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Selenium: an element for life

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Abstract

This review aims to illustrate the importance of selenium (Se) for maintenance of overall health, especially for the thyroid, immunity, and homeostasis. Furthermore, it outlines the role of Se in reproduction and in virology and discusses the effects of Se supplementation in critical illness. The multifaceted aspects of this essential nutrient have attracted worldwide clinical and research interest in the last few decades. Se exerts its activity in the form of the aminoacid selenocysteine incorporated in selenoproteins. The impact of Se administration should be considered in relation to its apparent U shaped effects, i.e., exhibiting major advantages in Se-deficient individuals but specific health risks in those with Se excess. Addition of selenium to the administration of levothyroxine may be useful in patients with low Se intake and with mild-form or early-stage Hashimoto’s thyroiditis (HT). Serum Se concentration (possibly also at tissue level) decreases in inflammatory conditions and may vary with the severity and duration of the inflammatory process. In such cases, the effect of Se supplementation seems to be useful and rational. Meanwhile, Se’s ability to improve the activity of T cells and the cytotoxicity of natural killer cells could render it effective in viral disease. However, the evidence, and this should be stressed, is at present conflicting as to whether Se supplementation is of benefit in patients with HT, though there are indications that it is advantageous in cases of mild/moderate Graves’ Orbitopathy. The role of Se in type 2 diabetes mellitus (T2DM) is ambiguous, driven by both Se intake and serum levels. The evidence that insulin and glycaemia influence the transport and activity of Se, via regulatory activity on selenoproteins, and that high serum Se may have a diabetogenic effect suggests a ‘Janus-effect’ of Se in T2DM. Though the evidence is not as yet clear-cut, the organic form (selenomethionine), due to its pharmacokinetics, is likely to be more advantageous in long-term prevention, and supplementation efforts, while the inorganic form (sodium selenite) has proven effective in an acute, e.g., sepsis, clinical setting. Recent data indicate that functional selenoprotein single-nucleotide polymorphisms (SNPs) may interfere with Se utilization and effectiveness.

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References

  1. J.J. Berzelius, Lettre de M. Berzelius à M. Berthollet sur deux nouveaux métaux (Letter from Mr. Berzelius to Mr. Berthollet on two new metals). Annales Chimie et Physique 187, 199–200 (1817)

  2. W. von Gümbel, M. von Reichenstein, F.J. Freiherr, Allgemeine Deutsche Biographie (ADB) (in German) 22, Leipzig: Duncker & Humblot 702–703 (1885)

  3. R. Meyer, Martin Heinrich Klaproth, ein deutscher Chemiker des 18. Jahrhunderts. Zeitschrift für Angewandte Chemie 34, 1–3 (1921)

    Google Scholar 

  4. K. Schwarz, C.M. Foltz, Selenium as an integral part of factor 3 against dietary necrotic liver degeneration. J. Am. Chem. Soc. 79, 3292–3293 (1957)

    CAS  Google Scholar 

  5. K.M. Brown, R. Arthur, Selenium, selenoproteins and human health: a review. Public Health Nutr. 4, 593–599 (2001)

    CAS  PubMed  Google Scholar 

  6. M.P. Rayman, Selenoproteins and human health: insights from epidemiological data. Biochim. Biophys. Acta 11, 1533–1540 (2009). doi:10.1016/j.bbagen.2009.03.014

    Google Scholar 

  7. C.D. Thomson, M.F. Robinson, Selenium in human health and disease with emphasis on those aspects peculiar to New Zealand. Am. J. Clin. Nutr. 33, 303–323 (1980)

    CAS  PubMed  Google Scholar 

  8. C.D. Thomson, M.F. Robinson, Selenium content of foods consumed in Otago, New Zealand. N Z Med. J. 103(886), 130–135 (1990)

    CAS  PubMed  Google Scholar 

  9. N.D. Grace, S.O. Knowles, Trace element supplementation of livestock in new zealand: meeting the challenges of free-range grazing systems. Vet. Med. Int. 2012, 639472–639479 (2012). doi:10.1155/2012/639472

    PubMed Central  PubMed  Google Scholar 

  10. W. Wasowicz, J. Gromadzinska, K. Rydzynski, J. Tomczak, Selenium status of low-selenium area residents: polish experience. Toxicol. Lett. 137, 95–101 (2003)

    CAS  PubMed  Google Scholar 

  11. F. Gondi, G. Pantó, J. Fehér, G. Bogye, G. Alfthan, Selenium in Hungary. The rock-soil-human system. Biol. Trace Elem. Res. 35, 299–306 (1992)

    CAS  PubMed  Google Scholar 

  12. G.F. Jr, Combs, Selenium in global food systems. Br. J. Nutr. 85, 517–547 (2001)

    Google Scholar 

  13. C. Thiry, A. Ruttens, L. Pussemier, Y.J. Schneider, An in vitro investigation of species-dependent intestinal transport of selenium and the impact of this process on selenium bioavailability. Br. J. Nutr. 109, 2126–2134 (2013). doi:10.1017/S0007114512004412

    CAS  PubMed  Google Scholar 

  14. C.M. Weekley, H.H. Harris, Which form is that? The importance of selenium speciation and metabolism in the prevention and treatment of disease. Chem. Soc. Rev. 42, 8870–8894 (2013)

    CAS  PubMed  Google Scholar 

  15. M.P. Rayman, H.G. Infante, M. Sargent, Food-chain selenium and human health: spotlight on speciation. Br. J. Nutr. 100, 238–253 (2008). doi:10.1017/S0007114508922522

    CAS  PubMed  Google Scholar 

  16. Y. Kobayashi, Y. Ogra, K. Ishiwata, H. Takayama, N. Aimi, K.T. Suzuki, Selenosugars are key and urinary metabolites for selenium excretion within the required to low-toxic range. Proc. Natl. Acad. Sci. USA. 99, 15932–15936 (2002)

    PubMed Central  CAS  PubMed  Google Scholar 

  17. N. Waegeneers, C. Thiry, L. De Temmerman, A. Ruttens, Predicted dietary intake of selenium by the general adult population in Belgium. Food Addit. Contam. Part A. Chem. Anal. Control Expo. Risk Assess. 30, 278–285 doi:10.1080/19440049.2012.746474 (2013)

  18. K. Park, E. Rimm, D. Siscovick, D. Spiegelman, J.S. Morris, D. Mozaffarian, Demographic and lifestyle factors and selenium levels in men and women in the U.S. Nutr. Res. Pract. 5, 357–364 (2011). doi: 10.4162/nrp.2011.5.4.357

  19. M. Spadoni, M. Voltaggio, M. Carcea, E. Coni, A. Raggi, F. Cubadda, Bioaccessible selenium in Italian agricultural soils: comparison of the biogeochemical approach with a regression model based on geochemical and pedoclimatic variables. Sci. Total Environ. 376, 160–177 (2007)

    CAS  PubMed  Google Scholar 

  20. J.W. Finley, Bioavailability of selenium from foods. Nutr. Rev. 64, 146–151 (2006)

    PubMed  Google Scholar 

  21. J.M. Finley, M.A. Grusak, A.S. Keck, B.R. Gregoire, Bioavailability of selenium from meat and broccoli as determined by retention and distribution of 75Se. Biol. Trace Elem. Res. 99, 191–209 (2004)

    CAS  PubMed  Google Scholar 

  22. A. Haug, R.D. Graham, O.A. Christophersen, G.H. Lyons, How to use the world’s scarce selenium resources efficiently to increase the selenium concentration in food. Microb Ecol Health Dis. 19, 209–228 (2007)

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Keshan Disease Research Group, Epidemiological studies on the etiologic relationship of selenium in Keshan disease. Chin. Med. J. 92, 471–476 (1979)

    Google Scholar 

  24. Q. Li, M. Liu, J. Hou, C. Jiang, S. Li, T. Wang, The prevalence of Keshan disease in China. Int. J. Cardiol. 168, 1121–1126 (2013). doi:10.1016/j.ijcard.2012.11.046

  25. B. Contempre, G. Morreale de Escobar, J.F. Denef, J.E. Dumont, M.C. Many, Thiocyanate induces cell necrosis and fibrosis in selenium- and iodine-deficient rat thyroids: a potential experimental model for myxedematous endemic cretinism in central Africa. Endocrinology 145, 994–1002 (2004)

    CAS  PubMed  Google Scholar 

  26. J.E. Dumont, B. Corvilain, B. Contempre, The biochemistry of endemic cretinism: roles of iodine and selenium deficiency and goitrogens. Mol. Cell. Endocrinol. 100, 163–166 (1994)

    CAS  PubMed  Google Scholar 

  27. G. Yang, L. Zhu, S. Liu, Human selenium requirements in China, in Selenium in biology and medicine, eds. by G.F. Combs, J.E. Spallholz, O.A. Levander, J.E. Oldfield (eds.) (Nostrand Rheinhold/AVI, New York, 1987) pp.589–607

  28. M.F. Robinson, The New Zealand selenium experience. Am. J. Clin. Nutr. 48, 521–534 (1989)

    Google Scholar 

  29. J.T. Salonen, G. Alfthan, J.K. Huttunen, J. Pikkarainen, P. Puska, Association between cardiovascular death and myocardial infarction and serum selenium in a matched pair longitudinal study. Lancet 2, 175–179 (1982)

    CAS  PubMed  Google Scholar 

  30. J. Virtamo, E. Valkeila, G. Alfthan, S. Punsar, J.K. Huttunen, M.J. Karvonen, Serum selenium and the risk of coronary heart disease and stroke. Am. J. Epidemiol. 122, 276–282 (1985)

    CAS  PubMed  Google Scholar 

  31. B. Lloyd, R.S. Loyd, B.E. Clayton, Effect of smoking, alcohol, and other factors on the selenium status of a healthy population. J. Epidemiol. Commun. Health 37, 213–217 (1983)

    CAS  Google Scholar 

  32. Commission of the European Communities, Nutrient and energy intakes for the European Community. Reports of the Scientific Committee for Food, thirty first series, Office for Official Publications of the European Communities, Luxembourg (1993)

  33. Italian Society of Human Nutrition, Document Revision 2012 RDAs (Reference Levels of Nutrients intake and energy for the Italian population) of the Italian Society of Human Nutrition (XXXV Congress SINU, Bologna 22–23 October 2012)

  34. Food and Nutrition Board, Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids. (National Academy Press, Washington, DC, 2000), pp 284–324

  35. M. Mihajlovic, Selenium toxicity in domestic animals. Glas. Srp. Akad. Nauka. Med. 42, 131–144 (1992)

    PubMed  Google Scholar 

  36. S. Shao, B. Zheng, The biogeochemistry of selenium in Sunan grassland, Gansu, Northwest China, casts doubt on the belief that Marco Polo reported selenosis for the first time in history. Environ. Geochem. Health 30, 307–314 (2008)

    CAS  PubMed  Google Scholar 

  37. J.S. Morris, S.B. Crane, Selenium toxicity from a misformulated dietary supplement, adverse health effects, and the temporal response in the nail biologic monitor. Nutrients 5, 1024–1057 (2013)

    PubMed Central  CAS  PubMed  Google Scholar 

  38. K. Helzslouer, R. Jacobs, S. Morris, Acute selenium intoxication in the United States. Fed. Proc. 44, 1670 (1985)

    Google Scholar 

  39. J.K. McFarquhar, D.L. Broussard, P. Melstrom, R. Hutchinson, A. Wolkin, C. Martin, R.F. Burk, J.R. Dunn, A.L. Green, R. Hammond, W. Schaffner, T.F. Jones, Acute selenium toxicity associated with a dietary supplement. Arch. Int. Med. 170, 256–261 (2010)

    Google Scholar 

  40. B.M. Aldosary, M.E. Sutter, M. Schwartz, B.M. Morgan, Case series of selenium toxicity from a nutritional supplement. Clin. Toxicol. (Philadelphia, Pa.) 50, 57–64 (2012)

  41. G. Yang, S. Wang, R. Zhou, S. Sun, Endemic selenium intoxication of humans in China. Am. J. Clin. Nutr. 37, 872–881 (1983)

    CAS  PubMed  Google Scholar 

  42. G. Yang, S. Yin, L. Zhou, Studies of safe maximal dietary Se intake in a seleniferous area in China. Part II. Relation between Se intake and the manifestation of clinical signs and certain biochemical alterations in blood and urine. J. Trace Elem. Electrol. Health Dis. 3, 123–130 (1989)

  43. S. Huang, M. Hua, J. Feng, X. Zhong, Y. Jin, B. Zhu, H. Lu, Assessment of selenium pollution in agricultural soils in the Xuzhou District, Northwest Jiangsu, China. J. Environ. Sci. (China) 21, 481–487 (2009)

    CAS  Google Scholar 

  44. M.E. Reid, M.S. Stratton, A.J. Lillico, M. Fakih, R. Natarajan, L.C. Clark, J.R. Marshall, A report of high-dose selenium supplementation: response and toxicities. J. Trace Elem. Med Biol. 18, 69–74 (2004)

    CAS  PubMed  Google Scholar 

  45. M. Vinceti, G. Dennert, C.M. Crespi, M. Zwahlen, M. Brinkman, M.P. Zeegers, M. Horneber, R. D’Amico, C. Del Giovane C. Selenium for preventing cancer. Cochrane Database Syst Rev. 30;3:CD005195 (2014). doi:10.1002/14651858.CD005195.pub3

  46. M. Vinceti, F. Bonvicini, K.J. Rothman, L. Vescovi, F. Wang, The relation between amyotrophic lateral sclerosis and inorganic selenium in drinking water: a population-based case-control study. Environ. Health. 9, 77 (2010). doi:10.1186/1476-069X-9-77

    PubMed Central  CAS  PubMed  Google Scholar 

  47. M. Ben-Porath, L. Case, E. Kaplan. The biological half-life of 75Se selenomethionine in man. J. Nucl. Med. 9, 168–169 (l968)

  48. C.A. Swanson, B.H. Patterson, O.A. Levander, C. Veillon, P.R. Taylor, K. Helzlsouer, P.A. McAdam, L.A. Zech, Human [74Se] selenomethionine metabolism: a kinetic model. Am. J. Clin. Nutr. 54, 917–926 (1991)

    CAS  PubMed  Google Scholar 

  49. B.H. Patterson, O.A. Levander, K. Helzlsouer, P.A. McAdam, S.A. Lewis, P.R. Taylor, C. Veillon, L.A. Zech, Human selenite metabolism: a kinetic model. Am. J. Physiol. 257, R556–R567 (1989)

    CAS  PubMed  Google Scholar 

  50. C.D. Thomson, C.E. Burton, M.F. Robinson, On supplementing the selenium intake of New Zealanders. I. Short experiments with large doses of selenite or selenomethionine. Br. J. Nutr. 39, 579–587 (1978)

    CAS  PubMed  Google Scholar 

  51. M.F. Robinson, H.M. Rca, G.M. Friend, R.D.H. Stewart, P.C. Snow, C.D. Thomson, On supplementing the selenium intake of New Zealanders. 2. Prolonged metabolic experiments with daily supplements of selenomethionine, selenite and fish. Br. J. Nutr. 39, 589–600 (1978)

    CAS  PubMed  Google Scholar 

  52. M.E. Wastney, G.F. Combs Jr, W.K. Canfield, P.R. Taylor, K.Y. Patterson, A.D. Hill, J.E. Moler, B.H. Patterson, A human model of selenium that integrates metabolism from selenite and selenomethionine. J. Nutr. 141, 708–717 (2011). doi:10.3945/jn.110.129049

    PubMed Central  CAS  PubMed  Google Scholar 

  53. B. Gammelgaard, L.H. Rasmussen, C. Gabel-Jensen, B. Steffansen, Estimating intestinal absorption of inorganic and organic selenium compounds by in vitro flux and biotransformation studies in Caco-2 cells and ICP-MS detection. Biol. Trace Elem. Res. 145, 248–256 (2012). doi:10.1007/s12011-011-9174-y

    CAS  PubMed  Google Scholar 

  54. M.J. Berry, L. Banu, Y.Y. Chen, S.J. Mandel, J.D. Kieffer, J.W. Harney, P.R. Larsen, Recognition of UGA as a selenocysteine codon in type I deiodinase requires sequences in the 3′ untranslated region. Nature 353, 273–276 (1991)

    CAS  PubMed  Google Scholar 

  55. M.T. Howard, B.A. Carlson, C.B. Anderson, D.L. Hatfield, Translational redefinition of UGA codons is regulated by selenium availability. J. Biol. Chem. 288, 19401–19413 (2013). doi:10.1074/jbc.M113.481051

    PubMed Central  CAS  PubMed  Google Scholar 

  56. M.J. Berry, L. Banu, J.W. Harney, P.R. Larsen, Functional characterization of the eukaryotic SECIS elements which direct selenocysteine insertion at UGA codons. EMBO J. 12, 3315–3322 (1993)

    PubMed Central  CAS  PubMed  Google Scholar 

  57. J. Köhrle, F. Jakob, B. Contempré, J.E. Dumont, Selenium, the thyroid and the endocrine system. Endocr. Rev. 26, 944–984 (2005)

    PubMed  Google Scholar 

  58. M.J. Berry, L. Banu, P.R. Larsen, Type I iodothyronine deiodinase is a selenocysteine-containing enzyme. Nature 349, 438–440 (1991)

    CAS  PubMed  Google Scholar 

  59. A.C. Bianco, D. Salvatore, B. Gereben, M.J. Berry, P.R. Larsen, Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr. Rev. 23, 38–89 (2002)

    CAS  PubMed  Google Scholar 

  60. U. Schweizer, F. Streckfuss, P. Pelt, B.A. Carlson, D.L. Hartfeld, J. Koehrle, L. Schomburg, Hepatically derived selenoprotein P is a key factor for kidney but not for brain selenium supply. Biochem. J. 386, 221–226 (2005)

    PubMed Central  CAS  PubMed  Google Scholar 

  61. K.E. Hill, S. Wu, A.K. Motley, T.D. Stevenson, V.P. Winfrey, M.R. Capecchi, J.F. Atkins, R.F. Burk, Production of selenoprotein P (Sepp1) by hepatocytes is central to selenium homeostasis. J. Biol. Chem. 287, 40414–40424 (2012). doi:10.1074/jbc.M112.421404

    PubMed Central  CAS  PubMed  Google Scholar 

  62. K. Renko, M. Werner, I. Renner-Müller, T.G. Cooper, C.H. Yeung, B. Hollenbach, M. Scharpf, J. Köhrle, L. Schomburg, U. Schweizer, Hepatic selenoprotein P (SePP) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. Biochem. J. 409, 741–749 (2008)

    CAS  PubMed  Google Scholar 

  63. K.E. Hill, J. Zhou, W.J. McMahan, A.K. Motley, R.F. Burk, Neurological dysfunction occurs in mice with targeted deletion of the selenoprotein P gene. J. Nutr. 134, 157–161 (2004)

    CAS  PubMed  Google Scholar 

  64. J. Mittag, T. Behrends, C.S. Hoefig, B. Vennström, L. Schomburg, Thyroid hormones regulate selenoprotein expression and selenium status in mice. PLoS One 5, e12931 (2010)

    PubMed Central  PubMed  Google Scholar 

  65. N. Karunasinghe, D.Y. Han, S. Zhu, J. Yu, K. Lange, H. Duan, R. Medhora, N. Singh, J. Kan, W. Alzaher, B. Chen, S. Ko, C.M. Triggs, L.R. Ferguson, Serum selenium and single-nucleotide polymorphisms in genes for selenoproteins: relationship to markers of oxidative stress in men from Auckland, New Zealand. Genes Nutr. 7, 179–190 (2012)

    PubMed Central  CAS  PubMed  Google Scholar 

  66. C. Méplan, L.K. Crosley, F. Nicol, G.J. Beckett, A.F. Howie, K.E. Hill, G. Horgan, J.C. Mathers, J.R. Arthur, J.E. Hesketh, Genetic polymorphisms in the human selenoprotein P gene determine the response of selenoprotein markers to selenium supplementation in a gender-specific manner (the SELGEN study). FASEB J. 21, 3063–3074 (2007)

    PubMed  Google Scholar 

  67. N. Karunasinghe, D.Y. Han, S. Zhu, H. Duan, Y.J. Ko, J.F. Yu, C.M. Triggs, L.R. Ferguson, Effects of supplementation with selenium, as selenized yeast, in a healthy male population from New Zealand. Nutr. Cancer 65, 355–366 (2013). doi:10.1080/01635581.2013.760743

    CAS  PubMed  Google Scholar 

  68. J. Aaseth, H. Frey, E. Glattre, G. Norheim, J. Ringstad, Y. Thomassen, Selenium concentration in the human thyroid gland. Biol. Trace Elem. Res. 24, 147–152 (1990)

    CAS  PubMed  Google Scholar 

  69. B. Tiran, E. Karpf, A. Tiran, Age dependency of selenium and cadmium content in human liver, kidney, and thyroid. Arch. Environ. Health 50, 242–246 (1995)

    CAS  PubMed  Google Scholar 

  70. J. Koehrle, The trace element selenium and the thyroid gland. Biochimie 81, 527–533 (1999)

    Google Scholar 

  71. G.J. Beckett, J.R. Arthur, Selenium and endocrine systems. J. Endocrinol. 184, 455–465 (2005)

    CAS  PubMed  Google Scholar 

  72. L. Flohé, K.-D. Aumann, P. Steinert P. Role of selenium in the enzymatic reduction of hydroperoxides. Phosphorus Orous Sulfur Silicon. 136-138, 25–42 (1998)

  73. L. Tan, Z.N. Sang, J. Shen, Y.T. Wu, Z.X. Yao, J.X. Zhang, N. Zhao, W.Q. Zhang, Selenium supplementation alleviates autoimmune thyroiditis by regulating expression of TH1/TH2 cytokines. Biomed. Environ. Sci. 26, 920–925 (2013). doi:10.3967/bes2013.022

    CAS  PubMed  Google Scholar 

  74. J. Köhrle, R. Gärtner, Selenium and thyroid. Best Pract. Res. Clin. Endocrinol. Metab. 23(6), 815–827 (2009). doi:10.1016/j.beem.2009.08.002

    PubMed  Google Scholar 

  75. G.J. Beckett, S.E. Beddows, P.C. Morrice, F. Nicol, J.R. Arthur, Inhibition of hepatic deiodination of thyroxine is caused by selenium deficiency in rats. Biochem. J. 248, 443–447 (2003)

    Google Scholar 

  76. J. Chiu-Ugalde, E.K. Wirth, M.O. Klein, R. Sapin, N. Fradejas-Villar, K. Renko, L. Schomburg, J. Köhrle, U. Schweizer, Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells. Antioxid. Redox Signal. 17, 902–913 (2012). doi:10.1089/ars.2011.4055

    CAS  PubMed  Google Scholar 

  77. S.J. Tsai, U. Sen, L. Zhao, W.B. Greenleaf, J. Dasgupta, E. Fiorillo, V. Orrú, N. Bottini, X.S. Chen, Crystal structure of the human lymphoid tyrosine phosphatase catalytic domain: insights into redox regulation. Biochem. 48, 4838–4845 (2009)

    CAS  Google Scholar 

  78. B. Contempré, J.E. Dumont, N. Bebe, C.H. Thilly, A.T. Diplock, J. Vanderpas, Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J. Clin. Endocrinol. Metab. 73, 213–215 (1991)

    PubMed  Google Scholar 

  79. B. Contempré, O. Le Moine, J.E. Dumont, J.F. Denef, M.C. Many, Selenium deficiency and thyroid fibrosis. A key role for macrophages and transforming growth factor beta (TGF-beta). Mol. Cell. Endocrinol. 124, 7–15 (1996)

    PubMed  Google Scholar 

  80. J.B. Vanderpas, B. Contempré, N.L. Duale, H. Deckx, N. Bebe, A.O. Longombé, C.H. Thilly, A.T. Diplock, J.E. Dumont, Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects. Am. J. Clin. Nutr. 57, 271S–275S (1993)

    CAS  PubMed  Google Scholar 

  81. G. Karanikas, M. Schuetz, S. Kontur, H. Duan, S. Kommata, R. Schoen, A. Antoni, K. Kletter, R. Dudczak, M. Willheim, No immunological benefit of selenium in consecutive patients with autoimmune thyroiditis. Thyroid. 18, 7–12 (2008)

    CAS  PubMed  Google Scholar 

  82. W. Bonfig, R. Gärtner, H. Schmidt, Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis. Sci. World J. 10, 990–996 (2010)

    CAS  Google Scholar 

  83. S.A. Eskes, E. Endert, E. Fliers, E. Birnie, B. Hollenbach, L. Schomburg, J. Köhrle, W.M. Wiersinga, Selenite supplementation in euthyroids subjects with thyroid peroxidase antibodies. Clin. Endocrinol. (Oxf) (2013). doi:10.1111/cen.12284

    Google Scholar 

  84. R. Gärtner, B.C. Gasnier, J.W. Dietrich, B. Krebs, M.W. Angstwurm, Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations. J. Clin. Endocrinol. Metab. 87, 1687–1691 (2002)

    PubMed  Google Scholar 

  85. R. Gärtner, B.C. Gasnier, Selenium in the treatment of autoimmune thyroiditis. BioFactors 19, 165–170 (2003)

    PubMed  Google Scholar 

  86. D. Nacamulli, C. Mian, D. Petricca, F. Lazzarotto, S. Barollo, D. Pozza, S. Masiero, D. Faggian, M. Plebani, M.E. Girelli, F. Mantero, C. Betterle, Influence of physiological dietary selenium supplementation on the natural course of autoimmune thyroiditis. Clin. Endocrinol. (Oxf) 73, 535–539 (2010)

    CAS  Google Scholar 

  87. R. Negro, G. Greco, T. Mangieri, A. Pezzarossa, D. Dazzi, H. Hassan, The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J. Clin. Endocrinol. Metab. 92, 1263–1268 (2007)

    CAS  PubMed  Google Scholar 

  88. L.H. Duntas, E. Mantzou, D.A. Koutras, Effects of a six month treatment with selenomethionine in patients with autoimmune thyroiditis. Eur. J. Endocrinol. 148, 389–393 (2003)

    CAS  PubMed  Google Scholar 

  89. E.E. Mazokopakis, J.A. Papadakis, M.G. Papadomanolaki, A.G. Batistakis, T.G. Giannakopoulos, E.E. Protopapadakis, E.S. Ganotakis, Effects of 12 months treatment with L-selenomethionine on serum anti-TPO levels in patients with Hashimoto’s thyroiditis. Thyroid. 17, 609–612 (2007)

    CAS  PubMed  Google Scholar 

  90. O. Turker, K. Kumanlioglu, I. Karapolat, I. Dogan, The Selenium treatment in autoimmune thyroiditis: 9-month follow-up with variable doses. J. Endocrinol. 190, 151–156 (2006)

    CAS  PubMed  Google Scholar 

  91. C. Balázs, The effect of selenium therapy on autoimmune thyroiditis. Orv. Hetil. 149, 1227–1232 (2008)

    PubMed  Google Scholar 

  92. L. Zhu, X. Bai, W.P. Teng, Z.Y. Shan, W.W. Wang, C.L. Fan, H. Wang, H.M. Zhang, Effects of selenium supplementation on antibodies of autoimmune thyroiditis. Zhonghua Yi Xue Za Zhi 92, 2256–2260 (2012)

    CAS  PubMed  Google Scholar 

  93. K.A. Toulis, A.D. Anastasilakis, T.G. Tzellos, D.G. Goulis, D. Kouvelas, Selenium supplementation in the treatment of Hashimoto’s thyroiditis: a systematic review and a meta-analysis. Thyroid 20, 1163–1173 (2010)

    CAS  PubMed  Google Scholar 

  94. E.J. van Zuuren, A.Y. Albusta, Z. Fedorowicz, B. Carter, H. Pijl, Selenium supplementation for Hashimoto’s thyroiditis. Cochrane Database Syst. Rev. 6, CD01:0223 (2013)

  95. L.H. Duntas, Selenium and the thyroid: a close-knit connection. J. Clin. Endocrinol. Metab. 95, 5180–5188 (2010)

    CAS  PubMed  Google Scholar 

  96. D. Nacamulli, D. Petricca, C. Mian, Selenium and autoimmune thyroiditis. J. Endocrinol. Invest. 36(10 Suppl), 8–14 (2013)

    CAS  PubMed  Google Scholar 

  97. J.E. Curran, J.B. Jowett, K.S. Elliott, Y. Gao, K. Gluschenko, J. Wang, D.M. Abel Azim, G. Cai, M.C. Mahaney, A.G. Comuzzie, T.D. Dyer, K.R. Walder, P. Zimmet, J.W. MacCluer, G.R. Collier, A.H. Kissebah, J. Blangero, Genetic variation in selenoprotein S influences inflammatory response. Nat. Genet. 37, 1234–1241 (2005)

    CAS  PubMed  Google Scholar 

  98. L.R. Santos, C. Durães, A. Mendes, H. Prazeres, I. Alvelos, C.S. Moreira, P. Canedo, C. Esteves, C. Neves, D. Carvalho, M.S. Simões, P. Soares, A polymorphism in the promoter region of Selenoprotein S gene (SEPS1) contributes to Hashimoto’s thyroiditis susceptibility. J. Clin. Endocrinol. Metab. 99, jc20133539 (2014)

    Google Scholar 

  99. C. Marcocci, G.J. Kahaly, G.E. Krassas, L. Bartalena, M. Prummel, M. Stahl, M.A. Altea, M. Nardi, S. Pitz, K. Boboridis, P. Sivelli, G. von Arx, M.P. Mourits, L. Baldeschi, W. Bencivelli, W. Wiersinga, European Group on Graves’ Orbitopathy. Selenium and the course of mild Graves’ orbitopathy. N. Engl. J. Med. 364, 1920–1931 (2011)

    CAS  PubMed  Google Scholar 

  100. I. Bülow Pedersen, N. Knudsen, A. Carlé, L. Schomburg, J. Köhrle, T. Jørgensen, L.B. Rasmussen, L. Ovesen, P. Laurberg, Serum selenium is low in newly diagnosed Graves’ disease: a population-based study. Clin. Endocrinol. (Oxf) 79, 584–590 (2013)

    Google Scholar 

  101. A. Drutel, F. Archambeaud, P. Caron, Selenium and the thyroid gland: more good news for clinicians. Clin. Endocrinol. (Oxf) 78, 156–164 (2013). doi:10.111/cen.12066

    Google Scholar 

  102. T. Wertenbruch, H.S. Willenberg, C. Sagert, T.B. Nguyen, M. Bahlo, J. Feldkamp, C. Groeger, D. Hermsen, W.A. Scherbaum, M. Schott, Serum selenium levels in patients with remission and relapse of Graves’ disease. Med. Chem. 3, 281–284 (2007)

    CAS  PubMed  Google Scholar 

  103. G.M. Lehmann, S.E. Feldon, T.J. Smith et al., Immune mechanisms in thyroid eye disease. Thyroid 18, 959–965 (2008)

    PubMed Central  CAS  PubMed  Google Scholar 

  104. N. Xia, S. Zhou, Y. Liang, C. Xiao, H. Shen, H. Pan, H. Deng, N. Wang, Q.Q. Li, CD4+T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves’ ophthalmopathy. Int. J. Mol. Med. 17, 911–916 (2006)

    PubMed  Google Scholar 

  105. L. Kiremidjian-Schumacher, M. Roy, H.I. Wishe, M.W. Cohen, G. Stotzky, Selenium and immune cell functions. I. Effect on lymphocyte proliferation and production of interleukin 1 and interleukin 2. Proc. Soc. Exp. Biol. Med. 193, 136–142 (1990)

    CAS  PubMed  Google Scholar 

  106. Z. Zhang, W. Yu, J.L. Hargrove, P. Greenspan, R.G. Dean, E.W. Taylor, D.K. Hartle, Inhibition of TNF-α induced ICAM-1, VCAM-1 and E-selectin expression by selenium. Atherosclerosis 161, 381–386 (2002)

    CAS  PubMed  Google Scholar 

  107. L.H. Duntas, The evolving role of selenium in the treatment of graves’ disease and ophthalmopathy. J. Thyroid Res. (2012). doi:10.1155/2012/736161

    Google Scholar 

  108. Z. Huang, A.H. Rose, P.R. Hoffmann, The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal. 16 (2012). doi:10.1089/Ars.2011.4145

  109. L.B. Rasmussen, L. Schomburg, J. Köhrle, I.B. Pedersen, B. Hollenbach, A. Hög, S. Ovesen, H. Perrild, P. Laurberg, Selenium status, thyroid volume, and multiple nodule formation in a area with mild iodine deficiency. Eur. J. Endocrinol. 164, 585–590 (2011)

    CAS  PubMed  Google Scholar 

  110. V.F. Brauer, U. Schweizer, J. Köhrle, R. Paschke, Selenium and goiter prevalence in borderline iodine sufficiency. Eur. J. Endocrinol. 155, 807–812 (2006)

    CAS  PubMed  Google Scholar 

  111. H. Derumeaux, P. Valeix, K. Castetbon, M. Bensimon, M.C. Boutron-Ruault, J. Arnaud, S. Hercberg, Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults. Eur. J. Endocrinol. 148, 309–315 (2003)

    CAS  PubMed  Google Scholar 

  112. H. Xue, W. Wang, Y. Li, Z. Shan, Y. Li, X. Teng, Y. Gao, C. Fan, W. Teng, Selenium upregulates CD4 (+) CD25 (+) regulatory T cells in iodine-induced autoimmune thyroiditis model of NOD.H-2(h4) mice. Endocr. J. 57, 595–601 (2010)

    CAS  PubMed  Google Scholar 

  113. C. Balázs, V. Kaczur, Effect of selenium on expression of HLA-DR thyrocytes. Autoimmune Dis. 37, 4635 (2012)

    Google Scholar 

  114. R. Krysiak, B. Okopien, The effect of levothyroxine and selenomethionine on lymphocyte and monocyte cytokine release in women with Hashimoto’s thyroiditis. J. Clin. Endocrinol. Metab. 96, 2206–2215 (2011). doi:10.1210/jc.2010-2986

    CAS  PubMed  Google Scholar 

  115. B.A. Carlson, M.H. Yoo, R.K. Shrimali, R. Irons, V.N. Gladyshev, D.L. Hatfield, J.M. Park, Role of selenium-containing proteins in T-cell and macrophage function. Proc. Nutr. Soc. 69, 300–331 (2010)

    PubMed Central  CAS  PubMed  Google Scholar 

  116. R.K. Shrimali, R.D. Irons, B.A. Carlson, Y. Sano, V.N. Gladyshev, J.M. Park, D.L. Hatfield, Selenoproteins mediate T cell immunity through an antioxidant mechanism. J. Biol. Chem. 283, 20181–20185 (2008)

    PubMed Central  CAS  PubMed  Google Scholar 

  117. A. Dumitrescu, S. Refetoff, Inherited defects of thyroid hormone metabolism. Ann. Endocrinol. (Paris) 72, 95–98 (2011)

    CAS  Google Scholar 

  118. A.M. Dumitrescu, X.H. Liao, M.S. Abdullah, J. Lado-Abeal, F.A. Majed, L.C. Moeller, G. Boran, L. Schomburg, R.E. Weiss, S. Refetoff, Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. Nat. Genet. 37, 1247–1252 (2005)

    CAS  PubMed  Google Scholar 

  119. M.F. Azevedo, G.B. Barra, L.A. Naves, L.F. Ribeiro Velasco, P. Godoy Garcia Castro, L.C. de Castro, A.A. Amato, A. Miniard, D. Driscoll, L. Schomburg, F. de Assis Rocha Neves, Selenoprotein-related disease in a young girl caused by nonsense mutations in the SBP2 gene. J. Clin. Endocrinol. Metab. 95, 4066–4071 (2010). doi:10.1210/jc.2009-2611

    CAS  PubMed  Google Scholar 

  120. E. Shoenmakers, M. Agostini, C. Mitchell, N. Schoenmakers, L. Papp, O. Rajanayagam, R. Padidela, L. Ceron-Gutierrez, R. Döffinger, C. Provost, J. Luan, S. Montano, J. Lu, M. Castanet, N. Clemons, M. Groeneveld, P. Castets, M. Karbaschi, S. Aitken, A. Dixon, J. Williams, I. Campi, M. Blount, H. Burton, F. Muntoni, D. O’Donovan, A. Dean, A. Warren, C. Brierley, D. Baguley, P. Guicheney, R. Fitzgerald, A. Coles, H. Gaston, P. Todd, A. Holmgren, K.K. Khanna, M. Cooke, R. Semple, D. Halsall, N. Wareham, J. Schwabe, L. Grasso, P. Beck-Peccoz, A. Ogunko, M. Dattani, M. Gurnell, K. Chatterjee, Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. J. Clin. Invest. 120, 4220–4235 (2010)

    Google Scholar 

  121. C. Di Cosmo, N. McLellan, X.H. Liao, K.K. Khanna, R.E. Weiss, L. Papp, S. Refetoff, Clinical and molecular characterization of nine selenocysteine insertion sequence-binding protein 2 (SBP2) gene mutation (R128X). J. Clin. Endocrinol. Metab. 94, 4003–4009 (2009)

    PubMed Central  PubMed  Google Scholar 

  122. L. Schomburg, A.M. Dumitrescu, X.H. Liao, B. Bin-Abbas, J. Hoeflich, J. Köhrle, S. Refetoff, Selenium supplementation fails to correct the selenoprotein synthesis defect in subjects with SBP2 gene mutations. Thyroid 19, 277–281 (2009)

    PubMed Central  CAS  PubMed  Google Scholar 

  123. J. Bleys, A. Navas-Acien, E. Guallar, Serum selenium and diabetes in U.S adults. Diabetes Care 30, 829–834 (2007)

    CAS  PubMed  Google Scholar 

  124. M. Laclaustra, A. Navas-Acien, S. Stranges, J.M. Ordovas, E. Guallar, Serum selenium concentrations and diabetes in U.S. adults: National Health and Nutrition Examination Survey (NHANES) 2003–2004. Environ. Health Perspect. 117, 1409–1413 (2009). doi:10.1289/ehp.0900704

    PubMed Central  CAS  PubMed  Google Scholar 

  125. S. Stranges, J.R. Marshall, R. Natarajan, R.P. Donahue, M. Trevisan, G.F. Combs, F.P. Cappuccio, A. Ceriello, M.E. Reid, Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann. Int. Med. 147, 217–223 (2007)

    PubMed  Google Scholar 

  126. S.M. Lippman, E.A. Klein, P.J. Goodman, M.S. Lucia, I.M. Thompson, L.G. Ford, H.L. Parnes, L.M. Minasian, J.M. Gaziano, J.A. Hartline, J.K. Parsons, J.D. Bearden 3rd, E.D. Crawford, G.E. Goodman, J. Claudio, E. Winquist, E.D. Cook, D.D. Karp, P. Walther, M.M. Lieber, A.R. Kristal, A.K. Darke, K.B. Arnold, P.A. Ganz, R.M. Santella, D. Albanes, P.R. Taylor, J.L. Probstfield, T.J. Jagpal, J.J. Crowley, F.L. Meyskens Jr, L.H. Baker and C.A. Coltman Jr., Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 301, 39–51 (2009)

  127. J. Arnaud, T.N. Akbaraly, I. Hininger, A.M. Roussel, C. Berr, Factors associated with longitudinal plasma selenium decline in the elderly: the EVA study. J. Nutr. Biochem. 18, 482–487 (2007)

    PubMed Central  CAS  PubMed  Google Scholar 

  128. N.T. Akbaraly, J. Arnaud, I. Favier Hininger, V. Gourlet, A.M. Roussel, C. Berr, Selenium and mortality in the elderly: results from the EVA study. Clin. Chem. 51, 2117–2123 (2005)

    CAS  PubMed  Google Scholar 

  129. S. Mao, A. Zhang, S. Huang, Selenium supplementation and the risk of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Endocrine (2014) Epub ahead of print

  130. M.P. Rayman, G. Blundell-Pound, R. Pastor-Barriuso, E. Guallar, H. Steinbrenner, S. Stranges, A randomized trial of selenium supplementation and risk of type-2 diabetes, as assessed by plasma adiponectin. PLoS One 7, e45269 (2012). doi:10.1371/journal.pone.0045269

    PubMed Central  CAS  PubMed  Google Scholar 

  131. J.N. Hellwege, N.D. Palmer, J.T. Ziegler, C.D. Langefeld, C. Lorenzo, J.M. Norris, T. Takamura, D.W. Bowden, Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics. Gene 534, 33–39 (2014)

    CAS  PubMed  Google Scholar 

  132. B.J. Ko, S.M. Kim, K.H. Park, H.S. Park, C.S. Mantzoros, Levels of circulating selenoprotein P, fibroblast growth factor (FGF) 21 and FGF23 in relation to the metabolic syndrome in young children. Int. J. Obes. (Lond) 18 (2014). doi:10.1038/ijo.2014.45

  133. H. Misu, K. Ishikura, S. Kurita, Y. Takeshita, T. Ota, Y. Saito, K. Takahashi, S. Kaneko, T. Takamura, Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes. PLoS One 7, e34952 (2012). doi:10.1371/journal.pone.0034952

    PubMed Central  CAS  PubMed  Google Scholar 

  134. H. Steinbrenner, Interference of selenium and selenoproteins with the insulin-regulated carbohydrate and lipid metabolism. Free Radic. Biol. Med. 65, 1538–1547 (2013). doi:10.1016/j.freeradbiomed.2013.07.016

    CAS  PubMed  Google Scholar 

  135. C. Kornhauser, J.R. Garcia-Ramirez, K. Wrobel, E.L. Pérez-Luque, M.E. Garay-Sevilla, K. Wrobel, Serum selenium and glutathione peroxidase concentrations in type 2 diabetes mellitus patients. Prim. Care Diabetes. 2, 81–85 (2008)

    PubMed  Google Scholar 

  136. M. Navarro-Alarcón, H. López-G de la Serrana, V. Pérez-Valero, C. López-Martínez, Serum and urine selenium concentrations as indicators of body status in patients with diabetes mellitus. Sci. Total Environ. 228, 79–88 (1999)

    PubMed  Google Scholar 

  137. H. Steinbrenner, B. Speckmann, A. Pinto, H. Sies, High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism. J. Clin. Biochem. Nutr. 48, 40–45 (2011)

    PubMed Central  CAS  PubMed  Google Scholar 

  138. A. Pinto, D.T. Juniper, M. Sanil, L. Morgan, L. Clark, H. Sies, M.P. Rayman, H. Steinbrenner, Supranutritional selenium induces alterations in molecular targets related to energy metabolism in skeletal muscle and visceral adipose tissue of pigs. J. Inorg. Biochem. 114, 47–54 (2012). doi:10.1016/j.jinorgbio.2012.04.011

    CAS  PubMed  Google Scholar 

  139. X. Wang, W. Zhang, H. Chen, N. Liao, Z. Wang, X. Zhang, C. Hai, High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS. Toxicol. Lett. 224, 16–23 (2014). doi:10.1016/j.toxlet.2013.10.005

    CAS  PubMed  Google Scholar 

  140. A.S. Mueller, J. Pallauf, Compendium of the antidiabetic effects of supranutritional selenate doses. In vivo and in vitro investigations with type II diabetic db/db mice. J. Nutr. Biochem. 17, 548–560 (2006)

    CAS  PubMed  Google Scholar 

  141. C. Wang, S. Yang, N. Zhang, Y. Mu, H. Ren, Y. Wang, K. Li, Long-term supranutritional supplementation with selenate decreases hyperglycemia and promotes fatty liver degeneration by inducing hyperinsulinemia in diabetic db/db mice. PLoS One 9, e101315 (2014). doi:10.1371/journal.pone.0101315

    PubMed Central  PubMed  Google Scholar 

  142. C.R. Rocourt, W.H. Cheng, Selenium supranutrition: are the potential benefits of chemoprevention outweighed by the promotion of diabetes and insulin resistance? Nutrients 5, 1349–1365 (2013)

    PubMed Central  CAS  PubMed  Google Scholar 

  143. M.P. Rayman, S. Stranges, B.A. Griffin, R. Pastor-Barriuso, E. Guallar, Effect of supplementation with high-selenium yeast on plasma lipids: a randomized trial. Ann. Int. Med. 154, 656–665 (2011). doi:10.7326/0003-4819-154-10-201105170-00005

    PubMed  Google Scholar 

  144. M. Laclaustra, S. Stranges, A. Navas-Acien, J.M. Ordovas, E. Guallar, Serum selenium and serum lipids in US adults: National Health and Nutrition Examination Survey (NHANES) 2003–2004. Atherosclerosis. 210, 643–648 (2010). doi:10.1016/j.atherosclerosis

    PubMed Central  CAS  PubMed  Google Scholar 

  145. M.P. Rayman, S. Stranges, Epidemiology of selenium and type 2 diabetes: can we make sense of it? Free Radic. Biol. Med. 65, 1557–1564 (2013)

    CAS  PubMed  Google Scholar 

  146. M.P. Rayman, Selenium and human health. Lancet 379, 1256–1268 (2012)

    CAS  PubMed  Google Scholar 

  147. K. Rees, L. Hartley, C. Day, N. Flowers, A. Clarke, S. Stranges, Selenium supplementation for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 1, CD009671 (2013). doi:10.1002/14651858.CD009671.pub2

    PubMed  Google Scholar 

  148. L. Flohé, Selenium in mammalian spermiogenesis. Biol. Chem. 388, 987–995 (2007)

    PubMed  Google Scholar 

  149. G.E. Olson, V.P. Winfrey, S.K. Nagdas, K.E. Hill, R.F. Burk, Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J. Biol. Chem. 282, 12290–12297 (2007)

    CAS  PubMed  Google Scholar 

  150. D. Behne, H. Weiler, A. Kyriakopoulos, Effects of selenium deficiency on testicular morphology and function in rats. J. Reprod. Fertil. 106, 291–297 (1996)

    CAS  PubMed  Google Scholar 

  151. N.B. Oldereid, Y. Thomassen, K. Purvis, Selenium in human male reproductive organs. Hum. Reprod. 13, 2172–2176 (1998)

    CAS  PubMed  Google Scholar 

  152. C. Foresta, L. Flohe, A. Garolla, A. Roveri, F. Ursini, M. Maiorino, Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol. Reprod. 67, 967–971 (2002)

    CAS  PubMed  Google Scholar 

  153. K. Nayernia, M. Diaconu, G. Aumüller, G. Wennemuth, I. Schwandt, K. Kleene, H. Kuehn, W. Engel, Phospholipid hydroperoxide glutathione peroxidase: expression pattern during testicular development in mouse and evolutionary conservation in spermatozoa. Mol. Reprod. Dev. 67, 458–464 (2004)

    CAS  PubMed  Google Scholar 

  154. F. Ursini, S. Heim, M. Kiess, M. Maiorino, A. Roveri, J. Wissing, L. Flohe, Dual function of the selenoprotein PHGPX during sperm maturation. Science 285, 1393–1396 (1999)

    CAS  PubMed  Google Scholar 

  155. M. Maiorino, J.B. Wissing, R. Brigelius-Flohé, F. Calabrese, A. Roveri, P. Steinert, F. Ursini, L. Flohé, Testosterone mediates expression of the selenoprotein PHGPX by induction of spermatogenesis and not by direct transcriptional gene activation. FASEB J. 12, 1359–1370 (1998)

    CAS  PubMed  Google Scholar 

  156. M. Michaelis, O. Gralla, T. Behrends, M. Scharpf, T. Endermann, E. Rijntjes, N. Pietschmann, B. Hollenbach, L. Schomburg, Selenoprotein P in seminal fluid is a novel biomarker of sperm quality. Biochem. Biophys. Res. Commun. 443, 905–910 (2014). doi:10.1016/j.bbrc.2013.12.06

    CAS  PubMed  Google Scholar 

  157. M. Mirone, E. Giannetta, A.M. Isidori, Selenium and reproductive function. A systematic review. J. Endocrinol. Invest. 36, 28–36 (2013)

    CAS  PubMed  Google Scholar 

  158. R. Scott, A. MacPherson, R.W. Yates, B. Hussain, J. Dixon, The effect of oral selenium supplementation on human sperm motility. Br. J. Urol. 82, 76–80 (1998)

    CAS  PubMed  Google Scholar 

  159. S. Türk, R. Mändar, R. Mahlapuu, A. Viitak, M. Punab, T. Kullisaar, Male infertility: decreased levels of selenium, zinc and antioxidants. J. Trace Elem. Med Biol. 28, 179–185 (2014). doi:10.1016/j.jtemb.2013.12.005

    PubMed  Google Scholar 

  160. A. Duncan, D. Talwar, D.C. McMillan, F. Stefanowicz, D.S. O’Reilly, Quantitative data on the magnitude of the systemic inflammatory response and its effect on micronutrient status based on plasma measurements. Am. J. Clin. Nutr. 95, 64–71 (2012). doi:10.3945/ajcn.111.023812

    CAS  PubMed  Google Scholar 

  161. M. Harthill, Micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol. Trace Elem. Res. 143, 1325–1336 (2011). doi:10.1007/s12011-011-8977-1

    CAS  PubMed  Google Scholar 

  162. O.A. Levander, M.A. Beck, Selenium and viral virulence. Brit. Med. Bull. 55, 5528–5533 (1999)

    Google Scholar 

  163. M.A. Beck, Q. Shi, V.C. Morris, O.A. Levander, Rapid genomic evolution of a non-virulent coxsackievirus B3 in selenium-deficient mice results in selection of identical virulent isolates. Nat. Med. 1, 433–436 (1995)

    CAS  PubMed  Google Scholar 

  164. M.A. Beck, R.S. Esworthy, Y.S. Ho, F.F. Chu, Glutathione peroxidase protects mice from viral-induced myocarditis. FASEB J. 12, 1143–1149 (1998)

    CAS  PubMed  Google Scholar 

  165. L. Yu, L. Sun, Y. Nan, L.Y. Zhu, Protection from H1N1 influenza virus infections in mice by supplementation with selenium: a comparison with selenium-deficient mice. Biol. Trace Elem. Res. 141, 254–261 (2011)

    CAS  PubMed  Google Scholar 

  166. S. Verma, Y. Molina, Y.Y. Lo, B. Cropp, C. Nakano, R. Yanagihara, V.R. Nerurkar, In vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity. Virol. J. 5, 66 (2008). doi:10.1186/1743-422X-5-66

    PubMed Central  PubMed  Google Scholar 

  167. I. Jaspers, W. Zhang, L.E. Brighton, J.L. Carson, M. Styblo, M.A. Beck, Selenium deficiency alters epithelial cell morphology and responses to influenza. Free Radic. Biol. Med. 42, 1826–1837 (2007)

    PubMed Central  CAS  PubMed  Google Scholar 

  168. S.J. Allsup, A. Shenkin, M.A. Gosney, S. Taylor, W. Taylor, M. Hammond, M.C. Zambon, Can a short period of micronutrient supplementation in older institutionalized people improve response to influenza vaccine? A randomized, controlled trial. J. Am. Geriatr. Soc. 52, 20–24 (2004)

    PubMed  Google Scholar 

  169. C.S. Broome, F. McArdle, J.A. Kyle, F. Andrews, N.M. Lowe, C.A. Hart, J.R. Arthur, M.J. Jackson, An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status. Am. J. Clin. Nutr. 80, 154–162 (2004)

    CAS  PubMed  Google Scholar 

  170. C.A. Stone, K. Kawai, R. Kupka, W.W. Fawzi, Role of selenium in HIV infection. Nutr. Rev. 68, 671–681 (2010). doi:10.1111/j.1753-4887.2010.00337.x

    PubMed Central  PubMed  Google Scholar 

  171. M.C. Rousseau, C. Molines, J. Moreau, J. Delmont, Influence of highly active antiretroviral therapy on micronutrient profiles in HIV-infected patients. Ann. Nutr. Metab. 44, 212–216 (2000)

    CAS  PubMed  Google Scholar 

  172. G. Shor-Posner, M.J. Miguez, L.M. Pineda, A. Rodriguez, P. Ruiz, G. Castillo, X. Burbano, R. Lecusay, M. Baum, 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. 29, 169–173 (2002)

    CAS  PubMed  Google Scholar 

  173. X. Forceville, D. Vitoux, Selenium systemic immune response syndrome, sepsis and outcome in critically ill patients. Crit. Care Med. 26, 1536–1544 (1998)

    CAS  PubMed  Google Scholar 

  174. C. Sanmartin, D. Plano, M. Font, J.A. Palop, Selenium and clinical trials: new therapeutic evidence for multiple diseases. Curr. Med. Chem. 18, 4635–4650 (2011)

    CAS  PubMed  Google Scholar 

  175. J. Bleys, A. Navas-Acien, E. Guallar, Serum selenium levels and all-cause, cancer and cardiovascular mortality among US adults. Arch. Int. Med. 168, 404–410 (2008)

    CAS  Google Scholar 

  176. W. Alhazzani, J. Jacobi, A. Sindi, C. Hartog, K. Reinhart, S. Kokkoris, H. Gerlach, P. Andrews, T. Drabek, W. Manzanares, D.J. Cook, R.Z. Jaeschke, The effect of selenium therapy on mortality in patients with sepsis syndrome: a systematic review and meta-analysis of randomized controlled trials. Crit. Care Med. 41, 1555–1564 (2013)

    CAS  PubMed  Google Scholar 

  177. T.S. Huang, Y.C. Shyu, H.Y. Chen, L.M. Lin, C.Y. Lo, S.S. Yuan, P.J. Chen, Effect of parenteral selenium supplementation in critically ill patients: a systematic review and meta-analysis. PLoS One 8, e54431 (2013). doi:10.1371/journal.pone.0054431

    PubMed Central  CAS  PubMed  Google Scholar 

  178. F. Landucci, P. Mancinelli, A.R. De Gaudio, G. Virgili, Selenium supplementation in critically ill patients: a systematic review and meta-analysis. J. Crit. Care 29, 150–156 (2014). doi:10.1016/j.jcrc.2013.08.017

    CAS  PubMed  Google Scholar 

  179. Z. Kong, F. Wang, S. Ji, X. Deng, Z. Xia, Selenium supplementation for sepsis: a meta-analysis of randomized controlled trials. Am. J. Emerg. Med. 31, 1170–1175 (2013). doi:10.1016/j.ajem.2013.04.020

    PubMed  Google Scholar 

  180. G. Hardy, I. Hardy, W. Manzanares, Selenium supplementation in the critically ill. Nutr. Clin. Pract. 27, 21–33 (2012). doi:10.1177/0884533611434116

    PubMed  Google Scholar 

  181. H.A. Meyer, T. Endermann, C. Stephan, M. Stoedter, T. Behrends, I. Wolff, K. Jung, L. Schomburg, Selenoprotein P status correlates to cancer-specific mortality in renal cancer patients. PLoS One 7, e46644 (2012). doi:10.1371/journal.pone.0046644

    PubMed Central  CAS  PubMed  Google Scholar 

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Duntas, L.H., Benvenga, S. Selenium: an element for life. Endocrine 48, 756–775 (2015). https://doi.org/10.1007/s12020-014-0477-6

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