creatine

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(krē'ə-tēn', -tĭn) pronunciation also cre·a·tin (-tĭn)
n.
A nitrogenous organic acid, C4H9N3O2, that is found in the muscle tissue of vertebrates mainly in the form of phosphocreatine and supplies energy for muscle contraction.

[French créatine : from Greek kreas, kreat-, flesh.]


A derivative of the amino acids glycine and arginine, important in muscle as a store of phosphate for resynthesis of ATP during muscle contraction and work. Not a dietary essential, since it is synthesized in the body, but widely sold in supplements to improve athletic performance, with limited evidence of efficacy.

A chemical made naturally in the body from amino acids readily obtained from meat and fish. Inside the body, creatine is involved in energy expenditure during exercise. Much of it is phosphorylated (i.e. a phosphate group is added to it) to form phosphocreatine, an energy-rich compound used by muscles during very short bursts of explosive activity (see phosphagen system).

The average person's body has about 120 grams of creatine; 98 per cent in the muscles, 1.5 per cent in nervous tissue, and 0.5 per cent in other organs. The recommended intake is about a gram a day.

Studies have shown that dosages of about 24-30 g of creatine per day for two days can raise the level of phosphocreatine stored in muscle, increasing the energy available for high intensity exercise where there is a short recovery between bouts of activity. When individuals performed multiple sprints of 10-15 seconds duration with less than 30 seconds recovery between each sprint, then after the 6th, 7th, or 8th sprint those who consumed creatine were not so fatigued as those who took a placebo. Creatine supplementation increased power output by as much as 7 per cent in high intensity exercise of an intermittent nature, but there is no evidence that it improves peak power output or sprint ability in a continuous sprint. A dosage of 24 to 30 g per day is equivalent to eating approximately 6 kg (13lb) of beef. Ingesting so much meat would create dietary problems, so a pure form of creatine has been produced as a supplement. Further research has shown that the greatest improvements in short-term performance occur if exercise is performed immediately after taking the supplement, and the improvements are retained longer if relatively small doses of creatine are ingested over a long period of time.

Creatine supplements have been used by a number of successful sports people, including the Cambridge University crew who won the 1993 boat race, and many competitors at the Barcelona Olympics. However, there is concern that the large amounts consumed by athletes may put their health at risk because kidney failure can occur if too much creatinine (the end product of creatine metabolism) is excreted after muscle damage.

Drug Info:

Creatine

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Chemical formula:



Creatine powder

What is creatine?

Creatine is an non-prescription dietary supplement that is being promoted for its ability to enhance muscle strength and physical endurance. It is not officially endorsed by the FDA for this use, however, some medical literature does support its use. It is not banned by either the NCAA or the USOC, but many consider the use of high doses of supplements in competitive sport unethical.

What should I tell my health care provider before I take this medicine?

It is important for you to tell your prescriber or other health care professional that you are using creatine. Although interactions with other drugs have not been noted, it is important that your health care provider is aware you are taking this supplement.

How should I use this medicine?

Creatine powder should be taken orally. It should be mixed with a beverage of your choice. The beverage may be cold or hot. Do not cook or microwave the powder or beverages containing the powder. Beverages such as apple, grape, or orange juice may help the creatine work better for you. After mixing, use immediately. If you can not use it immediately, use it within 8 hours. To avoid stomach discomfort, allow at least 4 hours between doses.

What if I miss a dose?

Missing a dose is not harmful. If you miss a dose, simply resume taking it on your previous schedule. Do not take double doses to catch up.

What drug(s) may interact with creatine?

caffeine
cyclosporine
• ephedra, Ma huang
guarana

For many herbs and dietary supplements, interactions with other medications are unknown. That is why you should always be careful when mixing herbal remedies with traditional medications.

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

What should I watch for while taking creatine?

Creatine is generally regarded as safe. If you notice any changes in your physical health while taking creatine, you should contact your health care provider. Also, different brands of creatine might contain different amounts of active ingredient so try to use the same brand.

What side effects may I notice from using creatine?

Side effects that you should report to your prescriber or health care professional as soon as possible:
• diarrhea
• difficulty breathing
• rash
• severe muscle cramping or pain
• vomiting

Where can I keep my medicine?

Keep out of the reach of children.

Store at room temperature. Avoid storing in hot areas. Throw away any unused product after the expiration date.

GENERAL INFORMATION REGARDING DIETARY SUPPLEMENTS:
Dietary supplements include amino acids, vitamins, minerals, herbs, and other plant-derived substances, and extracts of these substances. Products are easy to identify as they must state "Dietary Supplement" on the label. A "Supplement Facts" panel is provided on the label for most products. Supplements are not drugs and are not regulated like pharmaceuticals. You should note that rigid quality control standards are not required for dietary supplements. Differences in the potency and purity of these products can occur. Scientific data to support the use of a dietary supplement for a certain condition may not be available. This product is not intended to diagnose, treat, cure or prevent any disease.

The Food and Drug Administration suggests the following to help consumers protect themselves:
• Always read product labels and follow directions.
• Look for products containing ingredients with the "USP" notation. This indicates the manufacturer followed the standards of the US Pharmacopoeia.
• "Natural" doesn't mean a product is safe for humans to consume.
• Supplements produced or distributed by a nationally known food or drug company are more likely to be made under tight controls as these companies have standards in place for their other products. You can write to the company or manufacturer for more information about the conditions under which the products are made.


Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

An amino acid made naturally in the body from other amino acids readily obtained from fish and meat. Inside the body, creatine is involved in energy exchanges during exercise. Much of it is phosphorylated to form phosphocreatine, an energy-rich compound used by muscles during very short bursts of explosive activity (see ATP-PCr system). Creatine supplements in the form of creatine monohydrate are quite widely taken to boost creatine levels in muscles, a process called creating loading. Several studies show that creatine loading can enhance performance in activities that require short bursts of intense activity, such as rowing, weight-lifting, and sprinting. Creatine is not on the World Anti-doping Agency's list of prohibited substances; therefore, its use is permitted. However, the long-term effects of ingesting creatine supplements are not known, but usage may not be risk-free (see formaldehyde).

Word Tutor:

creatine

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pronunciation

IN BRIEF: n. - An amino acid that does not occur in proteins but is found in the muscle tissue of vertebrates both in the free form and as phosphocreatine.

Tutor's tip: A "cretin" is an insensitive person, while "creatine" is an amino acid that assists muscular movements.

LearnThatWord.com is a free vocabulary and spelling program where you only pay for results!


N-(aminoiminomethyl)-N-methylglycine; an important metabolite in muscle, the precursor of phosphocreatine



.

Previous:cranin, crambin, cpm
Next:creatine kinase, creatine phosphate, creatinine

A nonprotein nitrogen substance synthesized in the body from three amino acids: arginine, glycine (aminoacetic acid) and methionine. Creatine readily combines with phosphate to form phosphocreatine, or creatine phosphate, which is present in muscle, where it serves as the storage form of high-energy phosphate necessary for intense muscle contraction.

  • c. kinase (CK) — an organ-specific enzyme catalyzing the transfer of a phosphate group from phosphocreatine to ATP. It has three isoenzymes: CK1, found primarily in the brain; CK2, found in the myocardium; and CK3, found in both skeletal muscle and the myocardium. In humans, the presence of CK2 in the blood is useful in diagnosing a recent myocardial infarction, but in animals CK3 is most commonly increased related to muscle damage. Called also creatine phosphokinase, Lohmann's enzyme.
  • c. phosphate — see creatine (above).
  • c. phosphokinase — called also CPK; see creatine kinase (above).
Creatine
Identifiers
CAS number 57-00-1 YesY
PubChem 586
ChemSpider 566 YesY
UNII MU72812GK0 YesY
EC number 200-306-6
DrugBank DB00148
KEGG C00300 YesY
MeSH Creatine
ChEBI CHEBI:16919 N
ChEMBL CHEMBL283800 YesY
RTECS number MB7706000
ATC code C01EB06
Beilstein Reference 907175
Gmelin Reference 240513
3DMet B00084
Jmol-3D images Image 1
Image 2
Properties
Molecular formula C4H9N3O2
Molar mass 131.13 g mol−1
Appearance White crystals
Odor Odourless
Melting point

255 °C, 528 K, 491 °F

Solubility in water 13.3 g L−1 (at 18 °C)
log P −1.258
Acidity (pKa) 3.429
Basicity (pKb) 10.568
Isoelectric point 8.47
Thermochemistry
Std enthalpy of
formation
ΔfHo298
−538.06–−536.30 kJ mol−1
Std enthalpy of
combustion
ΔcHo298
−2.3239–−2.3223 MJ mol−1
Standard molar
entropy
So298
189.5 J K−1 mol−1
Specific heat capacity, C 171.1 J K−1 mol−1 (at 23.2 °C)
Pharmacology
Elimination
half-life
3 hours
Hazards
GHS pictograms The exclamation-mark pictogram in the Globally Harmonized System of Classification and Labelling of Chemicals (GHS)
GHS signal word WARNING
GHS hazard statements H315, H319, H335
GHS precautionary statements P261, P305+351+338
EU classification Irritant Xi
R-phrases R36/37/38
S-phrases S26, S36
Related compounds
Related alkanoic acids
Related compounds
 N (verify) (what is: YesY/N?)
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 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.[1]

Contents

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.[2]

Creatine is not an essential nutrient, as it is manufactured in the human body from L-arginine, glycine, and L-methionine.[3]

In humans and animals, approximately half of stored creatine originates from food (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 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.[4] 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.[3]

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.[5]

The second enzyme in the pathway (GAMT, Guanidinoacetate N-methyltransferase, EC:2.1.1.2) is primarily expressed in the liver and pancreas.[5]

Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects.[6]

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 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.[7] 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.[7] 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.[8] For a review of the creatine kinase system and the pleiotropic actions of creatine and creatine supplementation see.[9]

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.[10] A survey of long-term use gives the creatine content of several foods. The Mayo Clinic states that creatine has been associated with asthmatic symptoms and warns against consumption by persons with known allergies.[11]

There was once some concern that creatine supplementation could affect hydration status and heat tolerance and lead to muscle cramping and diarrhea, but recent studies have shown these concerns to be unfounded.[12][13]

There are reports of kidney damage with creatine use, such as interstitial nephritis; patients with kidney disease should avoid use of this supplement.[11] 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.[14] 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.[15] The reports of damage to the kidneys by creatine supplementation have been scientifically refuted.[16][17]

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.[18][19]

Extensive research over the last decade[date missing] 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,[20] 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.[21][22]

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, 12-24 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 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 g daily is the standard amount to intake.[23][24][25]

Pregnancy and breastfeeding

Creatine cannot be recommended during pregnancy or breastfeeding due to a lack of scientific information.[citation needed] Pasteurized cow's milk contains higher levels of creatine than human milk.[26][27]

Treatment of diseases

Creatine has been demonstrated to cause modest increases in strength in people with a variety of neuromuscular disorders.[28] 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).[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.[29] 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.[30]

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."[31] A subsequent study found that creatine supplements improved cognitive ability in the elderly.[32] 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.[33]

See also

References

  1. ^ Cannan, R. K.; Shore, A. (1928). "The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine". Biochem. J. 22 (4): 920–29. PMC 1252207. PMID 16744118. http://www.biochemj.org/bj/022/0920/0220920.pdf. Retrieved 2010-10-29. 
  2. ^ "Creatine". MedLine Plus Supplements. U.S. National Library of Medicine. 2010-07-20. http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-creatine.html. Retrieved 2010-08-16. 
  3. ^ a b "Creatine". Beth Israel Deaconess Medical Center. http://www.bidmc.org/YourHealth/ConditionsAZ.aspx?ChunkID=21706. Retrieved 2010-08-23. 
  4. ^ 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. 
  5. ^ a b ETH ETH E-Collection: Methylglyoxal, creatine and mitochondrial micro-compartments - ETH E-Collection. E-collection.ethbib.ethz.ch. 2008-04-19. doi:10.3929/ethz-a-004636659. http://e-collection.ethbib.ethz.ch/ecol-pool/diss/fulltext/eth15180.pdf. Retrieved 2010-08-16. 
  6. ^ "L-Arginine:Glycine Amidinotransferase". http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602360. Retrieved 2010-08-16. 
  7. ^ a b Wallimann, T; Wyss, M; Brdiczka, D; Nicolay, K; Eppenberger, HM. "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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1130636. 
  8. ^ Spillane, M; Schoch, R; Cooke, M; Harvey, T; Greenwood, M; Kreider, R; Willoughby, DS. "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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2649889. 
  9. ^ doi:10.1007/s00726-011-0877-3.
  10. ^ "Creatine". Creatine Site. http://www.creatinesite.com/. Retrieved 19 January 2012. 
  11. ^ a b "Creatine: Safety". MayoClinic.com. http://www.mayoclinic.com/health/creatine/NS_patient-creatine/DSECTION=safety. Retrieved 2010-08-16. 
  12. ^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2657025. 
  13. ^ 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. 
  14. ^ 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. 
  15. ^ http://www.efsa.europa.eu/EFSA/efsa_locale-1178620753824_1178620761727.htm
  16. ^ doi:10.1007/s00421-007-0669-3.
  17. ^ doi:10.1023/A:1022469320296.
  18. ^ 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. 
  19. ^ "International Society of Sports Nutrition position stand: creatine supplementation and exercise". jissn. http://www.jissn.com/content/4/1/6. Retrieved 19 January 2012. 
  20. ^ 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. 
  21. ^ Bemben MG, Lamont HS (2005). "Creatine supplementation and exercise performance: recent findings". Sports Medicine 35 (2): 107–25. PMID 15707376. 
  22. ^ Kreider RB (February 2003). "Effects of creatine supplementation on performance and training adaptations". Molecular and Cellular Biochemistry 244 (1–2): 89–94. doi:10.1023/A:1022465203458. PMID 12701815. http://www.kluweronline.com/art.pdf?issn=0300-8177&volume=244&page=89. 
  23. ^ 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.
  24. ^ 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.
  25. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 366-368.
  26. ^ Hülsemann J, Manz F, Wember T, Schöch G (1987). "[Administration of creatine and creatinine with breast milk and infant milk preparations]" (in German). Klinische Pädiatrie 199 (4): 292–5. doi:10.1055/s-2008-1026805. PMID 3657037. 
  27. ^ Wallimann, Theo; Tokarska-Schlattner, Malgorzata; Schlattner, Uwe (2011-05-01). "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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3080659. 
  28. ^ Tarnopolsky M, Martin J (March 1999). "Creatine monohydrate increases strength in patients with neuromuscular disease". Neurology 52 (4): 854–7. PMID 10078740. http://www.neurology.org/cgi/pmidlookup?view=long&pmid=10078740. 
  29. ^ 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. 
  30. ^ 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. 
  31. ^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1691485. 
  32. ^ 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. 
  33. ^ 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. 

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