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'''Magnesium''' (chemical or element symbol '''Mg''') is an essential [[mineral]] in the human body. It plays a key role in [[DNA]] and [[RNA]] synthesis and in the production of [[ATP]]. It is a cofactor in more than 300 [[enzyme]] systems.<ref name="NihMagnesium">{{Citation | publisher = National Institutes of Health: Office of Dietary Supplements | title = Magnesium: Fact sheet for health professionals | access-date = 22 May 2018| date = 2 March 2018 | url = https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/}}</ref> Muscle and bone comprise 90% of the body's magnesium content. A serum value of 75โ95โmmol/L is considered normal but some research would indicate that serum levels less than 85โmmol/l should be considered deficient. An individual may be profoundly deficient in total body or intracellular Mg, yet have a serum value within normal range.<ref name=":1">{{Cite journal|last = Schwalfenberg|first = Gerry K. | last2 = Genuis | first2 = Stephen J. | date = 2017 | title=The Importance of Magnesium in Clinical Healthcare|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637834/|journal=Scientifica|volume=|doi=10.1155/2017/4179326|issn=2090-908X|pmc=5637834|pmid=29093983}}</ref> ==Role in the body== ==Deficiency== Symptoms of magnesium deficiency include loss of appetite, [[nausea]], vomiting, [[fatigue]], and weakness. As magnesium deficiency worsens, numbness, tingling, muscle contractions and cramps, [[seizures]], personality changes, abnormal heart rhythms, and coronary spasms can occur. Severe magnesium deficiency can result in [[hypocalcemia]] or [[hypokalemia]] (low serum calcium or potassium levels, respectively) because mineral homeostasis is disrupted.<ref name="NihMagnesium" /> Magnesium deficiency disrupts the [[Hypothalamic-pituitary-adrenal axis|HPA axis]] and increases susceptibility to physiological damage produced by stress. Deficiency can promote activation of the N-methyl-D-aspartic acid (NMDA) receptor which triggers inflammatory pathways and [[cortisol]] release.<ref>{{Cite journal|last = Rayssiguier | first = Yves | last2 = Libako | first2 = Patrycja | last3 = Nowacki | first3 = Wojciech | last4 = Rock | first4 = Edmond | date = Jun 2010 | title = Magnesium deficiency and metabolic syndrome: stress and inflammation may reflect calcium activation | url =https://www.ncbi.nlm.nih.gov/pubmed/20513641|journal=Magnesium Research|volume=23|issue=2 | pages = 73โ80|doi=10.1684/mrh.2010.0208|issn=1952-4021|pmid=20513641|pmc=|quote=|access-date=|via=}}</ref> People with [[gastrointestinal]]<ref name="NihMagnesium" /> disorders and [[chronic fatigue syndrome]] are at higher risk of magnesium deficiency. Deficiency increases the risk of [[osteoporosis]]. Magnesium supplementation may help prevent [[migraine]].<ref name="NihMagnesium" /> == Forms of administration== Magnesium may be taken as an oral supplement but may not be well absorbed. Magnesium oxide and citrate are poorly absorbed forms compared to glycinate and orotate.<ref name=":1" /> Magnesium malate is another popular form. Other forms of magnesium administration include transdermal magnesium and intramuscular magnesium sulphate injections. Magnesium is hypotonic. Administration can cause water to flow into cells in the local area where it is applied, which can cause a temporary stinging sensation. ==In human disease== === Chronic fatigue syndrome === In 1991, Cox et al., performed a randomized, double-blind, placebo-controlled trial of 20 United Kingdom [[CFS|chronic fatigue syndrome]] (CFS) patients finding that the subjects with CFS had lower [[red blood cell magnesium]] than healthy controls. Patients treated with intramuscular magnesium sulphate for six weeks had higher self-reported energy levels, better emotional state and less pain on the Nottingham health profile when compared to placebo.<ref name=":0">{{Cite journal | title = Red blood cell magnesium and chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/1672392|journal=Lancet (London, England) | date = 1991-03-30|issn=0140-6736|pmid=1672392 | pages = 757โ760|volume=337|issue=8744|first = I.M. | last = Cox | first2 = M.J. | last2 = Campbell | first3 = D. | last3 = Dowson}}</ref> In contrast, three subsequent caseโreport studies, two in the UK (Clague et al., 1992<ref>Clague JE, Edwards RH, Jackson MJ (1992). Intravenous magnesium loading in chronic fatigue syndrome. Lancet 340: 124โ125. PMID:1352002</ref> and Hinds et al., 1994<ref>Hinds G, Bell NP, McMaster D, McCluskey DR (1994). Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome. Ann Clin Biochem 31 (Pt 5): 459โ461. DOI:10.1177/000456329403100506</ref>), and one in the Netherlands (Swanink et al., 1995<ref>{{Cite journal|last = Swanink|first = C.M. | authorlink = | last2 = Vercoulen | first2 = J. H. | authorlink2 = | last3 = Bleijenberg | first3 = G. | authorlink3 = Gijs Bleijenberg | last4 = Fennis | first4 = J.F. | authorlink4 = | last5 = Galama | first5 = J.M. | author-link5 = | last6 = van der Meer | first6 = J.W. | authorlink6 = Jos van der Meer | date = May 1995 | title = Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group | url =https://www.ncbi.nlm.nih.gov/pubmed/7738491|journal=Journal of Internal Medicine|volume=237|issue=5 | pages = 499โ506|issn=0954-6820|pmid=7738491|quote=|via=}}</ref>), did not find magnesium deficiency in CFS trial subjects. === X-MEN === A 2014 study found magnesium transporter issues were linked to chronic [[Epstein-Barr virus]] infection, decreased [[Natural killer cell]] function, and neoplasia (sometimes-cancerous growths).<ref name="X-men_disease_1">{{Citation | last1 = Li | first1 = F.-Y. | authorlink1 = | last2 = Chaigne-Delalande | first2 = B | authorlink2 = | last3 = Su | first3 = H| last4 = Matthews | first4 = H| last5 = Lenardo | first5 = M.J. | authorlink3 = | display-authors =| title = XMEN disease: a new primary immunodeficiency affecting Mg2+ regulation of immunity against Epstein-Barr virus. | journal = Blood| year = 2014 | doi = 10.1182/blood-2013-11-538686 }}</ref> This disorder, termed 'X-MEN' (for X-linked, EBV, and neoplasia) was identified as a [https://en.wikipedia.org/wiki/X-linked_recessive_inheritance recessive, X-linked disorder] that would therefore be many times more common in men. Due to magnesium's role as a 'second messenger', this magnesium transporter disorder also would result in a primary [[immunodeficiency]] that would worsen with age.<ref name="X-men_disease_1" /> Patients also have impaired T-cell activation and decreased natural killer (NK) cell function due to a decreased expression of "the NK stimulatory receptor 'natural-killer group 2, member D' (NKG2D)."<ref name="X-men_disease_2" /> Although T-cells are affected, there is no direct evidence of B-cell effects in X-MEN disease.<ref name="X-men_disease_2">{{Citation | last1 = Ravell | first1 = J | authorlink1 = | last2 = Chaigne-Delalande | first2 = B | authorlink2 = | last3 = Lenardo | first3 = M| title = XMEN disease: a combined immune deficiency with magnesium defect. | journal = Current Opinion in Pediatrics | year = 2014| doi = 10.1097/MOP.0000000000000156}}</ref> Since chronic Epstein-Barr virus infection has been associated with chronic fatigue syndrome, this error in magnesium transport may be worth considering in male patients, especially with slow onset and history of childhood infection.<ref name="X-men_disease_1" /> ===Mast cell activation disorder=== Magnesium is a cofactor in the production of [[diamine oxidase]]. It is an enzyme that breaks down [[histamine]], which is released by [[mast cell]]s. ==Migraine == Magnesium has been shown to be effective for headaches and for [[migraine#migraine_prevention|migraine prevention]].<ref name="NCCIH">{{Cite web|url=https://www.nccih.nih.gov/health/providers/digest/dietary-supplements-for-headaches-science | title = Dietary Supplements for Headaches: What the Science Says|last = | first = | authorlink = | date = | website = [[National Center for Complementary and Integrative Health]]|language=en|archive-url=|archive-date=|url-status=|access-date=2021-10-13}}</ref><ref name="Sun2011">{{Cite journal|last = Sun-Edelstein | first = Christina | authorlink = | last2 = Mauskop | first2 = Alexander | authorlink2 = | date = Mar 2011 | title = Alternative Headache Treatments: Nutraceuticals, Behavioral and Physical Treatments: March 2011|url=https://onlinelibrary.wiley.com/doi/10.1111/j.1526-4610.2011.01846.x|journal=Headache: The Journal of Head and Face Pain|language=en|volume=51|issue=3 | pages = 469โ483|doi=10.1111/j.1526-4610.2011.01846.x|pmc=|pmid=|access-date=|quote=|via=}}</ref><ref name="Barmherzig2021">{{Cite journal|last = Barmherzig|first = Rebecca | last2 = Rajapakse | first2 = Thilinie | date = 2021-05-10 | title = Nutraceuticals and Behavioral Therapy for Headache|url=https://doi.org/10.1007/s11910-021-01120-3|journal=Current Neurology and Neuroscience Reports|language=en|volume=21|issue=7 | pages = 33|doi=10.1007/s11910-021-01120-3|issn=1534-6293}}</ref><ref name="Sun2009">{{Cite journal|last = Sun-Edelstein | first = Christina | authorlink = | last2 = Mauskop | first2 = Alexander | authorlink2 = | date = Jun 2009 | title = Foods and Supplements in the Management of Migraine Headaches|url=https://journals.lww.com/clinicalpain/Abstract/2009/06000/Foods_and_Supplements_in_the_Management_of.15.aspx|journal=The Clinical Journal of Pain|language=en-US|volume=25|issue=5 | pages = 446โ452|doi=10.1097/AJP.0b013e31819a6f65|issn=0749-8047|pmc=|pmid=|access-date=|quote=|via=}}</ref> == Notable studies == * 1991, Red blood cell magnesium and chronic fatigue syndrome<ref name=":0" /> - ([[pubmed:1672392|Abstract]]) * 1994, Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome<ref>{{Cite journal | title = Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome|url=https://www.ncbi.nlm.nih.gov/pubmed/7832571|journal=Annals of Clinical Biochemistry | date = Sep 1994|issn=0004-5632|pmid=7832571 | pages = 459โ461|volume=31|issue = Pt 5|doi=10.1177/000456329403100506|first = G. | last = Hinds | first2 = N.P. | last2 = Bell | first3 = D. | last3 = McMaster | first4 = D.R. | last4 = McCluskey}}</ref> - ([[pubmed:7832571|Abstract]]) * 1997, Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue<ref>{{Cite journal|last = Moorkens | first = G. | last2 = Manuel y Keenoy | first2 = B. | last3 = Vertommen | first3 = J. | last4 = Meludu | first4 = S. | last5 = Noe | first5 = M. | last6 = De Leeuw | first6 = I. | date = Dec 1997 | title = Magnesium deficit in a sample of the Belgian population presenting with chronic fatigue|url=https://www.ncbi.nlm.nih.gov/pubmed/9513929|journal=Magnesium Research|volume=10|issue=4 | pages = 329โ337|issn=0953-1424|pmid=9513929}}</ref> - ([[pubmed:9513929|Abstract]]) * 2006, Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients<ref>{{Cite journal|last = McCully|first = Kevin K | author-link = | last2 = Malucelli | first2 = Emil | authorlink2 = | last3 = Iotti | first3 = Stefano | date = 2006-01-11 | title = Increase of free Mg2+ in the skeletal muscle of chronic fatigue syndrome patients|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360067/|journal=Dynamic Medicine|volume=5|issue=|pages=1|doi=10.1186/1476-5918-5-1|issn=1476-5918|pmc=1360067|pmid=16405724|quote=|via=}}</ref> - ([https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1360067/ Full text]) == See also == * [[Electrolyte]] * [[Ion transportation]] * [[:Category:Minerals|Minerals]] * [[Red blood cell magnesium test]] * [[Migraine]] ==Learn more== *[https://www.ncbi.nlm.nih.gov/pubmed/?term=magnesium+chronic+fatigue+syndrome PubMed - magnesium and CFS] * [https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ National Institutes of Health: Office of Dietary Supplements] *[http://lpi.oregonstate.edu/mic/minerals/magnesium Magnesium-Linus Pauling Institute Micronutrient Information Center] ==References== {{Reflist}} [[Category:Potential treatments]] [[Category:Supplements]] [[Category:Minerals]] [[Category:Nutrients]] [[Category:Chemical elements]] [[Category:Electrolytes]] [[Category:Depression alternative treatments]] [[Category:Depression treatments]] [[Category:Antimigraine agents]]
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