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Revision as of 08:31, 20 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,044 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 20:16, 30 December 2024 edit undoMarchantiophyta (talk | contribs)Extended confirmed users641 edits rm claim backed by a 20-year-old citation & contradicted by more recent sources cited further down the sectionTags: Visual edit Mobile edit Mobile web edit
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			{{Short description|Chemical compound}}
	{{For|the use of creatine to increase athletic performance|Creatine supplements}}
	{{Distinguish|creatinine}}		{{distinguish|creatinine|keratin}}
			{{pp-pc}}
	{{Chembox		{{pp-pc}}
			{{Use dmy dates|date=January 2018}}
	| Watchedfields = changed
			{{chembox
	| verifiedrevid = 407787866
			| Verifiedfields = changed
	| ImageFileL1 = Creatine2.png
			| Watchedfields = changed
	| ImageFileL1_Ref = {{chemboximage|correct|??}}
			| verifiedrevid = 464366517
	| ImageSizeL1 = 121
			| ImageFile = CreatineStructure.png
	| ImageNameL1 = Skeletal formula of zwitterionic creatine
			| ImageFile_Ref = {{chemboximage|correct|??}}
	| ImageFileR1 = Creatine-3d.png
			| ImageClass = skin-invert
	| ImageFileR1_Ref = {{Chemboximage|correct|??}}
			| ImageCaption = Skeletal formula of neutral form of creatine
	| ImageSizeR1 = 121
	| ImageNameR1 = Spacefill model of zwitterionic creatine		| ImageName = Skeletal formula of neutral form of creatine
			| ImageFile1 = CreatineZwitter.png
	| IUPACName = 2-(Methylguanidino)ethanoic acid
			| ImageFile1_Ref = {{chemboximage|correct|??}}
	| SystematicName = 2-(1-Methylcarbamimidamido)acetic acid{{Reference necessary|date=February 2011}}
			| ImageClass1 = skin-invert
	| OtherNames = Creatin<br />
			| ImageCaption1 = Skeletal formula of one of the ] forms of creatine
	Kreatin<br />
			| ImageName1 = Skeletal formula of one of ] forms of creatine
	(α-Methylguanido)acetic acid
			| ImageFile2 = File:Creatine zwitterion ball.png
	| Section1 = {{Chembox Identifiers
			| ImageFile2_Ref = {{chemboximage|correct|??}}
	| CASNo = 57-00-1
			| ImageCaption2 = Ball and stick model of one zwitterionic form of creatine
	| CASNo_Ref = {{cascite|correct|CAS}}
	| PubChem = 586		| ImageSize2 = 160
			| ImageName2 = Ball and stick model of creatine
	| PubChem_Ref = {{Pubchemcite|correct|PubChem}}
			| SystematicName = 2-acetic acid
	| ChemSpiderID = 566
			| OtherNames = ''N''-Carbamimidoyl-''N''-methylglycine; Methylguanidoacetic acid; ''N''-amidinosarcosine
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| Section1 = {{Chembox Identifiers
	| UNII = MU72812GK0
			| CASNo = 57-00-1
	| UNII_Ref = {{fdacite|correct|FDA}}
			| CASNo_Ref = {{cascite|correct|CAS}}
	| EINECS = 200-306-6
			| PubChem = 586
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
			| ChemSpiderID = 566
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| UNII = MU72812GK0
			| UNII_Ref = {{fdacite|correct|FDA}}
			| EINECS = 200-306-6
	| DrugBank = DB00148		| DrugBank = DB00148
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| KEGG = C00300
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG = C00300
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| MeSHName = Creatine		| MeSHName = Creatine
	| ChEBI_Ref = {{ebicite|correct|EBI}}		| ChEBI = 16919
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 57947		| ChEMBL = 283800
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 283800
			| RTECS = MB7706000
	| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| RTECS = MB7706000		| Beilstein = 907175
			| Gmelin = 240513
	| ATCCode_prefix = C01
			| 3DMet = B00084
	| ATCCode_suffix = EB06
			| SMILES = CN(CC(=O)O)C(=N)N
	| Beilstein = 907175
			| StdInChI = 1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)
	| Gmelin = 240513
			| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| 3DMet = B00084
			| StdInChIKey = CVSVTCORWBXHQV-UHFFFAOYSA-N
	| SMILES = CN(CC(O)=O)C(N)=N
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| SMILES1 = /N=C(\N)/N(C)CC(=O)O
			}}
	| StdInChI = 1S/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)
			| Section2 = {{Chembox Properties
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| C=4 | H=9 | N=3 | O=2
	| InChI = 1/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9)
			| Appearance = White crystals
	| StdInChIKey = CVSVTCORWBXHQV-UHFFFAOYSA-N
			| Odor = Odourless
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| MeltingPtC = 255
	| InChIKey = CVSVTCORWBXHQV-UHFFFAOYAV}}
			| Solubility = 13.3 g L<sup>−1</sup> (at 18 °C)
	| Section2 = {{Chembox Properties
	| C = 4		| LogP = −1.258
	| H = 9		| pKa = 3.429
	| N = 3		| pKb = 10.568
	| O = 2		| IsoelectricPt = 8.47
			}}
	| ExactMass = 131.069476547 g mol<sup>-1</sup>
			| Section5 = {{Chembox Thermochemistry
	| Density = 1.3 (monohydrate),<ref>www.sciencelab.com/msds.php?msdsId=9923566</ref>
			| DeltaHf = −538.06–−536.30 kJ mol<sup>−1</sup>
	| MeltingPtC = 255
	| Solubility = 13.3 g dm<sup>-3</sup> (at 18 °C)		| DeltaHc = −2.3239–−2.3223 MJ mol<sup>−1</sup>
			| Entropy = 189.5 J K<sup>−1</sup> mol<sup>−1</sup>
	| SolubleOther = non-soluble in ethanol and ether <ref>http://chemyq.com/en/xz/xz1/9019vbolx.htm</ref>
			| HeatCapacity = 171.1 J K<sup>−1</sup> mol<sup>−1</sup> (at 23.2 °C)
	| LogP = -0.2
			}}
	| pKa = 3.429
			| Section6 = {{Chembox Pharmacology
	| pKb = 10.568
			| ATCCode_prefix = C01
	| IsoelectricPt = 8.47}}
			| ATCCode_suffix = EB06
	| Section3 = {{Chembox Hazards
	| EUClass = {{Hazchem Xi}}		| HalfLife = 3 hours
			}}
	| RPhrases = {{R36/37/38}}
	| SPhrases = {{S26}}, {{S36}}		| Section7 = {{Chembox Hazards
			| GHSPictograms = {{gHS exclamation mark}}
			| GHSSignalWord = '''WARNING'''
			| HPhrases = {{h-phrases|315|319|335}}
			| PPhrases = {{p-phrases|261|305+351+338}}
			}}
			| Section8 = {{Chembox Related
			| OtherFunction_label = alkanoic acids
			| OtherFunction = {{unbulleted list|]|]|]|]|]|]}}
			| OtherCompounds = ]
	}}		}}
	}}		}}
			'''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 ] with the nominal formula {{chem2|(H2N)(HN)CN(CH3)CH2CO2H}}. It exists in various ]s in solutions (among which are neutral form and various ] forms). Creatine is found in ]s, where it facilitates recycling of ] (ATP), primarily in ] and ] tissue. Recycling is achieved by converting ] (ADP) back to ATP via donation of ]s. Creatine also acts as a ].<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>
	'''Creatine''' is a ]ous ] that occurs naturally in ]s and helps to supply ] to all cells in the body, primarily ]. This is achieved by increasing the formation of ] (ATP). Creatine was identified in 1832 when ] discovered it as a component of ], which he later named creatine after the ] word for meat, κρέας (''kreas''). In solution, creatine is in equilibrium with ].<ref>{{Cite journal|author=Cannan, R. K.; Shore, A. |title=The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine |journal=Biochem. J. |volume=22 |issue=4 |pages=920–29 |year=1928 |pmid=16744118 |pmc=1252207 |url=http://www.biochemj.org/bj/022/0920/0220920.pdf |accessdate=2010-10-29}}</ref>
	==Biosynthesis==		==History==
			Creatine was first identified in 1832 when ] isolated it from the basified water-extract of ]. He later named the crystallized precipitate after the ] word for meat, κρέας (''kreas''). In 1928, creatine was shown to exist in ] with ].<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>
	Creatine is naturally produced in the human body from amino acids primarily in the kidney and liver. It is transported in the blood for use by muscles. Approximately 95% of the human body's total creatine is located in skeletal muscle.<ref>{{Cite web|url=http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-creatine.html |title=Creatine|work=MedLine Plus Supplements|publisher=]|date=2010-07-20 |accessdate=2010-08-16}}</ref>
			In 1912, ] researchers ] and ] 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 ] (creatine phosphate), and determined that creatine is a key player in the metabolism of ]. 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>
	Creatine is not an essential nutrient, as it is manufactured in the human body from ], ], and ].<ref name="Creatine">{{Cite web|url=http://www.bidmc.org/YourHealth/ConditionsAZ.aspx?ChunkID=21706|title=Creatine|publisher=]|accessdate=2010-08-23}}</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 = | 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=–16 |year=2007 |isbn=978-1-4020-6486-9 |publisher=Springer }}</ref>
	In humans and animals, approximately half of stored creatine originates from food (mainly from ]). A study, involving 18 vegetarians and 24 non-vegetarians, on the effect of creatine in vegetarians showed that total creatine was significantly lower than in non-vegetarians. Since vegetables do not represent the primary source of creatine, vegetarians can be expected to show lower levels of directly derived muscle creatine. However, the subjects happened to show the same levels after using supplements.<ref name="burke">{{Cite journal|author=Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M |title=Effect of creatine and weight training on muscle creatine and performance in vegetarians |journal=Medicine and science in sports and exercise |volume=35 |issue=11 |pages=1946–55 |year=2003 |pmid=14600563 |doi=10.1249/01.MSS.0000093614.17517.79}}</ref> Given the fact that creatine can be synthesized from the above mentioned amino acids, protein sources rich in these amino acids can be expected to provide adequate capability of native biosynthesis in the human body.<ref name="Creatine"/>
			While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the ] in ]. An August 7, 1992 article in '']'' reported that ], 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 ], who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, ''The Times'' also noted that 100 meter hurdler ] 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>
	The ] GATM (L-]:] amidinotransferase (]), ) is a ] ] responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the ] and ].<ref name="autogenerated1">{{cite journal|url=http://e-collection.ethbib.ethz.ch/ecol-pool/diss/fulltext/eth15180.pdf |title=ETH ETH E-Collection: Methylglyoxal, creatine and mitochondrial micro-compartments - ETH E-Collection |doi=10.3929/ethz-a-004636659. |publisher=E-collection.ethbib.ethz.ch |date=2008-04-19 |accessdate=2010-08-16}}</ref>
			] relays phosphate to ADP.]]
	The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, ) is primarily expressed in the liver and pancreas.<ref name="autogenerated1"/>
			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 ] (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= ] |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 ] 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>
			]
	Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.<ref>{{Cite web|url=http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602360 |title=L-Arginine:Glycine Amidinotransferase |publisher=|date= |accessdate=2010-08-16}}</ref>
			==Metabolic role==
	]; Met - ]; SAH - ]; SAM - ].</div>The color scheme is as follows:<span style="font-weight: bold;"><span style="color: blue;">enzymes</span>, <span style="color: rgb(219,155,36);">coenzymes</span> and <span style="color: rgb(219,155,36);">the Met part</span>, <span style="color: rgb(151,149,45);">substrate names</span>, <span style="color: red;">the Gly part</span>, <span style="color: green;">the Arg part</span></span>]]<div style="clear:left;" />
			Creatine is a naturally occurring non-protein compound and the primary constituent of phosphocreatine, which is used to regenerate ] within the cell. 95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the ], brain, testes, and other tissues.<ref name="pmid22817979">{{cite journal |vauthors=Cooper R, Naclerio F, Allgrove J, Jimenez A |title=Creatine supplementation with specific view to exercise/sports performance: an update |journal=Journal of the International Society of Sports Nutrition |volume=9 |issue=1 |pages=33 |date=July 2012 |pmid=22817979 |pmc=3407788 |doi=10.1186/1550-2783-9-33 |quote=Creatine is produced endogenously at an amount of about 1 g/d. Synthesis predominately occurs in the liver, kidneys, and to a lesser extent in the pancreas. The remainder of the creatine available to the body is obtained through the diet at about 1 g/d for an omnivorous diet. 95% of the bodies creatine stores are found in the skeletal muscle and the remaining 5% is distributed in the brain, liver, kidney, and testes . |doi-access=free }}</ref><ref name="pmid26874700">{{cite journal |vauthors=Brosnan ME, Brosnan JT |title=The role of dietary creatine |journal=Amino Acids |volume=48 |issue=8 |pages=1785–91 |date=August 2016 |pmid=26874700 |doi=10.1007/s00726-016-2188-1 |s2cid=3700484 |quote=The daily requirement of a 70-kg male for creatine is about 2&nbsp;g; up to half of this may be obtained from a typical omnivorous diet, with the remainder being synthesized in the body&nbsp;... More than 90% of the body’s creatine and phosphocreatine is present in muscle (Brosnan and Brosnan 2007), with some of the remainder being found in the brain (Braissant et al. 2011).&nbsp;... Creatine synthesized in liver must be secreted into the bloodstream by an unknown mechanism (Da Silva et al. 2014a)}}</ref> The typical creatine content of skeletal muscle (as both creatine and phosphocreatine) is 120&nbsp;mmol per kilogram of dry muscle mass, but can reach up to 160&nbsp;mmol/kg through supplementation.<ref name=":2">{{cite journal |vauthors=Hultman E, Söderlund K, Timmons JA, Cederblad G, Greenhaff PL |date=July 1996 |title=Muscle creatine loading in men |journal=Journal of Applied Physiology |volume=81 |issue=1 |pages=232–7 |doi=10.1152/jappl.1996.81.1.232 |pmid=8828669}}</ref> Approximately 1–2% of intramuscular creatine is degraded per day and an individual would need about 1–3 grams of creatine per day to maintain average (unsupplemented) creatine storage.<ref name=":2" /><ref>{{cite journal |vauthors=Balsom PD, Söderlund K, Ekblom B |title=Creatine in humans with special reference to creatine supplementation |journal=Sports Medicine |volume=18 |issue=4 |pages=268–80 |date=October 1994 |pmid=7817065 |doi=10.2165/00007256-199418040-00005|s2cid=23929060 }}</ref><ref name=":5">{{cite journal |vauthors=Harris RC, Söderlund K, Hultman E |title=Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation |journal=Clinical Science |volume=83 |issue=3 |pages=367–74 |date=September 1992 |pmid=1327657 |doi=10.1042/cs0830367 }}</ref> An omnivorous diet provides roughly half of this value, with the remainder synthesized in the liver and kidneys.<ref name="pmid22817979" /><ref name="pmid26874700" /><ref name="pmid21387089">{{cite journal |vauthors=Brosnan JT, da Silva RP, Brosnan ME |date=May 2011 |title=The metabolic burden of creatine synthesis |journal=Amino Acids |volume=40 |issue=5 |pages=1325–31 |doi=10.1007/s00726-011-0853-y |pmid=21387089 |quote=Creatinine loss averages approximately 2&nbsp;g (14.6&nbsp;mmol) for 70&nbsp;kg males in the 20- to 39-year age group.&nbsp;... Table 1 Comparison of rates of creatine synthesis in young adults with dietary intakes of the three precursor amino acids and with the whole body transmethylation flux<br />Creatine synthesis (mmol/day)&nbsp;&nbsp;&nbsp;8.3 |s2cid=8293857}}</ref>
			Creatine is not an ].<ref name="Creatine">{{Cite web|url=http://www.bidmc.org/YourHealth/ConditionsAZ.aspx?ChunkID=21706|title=Creatine|publisher=]|access-date=23 August 2010|archive-date=28 January 2011|archive-url=https://web.archive.org/web/20110128035754/http://www.bidmc.org/YourHealth/ConditionsAZ.aspx?ChunkID=21706|url-status=live}}</ref> It is an amino acid ], naturally produced in the human body from the ]s ] and ], with an additional requirement for ] (a derivative of ]) to catalyze the transformation of guanidinoacetate to creatine. In the first step of the ], the ] ] (AGAT, ) mediates the reaction of glycine and arginine to form ]. This product is then ] by ] (GAMT, ), using ] as the methyl donor. Creatine itself can be ] by ] to form ], which is used as an energy buffer in skeletal muscles and the brain. A cyclic form of creatine, called ], exists in equilibrium with its ] and with creatine.
	==The phosphocreatine system==
	Creatine, synthesized in the liver and kidney, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2-5 mM, which would result in a muscle contraction of only a few seconds.<ref name="ncbi.nlm.nih.gov">{{cite journal|pmc=1130636 |title=Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis |date=|volume=281|issue=Pt 1|pmid=1731757|last1=Wallimann|first1=T|last2=Wyss|first2=M|last3=Brdiczka|first3=D|last4=Nicolay|first4=K|last5=Eppenberger|first5=HM|pages=21–40|journal=The Biochemical journal }}</ref> Fortunately, during times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of ] (PCr) through a reversible reaction with the enzyme ] (CK). In skeletal muscle, PCr concentrations may reach 20-35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK.<ref name="ncbi.nlm.nih.gov"/> Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle’s ability to resynthesize ATP from ADP to meet increased energy demands.<ref>{{cite journal|pmc=2649889 |title=The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels |date=|volume=6|pmid=19228401|last1=Spillane|first1=M|last2=Schoch|first2=R|last3=Cooke|first3=M|last4=Harvey|first4=T|last5=Greenwood|first5=M|last6=Kreider|first6=R|last7=Willoughby|first7=DS|pages=6|doi=10.1186/1550-2783-6-6|journal=Journal of the International Society of Sports Nutrition }}</ref> For a review of the creatine kinase system and the pleiotropic actions of creatine and creatine supplementation see <ref>{{DOI|10.1007/s00726-011-0877-3}}.</ref>.
			]
	==Health effects==
	===Use as food supplement===
	{{Main|Creatine supplements}}
			===Phosphocreatine system===
	] are sometimes used by ]s, ]s, ], ] and others who wish to gain muscle mass, typically consuming 2 to 3 times the amount that could be obtained from a very-high-protein diet. A survey of long-term use gives the creatine content of several foods.<ref>{{Cite web|url=http://www.pponline.co.uk/encyc/creatine.htm |title=Creatine: is it really safe for long-term use? |publisher=Pponline.co.uk |date= |accessdate=2010-08-16}}</ref> The ] states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies.<ref name=mayo_creatine>{{Cite web|url=http://www.mayoclinic.com/health/creatine/NS_patient-creatine/DSECTION=safety |title=Creatine: Safety |publisher=MayoClinic.com |date= |accessdate=2010-08-16}}</ref>
			]
			Creatine is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ] in skeletal muscle is usually 2–5&nbsp;mM, which would result in a muscle contraction of only a few seconds.<ref name="ncbi.nlm.nih.gov">{{cite journal | vauthors = Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM | title = Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis | journal = The Biochemical Journal | volume = 281 ( Pt 1) | issue = Pt 1 | pages = 21–40 | date = January 1992 | pmid = 1731757 | pmc = 1130636 | doi = 10.1042/bj2810021 }}</ref> During times of increased energy demands, the ] (or ATP/PCr) system rapidly resynthesizes ATP from ] with the use of ] (PCr) through a reversible reaction catalysed by the enzyme ] (CK). The phosphate group is attached to an NH center of the creatine. In skeletal muscle, PCr concentrations may reach 20–35&nbsp;mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK.<ref name="ncbi.nlm.nih.gov" /> A proposed representation has been illustrated by Krieder et al.<ref name=":3" /> Creatine has the ability to increase muscle stores of PCr, potentially increasing the muscle's ability to resynthesize ATP from ADP to meet increased energy demands.<ref>{{cite journal | vauthors = Spillane M, Schoch R, Cooke M, Harvey T, Greenwood M, Kreider R, Willoughby DS | title = The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels | journal = Journal of the International Society of Sports Nutrition | volume = 6 | issue = 1 | pages = 6 | date = February 2009 | pmid = 19228401 | pmc = 2649889 | doi = 10.1186/1550-2783-6-6 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Wallimann T, Tokarska-Schlattner M, Schlattner U | title = The creatine kinase system and pleiotropic effects of creatine | journal = Amino Acids | volume = 40 | issue = 5 | pages = 1271–96 | date = May 2011 | pmid = 21448658 | pmc = 3080659 | doi = 10.1007/s00726-011-0877-3 }}.</ref><ref>T. Wallimann, M. Tokarska-Schlattner, D. Neumann u.&nbsp;a.: ''The Phosphocreatine Circuit: Molecular and Cellular Physiology of Creatine Kinases, Sensitivity to Free Radicals, and Enhancement by Creatine Supplementation.'' In: ''Molecular System Bioenergetics: Energy for Life.'' 22. November 2007. {{doi|10.1002/9783527621095.ch7}}C</ref>
			Creatine supplementation appears to increase the number of ] that satellite cells will 'donate' to damaged ]s, which increases the potential for growth of those fibers. This increase in myonuclei probably stems from creatine's ability to increase levels of the myogenic transcription factor MRF4.<ref>{{cite journal | vauthors = Hespel P, Eijnde BO, Derave W, Richter EA | title = Creatine supplementation: exploring the role of the creatine kinase/phosphocreatine system in human muscle | journal = Canadian Journal of Applied Physiology | volume = 26 Suppl | pages = S79-102 | year = 2001 | pmid = 11897886 | doi = 10.1139/h2001-045 }}</ref>
	While there was once some concern that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea, recent studies have shown these concerns to be unfounded.<ref name="Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM 2009 215–23">{{Cite journal|author=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|author=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 |year=2008 |month=July |pmid=18184753 |doi=10.1136/bjsm.2007.042473}}</ref>
			===Genetic deficiencies===
	There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement.<ref name=mayo_creatine/> In similar manner, liver function may be altered, and caution is advised in those with underlying liver disease although studies have shown little or no adverse impact on kidney or liver function from oral creatine supplementation.<ref>{{Cite journal|author=Poortmans JR, Francaux M |title=Adverse effects of creatine supplementation: fact or fiction? |journal=Sports Medicine |volume=30 |issue=3 |pages=155–70 |year=2000 |month=September |pmid=10999421 |doi=10.2165/00007256-200030030-00002}}</ref>
			Genetic deficiencies in the creatine biosynthetic pathway lead to various ].<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 ]. Deficiencies in the two synthesis enzymes can cause ] caused by variants in '']'' and ], caused by variants in '']''. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, ], is caused by mutations in '']'' 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>
			===Vegans and vegetarians===
	Long-term administration of large quantities of creatine is reported to increase the production of formaldehyde, which has the potential to cause serious unwanted side-effects. However, this risk is largely theoretical because urinary excretion of formaldehyde, even under heavy creatine supplementation, does not exceed normal limits.<ref>{{Cite journal|author=Francaux M, Poortmans JR |title=Side effects of creatine supplementation in athletes |journal=International Journal of Sports Physiology and Performance |volume=1 |issue=4 |pages=311–23 |year=2006 |month=December |pmid=19124889}}</ref>
			Vegan and vegetarian diets are associated with lower levels of muscle creatine, and athletes on these diets may benefit from creatine supplementation.<ref>{{cite journal |vauthors=Rogerson D |title=Vegan diets: practical advice for athletes and exercisers |journal=J Int Soc Sports Nutr |volume=14 |issue= |pages=36 |date=2017 |pmid=28924423 |pmc=5598028 |doi=10.1186/s12970-017-0192-9 |doi-access=free |url=}}</ref>
			==Pharmacokinetics==
	Extensive research over the last decade has shown that oral creatine supplementation at a rate of 5 to 20&nbsp;grams per day appears to be very safe and largely devoid of adverse side-effects,<ref>{{Cite journal|author=Bizzarini E, De Angelis L |title=Is the use of oral creatine supplementation safe? |journal=The Journal of Sports Medicine and Physical Fitness |volume=44 |issue=4 |pages=411–6 |year=2004 |month=December |pmid=15758854}}</ref> while at the same time effectively improving the physiological response to resistance exercise, increasing the maximal force production of muscles in both men and women.<ref>{{Cite journal|author=Bemben MG, Lamont HS |title=Creatine supplementation and exercise performance: recent findings |journal=Sports Medicine |volume=35 |issue=2 |pages=107–25 |year=2005 |pmid=15707376}}</ref><ref>{{Cite journal|author=Kreider RB |title=Effects of creatine supplementation on performance and training adaptations |journal=Molecular and Cellular Biochemistry |volume=244 |issue=1–2 |pages=89–94 |year=2003 |month=February |pmid=12701815 |url=http://www.kluweronline.com/art.pdf?issn=0300-8177&volume=244&page=89 |doi=10.1023/A:1022465203458}}</ref>
			Most of the research to-date on creatine has predominantly focused on the pharmacological properties of creatine, yet there is a lack of research into the pharmacokinetics of creatine. Studies have not established pharmacokinetic parameters for clinical usage of creatine such as volume of distribution, clearance, bioavailability, mean residence time, absorption rate, and half life. A clear pharmacokinetic profile would need to be established prior to optimal clinical dosing.<ref>{{cite journal | vauthors = Persky AM, Brazeau GA | title = Clinical pharmacology of the dietary supplement creatine monohydrate | journal = Pharmacological Reviews | volume = 53 | issue = 2 | pages = 161–76 | date = June 2001 | pmid = 11356982 }}</ref>
	===Pharmacokinetics===		=== Dosing ===
	Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12&nbsp;mg/L. A single 5&nbsp;g (5000&nbsp;mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120&nbsp;mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half-life, averaging just less than 3 hours, so to maintain an elevated plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day.
	After the "loading dose" period (1–2 weeks, 12-24&nbsp;g a day), it is no longer necessary to maintain a consistently high serum level of creatine. As with most supplements, each person has their own genetic "preset" amount of creatine they can hold. The rest is eliminated out of the body as waste. Creatine is consumed by the body fairly quickly, and if one wishes to maintain the high concentration of creatine, Post-loading dose, 2-5&nbsp;g daily is the standard amount to intake.<ref>Kamber M, Koster M, Kreis R, Walker G, Boesch C, Hoppeler H. Creatine supplementation--part I: performance, clinical chemistry, and muscle volume. Med. Sci. Sports Exer. 31: 1763-1769, 1999.</ref><ref>Deldicque L, Décombaz J, Zbinden Foncea H, Vuichoud J, Poortmans JR, Francaux M. Kinetics of creatine ingested as a food ingredient. Eur. J. Appl. Physiol. 102: 133-143, 2008.</ref><ref>R. Baselt, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 366-368.</ref>
	===Pregnancy and breastfeeding===		==== Loading phase ====
			]
	Creatine cannot be recommended during pregnancy or breastfeeding due to a lack of scientific information. Pasteurized cow's milk contains higher levels of creatine than human milk.<ref>{{Cite journal|author=Hülsemann J, Manz F, Wember T, Schöch G |title= |language=German |journal=Klinische Pädiatrie |volume=199 |issue=4 |pages=292–5 |year=1987 |pmid=3657037 |doi=10.1055/s-2008-1026805}}</ref><ref>{{Cite journal
			An approximation of 0.3 g/kg/day divided into 4 equal spaced intervals has been suggested since creatine needs may vary based on body weight.<ref name=":3" /><ref name=":2" /> It has also been shown that taking a lower dose of 3 grams a day for 28 days can also increase total muscle creatine storage to the same amount as the rapid loading dose of 20 g/day for 6 days.<ref name=":2" /> However, a 28-day loading phase does not allow for ] benefits of creatine supplementation to be realized until fully saturated muscle storage.
	| last1 = Wallimann | first1 = Theo
	| last2 = Tokarska-Schlattner | first2 = Malgorzata
	| last3 = Schlattner | first3 = Uwe
	| title = The creatine kinase system and pleiotropic effects of creatine
	| journal = Amino Acids
	| volume = 40
	| issue = 5
	| pages = 1271–1296
	| publisher = Springer Wien
	| date = 2011-05-01
	| issn = 0939-4451
	| doi = 10.1007/s00726-011-0877-3
	| pmid = 21448658
	| pmc = 3080659}}</ref>
			This elevation in muscle creatine storage has been correlated with ergogenic benefits discussed in the research section. However, higher doses for longer periods of time are being studied to offset creatine synthesis deficiencies and mitigating diseases.<ref>{{cite journal | vauthors = Hanna-El-Daher L, Braissant O | title = Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models? | journal = Amino Acids | volume = 48 | issue = 8 | pages = 1877–95 | date = August 2016 | pmid = 26861125 | doi = 10.1007/s00726-016-2189-0 | s2cid = 3675631 }}</ref><ref>{{cite journal | vauthors = Bender A, Klopstock T | title = Creatine for neuroprotection in neurodegenerative disease: end of story? | journal = Amino Acids | volume = 48 | issue = 8 | pages = 1929–40 | date = August 2016 | pmid = 26748651 | doi = 10.1007/s00726-015-2165-0 | s2cid = 2349130 }}</ref><ref name="creatinedefects" />
	==Treatment of diseases==
	{{Science review|date=February 2009}}
	Creatine has been demonstrated to cause modest increases in strength in people with a variety of ]s.<ref name="martin">{{Cite journal|author=Tarnopolsky M, Martin J |title=Creatine monohydrate increases strength in patients with neuromuscular disease |journal=Neurology |volume=52 |issue=4 |pages=854–7 |year=1999 |month=March |pmid=10078740 |url=http://www.neurology.org/cgi/pmidlookup?view=long&pmid=10078740}}</ref> Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (], ], ], disuse atrophy, gyrate atrophy, ], ], miscellaneous neuromuscular diseases, ]s, ], and ]).{{Citation needed|date=January 2009}}
			==== Maintenance phase ====
	A study demonstrated that creatine is twice as effective as the prescription drug ] in extending the lives of mice with the degenerative neural disease ] (], or ]). The neuroprotective effects of creatine in the mouse model of ALS may be due either to an increased availability of energy to injured nerve cells or to a blocking of the chemical pathway that leads to ].<ref name="klivenyi">{{Cite journal|author=Klivenyi P, Ferrante RJ, Matthews RT, ''et al.'' |title=Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis |journal=Nature Medicine |volume=5 |issue=3 |pages=347–50 |year=1999 |month=March |pmid=10086395 |doi=10.1038/6568}}</ref> A similarly promising result has been obtained in prolonging the life of ] mice affected by Huntington's disease. Creatine treatment lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal ], and delayed the development of ].<ref name="pmid11447996">{{Cite journal|author=Andreassen OA, Dedeoglu A, Ferrante RJ, ''et al.'' |title=Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease |journal=Neurobiology of Disease |volume=8 |issue=3 |pages=479–91 |year=2001 |month=June |pmid=11447996 |doi=10.1006/nbdi.2001.0406}}</ref>
			After the 5–7 day loading phase, muscle creatine stores are fully saturated and supplementation only needs to cover the amount of creatine broken down per day. This maintenance dose was originally reported to be around 2–3 g/day (or 0.03 g/kg/day),<ref name=":2" /> however, some studies have suggested 3–5 g/day maintenance dose to maintain saturated muscle creatine.<ref name=":4" /><ref name=":5" /><ref>{{cite journal |vauthors=Kreider RB |title=Effects of creatine supplementation on performance and training adaptations |journal=Molecular and Cellular Biochemistry |volume=244 |issue=1–2 |pages=89–94 |date=February 2003 |doi=10.1023/A:1022465203458 |pmid=12701815|s2cid=35050122 }}</ref><ref name=":6">{{cite journal |vauthors=Greenhaff PL, Casey A, Short AH, Harris R, Soderlund K, Hultman E |title=Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man |journal=Clinical Science |volume=84 |issue=5 |pages=565–71 |date=May 1993 |pmid=8504634 |doi=10.1042/cs0840565}}</ref>
			=== Absorption ===
	==Cognitive ability==
			]
	A placebo-controlled double-blind experiment found that a group of subjects composed of vegetarians and vegans who took 5&nbsp;grams of creatine per day for six weeks showed a significant improvement on two separate tests of ], ], and the backward digit span test from the ]. The treatment group was able to repeat longer sequences of numbers from memory and had higher overall ] scores than the control group. The researchers concluded that "supplementation with creatine significantly increased intelligence compared with placebo."<ref>{{Cite journal|author=Rae C, Digney AL, McEwan SR, Bates TC |title=Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial |journal=Proceedings. Biological Sciences / the Royal Society |volume=270 |issue=1529 |pages=2147–50 |year=2003 |month=October |pmid=14561278 |pmc=1691485 |doi=10.1098/rspb.2003.2492}}</ref> A subsequent study found that creatine supplements improved cognitive ability in the elderly.<ref>{{Cite journal|author=McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A |title=Creatine supplementation and cognitive performance in elderly individuals |journal=Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition |volume=14 |issue=5 |pages=517–28 |year=2007 |month=September |pmid=17828627 |doi=10.1080/13825580600788100}}</ref> A study on young adults (0.03 g/kg/day for six weeks, e.g., 2 g/day for 150-pound individual) failed to find any improvements.<ref>{{Cite journal|author=Rawson ES, Lieberman HR, Walsh TM, Zuber SM, Harhart JM, Matthews TC |title=Creatine supplementation does not improve cognitive function in young adults |journal=Physiology & Behavior |volume=95 |issue=1–2 |pages=130–4 |year=2008 |month=September |pmid=18579168 |doi=10.1016/j.physbeh.2008.05.009}}</ref>
			Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12&nbsp;mg/L. A single 5 gram (5000&nbsp;mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120&nbsp;mg/L at 1–2 hours post-ingestion. Creatine has a fairly short elimination half life, averaging just less than 3 hours, so to maintain an elevated plasma level it would be necessary to take small oral doses every 3–6 hours throughout the day.
	==See also==		==Exercise and sport==
			Creatine supplements are marketed in ], ], ], and ] forms.<ref name="Cooper2012">{{cite journal | vauthors = Cooper R, Naclerio F, Allgrove J, Jimenez A | title = Creatine supplementation with specific view to exercise/sports performance: an update | journal = Journal of the International Society of Sports Nutrition | volume = 9 | issue = 1 | pages = 33 | date = July 2012 | pmid = 22817979 | pmc = 3407788 | doi = 10.1186/1550-2783-9-33 | doi-access = free }}</ref>
	* ]
	* ]
	* ]
			Creatine supplementation for sporting performance enhancement is considered safe for short-term use but there is a lack of safety data for long term use, or for use in children and adolescents.<ref>{{cite journal |vauthors=Butts J, Jacobs B, Silvis M |title=Creatine Use in Sports |journal=Sports Health |volume=10 |issue=1 |pages=31–34 |date=2018 |pmid=29059531 |pmc=5753968 |doi=10.1177/1941738117737248 |url=}}</ref> Some athletes choose to cycle on and off creatine.<ref>{{Cite web |date=2024-09-04 |title=What Happens When You Stop Taking Creatine but Keep Working Out? |url=https://www.gimmegummiez.co/blogs/news/what-happens-when-you-stop-taking-creatine-but-keep-working-out |access-date=2024-11-24 |website=Gimme Gummiez |language=en}}</ref>
	==References==
	{{Reflist|2}}
			A 2018 ] in the ''Journal of the International Society of Sports Nutrition'' said that creatine monohydrate might help with energy availability for high-intensity exercise.<ref>{{cite journal |vauthors=Kerksick CM, Wilborn CD, Roberts MD, Smith-Ryan A, Kleiner SM, Jäger R, Collins R, Cooke M, Davis JN, Galvan E, Greenwood M, Lowery LM, Wildman R, Antonio J, Kreider RB |display-authors=6 |title=ISSN exercise & sports nutrition review update: research & recommendations |journal=Journal of the International Society of Sports Nutrition |volume=15 |issue=1 |pages=38 |date=August 2018 |pmid=30068354 |pmc=6090881 |doi=10.1186/s12970-018-0242-y |doi-access=free }}</ref>
	==External links==
	*
	* , Beth Lulinski, ]
	* , ''BBC News'', 12 August 2003
	* , Peter W. Schutz, ''The Science Creative Quarterly'', 2009
	* A primer for athletes
	* A mouse study
	* A recent Review from May 2011
			Creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work (periods of work and rest) by 5% to 15%.<ref>{{cite journal |vauthors=Bemben MG, Lamont HS |title=Creatine supplementation and exercise performance: recent findings |journal=Sports Medicine |volume=35 |issue=2 |pages=107–25 |year=2005 |pmid=15707376 |doi=10.2165/00007256-200535020-00002|s2cid=57734918 }}</ref><ref>{{cite journal |vauthors=Bird SP |title=Creatine supplementation and exercise performance: a brief review |journal=Journal of Sports Science & Medicine |volume=2 |issue=4 |pages=123–32 |date=December 2003 |pmid=24688272 |pmc=3963244}}</ref><ref>{{cite journal |vauthors=Lanhers C, Pereira B, Naughton G, Trousselard M, Lesage FX, Dutheil F |title=Creatine Supplementation and Lower Limb Strength Performance: A Systematic Review and Meta-Analyses |journal=Sports Medicine |volume=45 |issue=9 |pages=1285–1294 |date=September 2015 |pmid=25946994 |doi=10.1007/s40279-015-0337-4|s2cid=7372700 }}</ref> Creatine has no significant effect on aerobic ], though it will increase power during short sessions of high-intensity aerobic exercise.<ref>{{cite journal |vauthors=Engelhardt M, Neumann G, Berbalk A, Reuter I |title=Creatine supplementation in endurance sports |journal=Medicine and Science in Sports and Exercise |volume=30 |issue=7 |pages=1123–9 |date=July 1998 |pmid=9662683 |doi=10.1097/00005768-199807000-00016|doi-access=free }}</ref>{{Obsolete source|date=May 2018}}<ref name="Graham">{{cite journal |vauthors=Graham AS, Hatton RC |title=Creatine: a review of efficacy and safety |journal=Journal of the American Pharmaceutical Association |volume=39 |issue=6 |pages=803–10; quiz 875–7 |year=1999 |pmid=10609446 |doi=10.1016/s1086-5802(15)30371-5}}</ref>{{Obsolete source|date=May 2018}}
	{{Dietary supplement}}
	{{Use dmy dates|date=September 2010}}
			Creatine is proven to boost the recovery and work capacity of an athlete, and multi-applicable capabilities upon athletes have given it a lot of interest over the course of the past decade. A survey of 21,000 college athletes showed that 14% of athletes take creatine supplements to try to improve performance.<ref name=":1">{{Cite news|url=https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional/#creatine|title=Office of Dietary Supplements - Dietary Supplements for Exercise and Athletic Performance|access-date=2018-05-05|language=en|archive-date=8 May 2018|archive-url=https://web.archive.org/web/20180508185512/https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional/#creatine|url-status=live}}</ref> Compared to normal athletes, those with creatine supplementation have been shown to produce better athletic performance.<ref>{{Cite journal |title= Creatine for Exercise and Sports Performance, with Recovery Considerations for Healthy Populations|date=2021 |pmc=8228369 |last1=Wax |first1=B. |last2=Kerksick |first2=C. M. |last3=Jagim |first3=A. R. |last4=Mayo |first4=J. J. |last5=Lyons |first5=B. C. |last6=Kreider |first6=R. B. |journal=Nutrients |volume=13 |issue=6 |page=1915 |doi=10.3390/nu13061915 |doi-access=free |pmid=34199588 }}</ref> Non-athletes report taking creatine supplements to improve appearance.<ref name=":1" />
	]
			==Research ==
			===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 ] (due, for instance, to ]) 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|journal=Scientific Reports |volume= 14|issue= 1|pages=4937 |doi=10.1038/s41598-024-54249-9 |pmid= 38418482 |pmc=10902318|bibcode= 2024NatSR..14.4937G }}</ref>
			A 2018 ] 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=] |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=] |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 review study "...supported claims that creatine supplementation can increases brain creatine content but also demonstrated somewhat equivocal results for effects on cognition. It does, however, provide evidence to suggest that more research is required with stressed populations, as supplementation does appear to significantly affect brain content.<ref>{{Cite journal |last1=McMorris |first1=Terry |last2=Hale |first2=Beverley J. |last3=Pine |first3=Beatrice S. |last4=Williams |first4=Thomas B. |date=2024-04-04 |title=Creatine supplementation research fails to support the theoretical basis for an effect on cognition: Evidence from a systematic review |journal=Behavioural Brain Research |volume=466 |pages=114982 |doi=10.1016/j.bbr.2024.114982 |issn=1872-7549 |pmid=38582412|doi-access=free }}</ref>
			===Muscular disease===
			A meta-analysis found that creatine treatment increased muscle strength in ], and potentially improved functional performance.<ref name="Kley2013">{{cite journal | vauthors = Kley RA, Tarnopolsky MA, Vorgerd M | title = Creatine for treating muscle disorders | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD004760 | date = June 2013 | volume = 2013 | pmid = 23740606 | pmc = 6492334 | doi = 10.1002/14651858.CD004760.pub4 }}</ref> Creatine treatment does not appear to improve muscle strength in people who have ].<ref name="Kley2013" /> High doses of creatine lead to increased muscle pain and an impairment in ] when taken by people who have ].<ref name="Kley2013" />
			According to a clinical study focusing on people with various muscular dystrophies, using a pure form of creatine monohydrate can be beneficial in rehabilitation after injuries and immobilization.<ref>{{cite journal | vauthors = Walter MC, Lochmüller H, Reilich P, Klopstock T, Huber R, Hartard M, Hennig M, Pongratz D, Müller-Felber W | display-authors = 6 | title = Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study | journal = Neurology | volume = 54 | issue = 9 | pages = 1848–50 | date = May 2000 | pmid = 10802796 | doi = 10.1212/wnl.54.9.1848 | s2cid = 13304657 }}</ref>
			===Mitochondrial diseases===
			====Parkinson's disease====
			Creatine's impact on ]l function has led to research on its efficacy and safety for slowing ]. As of 2014, the evidence did not provide a reliable foundation for treatment decisions, due to risk of bias, small sample sizes, and the short duration of trials.<ref>{{cite journal | vauthors = Xiao Y, Luo M, Luo H, Wang J | title = Creatine for Parkinson's disease | journal = The Cochrane Database of Systematic Reviews | issue = 6 | pages = CD009646 | date = June 2014 | volume = 2014 | pmid = 24934384 | doi = 10.1002/14651858.cd009646.pub2 | pmc = 10196714 }}</ref>
			==== Huntington's disease ====
			Several primary studies<ref>{{cite journal | vauthors = Verbessem P, Lemiere J, Eijnde BO, Swinnen S, Vanhees L, Van Leemputte M, Hespel P, Dom R | display-authors = 6 | title = Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial | journal = Neurology | volume = 61 | issue = 7 | pages = 925–30 | date = October 2003 | pmid = 14557561 | doi = 10.1212/01.wnl.0000090629.40891.4b | s2cid = 43845514 }}</ref><ref>{{cite journal | vauthors = Bender A, Auer DP, Merl T, Reilmann R, Saemann P, Yassouridis A, Bender J, Weindl A, Dose M, Gasser T, Klopstock T | display-authors = 6 | title = Creatine supplementation lowers brain glutamate levels in Huntington's disease | journal = Journal of Neurology | volume = 252 | issue = 1 | pages = 36–41 | date = January 2005 | pmid = 15672208 | doi = 10.1007/s00415-005-0595-4 | s2cid = 17861207 }}</ref><ref>{{cite journal | vauthors = Hersch SM, Schifitto G, Oakes D, Bredlau AL, Meyers CM, Nahin R, Rosas HD | title = The CREST-E study of creatine for Huntington disease: A randomized controlled trial | journal = Neurology | volume = 89 | issue = 6 | pages = 594–601 | date = August 2017 | pmid = 28701493 | pmc = 5562960 | doi = 10.1212/WNL.0000000000004209 }}</ref> have been completed but no systematic review on ] has been completed yet.
			===ALS===
			It is ineffective as a treatment for ].<ref>{{cite journal | vauthors = Pastula DM, Moore DH, Bedlack RS | title = Creatine for amyotrophic lateral sclerosis/motor neuron disease | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | pages = CD005225 | date = December 2012 | issue = 12 | pmid = 23235621 | doi = 10.1002/14651858.CD005225.pub3 | pmc = 11403570 }}</ref>
			===Testosterone===
			A 2021 systemic review of studies found that "the current body of evidence does not indicate that creatine supplementation increases ], ], ] or causes hair loss/baldness".<ref>{{cite journal |title=Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? |journal=Journal of the International Society of Sports Nutrition |date=2021 |volume=18 |issue=13 |pmc=7871530 |last1=Antonio |first1=J. |last2=Candow |first2=D. G. |last3=Forbes |first3=S. C. |last4=Gualano |first4=B. |last5=Jagim |first5=A. R. |last6=Kreider |first6=R. B. |last7=Rawson |first7=E. S. |last8=Smith-Ryan |first8=A. E. |last9=Vandusseldorp |first9=T. A. |last10=Willoughby |first10=D. S. |last11=Ziegenfuss |first11=T. N. |page=13 |doi=10.1186/s12970-021-00412-w |pmid=33557850 |doi-access=free }}</ref>
			==Adverse effects==
			Side effects include:<ref>{{cite journal | vauthors = Francaux M, Poortmans JR | s2cid = 21330062 | title = Side effects of creatine supplementation in athletes | journal = International Journal of Sports Physiology and Performance | volume = 1 | issue = 4 | pages = 311–23 | date = December 2006 | pmid = 19124889 | doi = 10.1123/ijspp.1.4.311 }}</ref><ref>{{cite journal | vauthors = Buford TW, Kreider RB, Stout JR, Greenwood M, Campbell B, Spano M, Ziegenfuss T, Lopez H, Landis J, Antonio J | display-authors = 6 | title = International Society of Sports Nutrition position stand: creatine supplementation and exercise | journal = Journal of the International Society of Sports Nutrition | volume = 4 | pages = 6 | date = August 2007 | pmid = 17908288 | pmc = 2048496 | doi = 10.1186/1550-2783-4-6 | publisher = jissn | doi-access = free }}</ref>
			* Weight gain due to extra ] to the muscle
			* Potential muscle cramps / strains / pulls
			* Upset stomach
			* ]
			* Dizziness
			One well-documented effect of creatine supplementation is weight gain within the first week of the supplement schedule, likely attributable to greater water retention due to the increased muscle creatine concentrations by means of ].<ref name=":0">{{cite journal | vauthors = Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL | display-authors = 6 | title = International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine | journal = Journal of the International Society of Sports Nutrition | volume = 14 | pages = 18 | date = 2017-06-13 | pmid = 28615996 | pmc = 5469049 | doi = 10.1186/s12970-017-0173-z | doi-access = free }}</ref>
			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>
			Despite weight gain due to water retention and potential cramps being two seemingly "common" side effects, new research indicates that these side effects are likely not the result of creatine usage. In addition, the initial water retention is attributed to more short-term creatine use (the "loading" phase). Studies have shown that creatine usage does not necessarily affect total body water relative to muscle mass in the long-term.<ref>{{Cite journal | last1=Antonio | first1=Jose | date=2022 | title=Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? | journal=Journal of the International Society of Sports Medicine | volume=18 | issue=1 | page=13 | doi=10.1186/s12970-021-00412-w | doi-access=free | pmid=33557850 | pmc=7871530 }}</ref>
			=== Renal function ===
			A 2019 systematic review published by the ] investigated whether creatine supplementation had adverse effects on renal function.<ref>{{cite journal | vauthors = de Souza E, Silva A, Pertille A, Reis Barbosa CG, Aparecida de Oliveira Silva J, de Jesus DV, Ribeiro AG, Baganha RJ, de Oliveira JJ | display-authors = 6 | title = Effects of Creatine Supplementation on Renal Function: A Systematic Review and Meta-Analysis | journal = Journal of Renal Nutrition | volume = 29 | issue = 6 | pages = 480–489 | date = November 2019 | pmid = 31375416 | doi = 10.1053/j.jrn.2019.05.004 | s2cid = 199388424 }}</ref> They identified 15 studies from 1997 to 2013 that looked at standard creatine loading and maintenance protocols of 4–20 g/day of creatine versus placebo. They utilized serum creatinine, creatinine clearance, and serum urea levels as a measure of renal damage. While in general creatine supplementation resulted in slightly elevated creatinine levels that remained within normal limits, supplementation did not induce renal damage (P value< 0.001). Special populations included in the 2019 Systematic review included type 2 diabetic patients<ref>{{cite journal | vauthors = Gualano B, de Salles Painelli V, Roschel H, Lugaresi R, Dorea E, Artioli GG, Lima FR, da Silva ME, Cunha MR, Seguro AC, Shimizu MH, Otaduy MC, Sapienza MT, da Costa Leite C, Bonfá E, Lancha Junior AH | display-authors = 6 | title = Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial | journal = European Journal of Applied Physiology | volume = 111 | issue = 5 | pages = 749–56 | date = May 2011 | pmid = 20976468 | doi = 10.1007/s00421-010-1676-3 | s2cid = 21335546 }}</ref> and post-menopausal women,<ref>{{cite journal | vauthors = Neves M, Gualano B, Roschel H, Lima FR, Lúcia de Sá-Pinto A, Seguro AC, Shimizu MH, Sapienza MT, Fuller R, Lancha AH, Bonfá E | display-authors = 6 | title = Effect of creatine supplementation on measured glomerular filtration rate in postmenopausal women | journal = Applied Physiology, Nutrition, and Metabolism | volume = 36 | issue = 3 | pages = 419–22 | date = June 2011 | pmid = 21574777 | doi = 10.1139/h11-014 }}</ref> bodybuilders,<ref>{{cite journal | vauthors = Lugaresi R, Leme M, de Salles Painelli V, Murai IH, Roschel H, Sapienza MT, Lancha Junior AH, Gualano B | display-authors = 6 | title = Does long-term creatine supplementation impair kidney function in resistance-trained individuals consuming a high-protein diet? | journal = Journal of the International Society of Sports Nutrition | volume = 10 | issue = 1 | pages = 26 | date = May 2013 | pmid = 23680457 | pmc = 3661339 | doi = 10.1186/1550-2783-10-26 | doi-access = free }}</ref> athletes,<ref>{{cite journal | vauthors = Kreider RB, Melton C, Rasmussen CJ, Greenwood M, Lancaster S, Cantler EC, Milnor P, Almada AL | display-authors = 6 | title = Long-term creatine supplementation does not significantly affect clinical markers of health in athletes | journal = Molecular and Cellular Biochemistry | volume = 244 | issue = 1–2 | pages = 95–104 | date = February 2003 | doi = 10.1023/A:1022469320296 | pmid = 12701816 | s2cid = 25947100 }}</ref> and resistance trained populations.<ref>{{cite journal | vauthors = Cancela P, Ohanian C, Cuitiño E, Hackney AC | title = Creatine supplementation does not affect clinical health markers in football players | journal = British Journal of Sports Medicine | volume = 42 | issue = 9 | pages = 731–5 | date = September 2008 | pmid = 18780799 | doi = 10.1136/bjsm.2007.030700 | s2cid = 20876433 }}</ref><ref>{{cite journal| vauthors = Carvalho AP, Molina GE, Fontana KE |date=August 2011|title=Creatine supplementation associated with resistance training does not alter renal and hepatic functions|journal=Revista Brasileira de Medicina do Esporte|language=en|volume=17|issue=4|pages=237–241|doi=10.1590/S1517-86922011000400004|issn=1517-8692|doi-access=free}}</ref><ref>{{cite journal | vauthors = Mayhew DL, Mayhew JL, Ware JS | title = Effects of long-term creatine supplementation on liver and kidney functions in American college football players | journal = International Journal of Sport Nutrition and Exercise Metabolism | volume = 12 | issue = 4 | pages = 453–60 | date = December 2002 | pmid = 12500988 | doi = 10.1123/ijsnem.12.4.453 }}</ref> The study also discussed 3 case studies where there were reports that creatine affected renal function.<ref>{{cite journal | vauthors = Thorsteinsdottir B, Grande JP, Garovic VD | title = Acute renal failure in a young weight lifter taking multiple food supplements, including creatine monohydrate | journal = Journal of Renal Nutrition | volume = 16 | issue = 4 | pages = 341–5 | date = October 2006 | pmid = 17046619 | doi = 10.1053/j.jrn.2006.04.025 }}</ref><ref>{{cite journal | vauthors = Taner B, Aysim O, Abdulkadir U | title = The effects of the recommended dose of creatine monohydrate on kidney function | journal = NDT Plus | volume = 4 | issue = 1 | pages = 23–4 | date = February 2011 | pmid = 25984094 | pmc = 4421632 | doi = 10.1093/ndtplus/sfq177 }}</ref><ref>{{cite journal | vauthors = Barisic N, Bernert G, Ipsiroglu O, Stromberger C, Müller T, Gruber S, Prayer D, Moser E, Bittner RE, Stöckler-Ipsiroglu S | display-authors = 6 | title = Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy | journal = Neuropediatrics | volume = 33 | issue = 3 | pages = 157–61 | date = June 2002 | pmid = 12200746 | doi = 10.1055/s-2002-33679 | s2cid = 9250579 }}</ref>
			In a joint statement between the ], ], and Dietitians in Canada on performance enhancing nutrition strategies, creatine was included in their list of ergogenic aids and they do not list renal function as a concern for use.<ref name=":7">{{cite journal | vauthors = Rodriguez NR, Di Marco NM, Langley S | title = American College of Sports Medicine position stand. Nutrition and athletic performance | journal = Medicine and Science in Sports and Exercise | volume = 41 | issue = 3 | pages = 709–31 | date = March 2009 | pmid = 19225360 | doi = 10.1249/MSS.0b013e31890eb86 | doi-access = free }}</ref>
			The most recent position stand on creatine from the ''Journal of International Society of Sports Nutrition'' states that creatine is safe to take in healthy populations from infants to the elderly to performance athletes. They also state that long term (5 years) use of creatine has been considered safe.<ref name=":3">{{cite journal | vauthors = Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL | display-authors = 6 | title = International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine | journal = Journal of the International Society of Sports Nutrition | volume = 14 | pages = 18 | date = 2017 | pmid = 28615996 | pmc = 5469049 | doi = 10.1186/s12970-017-0173-z | doi-access = free }}</ref>
			It is important to mention that kidneys themselves, for normal physiological function, need phosphocreatine and creatine and indeed kidneys express significant amounts of creatine kinases (BB-CK and u-mtCK isoenzymes).<ref>ML.Guerrero, J.Beron, B.Spindler, P.Grosscurth, T.Wallimann and F.Verrey.''Metabolic support of Na+ pump in apically permeabilized A6 kidney cell epithelia: role of creatine kinase.''In: ''Am J Physiol.'' 1997 Feb;272(2 Pt 1):C697-706. ], {{PMID|9124314}}</ref> At the same time, the first of two steps for endogenous creatine synthesis takes place in the kidneys themselves. Patients with kidney disease and those undergoing dialysis treatment generally show significantly lower levels of creatine in their organs, since the pathological kidneys are both hampered in creatine synthesis capability and are in back-resorption of creatine from the urine in the distal tubules. In addition, dialysis patients lose creatine due to wash out by the dialysis treatment itself and thus become chronically creatine depleted. This situation is exacerbated by the fact that dialysis patients generally consume less meat and fish, the alimentary sources of creatine. Therefore, to alleviate chronic creatine depletion in these patients and allow organs to replenish their stores of creatine, it was proposed in a 2017 article in '']'' to supplement dialysis patients with extra creatine, preferably by intra-dialytic administration. Such a supplementation with creatine in dialysis patients is expected to significantly improve the health and quality of the patients by improving muscle strength, coordination of movement, brain function and to alleviate depression and chronic fatigue that are common in these patients.<ref>T. Wallimann, U. Riek, M. M. Möddel: ''Intradialytic creatine supplementation: A scientific rationale for improving the health and quality of life of dialysis patients.''In: ''Medical Hypotheses'' 2017 Febr;99, S. 1-14. ], {{PMID|28110688}}.</ref>{{Unreliable medical source|date=October 2023}}
			==Safety==
			===Contamination===
			A 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the ] recommendations in at least one contaminant. The most prevalent of these contaminants was ], a breakdown product of creatine also produced by the body.<ref>{{cite journal|vauthors=Moreta S, Prevarin A, Tubaro F|date=June 2011|title=Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements|journal=Food Chemistry|volume=126|issue=3|pages=1232–1238|doi=10.1016/j.foodchem.2010.12.028}}</ref> Creatinine was present in higher concentrations than the ] recommendations in 44% of the samples. About 15% of the samples had detectable levels of ] or a high ] concentration. Heavy metals contamination was not found to be a concern, with only minor levels of mercury being detectable. Two studies reviewed in 2007 found no impurities.<ref name="ReferenceA">{{cite book|chapter=Safety of Creatine Supplementation|vauthors=Persky AM, Rawson ES|title=Creatine and Creatine Kinase in Health and Disease|date=2007|isbn=978-1-4020-6485-2|series=Subcellular Biochemistry|volume=46|pages=275–89|doi=10.1007/978-1-4020-6486-9_14|pmid=18652082}}</ref>
			=== Food and cooking ===
			When creatine is mixed with protein and sugar at high temperatures (above 148&nbsp;°C), the resulting reaction produces carcinogenic ]s (HCAs).<ref>{{cite web|url=http://www.cancer.gov/cancertopics/factsheet/Risk/heterocyclic-amines|title=Heterocyclic Amines in Cooked Meats|date=15 Sep 2004|publisher=National Cancer Institute|access-date=2007-08-09|archive-date=21 December 2010|archive-url=https://web.archive.org/web/20101221034421/http://www.cancer.gov/cancertopics/factsheet/Risk/heterocyclic-amines|url-status=live}}</ref> Such a reaction happens when grilling or pan-frying meat.<ref>{{cite web|url=http://www.cancer.gov/cancertopics/factsheet/Risk/cooked-meats|title=Chemicals in Meat Cooked at High Temperatures and Cancer Risk|date=2 April 2018|publisher=]|access-date=22 February 2015|archive-date=6 November 2011|archive-url=https://web.archive.org/web/20111106080003/http://www.cancer.gov/cancertopics/factsheet/Risk/cooked-meats|url-status=live}}</ref> Creatine content (as a percentage of crude protein) can be used as an indicator of meat quality.<ref>{{cite journal| last=Dahl |first=Olle | name-list-style = vanc |date=1 July 1963|title=Meat Quality Measurement, Creatine Content as an Index of Quality of Meat Products|journal=Journal of Agricultural and Food Chemistry|volume=11|issue=4|pages=350–355|doi=10.1021/jf60128a026}}</ref>
			== Dietary considerations ==
			Creatine-monohydrate is suitable for vegetarians and vegans, as the raw materials used for the production of the supplement have no animal origin.<ref>{{Cite book|last=Gießing|first=Jürgen|name-list-style=vanc|url=https://books.google.com/books?id=_xxgDwAAQBAJ&pg=PP4|title=Kreatin: Eine natürliche Substanz und ihre Bedeutung für Muskelaufbau, Fitness und Anti-Aging|date=20 February 2019|isbn=9783752803969|pages=135–136, 207|publisher=BoD – Books on Demand |access-date=27 December 2021|archive-date=19 June 2022|archive-url=https://web.archive.org/web/20220619121802/https://books.google.com/books?id=_xxgDwAAQBAJ&pg=PP4|url-status=live}}</ref>
			== See also ==
			* ]
			* ]
			== References ==
			{{Reflist}}
			== External links ==
			* in the ]
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			{{dietary supplement}}
			{{Authority control}}
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