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Creatine

Common Name(s): Creatin, Creatine, Creatine monohydrate, Creatine phosphate, CrP, Kreatin, methylguanidine acetic acid, N-(aminoiminomethyl)-N-methylglycine, N-amidinosarcosine, Phosphocreatine

Medically reviewed by Drugs.com. Last updated on Sep 20, 2024.

Clinical Overview

Use

Creatine has enhanced performance in short-duration, high-intensity exercise in limited trials. Creatine supplementation has been extensively studied in myopathies and neurodegenerative disorders, but with limited efficacy. Further trials are ongoing.

Dosing

Dosage regimens in clinical trials vary from 2 to 20 g daily, and from 1 week up to 4 years.

Contraindications

Patients with a history of renal impairment or those taking nephrotoxic agents should avoid concomitant creatine supplementation or be monitored closely if supplementation is necessary.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Few adverse reactions have been reported in clinical studies among patients with neurological or muscle disorders, or in healthy individuals.

Concerns regarding renal and hepatic toxicity exist; unequivocal proof of safety is lacking and caution is warranted.

Case reports of adverse reactions among athletes include dehydration, electrolyte imbalance, and muscle cramping. Minor GI upset (diarrhea, GI pain, nausea), dizziness, and short-term loss in body mass have also been reported. The safety of creatine in children has not been established.

Toxicology

Information is limited; however, the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) has warned of the potential for production of cytotoxic compounds, especially at high dosages.

Source

Creatine is a constituent of skeletal muscle tissue of vertebrates, and is obtained through the diet or is endogenously synthesized in the body. Herring contains 6.5 to 10 g/kg of creatine, while beef, pork, salmon, and tuna all contain approximately 4 to 5 g/kg. A typical American/Western diet provides 1 to 5 g/day; vegetarians must meet their daily creatine needs via endogenous synthesis.

Approximately 1 to 2 g/day creatine is synthesized in the kidneys, pancreas, and liver. It is then transported via circulation to various tissues for storage and utilization, particularly in skeletal muscle (95%), with the balance in the brain, kidneys, and testes.

The majority of studies evaluating the effects of oral creatine supplementation have been conducted using creatine monohydrate or the phosphate salt. Creatine monohydrate is available in several doseforms, including bar, capsule, gel, gum, liquid, and powder. Creatine ester and creatine alcohols are marketed as supplements; however, the availability of actual creatine in the preparations is dependent on conversion to creatine within the body. The efficacy of conversion of some of these doseforms has not been demonstrated.1, 2, 3, 4

History

Creatine was discovered in 1832 by the French chemist Michel Chevreul as an organic constituent of meat. "Extractum carnis Liebig," a concentrated meat extract, was sold around the same period by German researcher Justus von Liebig. In 1847, it was observed that the flesh of wild foxes killed in the chase contained 10 times more creatine than those living in captivity, and in 1912 researchers from Harvard Medical School established a link between creatine ingestion and increased creatine in muscle tissue.

In the late 1960s, advances in biopsy techniques allowed researchers to study the breakdown and resynthesis of adenosine triphosphate (ATP) and creatine phosphate; however, it was not until the early 1990s that creatine's influence on exercise performance in humans was studied. Reports followed in 1992 of a 20% increase in human muscle mass subsequent to creatine supplementation, and athletes were reported to have used it prior to the 1992 Olympic Games.2, 5, 6

Chemistry

Creatine is a nitrogenous organic acid synthesized in the body from the amino acids glycine, arginine, and methionine within an enzymatic ally controlled pathway. Genetic deficiencies interrupting the biosynthesis of creatine lead to severe neuromuscular disorders. Creatinine, the product of creatine phosphate metabolism, is filtered from the blood and excreted via the kidneys.2, 7

Uses and Pharmacology

The role of creatine in facilitating energy distribution and responding to energy demand is explained by the "creatine phosphate shuttle." Creatine, released from contracting myofibrils during exercise, moves to the mitochondria and, in the presence of ATP, produces creatine phosphate and releases adenosine diphosphate (ADP). ADP then stimulates oxygen uptake. Creatine phosphate, synthesized in the mitochondria under anaerobic conditions, returns to the myofibril, where creatine kinase catalyzes the resynthesis of ATP as an energy source for subsequent contractions.7

Creatine deficiency syndromes include disorders of creatine synthesis or transport and include guanidinoacetate methyltransferase deficiency, arginine:glycine amidinotransferase deficiency, and X-linked creatine transporter deficiency. Use of creatine in such disorders should be under the guidance of a specialist health care provider.8, 9

Aging

Animal data

Increased lifespan has been demonstrated in mouse models of aging.10

Clinical data

The results of studies using creatine in elderly patients to reduce loss of muscle mass are equivocal. Timing and dose of supplementation, as well as proximity to resistance training sessions, may be important factors controlling efficacy.2, 11, 12 Bone mass trial data are also equivocal, with some studies reporting no effect; however, populations and dosages ranged widely.13

Limited studies suggest that topical and/or systemic administration of creatine or phosphocreatine may have beneficial effects in various skin conditions, such as photoaging and wound healing.14, 15

Amyotrophic lateral sclerosis/motor neuron disease

Animal data

Mouse models of amyotrophic lateral sclerosis (ALS) have shown increased survival with administration of creatine.16, 17, 18, 19

Clinical data

A Cochrane meta-analysis of 3 randomized, double-blind, placebo controlled trials (N = 386) found no statistical difference in survival or disease progression in ALS for creatine at 5 to 10 g/day.20 Further small, open-label studies have found equivocal results.3 Using magnetic resonance spectroscopy, a phase 1 open-label, dose-escalation study in 6 patients with ALS demonstrated increased in vivo brain creatine concentration at creatine 15 mg twice daily after 19 days.21 Results of a phase 3, multicenter, double-blind, placebo-controlled, randomized study evaluating creatine in ALS are pending.22

Other neurodegenerative disorders

Animal data

Creatine has been studied in animal models of Huntington disease and Parkinson disease.23, 24, 25, 26, 27

Clinical data

Only a few randomized double-blind, placebo-controlled trials have been conducted in Huntington disease with equivocal results. Likewise, results from open-label trials have been inconclusive.3, 28, 29 Limited trials have been conducted in patients with Parkinson disease with more promising, but still inconclusive, findings.3, 28, 30 A long-term phase 3, multicenter, double-blind, parallel-group, placebo controlled, randomized study (N = 1,741) evaluating the effect of creatine on 5-year disease progression in patients with newly disgnosed Parkinson disease (within the past 5 years) and controlled on dopaminergic therapy (for at least 90 days but no more than 2 years) was terminated early based on futility as assessed at a planned interim analysis. Compared with placebo, creatine monohydrate (10 g/day) did not provide any significant differences in clinical decline over at least 5 years.31, 88 A study among patients with Rett syndrome found increases in some, but not all, outcome measures.32

Exercise performance enhancement

Creatine is widely used among professional athletes; however, in 2000 the National Collegiate Athletic Association banned colleges from distributing creatine to student athletes.33

Animal data

Data from animal studies cannot readily be generalized to sports performance in humans.

Clinical data

There is a large volume of scientific literature dealing with creatine supplementation in exercise performance. Wide variations in study populations, types of exercise, dosing regimens, and outcome measures are found in the literature.

Possible mechanisms include increased muscle stores of creatine phosphate, more rapid resynthesis of creatine phosphate and reduced ATP degradation, enhanced oxygen uptake via the creatine-phosphate shuttle, and increased glycogen storage.34, 35, 36, 37, 38, 39

Meta-analyses of studies up to the year 2000 found improvement in the performance of repetitive, laboratory-based exercise tests but also found inconsistent results in sports-specific performance.40, 41

Equivocal results have been obtained for an ergogenic benefit, with some studies finding decreased performance (which may, in part, be due to increased body mass).35, 42, 43, 44, 45, 46, 47, 48 Other studies show improved performance in high-intensity, short-duration, intermittent exercise, and improved fatigue resistance.39, 44, 45, 47, 49, 50, 51, 52

A concept of "nonresponders" has also been discussed. Normal muscle creatine concentrations average 120 mmol/kg (range, 100 to 140 mmol/kg); a maximum total creatine concentration of 150 to 160 mmol/kg is achieved by approximately 20% of subjects, and individuals with an initial total creatine near or at the creatine saturation point do not demonstrate improved performance following creatine ingestion.40, 49, 53 Muscle creatine concentrations return to presupplementation concentrations within 4 weeks of discontinuation, suggesting reversible inhibition of endogenous creatine production.49, 54

Cardiovascular disease

Animal data

Studies in animals are largely irrelevant considering the availability of a meta-analysis of clinical trial data.55

Clinical data

The creatine kinase system is integral to energy homeostasis, cardiovascular contraction, and ischemic resistance; however, there is insufficient evidence to consider a place in therapy for creatine in heart failure or myocardial infarction. There is some evidence from trial data that creatine as an add-on to standard treatment may improve dysrhythmia and dyspnea.55, 56

CNS

Animal data

Studies in rats have been conducted primarily to demonstrate altered concentrations of creatine in different psychological states.57

Clinical data

Most, but not all, studies conducted in elderly patients report some improvement in memory with supplemental creatine. Dosages range widely in these studies (5 to 20 g daily, from 7 days to 6 weeks). No effect on cognition was reported in younger people.2, 3 A number of studies report on altered creatine concentrations in patients with mental health disorders, including major depression and bipolar disorder, with an observed spike in serum creatine kinase at the onset of a major psychotic event. Further trials evaluating a place in therapy for creatine in major depression are needed.2, 57, 58

Chronic obstructive pulmonary disease (COPD)

Animal data

Studies in animals are largely irrelevant considering the availability of clinical trial data.

Clinical data

A meta-analysis of 4 randomized, controlled trials found no improvement in quality of life indices and a lack of muscle strength enhancement. More clearly defined trials may be warranted.3, 59

Mitochondrial disease

Animal data

Clinical studies have been prompted as a result of exercise-related studies in healthy human populations rather than based solely on animal experiments.

Clinical data

A Cochrane review found no benefit in 2 of 3 included trials; increased muscle (handgrip) strength and improved exercise lactate following exercise was found in 1 trial. Dosages range widely in these studies (150 mg/kg to 20 g daily, from 4 to 6 weeks).3, 60, 61, 62

Muscular dystrophies

Animal data

Clinical studies have been conducted as a result of exercise-related studies in healthy human populations rather than based solely on animal experiments.

Clinical data

An updated Cochrane meta-analysis of 6 trials with 139 participants reported an increase in muscle strength (weighted mean difference of 8.47% [95% confidence interval, 3.55 to 13.38]). In addition, data from 4 of the trials reported a higher number of patients felt better during creatine treatment than with placebo. No clinically important adverse reactions were found.3, 61, 62

Other uses

Creatine supplementation has been evaluated in numerous medical conditions, including muscle wasting,63, 64 brain and spinal cord injury,9 osteoarthritis,65 diabetes,66, 67, 68, 69 cancer,70 and gyrate atrophy.9 Reviews on creatine are available.2, 3, 9

The American Academy of Neurology evidence based guidelines regarding the treatment of chorea in Huntington disease (2012) conclude that creatine (8 mg daily) is possibly ineffective in improving Huntington disease chorea to a very important extent based on a placebo-controlled, randomized trial. Lack of statistical precision suggests that moderate benefit cannot be excluded.87

Dosing

Dosage regimens in clinical trials vary from 2 to 20 g daily, and from 1 week up to 4 years.2, 3, 9

Skeletal muscle enhancement regimens include "high dose, short term" of 20 g daily for 7 days and a "lower dose, longer term" regimen of 2 to 5 g for 4 to 6 weeks.2

Evidence suggests that long-term intake of up to 5 g/day is relatively safe.71 Larger amounts have been used without adverse reactions and may be safe, but long-term safety data are lacking.4, 71

The safety of creatine in children has not been established, and creatine should be given under physician guidance.72

Different forms of creatine products may have differing bioavailability. Bioavailability of dietary creatine is considered to be absolute.4

Ginkgo Biloba, turmeric, saw palmetto

Pregnancy / Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking. Animal data are inconclusive.73, 74, 75

Interactions

None well documented.

Creatine drug interactions (more detail)

Adverse Reactions

In studies conducted in healthy individuals, reports of adverse reactions due to creatine monohydrate supplementation are lacking.(71, 76, 77, 78, 79) Clinical studies in patients with neurological or muscle disorders revealed few adverse reactions.(20, 21, 60, 61, 80)

Concerns regarding renal and hepatic toxicity exist.(81) Healthy kidneys appear to manage short-term creatine loading without compromised function,(81, 82) but patients with a history of renal impairment or diabetes, or those taking nephrotoxic agents should avoid creatine supplementation or be closely monitored with supplementation.(81, 82) Healthy individuals should consider regular testing to detect potential renal impairment because of possible decreased compensatory mechanisms.(78, 81) Supplementation studies using creatine for up to 8 weeks have reported minimal or no elevation of liver enzymes.(83, 84) However, some animal studies suggest caution is warranted where hepatic impairment exists, at least until unequivocal evidence is attained.(81) No evidence of hepatotoxicity has been reported in meta-analyses.(6, 20, 60, 61)

Data collected between 2004 and 2013 from 8 US centers in the Drug-induced Liver Injury Network revealed that 15.5% (130) of hepatotoxicity cases were caused by herbals and dietary supplements, whereas 85% (709) of cases were related to prescription medications. Of the 130 cases of liver injury related to supplements, 65% were from non-bodybuilding supplements and occurred most often in Hispanics/Latinos compared with non-Hispanic whites and non-Hispanic blacks. Liver transplant was also more frequent with toxicity from non-bodybuilding supplements (13%) than with conventional medications (3%) (P<0.001). Overall, the proportion of severe liver injury cases was significantly higher for supplements than for conventional medications (P=0.02). Of the 217 supplement products implicated in liver injury, 175 had identifiable ingredients, of which creatine was among the 32 (18%) single-ingredient products.(89)

Individuals with diabetes should avoid use or at least monitor their blood sugar more closely when using creatine.(68, 69)

Case reports of adverse reactions among athletes include dehydration, heat-related illnesses, reduced blood volume, electrolyte imbalances, and muscle cramping; however, there is insufficient evidence to support or refute these claims.(34, 78, 81, 85) Minor GI upset (diarrhea, GI pain, nausea), dizziness, and short-term loss in body mass have also been reported.(34, 79, 81) Case reports of muscle pain and seizures exist, but no causal relationship has been established.(78) Unilateral retinal vein occlusion leading to ischemic injury that manifested as a painless blind spot and decreased visual acuity in a 25-year-old weightlifter was attributed to excessive creatine supplementation (5 g/day × 5 years) and dehydration due to recent intentional water restriction.(90)

Creatine side effects (more detail)

Toxicology

Short- and long-term doses of creatine did not result in mutagenicity in rats, rabbits, or guinea pigs in limited experiments.4 The French Agency for Food, Environmental and Occupational Health & Safety (ANSES) has warned of the potential for production of cytotoxic methylamine and formaldehyde consequent to creatine consumption, especially at high dosage.81, 86

Production of carcinogenic and mutagenic amino-imidazo-azaarene has also been postulated, but a causal relationship with creatine consumption appears unlikely.6, 81

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

Frequently asked questions

1. Creatine. In: Sweetman SC, ed. Martindale: The Complete Drug Reference. 37th ed. London, England: Pharmaceutical Press; 2011.
2. Rawson ES, Venezia AC. Use of creatine in the elderly and evidence for effects on cognitive function in young and old. Amino Acids. 2011;40(5):1349-1362.2139460410.1007/s00726-011-0855-9
3. Gualano B, Artioli GG, Poortmans JR, Lancha Junior AH. Exploring the therapeutic role of creatine supplementation. Amino Acids. 2010;38(1):31-44.1925302310.1007/s00726-009-0263-6
4. Jäger R, Purpura M, Shao A, Inoue T, Kreider RB. Analysis of the efficacy, safety, and regulatory status of novel forms of creatine. Amino Acids. 2011;40(5):1369-1383.2142471610.1007/s00726-011-0874-6
5. Folin O, Denis W. Protein metabolism from the standpoint of blood and tissue analysis. J Biol Chem. 1912;12(1):141–162.
6. Poortmans JR, Rawson ES, Burke LM, Stear SJ, Castell LM. A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance Part 11. Br J Sports Med. 2010;44(10):765-766.2067097210.1136/bjsm.2010.076117
7. Strumia E, Pelliccia F, D'Ambrosio G. Creatine phosphate: pharmacological and clinical perspectives. Adv Ther. 2012;29(2):99-123.2229780210.1007/s12325-011-0091-4
8. Derave W, Eijnde BO, Hespel P. Creatine supplementation in health and disease: what is the evidence for long-term efficacy? Mol Cell Biochem. 2003;244(1-2):49-55.12701809
9. Evangeliou A, Vasilaki K, Karagianni P, Nikolaidis N. Clinical applications of creatine supplementation on paediatrics. Curr Pharm Biotechnol. 2009;10(7):683-690.19751179
10. Klopstock T, Elstner M, Bender A. Creatine in mouse models of neurodegeneration and aging. Amino Acids. 2011;40(5):1297-1303.2139053010.1007/s00726-011-0850-1
11. Candow DG, Chiliback PD. Effect of creatine supplementation during resistance training on muscle accretion in the elderly. J Nutr Health Aging. 2007;11(2):185-188.17435961
12. Candow DG. Sarcopenia: current theories and the potential beneficial effect of creatine application strategies. Biogerontology. 2011;12(4):273-281.2137389010.1007/s10522-011-9327-6
13. Candow DG, Chilibeck PD. Potential of creatine supplementation for improving aging bone health. J Nutr Health Aging. 2010;14(2):149-153.20126964
14. Zemtsov A. Skin phosphocreatine. Skin Res Technol. 2007;13(2):115-118.17374051
15. Blatt T, Lenz H, Koop U, et al. Stimulation of skin's energy metabolism provides multiple benefits for mature human skin. Biofactors. 2005;25(1-4):179-185.16873944
16. Derave W, Van Den Bosch L, Lemmens G, Eijnde BO, Robberecht W, Hespel P. Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment. Neurobiol Dis. 2003;13(3):264-267.12901841
17. Andreassen OA, Jenkins BG, Dedeoglu A, et al. Increases in cortical glutamate concentrations in transgenic amyotrophic lateral sclerosis mice are attenuated by creatine supplementation. J Neurochem. 2001;77(2):383-390.11299300
18. Zhang W, Narayanan M, Friedlander RM. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol. 2003;53(2):267-270.12557297
19. Klivenyi P, Kiaei M, Gardian G, Calingasan NY, Beal MF. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem. 2004;88(3):576-582.14720207
20. Pastula DM, Moore DH, Bedlack RS. Creatine for amyotrophic lateral sclerosis/motor neuron disease. Cochrane Database Syst Rev. 2010;(6):CD005225.2055676110.1002/14651858.CD005225.pub2
21. Atassi N, Ratai EM, Greenblatt DJ, et al. A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis. Amyotroph Lateral Scler. 2010;11(6):508-513.2069880810.3109/17482961003797130
22. The U.S. National Institutes of Health. ClinicalTrials.gov website. Study of Creatine Monohydrate in Patients With Amyotrophic Lateral Sclerosis. Identifier: NCT00069186. http://clinicaltrials.gov/ct2/show/NCT00069186?term=creatine+als&rank=3.
23. Dedeoglu A, Kubilus JK, Yang L, et al. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J Neurochem. 2003;85(6):1359-1367.12787055
24. Matthews RT, Yang L, Jenkins BG, et al. Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J Neurosci. 1998;18(1):156-163.9412496
25. Andreassen OA, Dedeoglu A, Ferrante RJ, et al. Creatine increases survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol Dis. 2001;8(3):479-491.11447996
26. Ferrante RJ, Andreassen OA, Jenkins BG, et al. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J Neurosci. 2000;20(12):4389-4397.10844007
27. Matthews RT, Ferrante RJ, Klivenyi P, et al. Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol. 1999;157(1):142-149.10222117
28. Ellis AC, Rosenfeld J. The role of creatine in the management of amyotrophic lateral sclerosis and other neurodegenerative disorders. CNS Drugs. 2004;18(14):967-980.15584767
29. Ryu H, Rosas HD, Hersch SM, Ferrante RJ. The therapeutic role of creatine in Huntington's disease. Pharmacol Ther. 2005;108(2):193-207.16055197
30. Chao J, Leung Y, Wang M, Chang RC. Nutraceuticals and their preventive or potential therapeutic value in Parkinson's disease. Nutr Rev. 2012;70(7):373-386.2274784010.1111/j.1753-4887.2012.00484.x
31. The U.S. National Institutes of Health. ClinicalTrials.gov website. NET-PD LS-1 Creatine in Parkinson's Disease. Identifier: NCT00449865. http://clinicaltrials.gov/ct2/show/NCT00449865?term=NCT00449865&rank=1.
32. Freilinger M, Dunkler D, Lanator I, et al. Effects of creatine supplementation in Rett syndrome: a randomized, placebo-controlled trial. J Dev Behav Pediatr. 2011;32(6):454-460.2165450610.1097/DBP.0b013e31822177a8
33. National Collegiate Athletic Association. The NCAA's Advertising and Promotional Standards. Health Related Products. http://www.ncaa.org/wps/wcm/connect/broadcast/media/broadcasting/broadcasting+manual/sect3/advstand. Accessed January 10, 2013.
34. Bishop D. Dietary supplements and team-sport performance. Sports Med. 2010;40(12):995-1017.21058748
35. Bemben MG, Lamont HS. Creatine supplementation and exercise performance: recent findings. Sports Med. 2005;35(2):107-125.15707376
36. Rawson ES, Volek JS. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. J Strength Cond Res. 2003;17(4):822-831.14636102
37. Racette SB. Creatine supplementation and athletic performance. J Orthop Sports Phys Ther. 2003;33(10):615-621.14620790
38. Volek JS, Rawson ES. Scientific basis and practical aspects of creatine supplementation for athletes. Nutrition. 2004;20(7-8):609-614.15212742
39. Kreider RB. Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem. 2003;244(1-2):89-94.12701815
40. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. 2003;13(2):198-226.12945830
41. Dempsey RL, Mazzone MF, Meurer LN. Does oral creatine supplementation improve strength? A meta-analysis. J Fam Pract. 2002;51(11):945-951.12485548
42. Deutekom M, Beltman JG, de Ruiter CJ, de Koning JJ, de Haan A. No acute effects of short-term creatine supplementation on muscle properties and sprint performance. Eur J Appl Physiol. 2000;82(3):223-229.10929216
43. Jones AM, Carter H, Pringle JS, Campbell IT. Effect of creatine supplementation on oxygen uptake kinetics during submaximal cycle exercise. J Appl Physiol. 2002;92(6):2571-2577.12015375
44. Syrotuik DG, Game AB, Gillies EM, Bell GJ. Effects of creatine monohydrate supplementation during combined strength and high intensity rowing training on performance. Can J Appl Physiol. 2001;26(6):527-542.11842271
45. Cottrell GT, Coast JR, Herb RA. Effect of recovery interval on multiple-bout sprint cycling performance after acute creatine supplementation. J Strength Cond Res. 2002;16(1):109-116.11834115
46. Preen D, Dawson B, Goodman C, Lawrence S, Beilby J, Ching S. Pre-exercise oral creatine ingestion does not improve prolonged intermittent sprint exercise in humans. J Sports Med Phys Fitness. 2002;42(3):320-329.12094123
47. Finn JP, Ebert TR, Withers RT, et al. Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling. Eur J Appl Physiol. 2001;84(3):238-243.11320642
48. Edwards MR, Rhodes EC, McKenzie DC, Bekastro AN. The effect of creatine supplementation on anaerobic performance in moderately active men. J Strength Cond Res. 2000;14(1):75-79.
49. Casey A, Greenhaff PL. Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance? Am J Clin Nutr. 2000;72(2 suppl):607S-617S.10919967
50. Mujika I, Padilla S, Ibañez J, Izquierdo M, Gorostiaga E. Creatine supplementation and sprint performance in soccer players. Med Sci Sports Exerc. 2000;32(2):518-525.10694141
51. Burke DG, Silver S, Holt LE, Smith Palmer T, Culligan CJ, Chilibeck PD. The effect of continuous low dose creatine supplementation on force, power, and total work. Int J Sport Nutr Exerc Metab. 2000;10(3):235-244.10997950
52. Skare OC, Skadberg, Wisnes AR. Creatine supplementation improves sprint performance in male sprinters. Scand J Med Sci Sports. 2001;11(2):96-102.11252467
53. Bessman SP, Carpenter CL. The creatine-creatine phosphate energy shuttle. Annu Rev Biochem. 1985;54:831-862.3896131
54. McKenna MJ, Morton J, Selig SE, Snow RJ. Creatine supplementation increases muscle total creatine but not maximal intermittent exercise performance. J Appl Physiol. 1999;87(6):2244-2252.10601174
55. Horjus DL, Oudman I, van Montfrans GA, Brewster LM. Creatine and creatine analogues in hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2011;(11):CD005184.2207181910.1002/14651858.CD005184.pub2
56. Cornelissen VA, Defoor JG, Stevens A, et al. Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: A randomized controlled trial. Clin Rehabil. 2010;24(11):988-999.2057666510.1177/0269215510367995
57. Allen PJ. Creatine metabolism and psychiatric disorders: does creatine supplementation have therapeutic value? Neurosci Biobehav Rev. 2012;36(5):1442-1462.2246505110.1016/j.neubiorev.2012.03.005
58. D'Anci KE, Allen PJ, Kanarek RB. A potential role for creatine in drug abuse? Mol Neurobiol. 2011;44(2):136-141.2139993610.1007/s12035-011-8176-2
59. Al-Ghimlas F, Todd DC. Creatine supplementation for patients with COPD receiving pulmonary rehabilitation: a systematic review and meta-analysis. Respirology. 2010;15(5):785-795.2049738610.1111/j.1440-1843.2010.01770.x
60. Pfeffer G, Majamaa K, Turnbull DM, Thorburn D, Chinnery PF. Treatment for mitochondrial disorders. Cochrane Database Syst Rev. 2012;4:CD004426.2251392310.1002/14651858.CD004426.pub3
61. Kley RA, Tarnopolsky MA, Vorgerd M. Creatine for treating muscle disorders. Cochrane Database Syst Rev. 2011;(2):CD004760.2132826910.1002/14651858.CD004760.pub3
62. Tarnopolsky MA. Creatine as a therapeutic strategy for myopathies. Amino Acids. 2011;40(5):1397-1407.2139991810.1007/s00726-011-0876-4
63. Weitzel LR, Sandoval PA, Mayles WJ, Wischmeyer PE. Performance-enhancing sports supplements: role in critical care. Crit Care Med. 2009;37(10 suppl):S400-S409.2004612710.1097/CCM.0b013e3181b6f2e6
64. Sakkas GK, Schambelan M, Mulligan K. Can the use of creatine supplementation attenuate muscle loss in cachexia and wasting? Curr Opin Clin Nutr Metab Care. 2009;12(6):623-627.1974151410.1097/MCO.0b013e328331de63
65. Neves M Jr, Gualano B, Roschel H, et al. Beneficial effect of creatine supplementation in knee osteoarthritis. Med Sci Sports Exerc. 2011;43(8):1538-1543.2131136510.1249/MSS.0b013e3182118592
66. Gualano B, DE Salles Painneli V, Roschel H, et al. Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Med Sci Sports Exerc. 2011;43(5):770-778.2088187810.1249/MSS.0b013e3181fcee7d
67. Gualano B, Lugaresi R, de Salles Painelli V, et al. Creatine supplementation does not augment muscle carnosine content in type 2 diabetic patients. Appl Physiol Nutr Metab. 2011;36(5):764-767.2199929910.1139/h11-083
68. Ročić B, Znaor A, Ročić P, et al. Comparison of antihyperglycemic effects of creatine and glibenclamide in type II diabetic patients. Wien Med Wochenschr. 2011;161(21-22):519-523. Epub 2011 Jul 29.2179252710.1007/s10354-011-0905-7
69. Gualano B, DE Salles Painneli V, et al. Creatine in type 2 diabetes: a randomized, double-blind, placebo-controlled trial. Med Sci Sports Exerc. 2011;43(5):770-778.
70. Patra S, Ghosh A, Roy SS, et al. A short review on creatine-creatine kinase system in relation to cancer and some experimental results on creatine as adjuvant in cancer therapy. Amino Acids. 2012;42(6):2319-2330.2176949910.1007/s00726-011-0974-3
71. Shao A, Hathcock JN. Risk assessment for creatine monohydrate. Regul Toxicol Pharmacol. 2006;45(3):242-251.16814437
72. Yoshizumi WM, Tsourounis C. Effects of creatine supplementation on renal function. J Herb Pharmacother. 2004;4(1):1-7.15273072
73. Vallet JL, Miles JR, Rempel LA. Effect of creatine supplementation during the last week of gestation on birth intervals, stillbirth, and preweaning mortality in pigs [published online March 5, 2013]. J Anim Sci.2346355910.1203/PDR.0b013e3181f1c048
74. Ireland Z, Castillo-Melendez M, Dickinson H, Snow R, Walker DWl. A maternal diet supplemented with creatine from mid-pregnancy protects the newborn spiny mouse brain from birth hypoxia. Neuroscience. 2011;194:372-379.21640166
75. Cannata DJ, Ireland Z, Dickinson H, et al. Maternal creatine supplementation from mid-pregnancy protects the diaphragm of the newborn spiny mouse from intrapartum hypoxia-induced damage. Pediatr Res. 2010 ;68(5):393-398.20639795
76. Bizzarini E, De Angelis L. Is the use of oral creatine supplementation safe? J Sports Med Phys Fitness. 2004;44(4):411-416.15758854
77. Mihic S, MacDonald JR, McKenzie S, Tarnopolsky MA. Acute creatine loading increases fat-free mass, but does not affect blood pressure, plasma creatinine, or CK activity in men and women. Med Sci Sports Exerc. 2000;32(2):291-296.10694109
78. Poortmans J, Francaux M. Adverse effects of creatine supplementation: fact or fiction? Sports Med. 2000;30(3):155-170.10999421
79. Groeneveld GJ, Beijer C, Veldink JH, Kalmijn S, Wokke JH, van den Berg LH. Few adverse effects of long-term creatine supplementation in a placebo-controlled trial. Int J Sports Med. 2005;26(4):307-313.15795816
80. Verbessem P, Lemiere J, Ejinde BO, et al. Creatine supplementation in Huntington's disease: a placebo-controlled pilot trial. Neurology. 2003;61(7):925-930.14557561
81. Kim HJ, Kim CK, Carpentier A, Poortmans JR. Studies on the safety of creatine supplementation. Amino Acids. 2011;40(5):1409-1418.2139991710.1007/s00726-011-0878-2
82. Pline KA, Smith CL. The effect of creatine intake on renal function. Ann Pharmacother. 2005;39(6):1093-1096.15886291
83. Robinson TM, Sewell DA, Casey A, Steenge G, Greenhaff PL. Dietary creatine supplementation does not affect some haematological indices, or indices of muscle damage and hepatic and renal function. Br J Sports Med. 2000;34(4):284-288.10953902
84. Mayhew DL, Mayhew JL, Ware JS. Effects of long-term creatine supplementation on liver and kidney functions in American college football players. Int J Sport Nutr Exerc Metab. 2002;12(4):453-460.12500988
85. Dalbo VJ, Roberts MD, Stout JR, Kerksick CM. Putting to rest the myth of creatine supplementation leading to muscle cramps and dehydration. Br J Sports Med. 2008;42(7):567-573.1818475310.1136/bjsm.2007.042473
86. Yu PH, Deng Y. Potential cytotoxic effect of chronic administration of creatine, a nutrition supplement to augment athletic performance. Med Hypotheses. 2000;54(5):726-728.10859677
87. Armstrong MJ, Miyasaki JM; American Academy of Neurology. Evidence-based guideline: pharmacologic treatment of chorea in Huntington disease: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2012;79(6):597-603.22815556
88. Writing Group for the NINDS Exploratory Trials in Parkinson Disease (NET-PD) Investigators. Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. JAMA. 2015;313(6):584-593.25668262
89. Navarro VJ, Barnhart H, Bonkovsky HL, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399-1408.
90. Moussa O, Chen RWS. Central retinal vein occlusion associated with creatine supplementation and dehydration. Am J Ophthalmol Case Rep. 2021;23:101128. doi:10.1016/j.ajoc.2021.10112834169179

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