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Skeletal formula of creatine
Ball and stick model of creatine
Systematic IUPAC name
2-[Carbamimidoyl(methyl)amino]acetic acid
Other names
N-Carbamimidoyl-N-methylglycine; Methylguanidoacetic acid
3D model (JSmol)
3DMet B00084
ECHA InfoCard 100.000.278
EC Number 200-306-6
MeSH Creatine
RTECS number MB7706000
Molar mass 131.14 g·mol−1
Appearance White crystals
Odor Odourless
Melting point 255 °C (491 °F; 528 K)
13.3 g L−1 (at 18 °C)
log P −1.258
Acidity (pKa) 3.429
Basicity (pKb) 10.568
Isoelectric point 8.47
171.1 J K−1 mol−1 (at 23.2 °C)
189.5 J K−1 mol−1
−538.06–−536.30 kJ mol−1
−2.3239–−2.3223 MJ mol−1
C01EB06 (WHO)
3 hours
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word WARNING
H315, H319, H335
P261, P305+351+338
Related compounds
Related alkanoic acids
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

Creatine (/ˈkrətn/ or /ˈkrətɪn/[1][2]) is a nitrogenous organic acid that occurs naturally in vertebrates. Its main role is to facilitate recycling of adenosine triphosphate (ATP), the energy currency of the cell, primarily in muscle and brain tissue. This is achieved by recycling adenosine diphosphate (ADP) to ATP via donation of phosphate groups. Creatine also acts as a pH buffer in tissues.[3]

Creatine synthesis primarily occurs in the liver and kidneys.[3][4] On average, it is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[4][5] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[4][6] Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[5][6]

Creatine was 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 Greek word for meat, κρέας (kreas). In solution, creatine is in equilibrium with creatinine.[7] Creatine is a derivative of the guanidinium cation.


Creatine is not an essential nutrient[8] as it is naturally produced in the human body from the amino acids glycine and arginine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase (AGAT, EC: to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase (GAMT,EC:, using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.


Synthesis primarily takes place in the kidney and liver, with creatine then being transported to the muscles via the blood. The majority of the human body's total creatine and phosphocreatine stores are located in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues.[5][6][9] On average, creatine is produced endogenously at an estimated rate of about 8.3 mmol or 1 gram per day in young adults.[4][5] Creatine is also obtained through the diet at a rate of about 1 gram per day from an omnivorous diet.[5][6] Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since vegetables are not a primary source of creatine. However, subjects happened to show the same levels after using supplements.[10] Given that creatine can be synthesized from the above-mentioned amino acids, protein sources rich in these amino acids can be expected to provide sufficient native biosynthesis in the body.[8]

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[11] Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency and guanidinoacetate methyltransferase deficiency. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.[12]

Phosphocreatine system[edit]

Creatine, which is synthesized in the liver and kidneys, 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.[13] Fortunately, during times of increased energy demands, the phosphagen (or ATP/PCr) system rapidly resynthesizes ATP from ADP with the use of phosphocreatine (PCr) through a reversible reaction with the enzyme creatine kinase (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.[13] 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.[14][15][16]

The pathway for the synthesis of creatine
Arg – Arginine; GATM – Glycine amidinotransferase; GAMT – Guanidinoacetate N-methyltransferase; Gly – Glycine; Met – Methionine; SAH – S-adenosyl homocysteine; SAM – S-adenosyl methionine.
The color scheme is as follows:enzymes, coenzymes and the Met part, substrate names, the Gly part, the Arg part

Health effects[edit]


Creatine supplements are used by athletes, bodybuilders, wrestlers, sprinters, and others who wish to gain muscle mass. The Mayo Clinic states that creatine has been associated with asthmatic symptoms.[17]

A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.[18][19]

There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement.[17] 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.[20] In 2004 the European Food Safety Authority (EFSA) published a record which stated that oral long-term intake of 3 g pure creatine per day is risk-free.[21] A 2003 study on athletes who took creatine for 21 months found no significant changes in markers of kidney function;[22] a 2008 study on athletes who took creatine for 3 months found no evidence of kidney damage during that time.[23] A review found creatine to have no effects on liver or kidney function in over months of supplementation in both young and old population. However authors still cautioned against using high doses(>3g-5g) in those with impaired kidney functioning, and suggested further studies are needed relating to claims of mutagenicity and carcinogenicity.[24]

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.[citation needed] However, this risk is largely theoretical because urinary excretion of formaldehyde, even under heavy creatine supplementation, does not exceed normal limits.[25][26]

Extensive research has shown that oral creatine supplementation at a rate of five to 20 grams per day appears to be very safe and largely devoid of adverse side-effects,[27] 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.[28][29]

Many meta analyses found that creatine treatment resulted in no abnormal kidney, liver, heart, or muscle function.[30][31] It is ineffective as a treatment for amyotrophic lateral sclerosis.[32]

While some research indicates that supplementation with pure creatine is safe, a 2011 survey of 33 supplements commercially available in Italy found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant. The most prevalent of these contaminants was creatinine, a breakdown product of creatine also produced by the body.[33] Creatinine was present in higher concentrations than the European Food Safety Authority recommendations in 44% of the samples. About 15% of the samples had detectable levels of dihydro-1,3,5-triazine or a high dicyandiamide 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.[30]


This graph shows the mean plasma creatine concentration (measured in μmol/L) over an 8-hour period following ingestion of 4.4 grams of creatine in the form of creatine monohydrate (CrM), tri-creatine citrate (CrC), or creatine pyruvate (CrPyr).[34]

Endogenous serum or plasma creatine concentrations in healthy adults are normally in a range of 2–12 mg/L. A single 5 g (5000 mg) oral dose in healthy adults results in a peak plasma creatine level of approximately 120 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 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 as waste. A typical post-loading dose is 2–5 g daily.[35][36][37]

Pregnancy and breastfeeding[edit]

While research is limited, some recent retrospective studies show higher maternal serum creatine to correlate with higher birth weight and better birth outcomes. However, as of 2014, there were no randomised controlled trials establishing its effectiveness when supplemented, for neuroprotection of the fetus.

Pasteurized cow's milk contains higher levels of creatine than human milk.[38][39]

Muscle disorders[edit]

A meta analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance.[40] Creatine treatment does not appear to improve muscle strength in people who have metabolic myopathies.[40] High doses of creatine leads to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease.[40] It has also been implicated in decreasing mutagenesis in DNA.[41]

Heterocyclic amines[edit]

When creatine is mixed with protein and sugar at high temperatures (above 148 °C), the resulting reaction produces heterocyclic amines (HCAs). Such a reaction happens when grilling or pan frying meat.[42] Creatine content (as a percentage of crude protein) can be used as an indicator of meat quality.[43]

A Meta-analysis from 2011 concluded that "search for the excretion of heterocyclic amines remains a future task to definitively exclude the unproved allegation made by some national agencies".[31]

See also[edit]


  1. ^ Entry "creatine" in Merriam-Webster Online Dictionary.
  2. ^ Wells, J. C. (2000). Longman Pronunciation Dictionary. Harlow, England: Pearson Education Ltd.
  3. ^ a b Barcelos RP, Stefanello ST, Mauriz JL, Gonzalez-Gallego J, Soares FA (2016). "Creatine and the Liver: Metabolism and Possible Interactions". Mini Rev Med Chem. 16 (1): 12–8. PMID 26202197. 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. 
  4. ^ a b c d Brosnan JT, da Silva RP, Brosnan ME (2011). "The metabolic burden of creatine synthesis". Amino Acids. 40 (5): 1325–31. doi:10.1007/s00726-011-0853-y. PMID 21387089. Creatinine loss averages approximately 2 g (14.6 mmol) for 70 kg males in the 20- to 39-year age group. ... 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
    Creatine synthesis (mmol/day)   8.3
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External links[edit]