Creatine

Creatine
IUPAC name 2-(methylguanidino) ethanoic acid
Other names • (α-Methylguanido)acetic acid • Creatin • Kreatin
Identifiers
CAS number	57-00-1 Y
PubChem	586
ChemSpider	566
EC number	200-306-6
SMILES O=C(O)CN(C(=[N@H])N)C
InChI InChI=1/C4H9N3O2/c1-7(4(5)6)2-3(8)9/h2H2,1H3,(H3,5,6)(H,8,9) Key: CVSVTCORWBXHQV-UHFFFAOYAV
Properties
Molecular formula	C4H9N3O2
Molar mass	131.13 g mol−1
Melting point	303 °C (decomp.)
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Creatine is a nitrogenous organic acid that occurs naturally in vertebrates and helps to supply energy to muscle. Creatine was identified in 1832 when Michel Eugène Chevreul discovered it as a component of skeletal muscle, which he later named creatine after the Greek word for flesh, κρέας (kreas).

Biosynthesis

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.^[1]

Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine.^[2]

In humans and animals, approximately half of stored creatine originates from food (mainly from meat). Since vegetables do not contain creatine, vegetarians show lower levels of muscle creatine, but show the same levels after using supplements.^[3]

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

The enzyme GATM (L-arginine:glycine amidinotransferase (AGAT), EC 2.1.4.1) is a mitochondrial enzyme responsible for catalyzing the first rate-limiting step of creatine biosynthesis, and is primarily expressed in the kidneys and pancreas.^[4]

The second enzyme in the pathway (GAMT, guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas.^[4]

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.^[5]

Health effects

Use as food supplement

Creatine supplements are sometimes used by athletes, bodybuilders, 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-time use gives the creatine content of several foods.^[6] The Mayo Clinic states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies.^[7]

While there was once some concern that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping, recent studies have shown these concerns to be unfounded.^[8][8][9][9]

There is less concern today than there used to be about possible kidney damage from creatine, although there are reports of kidney damage, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement.^[7] 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.^[10]

In theory, creatine may alter the activities of insulin. Caution is advised in patients with diabetes or hypoglycemia, and in those taking drugs, herbs, or supplements that affect blood sugar. Serum glucose levels may need to be monitored by a health-care professional, and medication adjustments may be necessary.

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.^[11]

Extensive research over the last decade 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 ^[12] 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.^[13][14]

Creatine has become increasingly commonly used by body builders to improve their ability to build muscle tissue. By allowing body builders to perform more work as a result of additional energy, increased protein synthesis is stimulated. Also, when an abundance of creatine phosphate is stored in the muscle, the muscle will hold more water in its cells. This process is called, "Cell Hydration", and is often confused with water retention. But, in this case, water is stored within the cell. Whereas, with "water retention" the water is outside the cell. The more water is held in a muscle cell, the more it will promote the synthesis of protein as well as deter protein breakdown.^[15]

Pharmacokinetics

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, 12-24g a day), it is no longer necessary to maintain a consistantly high serum level of Cr. 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 Cr ,Post - loading dose, 2-5g daily is the standard amount to intake.^[16][17][18]

Pregnancy and breastfeeding

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.^[19]

Treatment of diseases

Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.^[20] 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).

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.^[21] 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.^[22]

Cognitive ability

A placebo-controlled double-blind experiment found that vegetarians 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."^[23] A subsequent study found that creatine supplements improved cognitive ability in the elderly.^[24] A study on young adults (0.03 g/kg/day for six weeks, e.g., 2 g/day for 150-pound individual) failed, however, to find any improvements.^[25]

See also

• Adenosine triphosphate
• Beta-alanine
• Creatine phosphate

References

External links

• NCBI Online Mendelian Inheritance In MAN (OMIM) GATM human mutation record
• Quackwatch on creatine
• Study on Safety of Creatine for Supplementation, 2010
• Creatine side effects: Fact or fiction?, 2010
• Creatine 'boosts brain power', BBC News, 12 August 2003
• Creatine: From Muscle to Brain, Peter W. Schutz, The Science Creative Quarterly, 2009
• Creatine during Pregnancy and Protection of Babies against Anoxia A mouse study