Creatine
  
Creatine
Background
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 is also found in meat and fish, with most U.S. adults consuming 1-2 grams daily on average.
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 carbohydrate enhances muscle creatine uptake increased the market for creatine multi-ingredient sports drinks.
Annual consumption of creatine products is estimated to exceed four million kilograms. 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 U.S. was estimated at $200 million. Most athletic associations have not banned this supplement, including the International Olympic Committee, the International Amateur Athletic Federation, and the National Collegiate Athletic Association.
Creatinine excreted in urine is derived from creatine stored in muscle.
Synonyms
N-amidinosarcosine, N- (aminoiminomethyl) -N methyl glycine, Athletic series creatine, beta-GPA, Challenge Creatine Monohydrate, Creapure TM creatine monohydrate powder, Creatine Booster®, creatine citrate, Creatine Monohydrate Powder, creatine phosphate, Creatine Powder Drink Mix, Creatine Xtreme Punch®, Creatine Xtreme Lemonade®, Creavescent®, cyclocreatine, Hardcore Formula Creatine Powder®, HPCE Pure Creatine Monohydrate®, methyl guanidine-acetic acid, Neoton®, Performance Enhancer Creatine Fuel®, Phosphagen TM , Phosphagen Pure Creatine Monohydrate Power Creatine®, Total Creatine Transport®.
Selected combination products which include creatine: Phosphagain TM (64g daily carbohydrate, 67g daily protein, 5g daily fat, 20g daily creatine, yeast derived RNA, taurine); Muscle Link/Effervescent Creatine elite® (5g 99.5 % pure creatine monohydrate, 20g dextrose; Met-Rx® anabolic drive series (12.4 g micronized creatine, 400mg alpha-lipoic acid, 10g glutamine peptide); Creatine Xtreme Punch® (6g creatine monohydrate, 1000mg taurine, 500mg L-glutamine, 500mg L-glutamicacid, 200mg hydroxycitrate, 15mg vanadyl nicotinate, 120g chromium); Optimum nutrition creatine liquid energy tropical punch® (6g of 99% pure pharmaceutical grade creatine monohydrate and 500mg methylsulfonylmethane).
Evidence
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
Multiple studies suggest that creatine may improve muscle mass and strength in men and women, particularly when accompanied by increased physical activity. However, studies of creatine in athletes have disagreed with each other. Although many experts believe that creatine may be useful for high-intensity, short-duration exercise, it has not been demonstrated effective in endurance sports. Benefit may be greatest when levels of creatine prior to supplementation are low, and in specific sub-populations such as older men. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% report statistically significant results while the remaining studies generally report non-significant gains in performance. Due to methodological problems with available studies, a firm conclusion cannot be reached.
C
Enhanced athletic sprinting
Creatine has been suggested to enhance athletic performance and to delay onset of fatigue during short sprints. Effects have been attributed to increased creatine concentrations in muscle. Although results from different studies disagree with each other, most research reports some improvement when creatine is used as a supplement. Creatine may enhance performance when used during brief bursts of aerobic activities, and when there are short recovery times between bouts of activity. Better research is necessary before a firm conclusion can be reached.
C
Enhanced athletic endurance
It has been suggested that creatine may help improve athletic endurance by increasing time to fatigue (possibly by shortening muscle recovery periods). However, the results of research evaluating this claim are mixed. Findings from different studies disagree with each other, and most studies do not support the use of creatine to enhance sustained aerobic activities.
C
Congestive heart failure (chronic)
Cardiac creatine levels are reported as depressed in chronic heart failure. Several studies report that creatine supplementation is associated with improved heart muscle strength and endurance in patients with heart failure. However, it is not clear what dose may be safe or effective. Supplementation is also reported to increase creatine in skeletal muscle in these patients, helping to increase strength and endurance. Comparisons with drugs used to treat heart failure have not been conducted. Heart failure should be treated by a qualified healthcare provider.
C
Myocardial infarction (heart attack)
There is early evidence that intravenous creatine following a heart attack may be beneficial to heart muscle function, and may prevent ventricular arrhythmias. Further study is needed before a recommendation can be made in this area. It has been reported that use of creatine phosphate may have a favorable effect on mental deterioration in "cardio-cerebral syndrome" following heart attacks in the elderly.
C
Heart muscle protection during heart surgery
There is early evidence that heart muscle may recover better and more rapidly after open-heart surgery if intravenous creatinine is administered during the operation. Further study is needed before a recommendation can be made.
C
Hyperornithinemia (high levels of ornithine in the blood)
Ornithine is a byproduct formed in the liver. Some individuals are born with a genetic disorder that prevents them from appropriately breaking down ornithine, and blood levels of ornithine become too high. High amounts of ornithine can 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.
C
Muscular dystrophy
Creatine loss is suspected to cause muscle weakness and breakdown in Duchenne muscular dystrophy. Animal studies report increased muscle formation and survival with creatine. Studies in humans have been small, although early evidence suggests that creatine may be beneficial in treating muscular dystrophies. Further research is needed.
C
Neuromuscular disorders
Numerous studies suggest that creatine may be helpful in the treatment of various neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS) and myasthenia gravis, and may delay onset of symptoms when used as an adjunct to conventional 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. Although early studies were encouraging, recent research reports no beneficial effects on survival or disease progression. Additional studies are needed to provide clearer answers.
C
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. Although there is only limited research in this area, significant improvements were noted in two individuals who were given supplemental creatine, suggesting that this supplement may be an effective treatment for disorders caused by a lack of creatine.
C
High cholesterol
There is limited research in this area, and results from different studies disagree with each other (with some trials noting reductions in total cholesterol and triglyceride levels). It remains unclear what effect creatine has on lipids. Additional studies are needed before a clear conclusion can be drawn.
C
McArdle's disease
In McArdle's disease, there is a deficiency of energy compounds stored in muscle. 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 disagree with each other. Therefore, it remains unclear if creatine offers any benefits to patients with McArdle's disease.
C
* 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 (it may not work);
F: Strong scientific evidence against this use (it likely does not work).
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, anti-convulsant, anti-inflammatory, antioxidant, breast cancer, cervical cancer, circadian clock acceleration, colon cancer, diabetes, diabetic complications, disuse muscle atrophy, fibromyalgia, growth, herpes, Huntington's disease, hyperhomocysteinemia, mitochondrial diseases, neuroprotection, Parkinson's disease, rheumatoid arthritis, hypoxic seizures, wasting of brain regions.
Dosing
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.
Standardization:
Standardization involves measuring the amount of certain chemicals in products to try to make different preparations similar to each other. It is not always known if the chemicals being measured are the "active" ingredients. Various creatine products contain different forms (creatine monohydrate, creatine monophosphate) in varying concentrations, as well as creatine in combination with other supplements. There are no standard doses of creatine, and many different doses are used.
Adults (18 years and older):
Note : Creatine appears to be best absorbed as a solution, although ingestion as meat or in solid form is also readily absorbed. Elevation of muscle creatine levels may best be achieved by taking creating with carbohydrates. Experts often recommend maintaining good hydration during creatine use.
Oral (powder): A wide range of dosing has been used or studied. For enhanced athletic performance, 9-20 grams daily in divided doses for 4-7 days has been used, with maintenance doses ranging between 2-5 grams daily or 0.3 milligrams per kilogram of body weight daily. For cholesterol reduction, 20-25 grams daily for 5 days followed by 5-10 grams thereafter has been used. For hyperornithinemia, 1.5 grams daily has been used. For neuromuscular diseases, including muscular dystrophy, 10 grams daily has been suggested, although lower doses (5 grams) and higher doses (20 grams) have also been used. For GAMT deficiency, 400-670 milligrams per kilogram of body weight daily has been used. For congestive heart failure, 20 grams per day has been studied. For symptomatic treatment in ALS, 20 grams daily for 7 days then 3 grams daily for 3-6 months has been used. For McArdle's disease, 150 milligrams per kilogram of body weight has been used daily for 5 days, followed by 60 milligrams per kilogram daily for 5 weeks.
Intravenous/intramuscular: Numerous dosing regimens have been used in studies in humans. Intravenous dosing should be conducted only under strict medical supervision.
Children (younger than 18 years):
Dosing in children should be under medical supervision because of potential adverse effects. A dose of 5 grams daily has been used in children with muscular dystrophy, and various doses have been used in children with GAMT deficiency, including 2 grams per kilogram of body weight, 4-8 grams daily in an infant, and 400-670 milligrams per kilogram of body weight.
Safety
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.
Allergies
Creatine has been associated with asthmatic symptoms. People should avoid creatine if they have a known allergy to this supplement.
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 provider. Users are advised to inform their physician or other healthcare provider.
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. 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 provider, and medication adjustments may be necessary.
Chronic administration of a large quantity of creatine is reported to increase the production of formaldehyde, which may potentially cause serious unwanted side-effects.
Based on a case report, creatinine 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.
Pregnancy and Breastfeeding
Creatine cannot be recommended during pregnancy or breast-feeding 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.
References
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January 01, 2004 
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