Systematic IUPAC name
N-Carbamimidoyl-N-methylglycine; Methylguanidoacetic acid
|Molar mass||131.14 g·mol−1|
|Melting point||255 °C (491 °F; 528 K)|
|13.3 g L−1 (at 18 °C)|
|171.1 J K−1 mol−1 (at 23.2 °C)|
|189.5 J K−1 mol−1|
Std enthalpy of
|−538.06–−536.30 kJ mol−1|
Std enthalpy of
|−2.3239–−2.3223 MJ mol−1|
|GHS signal word||WARNING|
|H315, H319, H335|
EU classification (DSD)
Related alkanoic acids
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|(: / ?)|
Creatine ( or ) is a vertebrates and helps to supply energy to all cells in the body, primarily muscle. This is achieved by increasing the formation of adenosine triphosphate (ATP). 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). Early analysis showed that human blood is approximately 1% creatine, and the highest concentrations are found in animal blood, brain (0.14%), muscle (0.50%), and testes (0.18%). The liver and kidney contain approximately 0.01% creatine. Today, creatine content (as a percentage of crude protein) can be used as an indicator of meat quality.
Creatine is a derivative of the guanidinium cation.
- Biosynthesis 1
- The phosphocreatine system 2
Health effects 3
- Supplements 3.1
- Pharmacokinetics 3.2
- Pregnancy and breastfeeding 3.3
- Muscle disorders 3.4
- Testicular Cancer 3.5.1
- See also 4
- References 5
- External links 6
Creatine is not an essential nutrient 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:220.127.116.11) to form guanidinoacetate, this is then methylated by guanidinoacetate N-methyltransferase (GAMT,EC:18.104.22.168), 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 reserve 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. Approximately 95% of the human body's total creatine is located in skeletal muscle. In humans and animals, approximately half of stored creatine originates from food (about 1 g/day, mainly from meat). 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 are not 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. 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.
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects. Clinically, there are three distinct disorders of creatine metabolism. Deficiencies of the two synthetic 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.
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. 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. 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. For a review of the creatine kinase system and the pleiotropic actions of creatine and creatine supplementation see.
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 and warns against consumption by persons with known allergies to creatine.
A 2009 systematic review discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.
There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement. 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. In 2004 the European Food Safety Authority (EFSA) published a record which stated that oral long-term intake of 3g pure creatine per day is risk-free. A 2003 study on athletes who took creatine for 21 months, found no significant changes in markers of renal function; a 2008 study on athletes who took creatine for 3 months, found no evidence of kidney damage during that time.
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.
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, 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.
Many meta analyses found that creatine treatment resulted in no abnormal renal, hepatic, cardiac, or muscle function.
While some research indicates that supplementation with pure creatine is safe, a survey of 33 commercially available in Italy supplements 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. 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. Both two studies reviewd in 2007 found no impurities.
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.
Pregnancy and breastfeeding
There is a lack of scientific information on the effects of creatine supplementation during pregnancy and breastfeeding. As of 2014 it is not clear if taking creatine during pregnancy affects the rate of cerebral palsy or other neurological problems.
Pasteurized cow's milk contains higher levels of creatine than human milk.
A meta analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance. It has also been implicated in decreasing mutagenesis in DNA
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. HCAs are known to cause cancer in animals and may cause cancer in humans as well. This could be a mechanism why consumption of meat increases risk of colon, breast and prostate cancer. Metaanalysis 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". Study from 2015 indicated that "diet rather than creatine supplementation was the main responsible factor for HCA".
In March 2015, a study published by the British Journal of Cancer found that men using supplements containing creatine may have a higher risk of getting testicular cancer 
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