2 diabetesthan in non-diabetic men.16 Likewise, inthose individuals who had type 2 dia-betes for four to six years, lower plasmalevels of selenium were found.17 Inter-

estingly, serum selenium levels werealso found to be lower in relatives ofdiabetic patients, compared tocontrols.18 In addition, low selenium andglutathione peroxidase (a selenoprotein)activity observed in diabetic patients isassociated with thrombosis and cardio-vascular complications19, and may beimplicated in diabetic nephropathy (kid-ney disease).20

Conversely, other research has report-ed higher serum selenium levels in type2 diabetics21, and a recent randomized,double-blind, placebo-controlled studyin 1,202 men and women found thatselenium supplementation (200mcg/day) was linked to an increase inprevalence of type 2 diabetes.22

Although the mechanism associatedwith this increased risk is not under-stood, it may make sense for individualsat risk for diabetes to limit their dailyintake to 100 mcg. Another considera-tion is that in animal research, supple-mentation with a form of seleniumknown as methylsenocysteine (MSC)was associated with an improvement ofboth blood glucose levels and kidneyfunction.23 Consequently, it may be wisefor diabetics or those at risk to use MSCif they plan to supplement with seleni-um.

Immune Response: In studies ofhealthy individuals24,25 and those withhead and neck cancer26 who were sup-plemented with 200 mcg/day of seleni-um as sodium selenite for eight weeksshowed enhanced immune cellresponse to foreign antigens comparedwith those taking a placebo. Researchalso indicates that selenium plays a rolein regulating the expression of cell-sig-naling molecules called cytokines, whichorchestrate the immune response.27

Cancer Cells: A case-control studywithin a prospective study of more than50,000 male health professionals in theU.S. found a significant inverse relation-ship between selenium status in thebody and the incidence of prostate can-cer cell development.28 Individualswhose selenium status was consistentwith an average dietary intake of 159mcg/day of selenium daily had a 65percent lower incidence of risk ofprostate cancer cell development com-pared to those whose selenium statuswas consistent with an average intake of86 mcg/day. Similar results were seen inother studies of examining seleniumintake and the incidence of cancer cellsfrom the lung29,30 and liver.31

Cardiovascular Health: Promotingselenoprotein activity could help pro- Circle Reader Service #19

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mote healthy cardiovascular function bydecreasing lipid peroxidation and influ-encing the metabolism of cell-signalingmolecules known as prostaglandins.8

Research has demonstrated a higherrate of cardiovascular disease in individ-uals with lower serum selenium levelscompared to those with higher levels.32-34

In a multi-center study in Europe, thelowest levels of selenium status werealso associated with myocardial infarc-tion (i.e., heart attack).35

Rheumatoid Arthritis: Surveys indi-cate that individuals with rheumatoidarthritis often have reduced seleniumlevels in their blood.36,37 In addition,some of these same individuals have alow selenium intake.38 The rationale forthe interplay between selenium andjoint function has to do with selenium’santioxidant properties. Consider thatthe body’s immune system naturallymakes free radicals that can helpdestroy invading organisms and dam-aged tissue, but that can also harmhealthy tissue39 such as joint tissue. Asan antioxidant, selenium may help con-trol levels of free radicals in jointtissue40, which in turn may help supporta healthy inflammatory response.

Intake & Rationale forSupplementationBenefits for immune response andreduced incidence of cancer cell devel-opment were associated with supple-mentation of 200 mcg daily of seleniumsupplementation or 159 mcg daily ofselenium from the diet. However, stan-dard dietary intake of selenium in theU.S. is about 100 mcg daily.41 Thatmeans to enjoy these benefits we stillneed roughly another 50 to 100 mcg ofselenium daily. Clearly, this can beachieved through supplementation.

References:1 Rayman MP. The importance of selenium to

human health. Lancet, 2000;356(9225):233-241.2 Higdon J, Drake VJ. Selenium. Linus Pauling

Institute, Micronutrient Information Center. OregonState University. Last updated 1/22/09. RetrievedSeptember 13, 2012 from lpi.oregonstate.edu/infocen-ter/minerals/selenium/.

3 Sword JT, Pope AL, Hoekstra WG. Endotoxin andlipid peroxidation in vitro in selenium- and vitamin E-deficient and -adequate rat tissues. J Nutr, 1991;121(2):258-264.

4 Burk RF, Olson GE, Hill KE. Deletion of selenopro-tein P gene in the mouse. In: Hatfield DL, Berry MJ,Gladyshev VN, eds. Selenium: Its Molecular Biology andRole in Human Health, 2nd ed. New York: Springer;2006:111-122.

5 Selenium monograph. Micronutrient InformationCenter, Linus Pauling Institute. Oregon State University.Updated January 2009. Retrieved August 15, 2009from lpi.oregonstate.edu/infocenter/minerals/selenium.

6 Rayman MP. The importance of selenium to

human health. Lancet, 2000;356(9225):233-241.7 Gartner R, Gasnier BC, Dietrich JW, et al.

Selenium supplementation in patients with autoim-mune thyroiditis decreases thyroid peroxidase anti-bodies concentrations. J Clin Endocrinol Metab,2002;87:1687-91.

8 Duntas LH, Mantzou E, Koutras DA. Effects of asix month treatment with selenomethionine in patientswith autoimmune throiditis. Eur J Endocrinol, 2003;148:389-93.

9 Gartner R, Gasinier BC. Selenium in the treatmentof autoimmune thyroiditis. Biofactors, 2003;19:165-70.

10 Turker O, Kumanlioglu K, Karapolat I, Dogan I.Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J Endocrinol,2006;190:151-6.

11 Mazokopakis EE, Papadakis JA,Papadomanolaki MG, et al. Effects of 12 months treat-ment with L-selenomethionine on serum anti-TPO lev-els in patients with Hashimoto's thyroiditis. Thyroid,2007;17:609-12.

12 Toulis KA, Anastasilakis AD, Tzellos TG, et al.Selenium supplementation in the treatment ofHashimoto’s thyroiditis: A systematic review and ameta-analysis. Thyroid, 2010;20:1163-73.

13 Balaz C, Feher J. The effect of selenium therapyon autoimmune thyroiditis. Clinical and ExperimentalMedical Journal, 2009;3:269-77.

14 Rayman MP, Stranges S, Griffin BA, et al. Effectof supplementation with high-selenium yeast on plas-ma lipids: a randomized trial. Ann Intern Med, 2011;154:656-65.

15 Stapleton SR. Selenium: an insulin-mimetic. CellMol Life Sci, 2000;57:1874-1879.

16 Rajpathak S, Rimm E, Morris JS, Hu F. Toenailselenium and cardiovascular disease in men with dia-betes. J Am Coll Nutr, 2005;24(4):250-256.

17 Whiting PH, Kalansooriya A, Holbrook I, HaddadF, Jennings PE. The relationship between chronic gly-caemic control and oxidative stress in type 2 diabetesmellitus. Br J Biomed Sci. 2008;65(2):71-4.

18 Ozkaya M, Sahin M, Cakal E, Gisi K, Bilge F,Kilinc M. Selenium levels in first-degree relatives ofdiabetic patients. Biol Trace Elem Res, 2009;128(2):144-51.

19 Faure P. Protective effects of antioxidantmicronutrients (vitamin E, zinc and selenium) in type 2diabetes mellitus. Clin Chem Lab Med,2003;41(8):995-8.

20 Kornhauser C, Garcia-Ramirez JR, Wrobel K,Pérez-Luque EL, Garay-Sevilla ME, Wrobel K. Serumselenium and glutathione peroxidase concentrations intype 2 diabetes mellitus patients. Prim Care Diabetes,2008;2(2):81-5.

21 Bleys J, Navas-Acien A, Guallar E. Serum seleni-um and diabetes in U.S. adults. Diabetes Care, 2007;30(4):829-834.

22 Stranges S, Marshall JR, Natarajan R, et al.Effects of Long-Term Selenium Supplementation onthe Incidence of Type 2 Diabetes: A Randomized Trial.Ann Intern Med, 2007.

23 Kiersztan A, Baranska A, Hapka M, et al.Differential action of methylselenocysteine in controland alloxan-diabetic rabbits. Chem Biol Interact2009;177(2):161-71.

24 Roy M, Kiremidjian-Schumacher L, Wishe HI,Cohen MW, Stotzky G. Supplementation with seleniumand human immune cell functions. I. Effect on lym-phocyte proliferation and interleukin 2 receptorexpression. Biol Trace Elem Res, 1994;41(1-2):103-114.

25 Kiremidjian-Schumacher L, Roy M, Wishe HI,Cohen MW, Stotzky G. Supplementation with seleniumand human immune cell functions. II. Effect on cyto-toxic lymphocytes and natural killer cells. Biol TraceElem Res, 1994;41(1-2):115-127.

26 Kiremidjian-Schumacher L, Roy M, Glickman R,et al. Selenium and immunocompetence in patients

with head and neck cancer. Biol Trace Elem Res,2000; 73(2):97-111.

27 Baum MK, Miguez-Burbano MJ, Campa A, Shor-Posner G. Selenium and interleukins in persons infect-ed with human immunodeficiency virus type 1. JInfect Dis, 2000;182 Suppl 1:S69-73.

28 Yoshizawa K, Willett WC, Morris SJ, et al. Studyof prediagnostic selenium level in toenails and the riskof advanced prostate cancer. J Natl Cancer Inst, 1998;90(16):1219-1224.

29 Knekt P, Marniemi J, Teppo L, Heliovaara M,Aromaa A. Is low selenium status a risk factor for lungcancer? Am J Epidemiol, 1998;148(10):975-982.

30 Zhuo H, Smith AH, Steinmaus C. Selenium andlung cancer: a quantitative analysis of heterogeneity inthe current epidemiological literature. CancerEpidemiol Biomarkers Prev, 2004;13(5):771-778.

31 Yu MW, Horng IS, Hsu KH, Chiang YC, Liaw YF,Chen CJ. Plasma selenium levels and risk of hepato-cellular carcinoma among men with chronic hepatitisvirus infection. Am J Epidemiol, 1999;150(4):367-374.

32 Salonen JT, Alfthan G, Huttunen JK, PikkarainenJ, Puska P. Association between cardiovascular deathand myocardial infarction and serum selenium in amatched-pair longitudinal study. Lancet,1982;2(8291):175-179.

33 Virtamo J, Valkeila E, Alfthan G, Punsar S,Huttunen JK, Karvonen MJ. Serum selenium and therisk of coronary heart disease and stroke. Am JEpidemiol, 1985;122(2):276-282.

34 Suadicani P, Hein HO, Gyntelberg F. Serum sele-nium concentration and risk of ischaemic heart dis-ease in a prospective cohort study of 3000 males.Atherosclerosis, 1992;96(1):33-42.

35 ardinaal AF, Kok FJ, Kohlmeier L, et al.Association between toenail selenium and risk ofacute myocardial infarction in European men. TheEURAMIC Study. European Antioxidant MyocardialInfarction and Breast Cancer. Am J Epidemiol,1997;145(4):373-379.

36 Kose K, Dogan P, Kardas Y, Saraymen R. Plasmaselenium levels in rheumatoid arthritis. Biol TraceElem Res, 1996;53:51-6.

37 Heliovaara M, Knekt P, Aho K, Aaran RK, AlfthanG, Aromaa A. Serum antioxidants and risk of rheuma-toid arthritis. Ann Rheum Dis, 1994;53:51-3.

38 Stone J, Doube A, Dudson D, Wallace J.Inadequate calcium, folic acid, vitamin E, zinc, andselenium intake in rheumatoid arthritis patients:Results of a dietary survey. Semin Arthritis Rheum,1997;27:180-5.

39 Grimble RF. Nutritional antioxidants and themodulation of inflammation: Theory and practice. NewHorizons, 1994;2:175-85.

40 Aaseth J, Haugen M, Forre O. Rheumatoidarthritis and metal compounds- perspectives on therole of oxygen radical detoxification. Analyst, 1998;123:3-6.

41 Food and Nutrition Board, Institute of Medicine.Selenium. Dietary reference intakes for vitamin C,vitamin E, selenium, and carotenoids. WashingtonD.C.: National Academy Press; 2000:284-324.

SupplementScience

Gene Bruno, MS, MHS, the dean ofacademics for Huntington College ofHealth Sciences, is a nutritionist,herbalist, writer and educator. Formore than 30 years he has educatedand trained natural product retailersand health care professionals, hasresearched and formulated naturalproducts for dozens of dietary supple-ment companies, and has written arti-cles on nutrition, herbal medicine,nutraceuticals and integrative healthissues for trade, consumer magazinesand peer-reviewed publications.