Editing Creatine (section)

==History==
Creatine was first identified in 1832 when [[Michel Eugène Chevreul]] isolated it from the basified water-extract of [[skeletal muscle]]. He later named the crystallized precipitate after the [[Ancient Greek|Greek]] word for meat, {{lang|grc|κρέας}} (''{{lang|grc-Latn|kreas}}''). In 1928, creatine was shown to exist in [[Tautomer|equilibrium]] with [[creatinine]].<ref>{{cite journal | vauthors = Cannan RK, Shore A | title = The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine | journal = The Biochemical Journal | volume = 22 | issue = 4 | pages = 920–9 | year = 1928 | pmid = 16744118 | pmc = 1252207 | doi = 10.1042/bj0220920 }}</ref> Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement.<ref>{{cite book|chapter=Overview of Creatine Metabolism| first1 = Jeff S. | last1 = Volek | first2 = Kevin D. | last2 = Ballard | first3 = Cassandra E. | last3 = Forsythe | name-list-style = vanc |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|pages=1–23}}</ref>

In 1912, [[Harvard University]] researchers [[Otto Folin]] and [[Willey Glover Denis]] found evidence that ingesting creatine can dramatically boost the creatine content of the muscle.<ref>{{cite journal |last1=Folin |first1=Otto |last2=Denis |first2=W |name-list-style=vanc |title=Protein metabolism from the standpoint of blood and tissue analysis |journal=Journal of Biological Chemistry |volume=12 |issue=1 |year=1912 |pages=141–61 |doi=10.1016/S0021-9258(18)88723-3 |url=http://www.jbc.org/content/12/1/141.full.pdf+html |doi-access=free |access-date=8 May 2018 |archive-date=3 May 2018 |archive-url=https://web.archive.org/web/20180503042522/http://www.jbc.org/content/12/1/141.full.pdf+html |url-status=live }}</ref><ref>{{Cite journal |last=Antonio |first=Jose |date=February 8, 2021 |title=Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? |journal=Journal of the International Society of Sports Nutrition |volume=18 |issue=1 |page=13 |doi=10.1186/s12970-021-00412-w |pmid=33557850 |pmc=7871530 |doi-access=free }}</ref> In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered [[phosphocreatine]] (creatine phosphate), and determined that creatine is a key player in the metabolism of [[skeletal muscle]]. It is naturally formed in vertebrates.<ref>{{cite journal | vauthors = Brosnan JT, da Silva RP, Brosnan ME | title = The metabolic burden of creatine synthesis | journal = Amino Acids | volume = 40 | issue = 5 | pages = 1325–31 | date = May 2011 | pmid = 21387089 | doi = 10.1007/s00726-011-0853-y | s2cid = 8293857 }}</ref>

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, the enzyme [[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 noted that Christie was found guilty of doping later in his career).<ref>{{cite web | url=https://www.telegraph.co.uk/sport/othersports/athletics/4768790/Shadow-over-Christies-reputation.html | title=Shadow over Christie's reputation | date=22 August 2000 }}</ref> An article in ''Bodybuilding Monthly'' named [[Sally Gunnell]], who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler [[Colin Jackson]] began taking creatine before the Olympics.<ref>{{cite web |url=http://www.nationalreviewofmedicine.com/issue/2004_07_30/feature07_14.html |archive-url=https://web.archive.org/web/20061116021537/http://www.nationalreviewofmedicine.com/issue/2004_07_30/feature07_14.html |url-status=dead |archive-date=2006-11-16 |title=Supplement muscles in on the market |publisher=National Review of Medicine |date=2004-07-30 |access-date=2011-05-25 }}</ref><ref>{{cite book |title=Creatine |last=Passwater |first=Richard A. |name-list-style=vanc |year=2005 |isbn=978-0-87983-868-3 |page=9 |publisher=McGraw Hill Professional |url=https://books.google.com/books?id=umy67wOLOckC |access-date=8 May 2018 |archive-date=19 June 2022 |archive-url=https://web.archive.org/web/20220619121759/https://books.google.com/books?id=umy67wOLOckC |url-status=live }}</ref>

[[image:Phosphocreatine.svg|thumb|left|class=skin-invert-image|[[Phosphocreatine]] relays phosphate to ADP.]]
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called [[Experimental and Applied Sciences]] (EAS) introduced the compound to the sports nutrition market under the name ''Phosphagen''.<ref>{{Cite book |last= Stoppani |first= Jim |name-list-style= vanc |title= Creatine new and improved: recent high-tech advances have made creatine even more powerful. Here's how you can take full advantage of this super supplement |publisher= [[Muscle & Fitness]] |date= May 2004 |url= http://findarticles.com/p/articles/mi_m0801/is_5_65/ai_n6005938 |access-date= 2010-03-29 |archive-date= 11 July 2012 |archive-url= https://archive.today/20120711163221/http://findarticles.com/p/articles/mi_m0801/is_5_65/ai_n6005938/ |url-status= live }}</ref> Research performed thereafter demonstrated that the consumption of high [[Glycemic index|glycemic]] carbohydrates in conjunction with creatine increases creatine muscle stores.<ref name=":4">{{cite journal | vauthors = Green AL, Hultman E, Macdonald IA, Sewell DA, Greenhaff PL | title = Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans | journal = The American Journal of Physiology | volume = 271 | issue = 5 Pt 1 | pages = E821-6 | date = November 1996 | pmid = 8944667 | doi = 10.1152/ajpendo.1996.271.5.E821 }}</ref>

[[image:Creatinine-tautomerism-2D-skeletal.svg|left|thumb|class=skin-invert-image|The cyclic derivative creatinine exists in equilibrium with its tautomer and with creatine.]]