SELENIUM IN HUMAN HEALTH

SELENIUM IN HUMAN HEALTH

Selenium (Se) is an essential dietary trace element and is required for many functions regarding human health.[1]  Se has structural and enzymatic roles as a constituent of selenoproteins.[2], viagra [3]  Selenium is important for active thyroid hormone1 production and higher Se status reduces the risk of autoimmune thyroid disease.  Selenium is important for the proper functioning of the immune system.[4], information pills [5] Reduced cancer risk has been associated with elevated Se intake and Se is a key nutrient in counteracting the development of virulence as well as inhibiting HIV progression to AIDS.  Low Se status has been associated with cognitive decline, increased risk of mortality and poor immune function.[6]

SELENIUM and Immune Function   

Evidence on the importance of Se to immunity in humans is scarce.  According to Broome et al[7] cellular immune response was improved, virus cleared more rapidly and fewer mutations occurred in its genome, in Se-supplemented subjects.  Natural killer cell activity, increased cytotoxic lymphocyte-mediated tumour cytotoxicity and enhancement of proliferation of activated T cells are all immunostimulant effects from Se supplementation in Se-replete individuals.[8]

Supplementing with 400 mcg Se/d, total T-cell count was significantly increased in a group of elderly subjects. Proliferative response to antigen challenge was increased in elderly Belgian subjects receiving 100 mgc/d for six months.  Increase in cytotoxic-lymphocyte-mediated tumour cytotoxicity by 118% was seen in Se-replete subjects supplemented with Se at 200mcg/d, when compared to placebo.  Increase in NK-cell activity was 82% in the same group.  In a group of elderly subjects receiving Se (100 mcg/day) for 6 months, lymphocyte response to challenge increased by 138% in the Se group, compared with no change in the placebo group.  Se can restore immune response in age-related decline.[9]

SELENIUM and Cognitive Decline  

Lack of Se may lead to irreversible brain injury.[10]  Se is delivered to the brain by selenoprotein P (SEPP1) by binding to a member of the lipoprotein receptor family apoER2.2  SEPP1 is neuroprotective, prevents apoptotic cell death in response to amyloid-b-induced oxidative challenge and enhances neuronal survival.[11]  Evidence from human studies suggests a role for Se in cognitive decline, seizures, PD and coordination.6   The risk of dementia and AD has been linked to Se status in humans.  Subjects with low plasma Se at baseline were at greater risk of cognitive decline in the French EVA[12] cohort of 1166 people aged 60-70 years.  According to Akbaraly et al significant association between the magnitude of plasma Se decrease and cognitive decline was observed over 9 years[13].  Low nail Se concentration in 2000 rural Chinese adults was significantly associated with low cognitive scores.[14]

SELENIUM and Antiviral Effects

Se deficiency has been linked to disease progression of viral infections, or virulence.  Low Se status could lead to myocarditis-inducing mutations in the coxsackie virus which causes Keshan-disease cardiomyopathy. [16],[17],[18],[19],[20],[21]  Human subjects supplemented with Se at 100 mcg/d cleared attenuated poliovirus more quickly and fewer mutations in the viral genome were observed.  HIV-infected subjects commonly suffer from other infections.[22]  In a group of 259 HIV-1 –infected drug users, those with Se <135 mcg/L (plasma levels) had an increased risk (three-fold) of developing mycobacterial disease than those with higher plasma Se.

Evidence reveals benefits from Se supplementation in HIV-infection e.g. marked decrease in hospital admission rates, suppressed progression of HIV-1 viral burden and indirect improvement of CD4+cell count/viral load.[23],[24]   Kupka et al[25] found no effect in a RCT on HIV-viral load or on CD4+cell count in Tanzanian pregnant women, when supplemented with 200 mcg Se/d (reduction on child mortality was observed).  Reduced risk of immune decline and morbidity was observed with a single daily supplement containing multivitamins and 200 mcg Se in HIV-infected adults from Botswana.[26]

SELENIUM and Autoimmune Thyroid Function

The thyroid gland has a high Se concentration and Se is important for thyroid function.[27]  Se was significantly associated with less eye involvement, slower progression of Graves- orbitopathy and improved quality of life.[28]

Autoimmune thyroiditis (AIT) affects females (>15% >60yr) and males (2% [irrespective of age]).[29]  Supplementation of AIT patients with Se (80 or 200 mcg/d) decreased inflammation and thyroid peroxidase autoantibody (TPO-Ab) concentrations in 7 out of 11 RCT.29,[30]    Improved mood and/or general well being  was also reported.

Findings from Santos et al[31] support the existence of a link between selenoprotein S gene (SEPS1) promotor genetic variation and Hashimoto’s thyroiditis (HT) risk/susceptibility.

Positive TPO-Ab measurements in pregnancy can be associated with post-partum thyroid dysfunction and permanent hypothyroidism.6  In women receiving 200 mcg Se/d (as selenomethionine), post-partum thyroid disease and permanent hypothyroidism were significantly reduced as thyroid inflammatory activity fell[32]

SELENIUM and Cancer

Evidence from prospective studies exist on beneficial effects of Se on the risk of prostate[33],[34],[35],[36],[37], lung[38], bladder[39] and colorectal cancers.  In a dose-response meta-analysis[40] the risk of total- and advanced prostate cancer (PCa) decreased with increasing plasma/serum Se up to 170 ng/mL.  Reduction in PCa was observed with a toenail Se concentration between 0.85 and 0.94 mcg/g, in three high-quality studies of toenail Se and cancer risk.  Population with low baseline serum Se and high risk for cancer benefit from Se supplementation[41],[42]   Duffield-Lillico et al[43] reported a significant reduction in cancer mortality, cancer incidence and PCa incidence in the NPC trial.  Greater effect has been reported on advanced PCa (p=0.03) than on the local disease (P=0.02) with supplemental dietary Se.[44]  In the SELECT[45] trial no effect was found on PCa risk from Se or Se with vitamin E.[46]   Baseline Se status was higher than in the NPC trial in the subjects with no benefit from Se supplementation (Se-methionine), only 1% of the cases were non-localized and only one PCa death occurred.  Se supplementation increased the risk of high-grade PCa in men with higher Se status but had no effect in men with low Se status.[47]  Geybels et al[48] reported significantly reduced risk of advanced PCa with increasing Se status (p=0.001).

 CONCLUSION

Selenium is an essential dietary trace element.  Healthy selenium status is important for immune function, for preventing virulence and for preventing cancer.  Selenium is important for the brain and healthy cognition.

Copyright @ Jörth 2008-2017 

REFERENCES

1 Rayman MP. The importance of selenium to human health. Lancet 2000;356:233-241.

2 Burk RF, Hill KE, Motley AK. Selenoprotein metabolism and function: evidence fro more than one function for selenoprotein P. J Nutr 2003;133(5):1517S-1520S.

3 Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Omid Zehtab, et al. Characterization of mammalian selenoproteines. Science 2003;300(5624):1439-1443.

4 Kiremidjian-Schumacher L, Roy M, Wishe HI, Cohen MW, Stotzky G. Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells. Biol Trace Elem Res 1994;41(1-2):115-27.

5 Hoffman PR. Mechanisms by which selenium influences immune responses. Arch Immunol Ther Exp 2007;55:289-297

6 Rayman MP. Selenium and human health. Lancet 2012;379(8922):1256-68.

7 Broome CS, McArdle F, Kyle JA, et al. An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am J Clin Nutr 2004;80:154-62.

8 Wood SM, Becham C, Yosioka A, Darban H, Watson RR. b-Carotene and selenium supplementation inhances immune response in aged humans. Itegr Med 2000;2:85-92.

9 Peretz A, Neve J, Desmedt J, Duchateau J, Dramaix M, Famaey J. Lymphocyte response is enhanced by supplementation of elderly subjects with selenium-enriched yeast. Am J Clin Nutr 1991;53(5):1323-1328.

10 Burk RF, Hill KE. Selenoprotein P – expression, functions, and roles in mammals. BBA 2009;1790:1441-1447.

11 Takemoto AS, Berry MJ, Bellinger FP. Role of selenoprotein P in Alzheimer´s disease. Ethn Dis 2010; 20(1):S1-92-95.

12 Berr C, Balansard B, Arnaud J, Roussel AM, Alperovitch A. Cognitive decline is associated with systemic oxidative stress: the Eva study. Etude du Vieilisement Arteriel. J Am Geratr Soc 2000;48:1285-91.

13 Akbaraly TN, Hininger-Favier I, Carriere I, Arnaud J, Gourlet V, Roussel AM, et al. Plasma selenium over time and cognitive decline in the elderly. Epidemiology 2007;18(1):52-58.

14 Gao S, Jin Y, Hall KS, et al. Selenium level and cognitive function in rural elderly Chinese. Am J Epidemiol 2007;18:52-58.

15 Williams JW, Plassman BL, Burke J, Holsinger T, Benjamin S. Preventing Alzheimer´s disease and cognitive decline. Evidence Report/Technology Assessment No. 193. (Prepared by the Duke Evidence-based Practice Center under Contract No. HHSA 290-2007-10066-I.) Rockville, MD: Agency for Healthcare Research and Quality. April 2010. AHRQ Publication No. 10-E005.

16 Beck MA, Handy J, Levander OA. Host nutritional status: the neglect virulence factor. Trends Microbiol 2004;12:417-23.

17 Beck MA, Levander OA, Handy J. Selenium deficiency and viral infection. J Nutr 2003;133(1):1463S-67S.

18 Lei C, Niu X, Wei J, Zhu J, Zhu Y. Interaction of glutathione peroxidase-1 and selenium in endemic dilated cardiomyopathy. Clin Chim Acta 2009;399:102-08.

19 Beck MA, Shi Q, Morris VC, Levander OA. Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat Med 1995,1(5):433-6. [Abstract].

20 Beck MA, Esworthy RS, Ho Y, Chu F. Glutathione peroxidase protects mice from viral-induced myocarditis. FASEB J 1998;12(12):1143-1149.

21 Gu BQ. Pathology of Keshan disease. A comprehensive review. Chin Med J 1983;96:251-261.

22 Shor-Posner G, Miguez MJ, Pineda LM, Rodriguez A, Ruiz P, Castillo 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;29:169-73.

23 Burbano X, Miguez-Burano MJ, McCollister K, et al. Impact of a selenium chemoprevention clinical trial on hospital admissions of HIV-infected participants. HIV Clin Trials 2002;3:483-91.

24 Hurwitz BE, Klaus JR, Liabre MM, et al. Suppression of human immunodeficiency virus type 1 viral load with selenium supplementation: a randomized controlled trial. Arch Intern Med 2007;167:148-54.

25 Kupka R, Mugusi F, Aboud S, et al. Randomized, double-blind, placebo-controlled trial of selenium supplements among HIV-infected pregnant women in Tanzania: effects on maternal and child outcomes. Am J Clin Nutr 2008;871802-08.

26 Baum MK, Campa A, Lai S, Sales Martinez S, Tsalaile L, Burns P, et al. Effect of micronutrient supplementation on disease progression in asymptomatic, antiretroviral-naive, HIV-infected adults in Botswana: a randomized clinical trial. JAMA 2013;310(20);2154-63.

27 Schomburg L, Köhrle J. On the importance of selenium and iodine metabolism for thyroid hormone biosynthesis and human health. Mol Nutr Food Res 2008;52:1235-46.

28 Marcocci C, Kahaly GJ, Krassas GE, et al. European Group on Graves Orbitopathy. Selenium and the course of mild Graves orbitopathy. N Engl J Med 2011;364:192031.

29 Toulis KA, Anastasilakis AD, Tzellos TG, Goulis DG, Kouvelas D. Selenium supplementation in the treatment of Hashimoto´s thyroiditis: a systematic review and a meta-analysis. Thyroid 2010;20(10):1163-73

30 Nacamulli D, Mican C, Petricca D, Lazzarotto F, Barollo S, Pozza D, et al. Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. Clin Endocrinol 2010;73;535-539.

31 Santos LR, Duraes C, Mendes A, Prazeres H, Alvelos I, Moreira CS, et al. A polymorphism in the promoter region of selenoprotein S gene (SEPS1) contributes to Hashimoto´s thyroiditis susceptibility. J Clin Endocrinol Metab 2014;0, 0:0.

32 Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab 2007;92:1263-68.

33 Ryman MP. Selenoproteins and human health: insights from epidemiological data. Biochim Biophys Acta 2009,1790:1533-40.

34 Peters U, Takata Y. Selenium and the prevention of prostate and colorectal cancer. Mol Nutr Food Res 2008;52:1261-72.

35 Etminan M, FitzGerald JM, Gleave M, Chambers K. Intake of selenium in the prevention of prostate cancer: a systematic review and meta-analysis. Cancer Causes Control 2005;16:1125-31.

36 Rayman MP. Selenium. Milner JA, Romagnolo DF, ed. Bioactive compounds and cancer. New York: Humana Press, Springer, 2010;411-49.

37 Brinkman M, Reulen RC, Kellen E, Buntinx F, Zeegers MP. Are men with low selenium levels at increased risk of prostate cancer? Eur J Cancer 2006;42:2463-71.

38 Zhuo H, Smith AH, Steinmaus C. Selenium and lung cancer: a quantitative analysis of heterogeneity in the current epidemiological literature. Cancer Epidemiol Biomarkers Prev 2004;13:771-778.

39 Amaral AF, Cantor KP, Silverman DT, Malats N. Selenium and bladder cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2010;19:2407-15.

40 Hurst R, Hooper L, Norat T, Lau R, Aune D, Greenwood DC, et al. Selenium and prostate cancer: systematic review and meta-analysis. AJCN 2012;96(1):111-122.

41 Lee EH, Myung SK, Jeon YJ, Kim Y, Chang YJ, Ju W, et al. Effects of selenium supplements on cancer prevention: meta-analysis of randomized controlled trials. Nutr Cancer 2011;63(8):1185-95.

42 Dennert G, Zwahlen M, Brinkman M, Vinceti M, Zeegers M, Horneber M. Selenium for preventing cancer. Cochrane Database 2011;CD005195.

43 Duffield-Lillico AJ, Reid ME, Turnbull BW, Combs GF, Slate EH, et al. Baseline characteristics and the effect of selenium supplementation on cancer incidence in a randomized clinical trial: a summary report of the nutritional prevention of cancer trial. Cancer Epidemiol Biomarkers Prev 2002;11:630-9.

44 Clark LC, Krongarad A, Combs GF jr, Turnbull BW, Slate EH, Witherington R, et al. Decreased incidence of prostate cancer with selenium supplementation: results of a double-blind cancer prevention trial. Br J Urol 1998;81(5):730-4. [Abstract].

45 Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009,301(1):39-51.

46 Klein EA, Thompson IM, Tangen CM, Crowley JJ, Lucia S, Goodman PJ, et al. Vitamin E and the Risk of prostate cancer. The selenium and vitamin E cancer prevention trial (SELECT). JAMA 2011,306(14):1549-1556

47 Kristal AR, Darke AK, Morris S, Tangen CM, Goodman PJ, Thompson IM, et al. Baseline selenium status and effects of selenium and vitamin E supplementation on prostate cancer risk.  JNCI J Natl Cancer Inst 2014;djt456.

48 Geybels MS, Verhage B, van Schooten F, Goldbohm A, van den Brandt P.  Advanced prostate cancer risk in relation to toenail selenium levels. JNCI J Natl Cancer Inst 2013;105(18):1394-1401.

Copyright @ Jörth 2008-2017