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BackgroundReturn to top

Creatine is naturally synthesized in the human body from amino acids primarily in the kidney and liver and transported in the blood for use by muscles. Approximately 95% of the body's total creatine content is located in skeletal muscle.

Creatine was discovered in the 1800s as an organic constituent of meat. In the 1970s, Soviet scientists reported that oral creatine supplements may improve athletic performance during brief, intense activities such as sprints. Creatine gained popularity in the 1990s as a "natural" way to enhance athletic performance and build lean body mass. It was reported that skeletal muscle total creatine content increases with oral creatine supplementation, although response is variable. Factors that may account for this variation are carbohydrate intake, physical activity, training status, and muscle fiber type. The finding that carbohydrates enhance muscle creatine uptake increased the market for creatine multi-ingredient sports drinks.

Use of creatine is particularly popular among adolescent athletes, who are reported to take doses that are not consistent with scientific evidence, and to frequently exceed recommended loading and maintenance doses.

Published reports suggest that approximately 25% of professional baseball players and up to 50% of professional football players consume creatine supplements. According to a survey of high school athletes, creatine use is common among football players, wrestlers, hockey players, gymnasts, and lacrosse players. In 1998, the creatine market in the United States was estimated at $200 million. In 2000, the National Collegiate Athletic Association (NCAA) banned colleges from distributing creatine to their players.

Creatinine excreted in urine is derived from creatine stored in muscle.

SynonymsReturn to top

Athletic series creatine, beta-GPA, Challenge Creatine Monohydrate, Cr, CreapureTM creatine monohydrate powder, Creatine Booster®, creatine citrate, creatine ethyl ester, Creatine Monohydrate Powder, creatine phosphate, Creatine Powder Drink Mix, Creatine Xtreme Punch®, Creatine Xtreme Lemonade®, creatinine, Creavescent®, cyclocreatine, Hardcore Formula Creatine Powder®, HPCE Pure Creatine Monohydrate®, methyl guanidine-acetic acid, methylguanidine-acetic acid, N-amidinosarcosine, N-(aminoiminomethyl)-N methyl glycine, Neoton®, Performance Enhancer Creatine Fuel®, PhosphagenTM, Phosphagen Pure Creatine Monohydrate Power Creatine®, Runners Advantage creatine serum, Total Creatine Transport®.

EvidenceReturn to top

These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

Uses based on scientific evidenceGrade*
Enhanced muscle mass / strength

Several high-quality studies have shown an increase in muscle mass with the use of creatine. However, some weaker studies have reported mixed results. Overall, the available evidence suggests that creatine does increase lean body mass, strength, and total work. Future studies should take into account the effect of different individual fitness levels of study subjects.
Congestive heart failure (chronic)

Patients with chronic heart failure have low levels of creatine in their hearts. Several studies report that creatine supplements may improve heart muscle strength, body weight, and endurance in patients with heart failure. Studies comparing creatine with drugs used to treat heart failure are needed before a firm recommendation can be made. Heart failure should be treated by a qualified healthcare professional.
Adjunct in surgery (coronary heart disease)

Early studies suggest a potential benefit of creatine supplements in patients undergoing coronary artery surgery. Some evidence suggests that heart muscle may recover better and more rapidly after open-heart surgery if intravenous creatinine is used during the operation. Larger, well-designed studies are needed before a strong recommendation can be made.
Apnea (of prematurity)

Early studies of creatine in animals and humans have found mixed results in patients with a breathing disorder in infants, called apnea of prematurity. Well-designed studies are needed to better understand this relationship.
Bone density

Early studies examining the effect of creatine in aging suggest that creatine may increase bone density when combined with resistance training. Further studies in which creatine alone is compared with placebo are needed.
Chronic obstructive pulmonary disease

It is unclear if creatine can help treat chronic obstructive pulmonary disease. Study results are mixed. More clinical trials are needed before a strong recommendation can be made.

Early research suggests a potential beneficial of creatine supplements in depression. Creatine may have brought on a manic switch in patients with bipolar depression. Large, well-designed studies are needed.

Early studies suggest that creatine does not lower homocysteine levels in chronic hemodialysis patients. However, these patients were also using vitamin B12 and folate. Muscle cramps are also common complications of hemodialysis. Creatine may offer some benefit for this side effect. However, studies in which creatine alone is compared with placebo are needed.
Enhanced athletic performance and endurance

It has been suggested that creatine may help improve athletic performance or endurance by increasing time to fatigue (possibly by shortening muscle recovery periods). It has been studied in cyclists, females, high-intensity endurance athletes, rowers, runners, sprinters (general), swimmers, and the elderly. However, the results of research evaluating this claim are mixed.
GAMT deficiency

Some individuals are born with a genetic disorder in which there is a deficiency of the enzyme guanidinoacetate methyltransferase (GAMT). A lack of this enzyme causes severe developmental delays and abnormal movement disorders. The condition is diagnosed by a lack of creatine in the brain. However, there is limited evidence for the effect of creatine supplementation in this disorder. High-quality studies are needed.
High cholesterol

Early studies did not find a benefit of creatine in the treatment of high cholesterol. More studies are needed before a clear conclusion can be drawn.
Huntington's disease

There is not enough scientific information to make a firm recommendation about the use of creatine in Huntington's disease. High-quality studies are needed to clarify this relationship.
Hyperornithinemia (high levels of ornithine in the blood)

Ornithine is normally formed in the liver. Some individuals are born with a genetic disorder that prevents them from appropriately breaking down ornithine, which causes blood levels to become too high. High amounts of ornithine may lead to blindness, muscle weakness, and reduced storage of creatine in muscles and the brain. Although there is only limited research in this area, early evidence suggests that long-term, daily creatine supplements may help replace missing creatine and slow vision loss.
Ischemic heart disease

Early high-quality studies suggest a potential benefit of creatine in people with ischemic heart disease. More clinical trials are needed before a firm recommendation can be made.
McArdle's disease

In McArdle's disease, there is a deficiency of energy compounds stored in the muscles. This leads to muscle fatigue, exercise intolerance, and pain when exercising. Creatine has been proposed as a possible therapy for this condition. However, research is limited, and the results of existing studies are mixed. Therefore, it remains unclear if creatine offers any benefits to patients with McArdle's disease.

Early studies show that creatine may improve cognition in certain populations, such as vegetarians and the elderly. Further research is required before recommendations can be made.
Multiple sclerosis

Early study suggests that creatine supplementation does not improve work production in people with multiple sclerosis. However, large, well designed studies are required before a strong recommendation can be made.
Muscular dystrophy

Creatine loss is suspected to cause muscle weakness and breakdown in patients with Duchenne muscular dystrophy. Studies with creatine have found mixed results for this condition. Further research is needed before a strong recommendation can be made.
Myocardial infarction (heart attack)

There is early evidence that intravenous creatine after a heart attack may be beneficial to heart muscle function and may prevent irregular heart rhythms. Further study is needed before a recommendation can be made in this area. It has been reported that the use of creatine phosphate may have a favorable effect on mental deterioration in "cardio-cerebral syndrome" following heart attacks in the elderly. More research is needed.
Neuromuscular disorders (general, mitochondrial disorders)

Numerous studies suggest that creatine may help treat various neuromuscular diseases and may delay the onset of symptoms when used with standard treatment. However, creatine ingestion does not appear to have a significant effect on muscle creatine stores or high-intensity exercise capacity in individuals with multiple sclerosis and supplementation does not seem to help people with tetraplegia.Although early studies were encouraging, recent research reports no beneficial effects on survival or disease progression. Additional studies are needed to provide clearer answers.
Spinal cord injury

It is unclear if creatine is helpful in patients with spinal cord injuries. Results from early studies have been mixed. Further studies are required before a firm recommendation can be made.
Amyotrophic lateral sclerosis (ALS)

Overall, the evidence suggests that creatine supplementation does not offer benefit to individuals with amyotrophic lateral sclerosis (ALS).
Surgical recovery

Early studies suggest that creatine has no effect on strength or body composition in people undergoing soft tissue surgery. Creatine supplements are likely ineffective in this condition, and cannot be recommended without evidence from additional studies.

*Key to grades
A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use;
F: Strong scientific evidence against this use.

Grading rationale

Uses based on tradition or theory
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.

AGAT deficiency, Alzheimer's disease, anti-arrhythmic, anticonvulsant, anti-inflammatory, antioxidant, attention deficit hyperactivity disorder, bipolar disorder, brain damage, breast cancer, cervical cancer, circadian clock acceleration, colon cancer, diabetes, diabetic complications, disuse muscle atrophy, fibromyalgia, growth, herpes, hyperhomocysteinemia (an abnormally large level of homocysteine in the blood), mitochondrial diseases, mood disorder, neuroprotection, nutritional supplement, ophthalmologic disorders (gyrate atrophy), osteoarthritis, Parkinson's disease, rheumatoid arthritis, seizures (caused by lack of oxygen to the brain), sexual dysfunction, wasting of brain regions.

DosingReturn to top

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)
A wide range of dosing has been used or studied by mouth. 400 milligrams per kilogram of body weight or up to 25 grams per day has been studied for multiple conditions. Experts often recommend maintaining good hydration during creatine use.

To increase anaerobic work capacity, studies have used a dose of 5 grams four times per day for 5 days. For enhanced athletic strength and performance, studies have used a dose of 20 grams per day for 4-7 days. Daily maintenance doses of 2-5 grams or 0.3 milligrams per kilogram of body weight have been used.

Numerous dosing regimens for intravenous or intramuscular administration have been used in studies in humans. Intravenous dosing should only be done under strict medical supervision.

Children (younger than 18 years)
Dosing in children should be under medical supervision because of potential side effects. A daily dose of 5 grams has been used in children with muscular dystrophy, and a range of doses (400 milligrams to 2 grams per kilogram of body weight) have been used in children with GAMT deficiency. A dose of 100 milligrams per kilogram body weight has been used for one week to treat motor sensory neuropathy in children.

SafetyReturn to top

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Creatine has been associated with asthmatic symptoms. People should avoid creatine if they have known allergies to this supplement. Signs of allergy may include rash, itching, or shortness of breath.

Side Effects and Warnings
There is limited systematic study of the safety, pharmacology, or toxicology of creatine. Individuals using creatine, including athletes, should be monitored by a healthcare professional. Users are advised to inform their physicians or other qualified healthcare professionals.

Some individuals may experience gastrointestinal symptoms, including loss of appetite, stomach discomfort, diarrhea, or nausea.

Creatine may cause muscle cramps or muscle breakdown, leading to muscle tears or discomfort. Strains and sprains have been reported due to enthusiastic increases in workout regimens once starting creatine. Weight gain and increased body mass may occur. Heat intolerance, fever, dehydration, reduced blood volume, or electrolyte imbalances (and resulting seizures) may occur.

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. Similarly, liver function may be altered, and caution is advised in those with underlying liver disease.

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 healthcare professional, and medication adjustments may be necessary.

Long-term administration of large quantities of creatine is reported to increase the production of formaldehyde, which may potentially cause serious unwanted side effects.

Creatine may increase the risk of compartment syndrome of the lower leg, a condition characterized by pain in the lower leg associated with inflammation and ischemia (diminished blood flow), which is a potential surgical emergency.

Reports of other side effects include thirst, mild headache, anxiety, irritability, aggression, nervousness, sleepiness, depression, abnormal heart rhythm, fainting or dizziness, blood clots in the legs (called deep vein thrombosis), seizure, or swollen limbs.

Pregnancy and Breastfeeding
Creatine cannot be recommended during pregnancy or breastfeeding due to a lack of scientific information.

Pasteurized cow's milk appears to contain higher levels of creatine than human milk. The clinical significance of this is not clear.

InteractionsReturn to top

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs
In theory, creatine may alter the activities of insulin, particularly when taken with carbohydrates. Caution is advised when using medications that may also alter blood sugar levels. Patients taking drugs for diabetes by mouth or insulin should be monitored closely by a qualified healthcare professional. Medication adjustments may be necessary.

In theory, creatine may interact when taken in combination with acetaminophen/caffeine/CNS depressants, aspirin/caffeine/CNS depressants, or caffeine/ergotamine. It may interact with stimulants such as caffeine.

Use of creatine with probenecid may increase the levels of creatine in the body, leading to increased side effects.

Use of creatine with diuretics such as hydrochlorothiazide or furosemide (Lasix®) should be avoided because of the risks of dehydration and electrolyte disturbances. The likelihood of kidney damage may be greater when creatine is used with drugs that may damage the kidneys, such as trimethoprim, cimetidine (Tagamet®), anti-inflammatory drugs such as ibuprofen (Advil®, Motrin®), cyclosporine (Neoral®, Sandimmune®), amikacin, gentamicin or tobramycin.

It is possible that creatine may increase the cholesterol-lowering effects of other drugs commonly used to lower cholesterol levels, such as lovastatin (Mevacor®).

The combination of creatine and nonsteroidal anti-inflammatory drugs is more effective at reducing inflammation than either agent used alone.

Creatine and nifedipine, when used together, may enhance heart function, although research in this area is early.

In theory, creatine may also interact with aminoglycoside antibiotics, gallium nitrate, lansoprazole, sodium bicarbonate, tacrolimus, and valacyclovir.

Creatine supplements may enhance the activities and side effects of some cancer drugs.

Interactions with Herbs and Dietary Supplements
Creatine may increase the risk of adverse effects, including stroke, when used with caffeine and ephedra. In addition, caffeine may reduce the beneficial effects of creatine during intense intermittent exercise.

In theory, creatine may alter the activities of insulin. Caution is advised when using herbs or supplements that may also alter blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.

Creatine may reduce the effectiveness of vitamins A, D, E, and K.

Creatine may affect liver function, and should be used cautiously with potentially hepatotoxic (liver-damaging) or nephrotoxic (kidney damaging) herbs and supplements.

Use of creatine with diuretics should be avoided because of the risks of dehydration and electrolyte disturbances.

It is possible that creatine may increase the cholesterol-lowering effects of herbs and supplements that lower cholesterol levels, such as red yeast ( Monascus purpureus ).

In theory, creatine may interact with stimulants such as caffeine, which is found in green and black tea, or ephedra.

Creatine may interact with alpha-lipoic acid, arginine, hydroxymethylbutyrate, magnesium, pyruvate, and herbs and supplements broken down by the liver or kidneys. Creatine may also interact with anti-inflammatory and antineoplastic supplements.

Methodology Return to top

This information is based on a professional level monograph edited and peer-reviewed by contributors to the Natural Standard Research Collaboration ( Ethan Basch, MD (Memorial Sloan-Kettering Cancer Center); Stefan Bughi, MD (University of Southern California); Jessica Clubb, PharmD (Northeastern University); Dawn Costa, BA, BS (Natural Standard Research Collaboration); Cynthia Dacey, PharmD (Natural Standard Research Collaboration); Theresa Davies-Heerema, PhD (Boston School of Medicine); Jenna Hollenstein, MS, RD (Natural Standard Research Collaboration); Shaina Tanguay-Colucci, BS (Natural Standard Research Collaboration); Catherine Ulbricht, PharmD (Massachusetts General Hospital); Mamta Vora, PharmD (Natural Standard Research Collaboration); Wendy Weissner, BA (Natural Standard Research Collaboration); Jen Woods, BS (Natural Standard Research Collaboration).

Methodology details

Selected references Return to top

  1. 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.
  2. Cramer JT, Stout JR, Culbertson JY, et al. Effects of creatine supplementation and three days of resistance training on muscle strength, power output, and neuromuscular function. J Strength Cond Res 2007 Aug;21(3):668-77.
  3. Escolar DM, Buyse G, Henricson E, et al. CINRG Group. CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy.Ann Neurol 2005 Jul;58(1):151-5.
  4. Faager G, Söderlund K, Sköld CM, et al. Creatine supplementation and physical training in patients with COPD: a double blind, placebo-controlled study. Int J Chron Obstruct Pulmon Dis 2006;1(4):445-53.
  5. Groeneveld JG, Veldink JH, van der Tweel I, et al. A randomized sequential trial of creatine in amyotrophic lateral sclerosis. Ann Neurol 2003;53(4):437-445.
  6. Javierre C, Barbany JR, Bonjorn VM, et al. Creatine supplementation and performance in 6 consecutive 60 meter sprints.J Physiol Biochem. 2004 Dec;60(4):265-71.
  7. Kendall RW, Jacquemin G, Frost R, et al. Creatine supplementation for weak muscles in persons with chronic tetraplegia: a randomized double-blind placebo-controlled crossover trial. J Spinal Cord Med 2005;28(3):208-13.
  8. McMorris T, Mielcarz G, Harris RC, et al. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2007 Sep;14(5):517-28.
  9. NINDS NET-PD Investigators. A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology. 2006 Mar 14;66(5):664-71.
  10. Pluim BM, Ferrauti A, Broekhof F, et al. The effects of creatine supplementation on selected factors of tennis specific training. Br J Sports Med 2006 Jun;40(6):507-11; discussion 511-2.
  11. Roitman S, Green T, Osher Y, et al. Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord 2007 Nov;9(7):754-8.
  12. Roy BD, de Beer J, Harvey D, et al. Creatine monohydrate supplementation does not improve functional recovery after total knee arthroplasty. Arch Phys Med Rehabil 2005 Jul;86(7):1293-8.
  13. Schneider-Gold C, Beck M, Wessig C, et al. Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Neurology 2-11-2003;60(3):500-502.
  14. Skare OC, Skadberg, Wisnes AR. Creatine supplementation improves sprint performance in male sprinters. Scand.J Med Sci.Sports 2001;11(2):96-102.
  15. Vorgerd M, Zange J, Kley R, et al. Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: Double-blind, placebo-controlled crossover study. Arch Neurol 2002;59(1):97-101.

January 01, 2008.

Natural Standard Logo This evidence-based monograph was prepared by the Natural Standard Research Collaboration. The information provided should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. Talk to your health care provider before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Copyright© 2008 Natural Standard ( All Rights Reserved.