From WikiMD
Jump to navigation Jump to search


Template:Chembox_headerbar Template:Chembox IdentifiersTemplate:Chembox PropertiesTemplate:Chembox ThermochemistryTemplate:Chembox PharmacologyTemplate:Chembox HazardsTemplate:Chembox Related
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
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Template:Cross verify (what is Template:TickTemplate:Cross ?)
Infobox references

Template:Chembox Footer/trackingScript error: No such module "TemplatePar".

Creatine (Template:IPAc-en or Template:IPAc-en[1][2]) is a nitrogenous organic acid that occurs naturally in 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 discovered it as a component of skeletal muscle, which he later named after the Greek word for meat, κρέας (kreas). In solution, creatine is in equilibrium with creatinine.[3]


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.[4]

Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine.[5]

In humans and animals, approximately half of stored creatine originates from food (about 1 g/day, mainly from meat).[5] 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.[6] 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.[5]

The enzyme GATM (L-arginine:glycine amidinotransferase (AGAT), EC is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.[7]

The second enzyme in the pathway (GAMT, Guanidinoacetate N-methyltransferase, EC: is primarily expressed in the liver and pancreas.[7]

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[8] 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.[9]

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.[10] 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.[10] 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.[11] For a review of the creatine kinase system and the pleiotropic actions of creatine and creatine supplementation see.[12]

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

Use as a supplement

Creatine supplements are used by athletes, bodybuilders, wrestlers, sprinters, 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.[13] The Mayo Clinic states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies to creatine.[14]

Recent studies have discredited concerns that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea.[15][16]

There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement.[14] 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.[17] 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.[18] The reports of damage to the kidneys by creatine supplementation have been scientifically refuted.[19][20]

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.[21][22]

Extensive research has shown that oral creatine supplementation at a rate of 5 to 20 grams per day appears to be very safe and largely devoid of adverse side-effects,[23] 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.[24][25]

A meta analysis performed in 2008 found that creatine treatment resulted in no abnormal renal, hepatic, cardiac or muscle function.[26]

While some research indicates that supplementation with pure creatine is safe, many commercially available supplements were found to contain toxic impurities including heavy metals and organic contaminants.[27] A survey of 33 commercially available supplements found that over 50% of them exceeded the European Food Safety Authority recommendations in at least one contaminant.


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.[28][29][30]

Pregnancy and breastfeeding

There is a lack of scientific information on the effects of creatine supplementation during pregnancy and breastfeeding.[citation needed] Pasteurized cow's milk contains higher levels of creatine than human milk.[31][32]

Treatment of diseases

Template:Science review Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.[33] Creatine supplementation has been, and continues to be, investigated as a possible therapeutic approach for the treatment of muscular, neuromuscular, neurological and neurodegenerative diseases (arthritis, congestive heart failure, Parkinson's disease, disuse atrophy, gyrate atrophy, McArdle's disease, Huntington's disease, miscellaneous neuromuscular diseases, mitochondrial diseases, muscular dystrophy, and neuroprotection), and depression.[34][citation needed]

A study demonstrated that creatine is twice as effective as the prescription drug riluzole in extending the lives of mice with the degenerative neural disease amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). 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 cell death.[35] A similarly promising result has been obtained in prolonging the life of transgenic mice affected by Huntington's disease. Creatine treatment lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate, and delayed the development of hyperglycemia.[36]

Treatment of muscle disorders

A meta analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance.[37] It has also been implicated in decreasing mutagenesis in DNA[38]

Improved cognitive ability

A placebo-controlled double-blind experiment found that a group of subjects composed of vegetarians and vegans who took 5 grams of creatine per day for six weeks showed a significant improvement on two separate tests of fluid intelligence, Raven's Progressive Matrices, and the backward digit span test from the WAIS. The treatment group was able to repeat longer sequences of numbers from memory and had higher overall IQ scores than the control group. The researchers concluded that "supplementation with creatine significantly increased intelligence compared with placebo."[39] A subsequent study found that creatine supplements improved cognitive ability in the elderly.[40] A study on young adults (0.03 g/kg/day for six weeks, e.g., 2 g/day for a 70-kilogram (150 lb) individual) failed to find any improvements.[41]

See also


  1. Entry "creatine" in Merriam-Webster Online Dictionary.
  2. Wells, J. C. (2000). Longman Pronunciation Dictionary. Harlow, England: Pearson Education Ltd.
  3. Cannan, R. K.; Shore, A. (1928). "The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine" (PDF). Biochem. J. 22 (4): 920–29. PMC 1252207. PMID 16744118. Retrieved 29 October 2010.CS1 maint: multiple names: authors list (link)
  4. "Creatine". MedLine Plus Supplements. U.S. National Library of Medicine. 20 July 2010. Retrieved 16 August 2010.
  5. 5.0 5.1 5.2 "Creatine". Beth Israel Deaconess Medical Center. Retrieved 23 August 2010.
  6. Burke DG, Chilibeck PD, Parise G, Candow DG, Mahoney D, Tarnopolsky M (2003). "Effect of creatine and weight training on muscle creatine and performance in vegetarians". Medicine and science in sports and exercise. 35 (11): 1946–55. doi:10.1249/01.MSS.0000093614.17517.79. PMID 14600563.CS1 maint: multiple names: authors list (link)
  7. 7.0 7.1 "ETH ETH E-Collection: Methylglyoxal, creatine and mitochondrial micro-compartments - ETH E-Collection" (PDF). 19 April 2008. doi:10.3929/ethz-a-004636659. Retrieved 16 August 2010. Cite journal requires |journal= (help)
  8. "L-Arginine:Glycine Amidinotransferase". Retrieved 16 August 2010.
  9. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21390529, please use {{cite journal}} with |pmid=21390529 instead.
  10. 10.0 10.1 Wallimann, T; Wyss, M; Brdiczka, D; Nicolay, K; Eppenberger, HM (1992). "Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis". The Biochemical journal. 281 (Pt 1): 21–40. PMC 1130636. PMID 1731757. Unknown parameter |month= ignored (help)
  11. Spillane, M; Schoch, R; Cooke, M; Harvey, T; Greenwood, M; Kreider, R; Willoughby, DS (2009). "The effects of creatine ethyl ester supplementation combined with heavy resistance training on body composition, muscle performance, and serum and muscle creatine levels". Journal of the International Society of Sports Nutrition. 6: 6. doi:10.1186/1550-2783-6-6. PMC 2649889. PMID 19228401.
  12. Template:DOI.
  13. "Creatine - Sources in the Diet". Retrieved 22 January 2013.
  14. 14.0 14.1 "Creatine: Safety". Retrieved 16 August 2010.
  15. Lopez RM, Casa DJ, McDermott BP, Ganio MS, Armstrong LE, Maresh CM (2009). "Does Creatine Supplementation Hinder Exercise Heat Tolerance or Hydration Status? A Systematic Review With Meta-Analyses". Journal of Athletic Training. 44 (2): 215–23. doi:10.4085/1062-6050-44.2.215. PMC 2657025. PMID 19295968.CS1 maint: multiple names: authors list (link)
  16. Dalbo VJ, Roberts MD, Stout JR, Kerksick CM (July 2008). "Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration". British Journal of Sports Medicine. 42 (7): 567–73. doi:10.1136/bjsm.2007.042473. PMID 18184753.CS1 maint: multiple names: authors list (link)
  17. Poortmans JR, Francaux M (September 2000). "Adverse effects of creatine supplementation: fact or fiction?". Sports Medicine. 30 (3): 155–70. doi:10.2165/00007256-200030030-00002. PMID 10999421.
  19. Template:DOI.
  20. Template:DOI.
  21. Francaux M, Poortmans JR (December 2006). "Side effects of creatine supplementation in athletes". International Journal of Sports Physiology and Performance. 1 (4): 311–23. PMID 19124889.
  22. "International Society of Sports Nutrition position stand: creatine supplementation and exercise". jissn. Retrieved 19 January 2012.
  23. Bizzarini E, De Angelis L (December 2004). "Is the use of oral creatine supplementation safe?". The Journal of Sports Medicine and Physical Fitness. 44 (4): 411–6. PMID 15758854.
  24. Bemben MG, Lamont HS (2005). "Creatine supplementation and exercise performance: recent findings". Sports Medicine. 35 (2): 107–25. doi:10.2165/00007256-200535020-00002. PMID 15707376.
  25. Kreider RB (February 2003). "Effects of creatine supplementation on performance and training adaptations" (PDF). Molecular and Cellular Biochemistry. 244 (1–2): 89–94. doi:10.1023/A:1022465203458. PMID 12701815.
  26. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 18652082, please use {{cite journal}} with |pmid=18652082 instead.
  27. Moreta S, Prevarin A, Tubaro F. (June 2011). "Levels of creatine, organic contaminants and heavy metals in creatine dietary supplements". Food Chemistry. 126 (3): 1232–1238. doi:10.1016/j.foodchem.2010.12.028.CS1 maint: multiple names: authors list (link)
  28. 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.
  29. 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.
  30. R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 366-368.
  31. Hülsemann J, Manz F, Wember T, Schöch G (1987). "[Administration of creatine and creatinine with breast milk and infant milk preparations]". Klinische Pädiatrie (in German). 199 (4): 292–5. doi:10.1055/s-2008-1026805. PMID 3657037.CS1 maint: multiple names: authors list (link)
  32. Wallimann, Theo; Tokarska-Schlattner, Malgorzata; Schlattner, Uwe (1 May 2011). "The creatine kinase system and pleiotropic effects of creatine". Amino Acids. Springer Wien. 40 (5): 1271–1296. doi:10.1007/s00726-011-0877-3. ISSN 0939-4451. PMC 3080659. PMID 21448658.
  33. Tarnopolsky M, Martin J (March 1999). "Creatine monohydrate increases strength in patients with neuromuscular disease". Neurology. 52 (4): 854–7. doi:10.1212/WNL.52.4.854. PMID 10078740.
  34. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22864465, please use {{cite journal}} with |pmid=22864465 instead.
  35. Klivenyi P, Ferrante RJ, Matthews RT; et al. (March 1999). "Neuroprotective effects of creatine in a transgenic animal model of amyotrophic lateral sclerosis". Nature Medicine. 5 (3): 347–50. doi:10.1038/6568. PMID 10086395. Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  36. Andreassen OA, Dedeoglu A, Ferrante RJ; et al. (June 2001). "Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease". Neurobiology of Disease. 8 (3): 479–91. doi:10.1006/nbdi.2001.0406. PMID 11447996. Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  37. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21328269, please use {{cite journal}} with |pmid=21328269 instead.
  38. Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22080314, please use {{cite journal}} with |pmid=22080314 instead.
  39. Rae C, Digney AL, McEwan SR, Bates TC (October 2003). "Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial". Proceedings. Biological Sciences / the Royal Society. 270 (1529): 2147–50. doi:10.1098/rspb.2003.2492. PMC 1691485. PMID 14561278.CS1 maint: multiple names: authors list (link)
  40. McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A (September 2007). "Creatine supplementation and cognitive performance in elderly individuals". Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition. 14 (5): 517–28. doi:10.1080/13825580600788100. PMID 17828627.CS1 maint: multiple names: authors list (link)
  41. Rawson ES, Lieberman HR, Walsh TM, Zuber SM, Harhart JM, Matthews TC (September 2008). "Creatine supplementation does not improve cognitive function in young adults". Physiology & Behavior. 95 (1–2): 130–4. doi:10.1016/j.physbeh.2008.05.009. PMID 18579168.CS1 maint: multiple names: authors list (link)

External links

W8MD logo

Ad. Tired of being overweight?. W8MD's insurance weight loss can HELP*

Lose weight King of Prussia, PA | Lose weight NYC | Lose weight NJ | Lose weight Philadelphia | Advertise

Disclaimer: The entire contents of WIKIMD.ORG are for informational purposes only and do not render medical advice or professional services. If you have a medical emergency, you should CALL 911 immediately! Given the nature of the wiki, the information provided may not be accurate, misleading and or incorrect. Use the information on this wiki at your own risk! See full Disclaimer. * Individual results may vary for weight loss from our sponsors.

Our sponsors WikiMD is supported by W8MD weight loss, sleep and medical aesthetic centers.