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.

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)

Grading rationale

Evidence gradeCondition to which grade level applies
A

Enhanced muscle mass / strength

Several high-quality studies have shown an increase in muscle mass with creatine use. 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 include the effect of individual differences such as fitness levels, sex, and age.
B

Congestive heart failure (chronic)

Research supports the use of creatine supplementation in people with chronic heart failure. Several studies have reported a positive outcome of improved muscle strength and endurance.
C

Adjunct in surgery (coronary heart disease)

Some research supports creatine supplementation with cardioplegic solution in patients undergoing coronary artery surgery. Benefits include reduced irregular heartbeat and reduced need for defibrillation. Additional research is needed on this topic.
C

AGAT deficiency (lack of enzyme for creatine production)

Limited research suggests that long-term creatine use when started early in diagnosis may improve neurologic abilities. Further well-designed studies are needed before conclusions can be made.
C

Apnea (cessation of breathing)

Early studies of creatine have found mixed results in infants with a breathing disorder called apnea of prematurity. Well-designed studies are needed to better understand this relationship.
C

Athletic performance enhancement (aging)

Aging is associated with lower total creatine and phosphocreatine concentrations. Creatine-induced effects of increased muscle strength, body mass, and performance have not been confirmed in studies on elderly subjects. Additional research is needed in this area.
C

Athletic performance enhancement (cyclists)

Most studies lack support for creatine in improving performance in trained cyclists. Further research is needed on this topic.
C

Athletic performance enhancement (females)

Recent studies suggest creatine use in females increases the strength and endurance of muscle contractions. Additional research is needed in this area.
C

Athletic performance enhancement (high-intensity endurance)

Research suggests that creatine may increase endurance in high-intensity exercise. Further research is needed on this topic.
C

Athletic performance enhancement (rowers)

Creatine may offer benefit to rowers, for endurance and speed. Additional research is needed in this area.
C

Athletic performance enhancement (runners)

Studies using creatine in runners have mixed results. Overall, most evidence suggests a lack of benefits for runners. However, additional research is needed in this area.
C

Athletic performance enhancement (specific sports)

Overall, data suggests that creatine may benefit elite hockey players, football players, rowers, squash players, and wrestlers. Improvement was lacking in tennis players. Additional research is needed in this area.
C

Athletic performance enhancement (sprinters; general)

Evidence is mixed regarding creatine use during short bursts of anaerobic muscle activity with short recovery times. Additional research is needed in this area.
C

Athletic performance enhancement (swimmers)

Data on effectiveness of creatine for swimming performance shows mixed results. Additional research is needed in this area.
C

Bone Density

Early research suggests that creatine may benefit bone density effects combined with resistance training. More studies examining creatine alone are needed.
C

Cardiovascular health

Research shows mixed results for creatine use in various cardiac (heart) measurements. Additional research is needed in this area.
C

Chronic obstructive pulmonary disease

Limited research reports that creatine supplementation increased muscle mass and exercise performance. Additional research is needed on this topic.
C

Cognitive function

Studies evaluating creatine use on cognitive function have reported a lack of benefit. Further well-designed trials are needed in this area.
C

Dehydration

The effect of creatine on dehydration shows mixed results. Additional research is needed in this area.
C

Depression

Early research suggests a potential benefit of creatine supplements in depression. Additional research is required in this field.
C

Diabetes (type 2)

Studies suggest that creatine decreases glucose concentrations with short-term use. Further well-designed, long-term trials are needed.
C

Dialysis

Limited research suggests that creatine lacks an effect on homocysteine levels in hemodialysis patients. Creatine may offer some benefit for muscle cramping as a complication of hemodialysis. However, further studies are required on this topic.
C

Fibromyalgia (nervous system disorder)

Limited research reports significant effects on severe fibromyalgia when creatine is combined with current medical treatments. Further well-designed studies are needed before conclusions may be made.
C

GAMT deficiency (lack of an enzyme for creatine production)

Guanidinoacetate methyltransferase (GAMT) deficiency is diagnosed by a deficiency of creatine in the brain and has been treated with oral creatine supplementation. Early research suggests that creatine is a potentially effective treatment for disorders of creatine production. Further well-designed trials are required.
C

Heart attack

Preliminary evidence suggests that phosphocreatine use may offer benefits for heart attack when combined with nifedipine. Additional research is required in this area.
C

High cholesterol

Limited research suggests creatine may lower cholesterol. Additional, larger studies are needed to in this area.
C

Huntington's disease

Creatine supplementation has mixed results with regards to Huntingdon's disease. Further well-designed studies are required.
C

Hyperornithinemia (high ornithine levels)

High amounts of ornithine may lead to blindness, muscle weakness, and reduced storage of creatine in muscles and the brain. Early evidence suggests that long-term creatine supplements may help replace missing creatine and slow vision loss.
C

Insulin potentiation

Creatine may have significant effects in insulin release and glucose tolerance. Effects on diabetic patients are unclear. Further well-designed trials are required before conclusions can be made.
C

Ischemic heart disease

Early evidence suggests creatine has a potential benefit in the total number of premature ventricular beats. More research is needed in this area.
C

McArdle's disease (metabolism disorder)

Creatine may be beneficial for the treatment of McArdle's disease. However, larger trials are necessary before a conclusion can be made.
C

Memory

Studies suggest that creatine supplementation increases speed of brain processing in vegetarians and the elderly. Further information is required on this topic.
C

Multiple sclerosis

Preliminary results suggest that creatine supplementation does not improve work production in individuals with multiple sclerosis. Additional well-designed studies are required before a conclusion can be made.
C

Muscle wasting

According to preliminary research, creatine helped maintain or increase lean body and tissue mass, strength, and endurance in HIV-related and cast-induced muscle wasting. More well-designed clinical trials are needed before conclusions can be made.
C

Muscular dystrophy

The decrease of intracellular creatine in Duchenne muscular dystrophy may aggravate muscle weakness and deterioration. Some studies showed preliminary evidence supporting the use of creatine to alleviate these symptoms of muscular dystrophy. More clinical trials are required in this area.
C

Neuromuscular disorders (general, mitochondrial disorders)

The evidence for the use of creatine for individuals with neuromuscular diseases is unclear. It is possible that creatine may be useful in some, but not all, mitochondrial diseases. Future studies are needed in this area
C

Orthostatic hypotension (low blood pressure upon standing)

One study reported significant effects of creatine with glycerol on orthostatic hypotension. The effects of creatine alone are unclear. Further well-designed clinical trials are required before conclusions can be made.
C

Osteoarthritis

Limited research suggests that creatine may improve physical function, lower limb mass, and quality of life in postmenopausal women with osteoarthritis. The effect of creatine alone, without exercise, is unclear.
C

Parkinson's disease

In limited research, creatine was reported to slow progression of Parkinson's disease and slightly decrease the use of symptomatic treatment. Further well-designed clinical trials are required on this topic.
C

Rett syndrome (neurodevelopmental disorder)

Early research suggests that creatine may be beneficial for Rett syndrome. Additional well-designed trials are required before conclusions can be made.
C

Skin aging

Creatine skin products, in combination with other supplementation, may benefit skin aging conditions such as wrinkles, crow's feet, and (ultraviolet) UV damage. Further well-designed trials are needed before conclusions can be made.
C

Spinal cord injury

Limited research reports inconclusive results on creatine supplementation for spinal cord injury. Further studies are required in this field.
C

Traumatic brain injury

Preliminary evidence suggests creatine may reduce hospital stay and intubation duration in people with traumatic brain injury. Further well-designed clinical trials are needed on this topic.
D

Amyotrophic lateral sclerosis (ALS)

Overall, evidence suggests that creatine supplementation does not benefit individuals with amyotrophic lateral sclerosis (ALS). Additional research is needed in this area.
D

Athletic performance enhancement (endurance; general)

Data on the effectiveness of creatine in exercise is mixed. For increased endurance during aerobic exercise, the majority of studies failed to demonstrate benefit. Additional research in this area is warranted.
D

Coronary artery disease

Preliminary research on creatine supplementation reported a lack of benefit in quality of life, cholesterol, and triglyceride levels in people with coronary artery disease (heart disease). Further well-designed clinical trials are needed before conclusions can be made.
D

Neurologic disorders

Early research on the effects of creatine on Angelman syndrome, a genetic neurological disorder found that a combination supplement containing creatine was ineffective in reducing symptoms. Additional research on this topic is needed.
D

Spinal muscular atrophy

Early research on the effects of creatine on spinal muscular atrophy reported a lack of significant effects. Further well-designed trials are needed before conclusions can be made.
D

Surgical recovery

In preliminary research, creatine supplementation in individuals undergoing soft tissue surgery lacked effects on strength or body composition. Additional research is needed in this area.

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.

Alzheimer's disease, antiarrhythmic (abnormal heart rhythm), anti-inflammatory, antioxidant, attention-deficit hyperactivity disorder (ADHD), bipolar disorder, brain damage, breast cancer, cervical cancer, circadian clock acceleration, colon cancer, growth, herpes, hyperhomocysteinemia (high blood homocysteine), mitochondrial diseases, mood disorder, nutritional supplement (vegetarians), ophthalmologic disorders (gyrate atrophy), rheumatoid arthritis, seizure (hypoxic), sexual dysfunction, wasting of brain regions.

This evidence-based monograph was prepared by The Natural Standard Research Collaboration

www.naturalstandard.com