View source for Biology:Selenium in biology

{{Short description|Use of Selenium by organisms}}

[[File:Selenocysteine skeletal 3D.svg|thumb|[[Chemistry:Selenocysteine|Selenocysteine]] is the main organic molecule involving selenium in [[Humans|humans]].]]
[[Chemistry:Selenium|Selenium]] is an essential micronutrient for animals, though it is toxic in large doses. In plants, it sometimes occurs in toxic amounts as forage, e.g. [[Biology:Locoweed|locoweed]]. Selenium is a component of the [[Chemistry:Amino acid|amino acid]]s [[Chemistry:Selenocysteine|selenocysteine]] and [[Chemistry:Selenomethionine|selenomethionine]]. In humans, selenium is a trace element nutrient that functions as [[Biology:Cofactor (biochemistry)|cofactor]] for [[Biology:Glutathione peroxidase|glutathione peroxidase]]s and certain forms of [[Biology:Thioredoxin reductase|thioredoxin reductase]].<ref>S. J. Lippard, J. M. Berg "Principles of Bioinorganic Chemistry" University Science Books: Mill Valley, CA; 1994.  {{ISBN|0-935702-73-3}}.</ref> Selenium-containing proteins are produced from inorganic selenium via the intermediacy of selenophosphate (PSeO<sub>3</sub><sup>3−</sup>).

==Se-containing biomolecules==

Selenium is an essential micronutrient in mammals, but is also recognized as toxic in excess. Selenium exerts its biological functions through [[Biology:Selenoprotein|selenoprotein]]s, which contain the [[Chemistry:Amino acid|amino acid]] [[Chemistry:Selenocysteine|selenocysteine]]. Twenty-five selenoproteins are encoded in the [[Biology:Human genome|human genome]].<ref>{{cite book
|first1=Suguru 
|last1= Kurokawa
|first2= Marla J.
|last2= Berry
|editor=Astrid Sigel, Helmut Sigel and Roland K. O. Sigel
|title=Interrelations between Essential Metal Ions and Human Diseases
|series=Metal Ions in Life Sciences
|volume=13
|year=2013
|publisher=Springer
|pages=499–534 Selenium. Role of the Essential Metalloid in Health  
|doi=10.1007/978-94-007-7500-8_16
|pmid= 24470102
|pmc= 4339817
|chapter= Selenium. Role of the Essential Metalloid in Health
|isbn= 978-94-007-7499-5
}}</ref>

===Glutathione peroxidase===
The [[Biology:Glutathione peroxidase|glutathione peroxidase]] family of enzymes (abbreviated GSH-Px) catalyze reduction of [[Chemistry:Hydrogen peroxide|hydrogen peroxide]] and organic [[Chemistry:Hydroperoxide|hydroperoxide]]s:

:2GSH + H<sub>2</sub>O<sub>2</sub>   →   GSSG  +  2 H<sub>2</sub>O
The two H atoms are donated by thiols in a process that begins with oxidation of a [[Chemistry:Selenol|selenol]] side chain in GSH-Px.  The organoselenium compound [[Chemistry:Ebselen|ebselen]] is a drug used to supplement the action of GSH-Px.  It functions as a catalyst for the destruction of hydrogen peroxide.<ref>{{cite journal | author = Bhabak Krishna P., Mugesh Govindasamy | year = 2010 | title = Functional Mimics of Glutathione Peroxidase: Bioinspired Synthetic Antioxidants | journal = Acc. Chem. Res. | volume = 43 | issue = 11| pages = 1408–1419 | doi = 10.1021/ar100059g | pmid = 20690615 | last2 = Mugesh }}</ref>

A related selenium-containing enzyme in some plants and in animals ([[Biology:Thioredoxin reductase|thioredoxin reductase]]) generates reduced thioredoxin, a dithiol that serves as an electron source for peroxidases and also the important reducing enzyme [[Biology:Ribonucleotide reductase|ribonucleotide reductase]] that makes DNA precursors from RNA precursors.<ref name="Stadtman">{{cite journal |author=Stadtman TC |title=Selenocysteine |journal=Annual Review of Biochemistry |volume=65 |pages=83–100 |year=1996 |pmid=8811175 |doi=10.1146/annurev.bi.65.070196.000503}}</ref>

===Deiodinases===
Selenium also plays a role in the functioning of the [[Biology:Thyroid|thyroid]] gland.  It participates as a [[Biology:Cofactor (biochemistry)|cofactor]] for the three thyroid hormone [[Biology:Deiodinase|deiodinase]]s.  These enzymes activate and then deactivate various thyroid hormones and their metabolites.<ref>{{cite web |url = http://lpi.oregonstate.edu/infocenter/minerals/selenium/ |publisher = Linus Pauling Institute at Oregon State University |title = Selenium |access-date = 2009-01-05|date = 2014-04-23 }}</ref> It may inhibit [[Medicine:Hashimoto's thyroiditis|Hashimoto's disease]], an auto-immune disease in which the body's own thyroid cells are attacked by the immune system. A reduction of 21% on TPO antibodies was reported with the dietary intake of 0.2&nbsp;mg of selenium.<ref>{{cite journal |pmid=17696828 |title = Effects of 12 months treatment with L-selenomethionine on serum anti-TPO Levels in Patients with Hashimoto's thyroiditis |year=2007 |last1=Mazokopakis |first1=EE |last2=Papadakis |first2=JA |last3=Papadomanolaki |first3=MG |last4=Batistakis |first4=AG |last5=Giannakopoulos |first5=TG |last6=Protopapadakis |first6=EE |last7=Ganotakis |first7=ES |volume=17 |issue=7 |pages=609–12 |doi=10.1089/thy.2007.0040 |journal=Thyroid}}</ref>

===Formate dehydrogenase===
Some microorganisms utilize selenium in [[Biology:Formate dehydrogenase|formate dehydrogenase]]. Formate is produced in large amounts in the hepatic (liver cells) mitochondria of embryonic cells and in cancer cells by the folate cycle.<ref>H Frederik Nijhout, et al, In silico experimentation with a model of hepatic mitochondrial folate metabolism, Theoretical Biology and Medical Modeling, 2006, 3:40, link http://www.tbiomed.com/content/3/1/40/abstract).</ref>

Formate is reversibly oxidized by the enzyme [[Biology:Formate dehydrogenase|formate dehydrogenase]]:<ref>{{cite journal | author = Reda T., Plugge C. M., Abram N. J., Hirst J. | year = 2008 | title = Reversible interconversion of carbon dioxide and formate by an electroactive enzyme | journal = PNAS | volume = 105 | issue = 31| pages = 10654–10658 | doi = 10.1073/pnas.0801290105 | pmid = 18667702 | last2 = Plugge | last3 = Abram | last4 = Hirst | pmc = 2491486 | bibcode = 2008PNAS..10510654R | doi-access = free }}</ref>
:HCO<sub>2</sub><sup>−</sup>  →   CO<sub>2</sub>  +  H<sup>+</sup>  +  2 e<sup>−</sup>

=== Thioredoxin reductase ===
[[Biology:Thioredoxin reductase|Thioredoxin reductase]] uses a cysteine-selenocysteine pair to reduce the [[Biology:Disulfide|disulfide]] in [[Biology:Thioredoxin|thioredoxin]]. The selenocysteine  is arranged in an unusual Sec-His-Glu [[Biology:Catalytic triad|catalytic triad]], which tunes its pKa.<ref name=":0">{{cite journal|last1=Brandt|first1=Wolfgang|last2=Wessjohann|first2=Ludger A.|date=2005-02-04|title=The Functional Role of Selenocysteine (Sec) in the Catalysis Mechanism of Large Thioredoxin Reductases: Proposition of a Swapping Catalytic Triad Including a Sec-His-Glu State|journal=ChemBioChem|language=en|volume=6|issue=2|pages=386–394|doi=10.1002/cbic.200400276|pmid=15651042|s2cid=25575160|issn=1439-7633}}</ref>

==Indicator plants==
Certain species of plants are considered indicators of high selenium content of the soil, since they require high levels of selenium to thrive. The main selenium indicator plants are ''[[Biology:Astragalus (plant)|Astragalus]]'' species (including some [[Biology:Locoweed|locoweed]]s), prince's plume (''[[Biology:Stanleya (plant)|Stanleya]]'' sp.), woody asters (''[[Biology:Xylorhiza (plant)|Xylorhiza]]'' sp.), and false goldenweed (''[[Biology:Oonopsis|Oonopsis]]'' sp.)<ref>{{cite web |url = http://www.ars.usda.gov/SP2UserFiles/Place/54282000/PPClassPPSlides/3-27-08DavisSelenium.pdf |title = Selenium in Plants |access-date = 2008-12-05 |author= Zane Davis, T. |year = 2008 |page=8}}</ref>

==Medical use of synthetic selenium compounds==
The substance loosely called [[Chemistry:Selenium disulfide|selenium sulfide]] (with the approximate formula SeS<sub>2</sub>) is the active ingredient in some anti-dandruff shampoos.<ref>{{cite web |url = http://pharmacycode.com/Selenium(IV)_sulfide.html |title =Selenium(IV)_sulfide |publisher = Pharmacy Codes |access-date = 2009-01-06}}</ref> The selenium compound kills the scalp fungus ''[[Biology:Malassezia|Malassezia]]'', which causes shedding of dry skin fragments. The ingredient is also used in body lotions to treat [[Medicine:Tinea versicolor|Tinea versicolor]] due to infection by a different species of ''Malassezia'' fungus.<ref>{{cite web |url = http://dermnetnz.org/treatments/selenium.html |title = Selenium sulfide |publisher = DermNet NZ |access-date = 2009-01-06}}</ref>

Several clinical trials have assessed the use of selenium supplements in critically ill adults; however, the effectiveness and potential benefits of selenium supplementation in this context is not well understood.<ref>{{cite journal|last1=Allingstrup|first1=Mikkel|last2=Afshari|first2=Arash|date=2015-07-27|title=Selenium supplementation for critically ill adults|journal=The Cochrane Database of Systematic Reviews|volume=2018 |issue=7|pages=CD003703|doi=10.1002/14651858.CD003703.pub3|issn=1469-493X|pmc=6517228|pmid=26214143}}</ref>

==Detection in biological fluids==
Selenium may be measured in blood, plasma, serum or urine to monitor excessive environmental or occupational exposure, confirm a diagnosis of poisoning in hospitalized victims or to assist in a forensic investigation in a case of fatal overdosage. Some analytical techniques are capable of distinguishing organic from inorganic forms of the element. Both organic and inorganic forms of selenium are largely converted to monosaccharide conjugates (selenosugars) in the body prior to being eliminated in the urine. Cancer patients receiving daily oral doses of selenothionine may achieve very high plasma and urine selenium concentrations.<ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1416–1420.</ref>

==Toxicity==
Although selenium is an essential trace element, it is toxic if taken in excess. Exceeding the [[Chemistry: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 microgram ([[Microgram|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 = a report of the Panel on Dietary Antioxidants and Related Compounds, Subcommittees on Upper Reference Leves of Nutrients and of Interpretation and Use of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine.}}</ref> The 1992 study actually found the maximum safe dietary Se intake to be approximately 800 micrograms per day (15 micrograms per kilogram body weight), but suggested 400 micrograms per day to not only avoid [[Medicine:Toxicity|toxicity]], but also to avoid creating an imbalance of nutrients in the diet and to account for data from other countries.<ref>
{{cite journal
 |last = Yang |first = G.
 |author2 = Zhou, R.
 |year = 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 [[Chemistry:Shale|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 in literature.<ref>
{{cite journal
 |last = Yang |first = Guang-Qi
 |author2 = Xia, Yi-Ming
 |year = 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>

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 result in [[Medicine:Cirrhosis|cirrhosis]] of the liver, [[Medicine:Pulmonary edema|pulmonary edema]], and death.<ref name="tp92-c3">{{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 [[Physics:Selenide|selenide]]s have relatively low toxicities because of their low [[Chemistry:Bioavailability|bioavailability]]. By contrast, [[Chemistry:Selenate|selenate]]s and [[Chemistry:Selenite (ion)|selenites]] are very toxic, having an oxidant mode of action similar to that of arsenic trioxide. The chronic toxic dose of selenite for humans is about 2400 to 3000 micrograms of selenium per day for a long time.<ref>{{cite journal |last = Wilber |first = C. G. |title = Toxicology of selenium |year = 1980 |journal = Clinical Toxicology |volume = 17 |pages = 171–230 |doi = 10.3109/15563658008985076 |pmid = 6998645|issue = 2}}</ref> [[Chemistry:Hydrogen selenide|Hydrogen selenide]] is an extremely toxic, corrosive gas.<ref>{{cite journal |doi = 10.3109/10915818609140736 |title = Selenium Toxicity in Animals with Emphasis on Man |year = 1986 |author = Olson, O.E. |journal = International Journal of Toxicology |volume = 5 |page = 45|s2cid = 74619246 |doi-access = free }}</ref> Selenium also occurs in organic compounds, such as dimethyl selenide, [[Chemistry:Selenomethionine|selenomethionine]], [[Chemistry:Selenocysteine|selenocysteine]] and [[Chemistry:Methylselenocysteine|methylselenocysteine]], all of which have high [[Chemistry:Bioavailability|bioavailability]] and are toxic in large doses.

Selenium poisoning of water systems may result whenever new agricultural runoff courses through normally dry, undeveloped lands. This process leaches natural soluble selenium compounds (such as selenates) into the water, which may then be concentrated in new "wetlands" as the water evaporates. High selenium levels produced in this fashion have been found to have caused certain congenital disorders in wetland birds.<ref>{{cite book |chapter-url = https://books.google.com/books?id=qN0I3husm50C&pg=PA477 |chapter = Ecotoxicology of selenium |title = Handbook of ecotoxicology |first = H. M. |last = Ohlendorf |year = 2003 |pages = 466–491 |isbn = 978-1-56670-546-2 |publisher = Lewis Publishers |location = Boca Raton}}</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: Hamilton et al. 1990) or 45 days (Atlantic salmon: Poston et al. 1976) exposure to dietary selenium. The 10% lethality level (LC10=1.84 µg/g) was derived by applying the biphasic model of Brain and Cousens (1989) 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, low levels of selenium cause deficiency while high levels cause toxicity.  For example, in salmon, the optimal concentration of selenium in the fish tissue (whole body) is about 1 microgram selenium per gram of tissue (dry weight).  At levels much below that concentration, young salmon die from selenium deficiency;<ref name= Poston. >{{cite journal | last= Poston | first= H. A. |author2= Combs, G. F.|author3= Leibovitz, L.  | year= 1976| title=  Vitamin E and selenium interrelations in the diet of Atlantic salmon (Salmo salar): gross, histological and biochemical signs | journal= Journal of Nutrition | volume= 106 | issue =   7| pages= 892&ndash;904 | doi =  10.1093/jn/106.7.892| pmid= 932827 }}</ref> much above that level they die from toxic excess.<ref name= Hamilton >{{cite journal | last= Hamilton | first= Steven J. | author2= K. J. Buhl, N. L. Faerber, R. H. Wiedmeyer, and F. A. Bullard | year= 1990| title=  Toxicity of organic selenium in the diet to chinook salmon | journal= Environ. Toxicol. Chem. | volume= 9 | issue = 3| pages= 347&ndash;358 | doi =  10.1002/etc.5620090310}}</ref>

==Deficiency==
{{main|Medicine:Selenium deficiency}}
Selenium deficiency can occur in patients with severely compromised [[Chemistry: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 y1 |author = Ravaglia |volume = 71 |issue = 2 |pages = 590–598 |journal = American Journal of Clinical Nutrition |pmid = 10648276 |date=1 February 2000 |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 |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 [[Earth:New Zealand|New Zealand]] has low levels of selenium in its soil, adverse health effects have not been detected.<ref>{{cite web| url = http://www.medsafe.govt.nz/Profs/PUarticles/Sel.htm |work = 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 as defined by low (<60% of normal) selenoenzyme activity levels in brain and endocrine tissues only occurs when a low selenium status is linked with an additional stress, such as high exposures to mercury<ref>{{cite journal|last=Ralston|first=N.V.C.|author2=Raymond, L.J. |title=Dietary selenium's protective effects against methylmercury toxicity|journal=Toxicology|year=2010|volume=278|issue=1|pages=112–123|doi=10.1016/j.tox.2010.06.004|pmid=20561558}}</ref> or as a result of increased oxidant stress due to vitamin E deficiency.<ref>{{cite book| title =Essentials of Human Nutrition |edition = 2nd |publisher = Oxford University Press |year = 2002 |isbn = 978-0-19-262756-8 |first1 = Jim |last1 = Mann |first2 = A. Stewart |last2 = Truswell}}</ref>

Selenium interacts with other nutrients, such as [[Chemistry:Iodide|iodide]] and [[Chemistry:Vitamin E|vitamin E]]. The interaction is observed in the [[Philosophy:Etiology|etiology]] of many deficiency diseases in animals, and pure selenium deficiency is rare. The effect of selenium deficiency on health remains uncertain, particularly in relation to Kashin-Beck disease.<ref>{{cite journal |title = Selenium and iodine supplementation of rural Tibetan children affected by Kashin-Beck osteoarthropathy |first1 = Rodrigo |last1 =Moreno-Reyes |first2 = Jean |last2 =Mathieu| first3 = Marleen |last3 =Vanderpas| first4 = Françoise |last4 = Begaux| first5 = Carl |last5 =Suetens| first6 = Maria T. |last6 =Rivera| first7 = Jean |last7 =Nève| first8 = Noémi |last8 =Perlmutter |journal = American Journal of Clinical Nutrition |volume = 78 |issue = 1 |pages = 137–144 |year = 2003 |author9=V |pmid=12816783 |doi = 10.1093/ajcn/78.1.137 |doi-access = free }}</ref>

==Dietary recommendations==
The US Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for selenium in 2000. If there is not sufficient information to establish EARs and RDAs, an estimate designated Adequate Intake (AI) is used instead. The current EAR for selenium for people ages 14 and up is 45 μg/day. The RDA is 55 μg/day. RDAs are higher than EARs so as to identify amounts that will cover people with higher than average requirements. RDA for pregnancy is 60 μg/day. RDA for lactation is 70 μg/day. For children ages 1–13 years the RDA increases with age from 20 to 40 μg/day. As for safety, the IOM sets Tolerable upper intake levels (ULs) for vitamins and minerals when evidence is sufficient. In the case of selenium the UL is 400 μg/day. Collectively the EARs, RDAs, AIs and ULs are referred to as [[Chemistry:Dietary Reference Intake|Dietary Reference Intake]]s (DRIs).<ref name="DRItext">{{cite book | last1 = Institute of Medicine | title = Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids | chapter = Selenium | publisher = The National Academies Press | year = 2000 | location = Washington, DC | pages = 284–324 | doi = 10.17226/9810 | pmid = 25077263 | isbn = 978-0-309-06935-9 | chapter-url = https://www.nap.edu/read/9810/chapter/9| }}</ref>

The European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL defined the same as in United States. For women and men ages 15 and older the AI is set at 70 μg/day. AI for pregnancy is 70 μg/day, for lactation 85 μg/day. For children ages 1–14 years the AIs increase with age from 15 to 55 μg/day. These AIs are higher than the U.S. RDAs.<ref>{{cite web | title = Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic Products, Nutrition and Allergies| year = 2017| url = https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary_tables_jan_17.pdf}}</ref> The European Food Safety Authority reviewed the same safety question and set its UL at 300 μg/day, which is lower than the U.S. value.<ref>{{citation| title = Tolerable Upper Intake Levels For Vitamins And Minerals| publisher = European Food Safety Authority| year = 2006| url = http://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf}}</ref>

In the United States, selenium deficiency is not common. A federal survey of food consumption determined that for women and men over the age of 19, average consumption from foods and beverages was 89 and 125 μg/day, respectively. For women and men of all ages fewer than 3% consumed less than the EAR.<ref>[https://www.ars.usda.gov/SP2UserFiles/Place/80400530/pdf/0102/usualintaketables2001-02.pdf/ What We Eat In America, NHANES 2001–2002] {{webarchive|url=https://web.archive.org/web/20150106010550/https://www.ars.usda.gov/SP2UserFiles/Place/80400530/pdf/0102/usualintaketables2001-02.pdf |date=2015-01-06 }}. Table A15: Selenium.</ref>

===Labeling===
For US food and dietary supplement labeling purposes the amount in a serving is expressed as a percent of Daily Value (%DV). For selenium labeling purposes 100% of the Daily Value was 70 μg, but as of May 27, 2016 it was revised to 55 μg.<ref name="FedReg">{{cite web|url=https://www.gpo.gov/fdsys/pkg/FR-2016-05-27/pdf/2016-11867.pdf |title=Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels. FR page 33982.}}</ref><ref>{{cite web | title=Daily Value Reference of the Dietary Supplement Label Database (DSLD) | website=Dietary Supplement Label Database (DSLD) | url=https://www.dsld.nlm.nih.gov/dsld/dailyvalue.jsp | access-date=16 May 2020 | archive-date=7 April 2020 | archive-url=https://web.archive.org/web/20200407073956/https://dsld.nlm.nih.gov/dsld/dailyvalue.jsp | url-status=dead }}</ref> A table of the old and new adult daily values is provided at [[Chemistry:Reference Daily Intake|Reference Daily Intake]].

==Food sources==
Dietary selenium comes from nuts, cereals, meat, mushrooms, [[Biology:Fish|fish]], and eggs. [[Biology:Brazil nut|Brazil nut]]s are the richest ordinary dietary source and could cause selenium toxicity if consumed regularly – though the actual concentration of selenium (as with any plant-based food sources, such as another selenium-accumulating "paradise nut" [[Biology:Lecythis|Lecythis]], belonging to the same family [[Biology:Lecythidaceae|Lecythidaceae]]) is soil-dependent and may vary significantly by geographic location. In descending order of concentration, high levels are also found in kidney, [[Biology:Tuna|tuna]], [[Biology:Crab|crab]], and [[Biology:Lobster|lobster]].<ref>{{cite journal |last = Barclay |first = Margaret N. I. |author2=Allan MacPherson |author3=James Dixon  |year = 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>A list of selenium-rich foods can be found on [http://ods.od.nih.gov/factsheets/selenium.asp#h2 The Office of Dietary Supplements Selenium Fact Sheet].{{usgovpd}}</ref>

The human body's content of selenium is believed to be in the 13–20 milligram range.<ref>The most popular web reference for this is [http://www.osti.gov/energycitations/product.biblio.jsp?osti_id=6424964].</ref>

==Human health==

===Selenium in cancer===
[[File:Selenium paradox.jpg|thumb|300x300px|Selenium at nutritional levels is required for cell [[Homeostasis|homeostasis]], playing a role as an anti-oxidant through selenoproteins, thus, act chemo-preventive against cancer. In contrast, supra-nutritional levels act as pro-oxidant toxic in tumour cells.<ref name=":1">{{cite journal|last1=Razaghi|first1=Ali|last2=Poorebrahim|first2=Mansour|last3=Sarhan|first3=Dhifaf|last4=Björnstedt|first4=Mikael|date=September 2021|title=Selenium stimulates the antitumour immunity: Insights to future research|journal=European Journal of Cancer|volume=155|pages=256–267|doi=10.1016/j.ejca.2021.07.013|pmid=34392068|issn=0959-8049|doi-access=free}}</ref>]]
[[Chemistry:Selenium|Selenium]] has bimodal biological action depending on the concentration. At low nutritional doses, selenium acts as an [[Biology:Antioxidant|antioxidant]] through [[Biology:Selenoprotein|selenoprotein]]s, scavenging [[Biology:Reactive oxygen species|ROS]], supporting cell survival and growth; while, at supra-nutritional higher pharmacological doses, selenium acts as a [[Biology:Pro-oxidant|pro-oxidant]] generating [[Biology:Reactive oxygen species|ROS]] and inducing [[Biology:Cell death|cell death]]. In cancer, studies have been conducted mostly on the benefits of selenium intake in reducing the risk of cancer incidence at the nutritional level; however, fewer studies have explored the effects of supra-nutritional or pharmacological doses of selenium on cancer.<ref name=":1" />

"Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution... Conflicting results including inverse, null and direct associations have been reported for some cancer types... RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results... To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans."<ref>{{cite journal|last1=Vinceti|first1=Marco|last2=Filippini|first2=Tommaso|last3=Del Giovane|first3=Cinzia|last4=Dennert|first4=Gabriele|last5=Zwahlen|first5=Marcel|last6=Brinkman|first6=Maree|last7=Zeegers|first7=Maurice Pa|last8=Horneber|first8=Markus|last9=D'Amico|first9=Roberto|date=January 29, 2018|title=Selenium for preventing cancer|journal=The Cochrane Database of Systematic Reviews|volume=1|issue=2 |pages=CD005195|doi=10.1002/14651858.CD005195.pub4|issn=1469-493X|pmid=29376219|pmc=6491296}}</ref>

==== Selenium in anti-tumour immunity ====
To date, many studies have been conducted on the benefits of selenium intake in reducing the risk of cancer incidence at the nutritional level, indicating that likely selenium functions as an immunostimulator, i.e. reversing the [[Biology:Immunosuppression|immunosuppression]] in tumour microenvironment towards antitumour [[Medicine:Immunity (medical)|immunity]] by activating [[Biology:White blood cell|immune cells]] (e.g. [[Biology:Macrophage|M1 macrophages]] and CD8+ T-lymphocytes, the elevated number of [[Biology:Neutrophil|neutrophil]]s and activated cytotoxic [[Biology:Natural killer cell|NK cells]]) and releasing pro-inflammatory [[Biology:Cytokine|cytokine]]s such as IFNγ and [[Biology:Tumor necrosis factor|TNFα]].<ref name=":1" /> 
[[File:Selenium and anti-tumour immunity.jpg|thumb|300x300px|Selenium can either play a pro-oxidant role inducing ROS, activating the Akt–NF–кB pathway or play an antioxidant role through selenoprotein synthesis such as TXNRD relocating to the nucleus and activating NF-кB, resulting in further activation of leukocytes and pro-inflammatory [[Biology:Cytokine|cytokine]] genes.<ref name=":1" />

]]

===HIV/AIDS===
AIDS appears to involve a slow and progressive decline in levels of selenium in the body. Whether this decline in selenium levels is a direct result of the replication of HIV or related more generally to the overall malabsorption of nutrients by AIDS patients remains debated. Observational studies have found an association between decreased selenium levels and poorer outcomes in patients with HIV, though these studies were mostly done prior to the currently effective treatments with highly active antiretroviral therapy (HAART).  Currently there is inadequate evidence to recommend routine selenium supplementation for HIV patients, and further research is recommended.<ref>{{cite journal |vauthors=Stone CA, Kawai K, Kupka R, Fawzi WW |title=Role of selenium in HIV infection |journal=Nutr. Rev. |volume=68 |issue=11 |pages=671–81 |date=November 2010 |pmid=20961297 |pmc=3066516 |doi=10.1111/j.1753-4887.2010.00337.x }}</ref>

===Mortality===
Selenium supplementation has no effect on overall mortality.<ref>{{cite journal|pmid =22419320|year =2012|last1 =Bjelakovic|first1 =G|last2 =Nikolova|first2 =D|last3 =Gluud|first3 =LL|last4 =Simonetti|first4 =RG|last5 =Gluud|first5 =C|title =Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases|volume =2012|issue =3|pages =CD007176|doi =10.1002/14651858.CD007176.pub2|journal =Cochrane Database of Systematic Reviews|pmc =8407395|editor1-last =Bjelakovic|editor1-first =Goran|type =Submitted manuscript|hdl =10138/136201|hdl-access =free}}</ref>

===Tuberculosis===
As with other types of supplementation, there is no good evidence selenium supplementation helps in the treatment of tuberculosis.<ref>{{cite journal |vauthors=Grobler L, Nagpal S, Sudarsanam TD, Sinclair D |title=Nutritional supplements for people being treated for active tuberculosis |journal=Cochrane Database Syst Rev |issue=6 |pages=CD006086 |year=2016 |volume=2016 |pmid=27355911 |pmc=4981643 |doi=10.1002/14651858.CD006086.pub4 }}</ref>

===Diabetes===

A meta-analysis of four RCTs concluded that there is no support for selenium supplementation for prevention of type 2 diabetes mellitus in Caucasians.<ref>{{cite journal |vauthors=Mao S, Zhang A, Huang S |title=Selenium supplementation and the risk of type 2 diabetes mellitus: a meta-analysis of randomized controlled trials |journal=Endocrine |volume=47 |issue=3 |pages=758–63 |year=2014 |pmid=24858736 |doi=10.1007/s12020-014-0298-7 |s2cid=22669723 }}</ref>

===Human reproductive system===
Abnormally high or low levels of dietary selenium can have an adverse effect on sperm quality, with a consequent lowering of fertility.<ref>{{cite journal  |vauthors=Ahsan U, Kamran Z, Raza I, etal |title=Role of selenium in male reproduction - a review |journal=Anim. Reprod. Sci. |volume=146 |issue=1–2 |pages=55–62 |date=April 2014  |pmid=24613013 |doi=10.1016/j.anireprosci.2014.01.009 |type=Review|doi-access=free }}</ref>

===COVID-19===
During the COVID-19 pandemic, some studies attempted to establish a correlation between selenium plasma level and severity of COVID-19 cases. One study done on 33 patients concluded that low plasma selenium levels were correlated with a high mortality rate among COVID-19 patients. However, the median age of deaths in this study was 89 years old; in contrast, survivors' median age was 69 years old, and the study stated that the causality remains unknown.<ref>{{cite journal | vauthors = Moghaddam A, Heller RA, Sun Q, Seelig J, Cherkezov A, Seibert L, Hackler J, Seemann P, Diegmann J, Pilz M, Bachmann M, Minich WB, Schomburg L | title = Selenium Deficiency Is Associated with Mortality Risk from COVID-19 | journal = Nutrients | volume = 12 | issue = 7 | date = July 2020 | page = 2098 | pmid = 32708526 | pmc = 7400921 | doi = 10.3390/nu12072098 | doi-access = free }}</ref>  
On the other hand, another study revealed that the mean selenium plasma level was within the normal range among all included COVID-19 patients; however, the mean selenium plasma level was elevated among severe cases of COVID-19. This study concluded that there was a significant elevation of selenium serum level among severe cases compared to non-severe cases of COVID-19, and could be correlated with the disease severity.<ref>{{cite journal|doi=10.1080/20905068.2020.1870788|title=Correlation between Micronutrient plasma concentration and disease severity in COVID-19 patients|year=2021|last1=Alkattan|first1=Abdullah|last2=Alabdulkareem|first2=Khaled|last3=Kamel|first3=Amr|last4=Abdelseed|first4=Heba|last5=Almutairi|first5=Yousef|last6=Alsalameen|first6=Eman|journal=Alexandria Journal of Medicine|volume=57|pages=21–27|doi-access=free}}</ref>

=== Mercury poisoning ===
Selenium has a protective effect towards mercury toxicity. Mercury binds to selenium with high affinity, so this metal can inhibit selenium-dependent enzymes. However, increased selenium intake can preserve the enzyme activities, reducing the adverse effects caused by mercury exposure.<ref>{{cite journal |last1=Berry |first1=Marla J. |last2=Ralston |first2=Nicholas V. C. |date=2008-12-01 |title=Mercury Toxicity and the Mitigating Role of Selenium |url=https://doi.org/10.1007/s10393-008-0204-y |journal=EcoHealth |language=en |volume=5 |issue=4 |pages=456–459 |doi=10.1007/s10393-008-0204-y |pmid=19198945 |s2cid=29418315 |issn=1612-9210}}</ref> <ref>{{cite journal |last=Spiller |first=Henry A. |date=2018-05-04 |title=Rethinking mercury: the role of selenium in the pathophysiology of mercury toxicity |url=https://doi.org/10.1080/15563650.2017.1400555 |journal=Clinical Toxicology |volume=56 |issue=5 |pages=313–326 |doi=10.1080/15563650.2017.1400555 |issn=1556-3650 |pmid=29124976|s2cid=4295652 }}</ref>

==Evolution in biology and biosynthetic considerations==

Selenium is incorporated into several prokaryotic selenoprotein families in bacteria, archaea, and eukaryotes as selenocysteine,<ref name="glady">{{cite journal |vauthors=Gladyshev VN, Hatfield DL |title=Selenocysteine-containing proteins in mammals |journal=Journal of Biomedical Science |volume=6 |issue=3 |pages=151–60 |year=1999 |pmid=10343164 |doi=10.1007/BF02255899|url=https://digitalcommons.unl.edu/biochemgladyshev/77 |type=Submitted manuscript }}</ref> where selenoprotein peroxiredoxins protect bacterial and eukaryotic cells against oxidative damage. Selenoprotein families of GSH-Px and the deiodinases of eukaryotic cells seem to have a bacterial [[Biology:Phylogenetics|phylogenetic]] origin. The selenocysteine-containing form occurs in species as diverse as green algae, diatoms, sea urchin, fish and chicken. Selenium enzymes are involved in utilization of the small reducing molecules [[Chemistry:Glutathione|glutathione]] and [[Biology:Thioredoxin|thioredoxin]].

Trace elements involved in GSH-Px and superoxide dismutase enzymes activities, i.e. selenium, [[Chemistry:Vanadium|vanadium]], [[Chemistry:Magnesium|magnesium]], [[Chemistry:Copper|copper]], and [[Chemistry:Zinc|zinc]], may have been lacking in some terrestrial mineral-deficient areas.<ref name="glady" /> Marine organisms retained and sometimes expanded their seleno-proteomes, whereas the seleno-proteomes of some terrestrial organisms were reduced or completely lost. These findings suggest that aquatic life supports selenium utilization, whereas terrestrial habitats lead to reduced use of this trace element.<ref>{{cite journal |vauthors=Lobanov AV, Fomenko DE, Zhang Y, Sengupta A, Hatfield DL, Gladyshev VN |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 |year=2007 |pmid=17880704 |pmc=2375036 |doi=10.1186/gb-2007-8-9-r198 |doi-access=free }}</ref><ref>{{cite journal|title = The selenium content of SEPP1 versus selenium requirements in vertebrates|journal = PeerJ|pmc = 4699779|pmid = 26734501|volume = 3|pages = e1244|doi = 10.7717/peerj.1244|first1 = Sam|last1 = Penglase|first2 = Kristin|last2 = Hamre|first3 = Ståle|last3 = Ellingsen|year = 2015 | doi-access=free }}</ref> Marine fishes and vertebrate thyroid glands have the highest concentration of selenium and iodine. From about 500 Mya, freshwater and terrestrial plants slowly optimized the production of "new" endogenous antioxidants such as [[Chemistry:Ascorbic acid|ascorbic acid]] (Vitamin C), [[Chemistry:Polyphenol|polyphenol]]s (including flavonoids), [[Chemistry:Tocopherol|tocopherol]]s, etc. A few of these appeared more recently, 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 [[Earth:Jurassic|Jurassic]] period.

About 200 Mya, new selenoproteins were developed as mammalian GSH-Px enzymes.<ref>{{cite journal  |vauthors=Castellano S, Novoselov SV, Kryukov GV, etal |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 |year=2004 |pmid=14710190 |pmc=1298953 |doi=10.1038/sj.embor.7400036}}</ref><ref>{{cite journal |vauthors=Kryukov GV, Gladyshev VN |title=The prokaryotic selenoproteome |journal=EMBO Reports |volume=5 |issue=5 |pages=538–43 |year=2004 |pmid=15105824 |pmc=1299047 |doi=10.1038/sj.embor.7400126}}</ref><ref>{{cite journal |vauthors=Wilting R, Schorling S, Persson BC, Böck A |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 |year=1997 |pmid=9102456 |doi=10.1006/jmbi.1996.0812}}</ref><ref>{{cite journal |vauthors=Zhang Y, Fomenko DE, Gladyshev VN |title=The microbial selenoproteome of the Sargasso Sea |journal=Genome Biology |volume=6 |issue=4 |pages=R37 |year=2005 |pmid=15833124 |pmc=1088965 |doi=10.1186/gb-2005-6-4-r37 |doi-access=free }}</ref>

==See also==
{{div col|colwidth=20em}}
* [[:Category:Biology and pharmacology of chemical elements|Biology and pharmacology of chemical elements]]
* {{annotated link|Biology:Action potential}}
* {{annotated link|Biology:Calcium in biology}}
* {{annotated link|Biology:Iodine in biology}}
* {{annotated link|Biology:Magnesium in biology}}
* {{annotated link|Biology:Membrane potential}}
* {{annotated link|Biology:Potassium in biology}}
* {{annotated link|Biology:Selenium yeast}}
* {{annotated link|Biology:Sodium in biology}}
* {{annotated link|Biology:SEPP1}}
{{div col end}}

==References==
{{Reflist}}

==External links==
{{Commons|Selenium}}
*[https://www.webelements.com/webelements/elements/text/Se/index.html WebElements – Selenium]
*[https://ods.od.nih.gov/factsheets/Selenium-Consumer/ NIH – Selenium Fact Sheet for Consumers]
*[https://www.sas-centre.org/assays/trace-elements/selenium Assay – Supra-Regional Assay Service]
*[https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=153&tid=28 ATSDR – Toxicological Profile for Selenium]
*[https://elements.vanderkrogt.net/element.php?sym=Se Elementymology & Elements Multidict – Selenium page by Peter van der Krogt]

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{{Antioxidants}}

{{DEFAULTSORT:Selenium In Biology}}
[[Category:Antioxidants]]
[[Category:Biological systems]]
[[Category:Biology and pharmacology of chemical elements]]
[[Category:Chalcogens]]
[[Category:Dietary minerals]]
[[Category:Selenium]]

{{Sourceattribution|Selenium in biology}}