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Line 1: {{Short description|Chemical compound {{distinguish|creatinine|keratin}} {{pp-pc}} Line 86: }} '''Creatine''' ({{IPAc-en|ˈ|k|r|iː|ə|t|iː|n}} or {{IPAc-en|ˈ|k|r|iː|ə|t|ɪ|n}})<ref>{{cite book|title=Essentials of Creatine in Sports and Health | veditors = Stout JR, Antonio J, Kalman E |year=2008|publisher=Humana|isbn=978-1-59745-573-2}}</ref> is an [[organic compound]] with the nominal formula {{chem2|(H2N)(HN)CN(CH3)CH2CO2H}}. It exists in various [[tautomer]]s in solutions (among which are neutral form and various [[zwitterionic]] forms). Creatine is found in [[vertebrate]]s, where it facilitates recycling of [[adenosine triphosphate]] (ATP), primarily in [[muscle]] and [[brain]] tissue. Recycling is achieved by converting [[adenosine diphosphate]] (ADP) back to ATP via donation of [[phosphate group]]s. Creatine also acts as a [[Buffer solution|buffer]].<ref name="pmid26202197">{{cite journal | vauthors = Barcelos RP, Stefanello ST, Mauriz JL, Gonzalez-Gallego J, Soares FA | title = Creatine and the Liver: Metabolism and Possible Interactions | journal = Mini Reviews in Medicinal Chemistry | volume = 16 | issue = 1 | pages = 12–8 | year = 2016 | pmid = 26202197 | doi = 10.2174/1389557515666150722102613 | quote = The process of creatine synthesis occurs in two steps, catalyzed by L-arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase (GAMT), which take place mainly in kidney and liver, respectively. This molecule plays an important energy/pH buffer function in tissues, and to guarantee the maintenance of its total body pool, the lost creatine must be replaced from diet or de novo synthesis. }}</ref> ==History== Line 95: The discovery of phosphocreatine<ref>{{cite book | last = Saks | first = Valdur | name-list-style = vanc | year = 2007 | title = Molecular system bioenergetics: energy for life | url = https://archive.org/details/molecularsystemb00saks | url-access = limited | place = Weinheim | publisher = Wiley-VCH | page = [https://archive.org/details/molecularsystemb00saks/page/n31 2] | isbn = 978-3-527-31787-5 }}</ref><ref name="ochoa">{{cite book | last = Ochoa | first = Severo | name-list-style = vanc | year = 1989 | editor-last = Sherman | editor-first = E. J. | editor2-last = National Academy of Sciences | title = David Nachmansohn | series = Biographical Memoirs | publisher = National Academies Press | volume = 58 | pages = 357–404 | isbn = 978-0-309-03938-3 }}</ref> was reported in 1927.<ref>{{cite journal | vauthors = Eggleton P, Eggleton GP | title = The Inorganic Phosphate and a Labile Form of Organic Phosphate in the Gastrocnemius of the Frog | journal = The Biochemical Journal | volume = 21 | issue = 1 | pages = 190–5 | year = 1927 | pmid = 16743804 | pmc = 1251888 | doi = 10.1042/bj0210190 }}</ref><ref>{{cite journal | vauthors = Fiske CH, Subbarow Y | title = The nature of the 'inorganic phosphate' in voluntary muscle | journal = Science | volume = 65 | issue = 1686 | pages = 401–3 | date = April 1927 | pmid = 17807679 | doi = 10.1126/science.65.1686.401 | bibcode = 1927Sci....65..401F }}</ref><ref name=ochoa/> In the 1960s, creatine kinase (CK) was shown to phosphorylate ADP using phosphocreatine (PCr) to generate ATP. It follows that ATP - not PCr - is directly consumed in muscle contraction. CK uses creatine to "buffer" the ATP/ADP ratio.<ref>{{cite book | vauthors = Wallimann T |chapter=Introduction – Creatine: Cheap Ergogenic Supplement with Great Potential for Health and Disease | veditors = Salomons GS, Wyss M |title=Creatine and Creatine Kinase in Health and Disease | url = https://archive.org/details/creatinecreatine00salo | url-access = limited |pages=[https://archive.org/details/creatinecreatine00salo/page/n16 1]–16 |year=2007 |isbn=978-1-4020-6486-9 |publisher=Springer }}</ref> While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the [[1992 Summer Olympics|1992 Olympics]] in [[Barcelona]]. An August 7, 1992 article in ''[[The Times]]'' reported that [[Linford Christie]], the gold medal winner at 100 meters, had used creatine before the Olympics (however, it should also be [[image:Phosphocreatine.svg|thumb|left|[[Phosphocreatine]] relays phosphate to ADP.]] Line 116: ===Genetic deficiencies=== Genetic deficiencies in the creatine biosynthetic pathway lead to various [[cerebral creatine deficiency|severe neurological defects]].<ref>{{Cite web |url=https://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602360 |title=L-Arginine:Glycine Amidinotransferase |access-date=16 August 2010 |archive-date=24 August 2013 |archive-url=https://web.archive.org/web/20130824195046/http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602360 |url-status=live }}</ref> Clinically, there are three distinct disorders of creatine metabolism, termed [[Cerebral creatine deficiency|cerebral creatine deficiencies]]. Deficiencies in the two synthesis enzymes can cause [[Arginine:glycine amidinotransferase|L-arginine:glycine amidinotransferase deficiency]] caused by variants in ''[[GATM (gene)|GATM]]'' and [[guanidinoacetate methyltransferase deficiency]], caused by variants in ''[[GAMT]]''. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, [[creatine transporter defect]], is caused by mutations in ''[[SLC6A8]]'' and is inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.<ref name="creatinedefects">{{cite journal | vauthors = Braissant O, Henry H, Béard E, Uldry J | title = Creatine deficiency syndromes and the importance of creatine synthesis in the brain | journal = Amino Acids | volume = 40 | issue = 5 | pages = 1315–24 | date = May 2011 | pmid = 21390529 | doi = 10.1007/s00726-011-0852-z | s2cid = 13755292 | url = https://serval.unil.ch/resource/serval:BIB_CE3937F9A69E.P001/REF.pdf | access-date = 8 July 2019 | archive-date = 10 March 2021 | archive-url = https://web.archive.org/web/20210310001947/https://serval.unil.ch/resource/serval:BIB_CE3937F9A69E.P001/REF.pdf | url-status = live }}</ref> ===Vegetarians=== Line 156: ===Cognitive performance=== Creatine is sometimes reported to have a beneficial effect on brain function and cognitive processing, although the evidence is difficult to interpret systematically and the appropriate dosing is unknown.<ref name=":8">{{Cite journal|last1=Dolan|first1=Eimear|last2=Gualano|first2=Bruno|last3=Rawson|first3=Eric S.|date=2019-01-02|title=Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury|url=https://www.tandfonline.com/doi/full/10.1080/17461391.2018.1500644|journal=European Journal of Sport Science|language=en|volume=19|issue=1|pages=1–14|doi=10.1080/17461391.2018.1500644|pmid=30086660|s2cid=51936612|issn=1746-1391|access-date=11 October 2021|archive-date=29 October 2021|archive-url=https://web.archive.org/web/20211029174808/https://www.tandfonline.com/doi/full/10.1080/17461391.2018.1500644|url-status=live}}</ref><ref name=":9">{{Cite journal|last1=Rawson|first1=Eric S.|last2=Venezia|first2=Andrew C.|date=May 2011|title=Use of creatine in the elderly and evidence for effects on cognitive function in young and old|url=http://link.springer.com/10.1007/s00726-011-0855-9|journal=Amino Acids|language=en|volume=40|issue=5|pages=1349–1362|doi=10.1007/s00726-011-0855-9|pmid=21394604|s2cid=11382225|issn=0939-4451|access-date=11 October 2021|archive-date=19 June 2022|archive-url=https://web.archive.org/web/20220619121803/https://link.springer.com/article/10.1007/s00726-011-0855-9|url-status=live}}</ref> The greatest effect appears to be in individuals who are [[Stress (biology)|stressed]] (due, for instance, to [[sleep deprivation]]) or cognitively impaired.<ref name=":8" /><ref name=":9" /><ref>{{Cite journal|vauthors = Gordji-Nejad|date= 2024 |title= Single dose creatine improves cognitive performance and induces changes in cerebral high energy phosphates during sleep deprivation A 2018 [[systematic review]] found that "generally, there was evidence that short term memory and intelligence/reasoning may be improved by creatine administration", whereas for other cognitive domains "the results were conflicting".<ref>{{cite journal |title=Effects of creatine supplementation on cognitive function of healthy individuals: A systematic review of randomized controlled trials |journal=[[Experimental Gerontology]] |date=2018 |volume=108 |pages=166–173 |pmc=6093191 |last1=Avgerinos |first1=K. I. |last2=Spyrou |first2=N. |last3=Bougioukas |first3=K. I. |last4=Kapogiannis |first4=D. |doi=10.1016/j.exger.2018.04.013 |pmid=29704637 }}</ref> Another 2023 review initially found evidence of improved memory function.<ref>{{cite journal |title=Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials |journal=[[Nutrition Reviews]] |date=2023 |volume=81 |issue=4 |pages=416–27 |doi=10.1093/nutrit/nuac064 |pmid=35984306 |last1=Prokopidis |first1=Konstantinos |last2=Giannos |first2=Panagiotis |last3=Triantafyllidis |first3=Konstantinos K. |last4=Kechagias |first4=Konstantinos S. |last5=Forbes |first5=Scott C. |last6=Candow |first6=Darren G. |pmc=9999677 }}</ref> However, it was later determined that faulty statistics lead to the statistical significance and after fixing the "double counting", the effect was only significant in older adults.<ref>{{cite journal |last1=Prokopidis |first1=Konstantinos |last2=Giannos |first2=Panagiotis |last3=Triantafyllidis |first3=Konstantinos K |last4=Kechagias |first4=Konstantinos S |last5=Forbes |first5=Scott C |last6=Candow |first6=Darren G |title=Author's reply: Letter to the Editor: Double counting due to inadequate statistics leads to false-positive findings in "Effects of creatine supplementation on memory in healthy individuals: a systematic review and meta-analysis of randomized controlled trials" |journal=Nutrition Reviews |date=16 January 2023 |volume=81 |issue=11 |pages=1497–1500 |doi=10.1093/nutrit/nuac111 |pmid=36644912 |url=https://academic.oup.com/nutritionreviews/advance-article-abstract/doi/10.1093/nutrit/nuac111/6987897?redirectedFrom=fulltext&login=false |access-date=31 August 2023}}</ref> A 2023 ===Muscular disease=== Line 193: A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.<ref name="Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM 2009 215–23">{{cite journal | vauthors = Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM | title = Does creatine supplementation hinder exercise heat tolerance or hydration status? A systematic review with meta-analyses | journal = Journal of Athletic Training | volume = 44 | issue = 2 | pages = 215–23 | year = 2009 | pmid = 19295968 | pmc = 2657025 | doi = 10.4085/1062-6050-44.2.215 }}</ref><ref name="Dalbo VJ, Roberts MD, Stout JR, Kerksick CM 2008 567–73">{{cite journal | vauthors = Dalbo VJ, Roberts MD, Stout JR, Kerksick CM | title = Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration | journal = British Journal of Sports Medicine | volume = 42 | issue = 7 | pages = 567–73 | date = July 2008 | pmid = 18184753 | doi = 10.1136/bjsm.2007.042473 | s2cid = 12920206 | url = http://hdl.cqu.edu.au/10018/55591 | access-date = 27 December 2021 | archive-date = 19 June 2022 | archive-url = https://web.archive.org/web/20220619121814/https://acquire.cqu.edu.au/articles/journal_contribution/Putting_to_rest_the_myth_of_creatine_supplementation_leading_to_muscle_cramps_and_dehydration/13449578 | url-status = live }}</ref>
=== Renal function === | |||