title: Biomarkers of selenium status.
abstract: The essential trace element, selenium (Se), has multiple biological activities, which depend on the level of Se intake. Relatively low Se intakes determine the expression of selenoenzymes in which it serves as an essential constituent. Higher intakes have been shown to have anti-tumorigenic potential; and very high Se intakes can produce adverse effects. This hierarchy of biological activities calls for biomarkers informative at different levels of Se exposure. Some Se-biomarkers, such as the selenoproteins and particularly GPX3 and SEPP1, provide information about function directly and are of value in identifying nutritional Se deficiency and tracking responses of deficient individuals to Se-treatment. They are useful under conditions of Se intake within the range of regulated selenoprotein expression, e.g., for humans <55 μg/day and for animals <20 μg/kg diet. Other Se-biomarkers provide information indirectly through inferences based on Se levels of foods, tissues, urine or feces. They can indicate the likelihood of deficiency or adverse effects, but they do not provide direct evidence of either condition. Their value is in providing information about Se status over a wide range of Se intake, particularly from food forms. There is need for additional Se biomarkers particularly for assessing Se status in non-deficient individuals for whom the prospects of cancer risk reduction and adverse effects risk are the primary health considerations. This would include determining whether supranutritional intakes of Se may be required for maximal selenoprotein expression in immune surveillance cells. It would also include developing methods to determine low molecular weight Se-metabolites, i.e., selenoamino acids and methylated Se-metabolites, which to date have not been detectable in biological specimens. Recent analytical advances using tandem liquid chromatography-mass spectrometry suggest prospects for detecting these metabolites.
authors.affiliation: Grand Forks Human Nutrition Research Center, USDA-ARS, 2420 2nd Ave N Grand Forks, ND 58202, USA. gerald.combs@ars.usda.gov.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Combs
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D009752:Nutritional Status; D012643:Selenium / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood*; D051140:Selenoproteins / Q000097:blood
chemical_list: D015415:Biomarkers; D051140:Selenoproteins; D005979:Glutathione Peroxidase; D012643:Selenium
references.citation: J Epidemiol Community Health. 1983 Sep;37(3):213-7
references.pmid: 6619720
references.citation: Biofactors. 2001;14(1-4):153-9
references.pmid: 11568452
references.citation: J Trace Elem Electrolytes Health Dis. 1989 Jun;3(2):77-87
references.pmid: 2535327
references.citation: Biochem J. 2004 Aug 1;381(Pt 3):841-6
references.pmid: 15117283
references.citation: J Nutr. 2011 Apr 1;141(4):708-17
references.pmid: 21289202
references.citation: Diabetes Care. 2007 Apr;30(4):829-34
references.pmid: 17392543
references.citation: J Nutr. 1996 Jan;126(1):138-45
references.pmid: 8558294
references.citation: Free Radic Biol Med. 2013 Dec;65:1538-1547
references.pmid: 23872396
references.citation: Am J Clin Nutr. 2010 Sep;92(3):525-31
references.pmid: 20573787
references.citation: J Agric Food Chem. 2007 Jan 24;55(2):516-22
references.pmid: 17227087
references.citation: Am J Clin Nutr. 1982 Jul;36(1):24-31
references.pmid: 7091033
references.citation: Pharmacol Ther. 1998 Sep;79(3):179-92
references.pmid: 9776375
references.citation: JAMA. 1996 Dec 25;276(24):1957-63
references.pmid: 8971064
references.citation: Br J Nutr. 2001 May;85(5):517-47
references.pmid: 11348568
references.citation: J Trace Elem Electrolytes Health Dis. 1989 Sep;3(3):123-30
references.pmid: 2535331
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8852-7
references.pmid: 15184668
references.citation: Am J Clin Nutr. 1999 Nov;70(5):896-903
references.pmid: 10539752
references.citation: Am J Clin Nutr. 2010 Apr;91(4):923-31
references.pmid: 20181815
references.citation: J Nutr. 2012 Aug;142(8):1410-6
references.pmid: 22739382
references.citation: Br J Nutr. 2008 Jun;99(6):1190-8
references.pmid: 18062829
references.citation: Am J Vet Res. 2005 Dec;66(12):2142-8
references.pmid: 16379660
references.citation: Biol Trace Elem Res. 2009 Dec;131(3):229-44
references.pmid: 19387567
references.citation: Crit Rev Food Sci Nutr. 2013;53(10):1077-96
references.pmid: 23952089
references.citation: Epidemiology. 1996 Jul;7(4):384-90
references.pmid: 8793364
references.citation: Clin Chim Acta. 2002 Feb;316(1-2):137-46
references.pmid: 11750284
references.citation: Experientia. 1983 Mar 15;39(3):293-4
references.pmid: 6825797
references.citation: Carcinogenesis. 2008 May;29(5):1005-12
references.pmid: 18310093
references.citation: Mol Biol Evol. 2005 Mar;22(3):383-6
references.pmid: 15483329
references.citation: Biol Trace Elem Res. 2010 Jun;134(3):235-51
references.pmid: 20306235
references.citation: Pediatr Res. 2002 Jan;51(1):71-5
references.pmid: 11756642
references.citation: Biochem Pharmacol. 1986 Aug 15;35(16):2763-6
references.pmid: 3741468
references.citation: Antioxid Redox Signal. 2011 Jun 15;14(12):2327-36
references.pmid: 21194350
references.citation: J Nutr Biochem. 2013 May;24(5):776-80
references.pmid: 22841391
references.citation: Am J Med. 2010 Aug;123(8):765-8
references.pmid: 20670733
references.citation: Lancet. 1982 Jun 5;1(8284):1312-3
references.pmid: 6123056
references.citation: Nutr J. 2011 Jul 18;10:75
references.pmid: 21767397
references.citation: Biochim Biophys Acta. 2007 Jul;1770(7):1053-61
references.pmid: 17451884
references.citation: Biol Trace Elem Res. 1988 Jan-Apr;15:125-38
references.pmid: 2484510
references.citation: Med J Aust. 1966 Mar 26;1(13):525-8
references.pmid: 5908595
references.citation: Comp Biochem Physiol A Comp Physiol. 1990;95(2):297-301
references.pmid: 1968824
references.citation: Free Radic Biol Med. 2013 Dec;65:1557-1564
references.pmid: 23597503
references.citation: Biol Trace Elem Res. 1997 Feb;56(2):215-24
references.pmid: 9164666
references.citation: J Clin Lab Anal. 2016 Mar;30(2):114-22
references.pmid: 25545464
references.citation: Antioxid Redox Signal. 2012 Apr 1;16(7):705-43
references.pmid: 21955027
references.citation: Virchows Arch A Pathol Anat Histopathol. 1983;401(1):1-15
references.pmid: 6412443
references.citation: Toxicol Appl Pharmacol. 1993 Jan;118(1):65-72
references.pmid: 8430425
references.citation: BJU Int. 2003 May;91(7):608-12
references.pmid: 12699469
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1441-7
references.pmid: 19345254
references.citation: Am J Clin Nutr. 1993 Feb;57(2 Suppl):271S-275S
references.pmid: 8427203
references.citation: J Biol Chem. 1997 Nov 14;272(46):29364-71
references.pmid: 9361018
references.citation: Am J Clin Nutr. 1986 Nov;44(5):659-63
references.pmid: 3766450
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 15;767(2):301-12
references.pmid: 11885859
references.citation: J Cell Biochem. 2012 Jan;113(1):61-9
references.pmid: 21866568
references.citation: Toxicol Lett. 1985 Jan;24(1):7-14
references.pmid: 3975931
references.citation: Curr Opin Endocrinol Diabetes Obes. 2013 Oct;20(5):441-8
references.pmid: 23974773
references.citation: J Inorg Biochem. 1987 Aug;30(4):299-308
references.pmid: 3668526
references.citation: Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):718-26
references.pmid: 18827575
references.citation: Mol Microbiol. 2010 Jan;75(1):149-60
references.pmid: 19919669
references.citation: Free Radic Biol Med. 2012 Apr 15;52(8):1335-42
references.pmid: 22342560
references.citation: Toxicol Lett. 2014 Jan 3;224(1):16-23
references.pmid: 24140496
references.citation: Toxicol Lett. 1987 Apr;36(2):167-72
references.pmid: 3576647
references.citation: FASEB J. 2011 Jul;25(7):2492-9
references.pmid: 21493887
references.citation: Antioxid Redox Signal. 2009 Nov;11(11):2631-40
references.pmid: 19453253
references.citation: J Trace Elem Med Biol. 2008;22(1):24-32
references.pmid: 18319137
references.citation: JAMA. 2009 Jan 7;301(1):39-51
references.pmid: 19066370
references.citation: J Nutr Biochem. 2013 Dec;24(12):2023-30
references.pmid: 24139672
references.citation: Occup Med (Chic Ill). 1947 May;3(5):439-56
references.pmid: 20255477
references.citation: Cancer Res. 1991 Jan 15;51(2):595-600
references.pmid: 1824684
references.citation: Science. 1973 Feb 9;179(4073):588-90
references.pmid: 4686466
references.citation: Arch Biochem Biophys. 1996 Jan 1;325(1):124-8
references.pmid: 8554336
references.citation: Biol Trace Elem Res. 2012 Dec;149(3):377-81
references.pmid: 22562596
references.citation: Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):537-41
references.pmid: 8421687
references.citation: Science. 2003 May 30;300(5624):1439-43
references.pmid: 12775843
references.citation: Am J Clin Nutr. 1983 Jun;37(6):887-97
references.pmid: 6846235
references.citation: Proc Soc Exp Biol Med. 1957 Aug-Sep;95(4):621-5
references.pmid: 13465748
references.citation: Biol Trace Elem Res. 2000 Feb;73(2):113-25
references.pmid: 11049204
references.citation: Environ Mol Mutagen. 2009 Jul;50(6):489-501
references.pmid: 19365873
references.citation: J Biol Chem. 1987 Sep 25;262(27):13372-5
references.pmid: 3654615
references.citation: Biochem Biophys Res Commun. 2009 Sep 11;387(1):158-63
references.pmid: 19576170
references.citation: Cancer Res. 2000 Nov 15;60(22):6381-3
references.pmid: 11103801
references.citation: J Am Diet Assoc. 1987 Mar;87(3):285-99
references.pmid: 3819246
references.citation: Biochem J. 2010 Jul 1;429(1):43-51
references.pmid: 20370716
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):15932-6
references.pmid: 12441402
references.citation: Proc Soc Exp Biol Med. 1957 Aug-Sep;95(4):617-20
references.pmid: 13465747
references.citation: PLoS One. 2014 Jan 20;9(1):e84972
references.pmid: 24465457
references.citation: Biol Trace Elem Res. 1991 Jun;29(3):289-94
references.pmid: 1726411
references.citation: FASEB J. 2007 Oct;21(12):3063-74
references.pmid: 17536041
references.citation: EMBO Rep. 2004 May;5(5):538-43
references.pmid: 15105824
references.citation: Biol Trace Elem Res. 1997 Feb;56(2):203-13
references.pmid: 9164665
references.citation: Int J Cancer. 2012 Sep 15;131(6):1260-6
references.pmid: 22095442
references.citation: Am J Clin Nutr. 1983 May;37(5):872-81
references.pmid: 6846228
references.citation: Cancer Res. 1990 Feb 15;50(4):1206-11
references.pmid: 2105164
references.citation: J Agric Food Chem. 2007 Sep 5;55(18):7337-41
references.pmid: 17685630
references.citation: Am J Clin Nutr. 1995 Dec;62(6 Suppl):1424S-1426S
references.pmid: 7495242
references.citation: Annu Rev Nutr. 1990;10:451-74
references.pmid: 2200474
references.citation: Gig Tr Prof Zabol. 1969 Nov;13(11):45-6
references.pmid: 5378721
references.citation: Br J Nutr. 2012 May;107(10):1514-25
references.pmid: 21936966
references.citation: Am J Clin Nutr. 2004 Jul;80(1):154-62
references.pmid: 15213043
references.citation: Arch Biochem Biophys. 1987 Oct;258(1):1-6
references.pmid: 3662536
references.citation: Adv Nutr. 2011 Mar;2(2):138-50
references.pmid: 22332043
references.citation: Br J Nutr. 1993 Mar;69(2):577-88
references.pmid: 8490010
references.citation: Carcinogenesis. 2014 Oct;35(10):2308-13
references.pmid: 25053624
references.citation: J Natl Cancer Inst. 1993 Sep 15;85(18):1483-92
references.pmid: 8360931
references.citation: Biochem Biophys Res Commun. 1976 Aug 23;71(4):952-8
references.pmid: 971321
references.citation: J Nutr Biochem. 2003 Nov;14(11):637-47
references.pmid: 14629895
references.citation: Chin Med J (Engl). 1979 Jul;92(7):471-6
references.pmid: 114371
references.citation: Nutrition. 1999 Mar;15(3):255
references.pmid: 10408880
references.citation: Cancer Res. 1994 Apr 1;54(7 Suppl):2029s-2031s
references.pmid: 8137333
references.citation: Br J Nutr. 1997 Apr;77(4):551-63
references.pmid: 9155505
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1520-32
references.pmid: 19344749
references.citation: Anal Bioanal Chem. 2005 Oct;383(3):509-15
references.pmid: 16158304
references.citation: J Nutr. 1989 Sep;119(9):1318-26
references.pmid: 2795246
references.citation: J Nutr. 1998 Nov;128(11):1845-54
references.pmid: 9808633
references.citation: J Biol Chem. 2014 Nov 7;289(45):31576-90
references.pmid: 25258323
references.citation: J Nutr. 1989 Jul;119(7):1010-2
references.pmid: 2754506
references.citation: Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1006-11
references.pmid: 8577704
references.citation: Ann Nutr Metab. 2012;60(2):157-68
references.pmid: 22517293
references.citation: Chem Res Toxicol. 2009 Nov;22(11):1795-801
references.pmid: 19715347
references.citation: Biol Trace Elem Res. 2011 Feb;139(2):188-96
references.pmid: 20229173
references.citation: Hepatology. 2008 Dec;48(6):1998-2006
references.pmid: 18972406
references.citation: J Nutr. 1985 Apr;115(4):454-9
references.pmid: 3981263
references.citation: Ann Intern Med. 2007 Aug 21;147(4):217-23
references.pmid: 17620655
references.citation: J Trace Elem Med Biol. 1995 Jul;9(2):65-73
references.pmid: 8825978
references.citation: Biol Trace Elem Res. 1997 Jan;56(1):117-24
references.pmid: 9152515
references.citation: Cancer Res. 2003 Jun 15;63(12):3347-51
references.pmid: 12810669
references.citation: Am J Clin Nutr. 1990 Dec;52(6):1087-93
references.pmid: 2239787
references.citation: Genome Biol. 2006;7(10):R94
references.pmid: 17054778
references.citation: Am J Clin Nutr. 2005 Apr;81(4):829-34
references.pmid: 15817859
references.citation: Biol Chem. 2007 Oct;388(10):1043-51
references.pmid: 17937618
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):804-10
references.pmid: 16614127