Editing Selenium (section)

==Biological role==
{{Main|Selenium in biology}}
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Although it is toxic in large doses, selenium is an essential [[micronutrient]] for animals. In plants, it occurs as a bystander mineral,<ref>{{Cite book |last=Atroshi |first=Faik |url=https://books.google.com/books?id=UCShDwAAQBAJ&dq=info:AK393JUK2tEJ:scholar.google.com/&pg=PR11 |title=Pharmacology and Nutritional Intervention in the Treatment of Disease |date=2014-05-28 |publisher=BoD – Books on Demand |isbn=978-953-51-1383-6 |language=en}}</ref> sometimes in toxic proportions in [[forage]] (some plants may accumulate selenium as a defense against being eaten by animals,<ref>{{Cite journal |last1=Freeman |first1=John L. |last2=Lindblom |first2=Stormy Dawn |last3=Quinn |first3=Colin F. |last4=Fakra |first4=Sirine |last5=Marcus |first5=Matthew A. |last6=Pilon-Smits |first6=Elizabeth A. H. |date=2007 |title=Selenium accumulation protects plants from herbivory by Orthoptera via toxicity and deterrence |journal=The New Phytologist |volume=175 |issue=3 |pages=490–500 |doi=10.1111/j.1469-8137.2007.02119.x |issn=0028-646X |pmid=17635224|s2cid=2330947 |doi-access=free |bibcode=2007NewPh.175..490F }}</ref> but other plants, such as [[locoweed]], require selenium, and their growth indicates the presence of selenium in soil).<ref>{{Cite report |date=1986 |title=Selenium concentrations in leaf material from Astragalus Oxyphysus (diablo locoweed) and Atriplex Lentiformis (quail bush) in the interior Coast Ranges and the western San Joaquin Valley, California |institution=U.S. Geological Survey |id=Water-Resources Investigations Report 86-4066|url=https://www.academia.edu/61786801}}</ref> The selenium content in the human body is believed to be in the range of 13–20&nbsp;mg.<ref>A common reference for this is {{cite journal |last1=Schroeder |first1=H. A. |last2=Frost |first2=D. V. |last3=Balassa |first3=J. J. |date=1970 |title=Essential trace metals in man: Selenium |journal=Journal of Chronic Diseases |volume=23 |issue=4 |pages=227–243 |doi=10.1016/0021-9681(70)90003-2 |osti=6424964 |pmid=4926392}}</ref>

Selenium is a component of the unusual [[amino acid]]s [[selenocysteine]] and [[selenomethionine]]. In humans, selenium is a [[dietary mineral|trace element]] nutrient that functions as [[Cofactor (biochemistry)|cofactor]] for [[redox|reduction]] of [[antioxidant]] enzymes, such as [[glutathione peroxidase]]s and certain forms of [[thioredoxin reductase]] found in animals and some plants (this enzyme occurs in all living organisms, but not all forms of it in plants require selenium).<ref>{{cite journal |doi=10.1152/physrev.00039.2013 |title=Selenoproteins: Molecular Pathways and Physiological Roles |date=2014 |last1=Labunskyy |first1=Vyacheslav M. |last2=Hatfield |first2=Dolph L. |last3=Gladyshev |first3=Vadim N. |journal=Physiological Reviews |volume=94 |issue=3 |pages=739–777 |pmid=24987004 |pmc=4101630 }}</ref>
 
The [[glutathione peroxidase]] family of enzymes (GSH-Px) catalyze reactions that remove reactive oxygen species such as [[hydrogen peroxide]] and organic [[hydroperoxide]]s.<ref>{{cite web | title = Entrez Gene: GPX1 glutathione peroxidase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2876}}</ref>

The [[Thyroid|thyroid gland]] and every cell that uses thyroid hormone also use selenium,<ref>{{Cite journal|last1=Pakdel|first1=Farzad|last2=Ghazavi|first2=Roghayeh|last3=Heidary|first3=Roghayeh|last4=Nezamabadi|first4=Athena|last5=Parvizi|first5=Maryam|last6=Haji Safar Ali Memar|first6=Mahsa|last7=Gharebaghi|first7=Reza|last8=Heidary|first8=Fatemeh|date=2019|title=Effect of Selenium on Thyroid Disorders: Scientometric Analysis|journal=Iranian Journal of Public Health|volume=48|issue=3|pages=410–420|issn=2251-6085|pmc=6570790|pmid=31223567}}</ref> which is a cofactor for the three of the four known types of [[Deiodinase|thyroid hormone deiodinases]], which activate and then deactivate various [[thyroid hormones]] and their metabolites; the [[iodothyronine deiodinase]]s are the subfamily of deiodinase enzymes that use selenium as the otherwise rare amino acid selenocysteine.

Increased dietary selenium reduces the effects of mercury toxicity,<ref>{{cite journal|last1=Ralston|first1=N. V.|last2=Ralston|first2=C. R.|last3=Blackwell|first3=JL III|last4=Raymond|first4=L. J.|doi=10.1016/j.neuro.2008.07.007|title=Dietary and tissue selenium in relation to methylmercury toxicity|url=http://www.soest.hawaii.edu/oceanography/courses_html/OCN331/Mercury3.pdf|journal=Neurotoxicology|volume=29|issue=5|pages=802–811|pmid=18761370|date=2008|bibcode=2008NeuTx..29..802R |citeseerx=10.1.1.549.3878|access-date=2012-09-28|archive-date=2012-07-24|archive-url=https://web.archive.org/web/20120724193621/http://www.soest.hawaii.edu/oceanography/courses_html/OCN331/Mercury3.pdf|url-status=dead}}</ref><ref>{{cite journal|last1=Penglase|first1=S.|last2=Hamre|first2=K.|last3=Ellingsen|first3=S.|title=Selenium prevents downregulation of antioxidant selenoprotein genes by methylmercury|journal=Free Radical Biology and Medicine|date=2014|volume=75|pages=95–104|doi=10.1016/j.freeradbiomed.2014.07.019|pmid=25064324|hdl=1956/8708|hdl-access=free}}</ref><ref>{{cite journal|last1=Usuki|first1=F.|last2=Yamashita|first2=A.|last3=Fujimura|first3=M.|title=Post-transcriptional defects of antioxidant selenoenzymes cause oxidative stress under methylmercury exposure|journal=The Journal of Biological Chemistry|date=2011|volume=286|issue=8|pages=6641–6649|doi=10.1074/jbc.M110.168872|pmid=21106535|pmc=3057802|doi-access=free}}</ref> although it is effective only at low to modest doses of mercury.<ref>{{cite journal|last1=Ohi|first1=G.|last2=Seki|first2=H.|last3=Maeda|first3=H.|last4=Yagyu|first4=H.|title=Protective effect of selenite against methylmercury toxicity: observations concerning time, dose and route factors in the development of selenium attenuation|journal=Industrial Health|date=1975|volume=13|issue=3|pages=93–99|doi=10.2486/indhealth.13.93|doi-access=free|bibcode=1975IndHe..13...93O }}</ref> Evidence suggests that the molecular mechanisms of mercury toxicity include the irreversible inhibition of selenoenzymes that are required to prevent and reverse oxidative damage in brain and endocrine tissues.<ref>{{cite journal |last1= Ralston |first1= N. V. C. |last2= Raymond |first2=L. J. |date= 2010 |title= Dietary selenium's protective effects against methylmercury toxicity |journal= Toxicology |volume= 278 |issue= 1|pages= 112–123 |doi= 10.1016/j.tox.2010.06.004 |pmid= 20561558 |bibcode= 2010Toxgy.278..112R }}</ref><ref>{{cite journal |last1= Carvalho |first1= C. M. L. |last2= Chew |first2= Hashemy S. I. |last3= Hashemy |first3= J. |last4= Lu |first4= A. |date= 2008 |title= Inhibition of the human thioredoxin system: A molecular mechanism of mercury toxicity |journal= Journal of Biological Chemistry |volume= 283 |issue= 18|pages= 11913–11923 |doi= 10.1074/jbc.M710133200 |pmid= 18321861 |last5= Holmgren |first5=A. |display-authors=3|doi-access= free }}</ref> The selenium-containing compound [[selenoneine]] is present in the blood of [[bluefin tuna]].<ref>Michiaki Yamashita, Shintaro Imamura, Md. Anwar Hossain, Ken Touhata, Takeshi Yabu, and Yumiko Yamashita, [http://www.fasebj.org/content/26/1_Supplement/969.13.short "Strong antioxidant activity of the novel selenium-containing imidazole compound 'selenoneine{{'"}}], ''The FASEB Journal'', vol. 26 no. 1, supplement 969.13, April 2012</ref><ref>{{cite journal | pmid = 21540999 | doi= 10.4331/wjbc.v1.i5.144 | volume=1 | issue= 5 | title=Discovery of the strong antioxidant selenoneine in tuna and selenium redox metabolism | pmc=3083957 | year=2010 | journal=World Journal of Biological Chemistry | pages=144–150 | last1 = Yamashita | first1 = Y. | last2 = Yabu | first2 = T. | last3 = Yamashita | first3 = M. | doi-access= free }}</ref> Certain plants are considered indicators of high selenium content of the soil because they require high levels of selenium to thrive. The main selenium indicator plants are ''[[Astragalus (plant)|Astragalus]]'' species (including some [[locoweed]]s), prince's plume (''[[Stanleya (plant)|Stanleya]]'' sp.), woody asters (''[[Xylorhiza (plant)|Xylorhiza]]'' sp.), and false goldenweed (''[[Oonopsis]]'' sp.).<ref>{{cite web |last=Zane Davis |first=T. |date=2008-03-27 |title=Selenium in Plants |url=http://www.ars.usda.gov/SP2UserFiles/Place/54282000/PPClassPPSlides/3-27-08DavisSelenium.pdf |access-date=2008-12-05 |page=8}}</ref>

===Evolution in biology===
{{Main|Evolution of dietary antioxidants}}

From about three billion years ago, [[prokaryotic]] selenoprotein families drove the evolution of the amino acid selenocysteine. Several selenoproteins are known in bacteria, archaea, and eukaryotes, invariably owing to the presence of selenocysteine,<ref name="glady">{{cite journal |title=Selenocysteine-containing proteins in mammals |journal=Journal of Biomedical Science |volume=6 |issue=3 |pages=151–160 |date=1999 |pmid=10343164 |doi=10.1007/BF02255899 |last1=Gladyshev |first1=Vadim N. |last2=Hatfield |first2=Dolph L.|url=https://digitalcommons.unl.edu/biochemgladyshev/77 }}</ref>  Just as for mammals, selenoprotein protect unicellular organisms against oxidative damage.

Selenoprotein families of GSH-Px and the deiodinases of eukaryotic cells seem to have a bacterial [[Phylogenetics|phylogenetic]] origin. The selenocysteine-containing form occurs in species as diverse as green algae, diatoms, sea urchins, fish, and chickens.<ref>{{cite journal |last=Stadtman |first=T. C. |title=Selenocysteine |journal=Annual Review of Biochemistry |volume=65 |pages=83–100 |date=1996 |issue=1 |pmid=8811175 |doi=10.1146/annurev.bi.65.070196.000503}}</ref>

Trace elements involved in GSH-Px and superoxide dismutase enzymes activities, i.e., selenium, [[vanadium]], [[magnesium]], [[copper]], and [[zinc]], may have been lacking in some terrestrial mineral-deficient areas.<ref name="glady" /> Marine organisms retained and sometimes expanded their selenoproteomes, whereas the selenoproteomes of some terrestrial organisms were lowered or completely lost. These findings suggest that, with the exception of [[vertebrate]]s, aquatic life supports selenium use, whereas terrestrial habitats lead to lowered use of this trace element.<ref>{{cite journal |title=Evolutionary dynamics of eukaryotic selenoproteomes: large selenoproteomes may associate with aquatic life and small with terrestrial life |journal=Genome Biology |volume=8 |issue=9 |pages=R198 |date=2007 |pmid=17880704 |pmc=2375036 |doi=10.1186/gb-2007-8-9-r198 |last1=Lobanov |first1=Alexey V. |last2=Fomenko |first2=Dmitri E. |last3=Zhang |first3=Yan |last4=Sengupta |first4=Aniruddha |last5=Hatfield |first5=Dolph L. |last6=Gladyshev |first6=Vadim N. |display-authors=3 |doi-access=free }}</ref> Marine fishes and vertebrate thyroid glands have the highest concentration of selenium and iodine. From about 500&nbsp;million years ago, freshwater and terrestrial plants slowly optimized the production of "new" endogenous antioxidants such as [[ascorbic acid]] (vitamin C), [[polyphenol]]s (including flavonoids), [[tocopherol]]s, etc. A few of these appeared in the last 50–200 million years in fruits and flowers of [[angiosperm]] plants. In fact, the angiosperms (the dominant type of plant today) and most of their antioxidant pigments evolved during the late [[Jurassic]] period.{{Citation needed|date=June 2016}}

About 200 million years ago, new selenoproteins were developed as mammalian GSH-Px enzymes.<ref>{{cite journal |title=Reconsidering the evolution of eukaryotic selenoproteins: a novel nonmammalian family with scattered phylogenetic distribution |journal=EMBO Reports |volume=5 |issue=1 |pages=71–7 |date=2004 |pmid=14710190 |pmc=1298953 |doi=10.1038/sj.embor.7400036 |last1=Castellano |first1=Sergi |last2=Novoselov |first2=Sergey V. |last3=Kryukov |first3=Gregory V. |last4=Lescure |first4=Alain |last5=Blanco |first5=Enrique |last6=Krol |first6=Alain |last7=Gladyshev |first7=Vadim N. |last8=Guigó |first8=Roderic |display-authors=3}}</ref><ref>{{cite journal |title=The prokaryotic selenoproteome |journal=EMBO Reports |volume=5 |issue=5 |pages=538–43 |date=2004 |pmid=15105824 |pmc=1299047 |doi=10.1038/sj.embor.7400126 |last1=Kryukov |first1=Gregory V. |last2=Gladyshev |first2=Vadim N.}}</ref><ref>{{cite journal |title=Selenoprotein synthesis in archaea: identification of an mRNA element of ''Methanococcus jannaschii'' probably directing selenocysteine insertion |journal=Journal of Molecular Biology |volume=266 |issue=4 |pages=637–41 |date=1997 |pmid=9102456 |doi=10.1006/jmbi.1996.0812 |last1=Wilting |first1=R. |last2=Schorling |first2=S. |last3=Persson |first3=B. C. |last4=Böck |first4=A.}}</ref><ref>{{cite journal |title=The microbial selenoproteome of the Sargasso Sea |journal=Genome Biology |volume=6 |issue=4 |pages=R37 |date=2005 |pmid=15833124 |pmc=1088965 |doi=10.1186/gb-2005-6-4-r37 |last1=Zhang |first1=Yan |last2=Fomenko |first2=Dmitri E. |last3=Gladyshev |first3=Vadim N. |doi-access=free }}</ref>

===Toxicity===
[[File:Selenium paradox.jpg|thumb|upright=1.3|Selenium at nutritional levels or low concentrations is required for cell [[homeostasis]], playing a role as an [[Antioxidant|anti-oxidant]] through [[selenoprotein]]s, thus, act chemo-preventive against cancer. In contrast, supra-nutritional levels or higher concentrations act as [[pro-oxidant]] in tumour cells, thus can be exploited as chemo-therapeutic against [[cancer]].<ref name=":0">{{Cite journal|last1=Razaghi|first1=Ali|last2=Poorebrahim|first2=Mansour|last3=Sarhan|first3=Dhifaf|last4=Björnstedt|first4=Mikael|date=2021-09-01|title=Selenium stimulates the antitumour immunity: Insights to future research|url=https://www.ejcancer.com/article/S0959-8049(21)00462-7/abstract|journal=European Journal of Cancer|language=English|volume=155|pages=256–267|doi=10.1016/j.ejca.2021.07.013|pmid=34392068|issn=0959-8049|doi-access=free}}</ref>]]
Although selenium is an essential [[dietary mineral|trace element]], it is toxic if taken in excess. Exceeding the [[Dietary Reference Intake|Tolerable Upper Intake Level]] of 400 micrograms per day can lead to selenosis.<ref>{{cite web |url= http://ods.od.nih.gov/factsheets/selenium.asp#h7 |title= Dietary Supplement Fact Sheet: Selenium |publisher= National Institutes of Health; Office of Dietary Supplements |access-date= 2009-01-05}}</ref> This 400&nbsp;μg Tolerable Upper Intake Level is based primarily on a 1986 study of five Chinese patients who exhibited overt signs of selenosis and a follow-up study on the same five people in 1992.<ref>{{cite book |title= Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids |publisher= Institute of Medicine |date= August 15, 2000 |pages= 314–315 |url= http://www.nap.edu/openbook.php?record_id=9810&page=315 |isbn= 978-0-309-06949-6 |author=((Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Levels of Nutrients and Interpretation and Uses of DRIs, Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine))|doi= 10.17226/9810 |pmid= 25077263 }}</ref> The 1992 study found the maximum safe dietary selenium intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to avoid creating an imbalance of nutrients in the diet and to accord with data from other countries.<ref>{{cite journal |last1= Yang |first1=G.|last2= Zhou |first2=R.|date= 1994 |title= Further Observations on the Human Maximum Safe Dietary Selenium Intake in a Seleniferous Area of China |journal= Journal of Trace Elements and Electrolytes in Health and Disease |volume= 8 |issue= 3–4 |pages= 159–165 |pmid=7599506
}}</ref> In China, people who ingested corn grown in extremely selenium-rich stony coal (carbonaceous [[shale]]) have suffered from selenium toxicity. This coal was shown to have selenium content as high as 9.1%, the highest concentration in coal ever recorded.<ref>{{cite journal |last1= Yang |first1=Guang-Qi|last2= Xia |first2=Yi-Ming|date= 1995 |title= Studies on Human Dietary Requirements and Safe Range of Dietary Intakes of Selenium in China and Their Application in the Prevention of Related Endemic Diseases |journal= Biomedical and Environmental Sciences |volume= 8 |issue= 3|pages= 187–201 |pmid= 8561918}}</ref>

Signs and symptoms of selenosis include a garlic odor on the breath, gastrointestinal disorders, hair loss, [[sloughing]] of nails, fatigue, irritability, and neurological damage. Extreme cases of selenosis can exhibit [[cirrhosis]] of the liver, [[pulmonary edema]], or death.<ref>{{cite web |url= http://www.atsdr.cdc.gov/toxprofiles/tp92-c3.pdf |publisher= Agency for Toxic Substances and Disease Registry |title= Public Health Statement: Health Effects |access-date= 2009-01-05}}</ref> Elemental selenium and most metallic [[selenide]]s have relatively low toxicities because of low [[bioavailability]]. By contrast, [[selenate]]s and [[Selenite (ion)|selenites]] have an oxidant mode of action similar to that of [[arsenic trioxide]] and are very toxic. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day.<ref>{{cite journal |last= Wilber |first=C. G. |title= Toxicology of selenium |date= 1980 |journal= Clinical Toxicology |volume= 17 |pages= 171–230 |doi= 10.3109/15563658008985076 |pmid= 6998645| issue= 2}}</ref> [[Hydrogen selenide]] is an extremely toxic, corrosive gas.<ref>{{cite journal |doi= 10.3109/10915818609140736 |title= Selenium Toxicity in Animals with Emphasis on Man |date= 1986 |journal= International Journal of Toxicology |volume= 5 |pages= 45–70 |last= Olson |first=O. E.|s2cid= 74619246 |doi-access= free }}</ref> Selenium also occurs in organic compounds, such as dimethyl selenide, [[selenomethionine]], [[selenocysteine]] and [[methylselenocysteine]], all of which have high [[bioavailability]] and are toxic in large doses.

On 19 April 2009, 21 [[Polo pony|polo ponies]] died shortly before a match in the United States Polo Open. Three days later, a pharmacy released a statement explaining that the horses had received an incorrect dose of one of the ingredients used in a vitamin/mineral supplement compound that had been incorrectly prepared by a [[compounding pharmacy]]. Analysis of blood levels of [[inorganic compound]]s in the supplement indicated the selenium concentrations were 10 to 15 times higher than normal in the [[blood sample]]s and 15 to 20 times higher than normal in the liver samples. Selenium was later confirmed to be the toxic factor.<ref>{{cite web| date= 2009-05-06| url= http://www.horsetalk.co.nz/news/2009/05/033.shtml| title= Polo pony selenium levels up to 20 times higher than normal| access-date= 2009-05-05| archive-date= 2016-08-19| archive-url= https://web.archive.org/web/20160819235242/http://www.horsetalk.co.nz/news/2009/05/033.shtml| url-status= dead}}</ref>

[[File:Se dose-response curve for juvenile salmon mortality - percent scale.jpg|thumb|Relationship between survival of juvenile salmon and concentration of selenium in their tissues after 90 days (Chinook salmon<ref name="Hamilton" />) or 45 days (Atlantic salmon<ref name="Poston" />) exposure to dietary selenium. The 10% lethality level (LC10=1.84 μg/g) was derived by applying the biphasic model of Brain and Cousens<ref>{{cite journal|last1=Brain |first1=P.|title=An equation to describe dose responses where there is stimulation of growth at low doses|journal=Weed Research|last2=Cousens |first2=R.|date=1989|doi=10.1111/j.1365-3180.1989.tb00845.x|volume= 29|pages= 93–96|issue=2|bibcode=1989WeedR..29...93B }}</ref> to only the Chinook salmon data. The Chinook salmon data comprise two series of dietary treatments, combined here because the effects on survival are indistinguishable.]]

In fish and other wildlife, selenium is necessary for life but toxic in high doses. For [[salmon]], the optimal selenium concentration is about 1 microgram selenium per gram of whole body weight. Much below that level, young salmon die from deficiency;<ref name="Poston">{{cite journal| last1= Poston|first1=H. A.| date= 1976| title= Vitamin E and selenium interrelations in the diet of Atlantic salmon (''Salmo salar''): gross, histological and biochemical signs|pmid=932827|journal= Journal of Nutrition|volume= 106|pages= 892–904| last2= Combs| first2=G. F. Jr.| last3= Leibovitz| first3=L.| issue= 7|doi=10.1093/jn/106.7.892}}</ref> much above, they die from toxic excess.<ref name="Hamilton">{{cite journal| last1= Hamilton|first1= Steven J. |date= 1990| title= Toxicity of organic selenium in the diet to chinook salmon|journal= Environ. Toxicol. Chem.|volume= 9|issue = 3| pages= 347–358|doi =10.1002/etc.5620090310| last2= Buhl| first2= Kevin J.| last3= Faerber| first3= Neil L.| last4= Bullard| first4= Fern A.| last5= Wiedmeyer| first5= Raymond H. |bibcode= 1990EnvTC...9..347H |display-authors=3}}</ref>

The [[Occupational Safety and Health Administration]] (OSHA) has set the legal limit ([[permissible exposure limit]]) for selenium in the workplace at 0.2&nbsp;mg/m<sup>3</sup> over an 8-hour workday. The [[National Institute for Occupational Safety and Health]] (NIOSH) has set a [[Recommended exposure limit]] (REL) of 0.2&nbsp;mg/m<sup>3</sup> over an 8-hour workday. At levels of 1&nbsp;mg/m<sup>3</sup>, selenium is [[IDLH|immediately dangerous to life and health]].<ref>{{Cite web|title = NIOSH Pocket Guide to Chemical Hazards – Selenium|url = https://www.cdc.gov/niosh/npg/npgd0550.html|publisher = National Institute for Occupational Safety & Health|location=United States|access-date = 2015-11-21}}</ref>

==== Detection in biological fluids ====
Selenium may be measured in blood, plasma, serum, or urine to monitor excessive environmental or occupational exposure, to confirm a diagnosis of poisoning in hospitalized victims, or to investigate a suspected case of fatal overdose. Some analytical techniques can distinguish organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body before elimination in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations.<ref>{{cite book |last=Baselt |first=R. |title=Disposition of Toxic Drugs and Chemicals in Man |date=2008 |publisher=Biomedical Publications |isbn=978-0-9626523-5-6 |edition=8th |place=Foster City, California |pages=1416–1420}}</ref>

===Deficiency===
{{Main|Selenium deficiency}}
Selenium deficiency can occur in patients with severely compromised [[intestine|intestinal]] function, those undergoing [[total parenteral nutrition]], and<ref>{{cite journal |title= Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged ≥90 y |volume= 71 |issue= 2 |pages= 590–598 |journal= American Journal of Clinical Nutrition |pmid= 10648276 |date=2000 |last1= Ravaglia |first1=G.|last2= Forti |first2=P. |last3= Maioli |first3=F. |last4= Bastagli |first4=L. |last5= Facchini |first5=A. |last6= Mariani |first6=E. |last7= Savarino |first7=L. |last8= Sassi |first8=S. |last9= Cucinotta |first9=D. |last10=Lenaz |first10=G. |display-authors=3|doi= 10.1093/ajcn/71.2.590 |doi-access= free }}</ref> in those of advanced age (over 90). Also, people dependent on food grown from selenium-deficient soil are at risk. Although [[New Zealand]] soil has low levels of selenium, the residents have not detected adverse health effects.<ref>{{cite web| url= http://www.medsafe.govt.nz/Profs/PUarticles/Sel.htm |website= Prescriber Update Articles |title= Selenium |access-date= 2009-07-13 |publisher= New Zealand Medicines and Medical Devices Safety Authority |author= MedSafe Editorial Team}}</ref>

Selenium deficiency, defined by low (<60% of normal) selenoenzyme activity levels in brain and endocrine tissues, occurs only when a low selenium level is linked with additional stress, such as high exposures to [[Mercury (element)|mercury]]<ref>{{cite journal|last1=Ralston |first1=N. V. C.|last2=Raymond |first2=L. J.|title=Dietary selenium's protective effects against methylmercury toxicity|journal=Toxicology|date=2010|volume=278|pages=112–123|doi=10.1016/j.tox.2010.06.004|pmid=20561558|issue=1|bibcode=2010Toxgy.278..112R }}</ref> or increased oxidant stress from vitamin E deficiency.<ref>{{cite book| title =Essentials of Human Nutrition |edition= 2nd |publisher= Oxford University Press |date= 2002 |isbn= 978-0-19-262756-8 |first1= Jim |last1= Mann |first2= A. Stewart |last2= Truswell}}</ref>

Selenium interacts with other nutrients, such as [[iodine]] and [[vitamin E]]. The effect of selenium deficiency on health remains uncertain, particularly concerning [[Kashin–Beck disease]].<ref>{{cite journal |title= Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy |first1=R. |last1= Moreno-Reyes |first2=F. |last2= Mathieu |first3=M. |last3= Boelaert |first4=F. |last4= Begaux |first5=C. |last5= Suetens |first6=M. T. |last6= Rivera |first7=J. |last7= Nève |first8=N. |last8= Perlmutter |first9=J. |last9= Vanderpas |journal= American Journal of Clinical Nutrition |volume= 78 |issue= 1 |pages= 137–144 |date= 2003 |pmid= 12816783 |display-authors= 3|doi= 10.1093/ajcn/78.1.137 |doi-access= free }}</ref> Also, selenium interacts with other minerals, such as [[zinc]] and [[copper]]. High doses of selenium supplements in pregnant animals might disturb the zinc:copper ratio and lead to zinc reduction; in such treatment cases, zinc levels should be monitored. Further studies are needed to confirm these interactions.<ref>{{cite journal|title= The effect of dietary organic and inorganic selenium supplementation on serum Se, Cu, Fe and Zn status during the late pregnancy in Merghoz goats and their kids|first1=R.|last1 =Kachuee |first2=M. |last2= Moeini |first3=M. |last3= Suori |volume= 110 |issue= 1 |pages= 20–27 |journal= Small Ruminant Research |date=2013 |doi=10.1016/j.smallrumres.2012.08.010}}</ref>

In the regions (e.g., regions within North America) where low selenium soil levels lead to low concentrations in the plants, some animal species may be deficient unless selenium is supplemented with diet or injection.<ref>National Research Council, Subcommittee on Sheep Nutrition (1985). ''Nutrient requirements of sheep''. 6th ed., National Academy Press, Washington, {{ISBN|0309035961}}.</ref> [[Ruminant]]s are particularly susceptible. In general, absorption of dietary selenium is lower in ruminants than in other animals and is lower in forages than in grain.<ref name="NRCsr2007">National Research Council, Committee on Nutrient Requirements of Small Ruminants (2007). ''Nutrient requirements of small ruminants''. National Academies Press, Washington, {{ISBN|0-309-10213-8}}.</ref> Ruminants grazing certain forages, e.g., some [[white clover]] varieties containing [[cyanogenic glycoside]]s, may have higher selenium requirements,<ref name="NRCsr2007" /> presumably because cyanide is released from the [[aglycone]] by [[glucosidase]] activity in the rumen<ref>{{cite journal|last1=Coop |first1=I. E.|last2=Blakely |first2=R. L. |date=1949|title= The metabolism and toxicity of cyanides and cyanogenic glycosides in sheep|journal= New Zealand Journal of Science and Technology|volume= 30|pages= 277–291}}</ref> and glutathione peroxidases are deactivated by the cyanide acting on the glutathione [[Moiety (chemistry)|moiety]].<ref>{{cite journal|last1=Kraus |first1=R. J.|last2=Prohaska |first2=J. R.|last3=Ganther |first3=H. E. |date=1980|title= Oxidized forms of ovine erythrocyte glutathione peroxidase. Cyanide inhibition of 4-glutathione:4-selenoenzyme|journal= Biochimica et Biophysica Acta (BBA) - Enzymology |pmid=7426660|volume=615|pages= 19–26|doi=10.1016/0005-2744(80)90004-2|issue=1}}</ref> Neonate ruminants at risk of [[Nutritional muscular dystrophy|white muscle disease]] may be administered both selenium and vitamin E by injection; some of the WMD [[Myopathy|myopathies]] respond only to selenium, some only to vitamin E, and some to either.<ref>Kahn, C. M. (ed.) (2005). ''Merck Veterinary Manual''. 9th ed. Merck & Co., Inc., Whitehouse Station, {{ISBN|0911910506}}.</ref>

==== Nutritional sources of selenium ====
Dietary selenium comes from meat, nuts, cereals, and mushrooms. [[Brazil nut]]s are the richest dietary source (though this is soil-dependent since the Brazil nut does not require high levels of the element for its own needs).<ref>{{cite journal |last1=Barclay |first1=Margaret N. I. |last2=MacPherson |first2=Allan |last3=Dixon |first3=James |date=1995 |title=Selenium content of a range of UK food |journal=Journal of Food Composition and Analysis |volume=8 |issue=4 |pages=307–318 |doi=10.1006/jfca.1995.1025}}</ref><ref>{{cite web |title=Selenium Fact Sheet |url=http://ods.od.nih.gov/factsheets/selenium.asp#h2 |publisher=The Office of Dietary Supplements, [[National Institutes of Health]] |place=United States}} Includes a list of selenium-rich foods.</ref>

The US [[Recommended Dietary Allowance]] (RDA) of selenium for teenagers and adults is 55&nbsp;[[Microgram|μg]]/day. Selenium as a dietary supplement is available in many forms, including multi-vitamins/mineral supplements, which typically contain 55 or 70&nbsp;μg/serving. Selenium-specific supplements typically contain either 100 or 200&nbsp;μg/serving.{{Citation needed|date=June 2024}} In June 2015, the US [[Food and Drug Administration]] (FDA) published its final rule establishing a requirement for minimum and maximum levels of selenium in [[infant formula]].<ref>{{Cite web |title=FDA Issues Final Rule to Add Selenium to List of Required Nutrients for Infant Formula |url=https://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm451982.htm |url-status=dead |archive-url=https://wayback.archive-it.org/7993/20171114120142/https://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm451982.htm |archive-date=November 14, 2017 |access-date=2015-09-10 |publisher=Food and Drug Administration |df=mdy-all}}</ref>

===General health effects===
{{Main article|Selenium in biology}}
The effects of selenium intake on cancer have been studied in several [[clinical trial]]s and [[Epidemiology|epidemiologic]] studies in humans. Selenium may have a [[Chemopreventive|chemo-preventive]] role in [[cancer]] risk as an [[Antioxidant|anti-oxidant]], and it might trigger the immune response. At low levels, it is used in the body to create anti-oxidant [[selenoprotein]]s, at higher doses than normal it causes cell death.<ref name=":0" />

Selenium (in close interrelation with [[iodine]]) plays a role in thyroid health. Selenium is a cofactor for the three thyroid hormone [[deiodinase]]s, helping activate and then deactivate various thyroid hormones and their metabolites. Isolated selenium deficiency is now being investigated for its role in the induction of autoimmune reactions in the thyroid gland in [[Hashimoto's thyroiditis|Hashimoto's disease]].<ref>{{Cite journal |last1=Rostami |first1=Rahim |last2=Nourooz-Zadeh |first2=Sarmad |last3=Mohammadi |first3=Afshin |last4=Khalkhali |first4=Hamid Reza |last5=Ferns |first5=Gordon |last6=Nourooz-Zadeh |first6=Jaffar |date=2020-10-31 |title=Serum Selenium Status and Its Interrelationship with Serum Biomarkers of Thyroid Function and Antioxidant Defense in Hashimoto's Thyroiditis |journal=Antioxidants |volume=9 |issue=11 |pages=E1070 |doi=10.3390/antiox9111070 |issn=2076-3921 |pmc=7692168 |pmid=33142736|doi-access=free }}</ref> In a case of combined iodine and selenium deficiency was shown to play a thyroid-protecting role.<ref>{{Cite journal |last1=Vanderpas |first1=J. B. |last2=Contempré |first2=B. |last3=Duale |first3=N. L. |last4=Deckx |first4=H. |last5=Bebe |first5=N. |last6=Longombé |first6=A. O. |last7=Thilly |first7=C. H. |last8=Diplock |first8=A. T. |last9=Dumont |first9=J. E. |date=February 1993 |title=Selenium deficiency mitigates hypothyroxinemia in iodine-deficient subjects |journal=The American Journal of Clinical Nutrition |volume=57 |issue=2 Suppl |pages=271S–275S |doi=10.1093/ajcn/57.2.271S |issn=0002-9165 |pmid=8427203|doi-access=free }}</ref>