Creatine

This page features 693 unique references to scientific papers.

Summary

All Essential Benefits/Effects/Facts & Information

Frequently asked questions and answers related to Creatine

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Things To Know

Also Known As

creatine monohydrate, creatine 2-oxopropanoate, a-methylguanidinoacetic acid

Do Not Confuse With

creatinine (metabolite), cyclocreatine (analogue), Creatinol O-Phosphate (analogue)

Things to Note

  • There have been some anecdotal reports of a subtle but noticeable stimulatory effect on alertness, but this may be a placebo effect.

  • There have been some anecdotal reports of restlessness when creatine is taken within an hour of sleep.

  • The water retention usually seen with higher loading doses can exceed five pounds (more than two kilograms). Lower doses may cause less water retention. While water mass is not muscle mass (though both count as lean mass), prolonged creatine supplementation is met with an increased rate of muscle growth.

  • Hyperhydration strategies (creatine plus glycerol) appear inefficacious as drug-masking strategies.[3]

Is a Form Of

Goes Well With

Caution Notice

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How to Take

Recommended dosage, active amounts, other details

There are many different forms of creatine available on the market, but creatine monohydrate is the cheapest and most effective. Micronized creatine monohydrate dissolves in water more easily, which can be more practical.

Creatine monohydrate can be supplemented through a loading protocol. To start loading, take 0.3 gram per kilogram of bodyweight per day for 5–7 days, then follow with at least 0.03 g/kg/day either for three weeks (if cycling) or indefinitely (without additional loading phases).

For an individual weighting 180 lb (82 kg), this translates as 25 g/day during the loading phase and 2.5 g/day henceforth, although many users take 5 g/day due to the low price of creatine and the possibility of increased benefits. Higher doses (up to 10 g/day) may be prudent for those with a high amount of muscle mass and high activity levels.

Stomach cramping can occur when creatine is supplemented without sufficient water. Diarrhea and nausea can occur when too much creatine is supplemented at once, in which case doses should be spread out over the day and taken with meals.

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Human Effect Matrix

The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects creatine has on your body, and how strong these effects are.

Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
Notes
Muscle Creatine Content Strong Very High See all 18 studies
Creatine supplementation is the reference compound for increasing muscular creatine levels; there is variability in this increase, however, with some nonresponders.
Power Output Strong Very High See all 66 studies
Creatine is the reference compound for power improvement, with numbers from one meta-analysis to assess potency being "Able to increase a 12% improvement in strength to 20% and able to increase a 12% increase in power to 26% following a training regiment using creatine monohydrate".
Weight Strong Very High See all 28 studies
Appears to have a large effect on increasing overall weight due to water retention in persons who respond to creatine supplementation. Degree of increase is variable.
Creatinine Notable Moderate See all 12 studies
Creatine supplementation usually increases serum creatinine levels during the loading phase (but usually not during maintenance), since creatinine is the breakdown product of creatine. This is not indicative of kidney damage.
Hydration Notable Very High See all 9 studies
Appears to be quite notable due to the increase in water weight in skeletal muscle tissue following creatine supplementation.
Anaerobic Running Capacity Minor High See all 19 studies
Appears to increase anaerobic cardiovascular capacity, not to a remarkable degree however.
Lean Mass Minor Very High See all 20 studies
Does appear to have inherent lean mass building properties, but a large amount of research is confounded with water weight gains (difficult to assess potency).
Swimming Performance - Moderate See all 17 studies
No reliable improvement in swimming performance. Acute supplementation prior to short sprint tests (50-100 m) may reduce time by around 2%.
Fatigue Notable High See all 7 studies
400 mg/kg/day in children and adolescents subject to traumatic brain injury reduces fatigue frequency from around 90% down to near 10%. Fatigue is also reduced, though to a lesser degree, in cases of sleep deprivation.
Blood Glucose Minor Low See all 4 studies
No apparent influence on fasting blood glucose, but an 11-22% reduction in the postprandial spike.
Bone Mineral Density Minor Low See all 3 studies
There is limited evidence in favor of improvements in bone mineral density.
Fatigue Resistance Minor Moderate See all 8 studies
Small degree of fatigue reduction during exercise, but appears unreliable.
Lipid Peroxidation Minor Low See all 3 studies
A minor reduction has been observed.
Muscle Damage Minor Moderate See all 6 studies
Not overly protective, but there appears to be a degree of protection.
Muscular Endurance Minor High See all 3 studies
Somewhat effective.
Subjective Well-Being Minor Moderate See all 10 studies
The influence of creatine on well being and general happiness is usually dependent on it treating a disease state; there does not appear to be a per se benefit to well being.
Testosterone Minor High See all 6 studies
Degree of testosterone spike is not overly notable, although it appears to be present
Treatment of Myotonic Dystrophy Minor High See all 3 studies
Preliminary evidence seems to support a minor to moderate benefit with regard to Myotonic Dystrophy type II (DM2) and a mild benefit or none with regard to DM1.
VO2 Max Minor Low See all 3 studies
Improvements in VO2 max are not wholly reliable, and appear to be low in magnitude.
Aerobic Exercise - Very High See all 7 studies
Does not appear to confer any apparent benefit to prolonged cardiovascular exercise.
Blood Pressure - Very High See all 4 studies
Does not appear to significantly influence blood pressure.
Cognition (Omnivores) - High See all 3 studies
No inherent benefit to omnivore cognition appears apparent, but it may benefit cognition in the sleep deprived.
Cortisol - Very High See all 4 studies
No effect on cortisol changes associated with sleep deprivation.
Exercise Capacity (with Heart Conditions) - Very High See all 3 studies
Although there may be a small reduction of power output (typical of creatine), the main parameter of interest (cardiorespiratory output) is mostly unaffected by creatine supplementation.
Exercise Capacity in COPD - Very High See all 3 studies
The main parameter of interest with exercise in COPD (cardiovascular capacity and aerobic exercise) is wholly unaffected with supplementation, although power output still can be increased.
Fat Mass - Very High See all 9 studies
Creatine reliably increases lean mass (water at first, then muscle with more prolonged supplementation) but does not appear to significantly alter fat mass.
Heart Rate - Very High See all 3 studies
No known influence on heart rate.
IGF-1 - Very High See all 5 studies
Insufficient evidence to support a role of creatine in increasing IGF-1
Insulin - Very High See all 3 studies
No effect on fasting insulin.
Kidney Function - Very High See all 10 studies
In otherwise healthy persons given creatine supplementation, there is no significant beneficial nor negative influence on kidney function.
Kidney function Low See all 3 studies
Lactate production - Moderate See all 6 studies
No apparent reduction or increase in lactate in swimmers after sprinting exercises.
Liver Enzymes - Very High See all 7 studies
No known influence on circulating liver enzymes, suggesting no liver toxicity in humans.
Lung Function - Very High See all 7 studies
No effect on healthy people or on disease states characterized by impaired lung function.
Total Cholesterol - High See all 4 studies
No effect on overall cholesterol levels in otherwise healthy males.
Treatment of Amyotrophic lateral sclerosis (ALS) - Very High See all 6 studies
Short term usage may increase power output like usual, but prolonged supplementation of creatine has failed to alter the deterioration of muscle and lung function. While no reduction in mortality has been noted statistically, two studies have noted a trend towards reductions in mortality suggesting an unknown protective effect.
Treatment of COPD - High See all 3 studies
No effect on cardiovascular exercise performance and lung and heart functions, the main parameters of concern when treating COPD.
VO2 max Low See all 3 studies
Depression Notable Very High See all 3 studies
Depression symptoms seem to improve noticeably. This improvement is probably related to serotonin (creatine supplementation appears to enhance SSRI therapy). Possible gender differences (a greater efficacy in females) require further study.
Glycogen Resynthesis Notable Very High See study
Degree of improvement is somewhat more potent than other supplemental options, and may be related to the improvements in glycemic control seen with creatine.
Growth Hormone
Notable
Low See all 4 studies
During exercise, creatine supplementation can suppress growth hormone secretion: up to 35% during loading; up to 5% during maintenance. At rest, creatine supplementation can spike growth hormone by up to 83±45%. This bidirectional effect is similar to that of Arginine supplementation.
Myostatin Notable Very High See study
The reduction in circulating Myostatin, while notable (17%), is of uncertain practical relevance.
Body Cell Mass Minor Very High See study
A possible increase in cell mass. Evidence is limited.
Cognition (Vegetarians) Minor Very High See 2 studies
Appears to be reliable in increasing cognition in vegetarians, but is based on limited evidence and not yet compared to a reference drug.
DHT Minor Very High See study
An increase in DHT independent of an increase in testosterone has been noted, but the study requires replication due to some potential issues (its location, the lack of biological plausibility, etc.).
DNA Damage Minor Very High See study
Creatine supplementation appears to reduce exercise-induced DNA damage. This is potentially promising with regard to cancer prevention.
DNA methylation Minor Very High See study
The effect of creatine supplementation on DNA methylation cannot be properly assessed due to a lack of comparisons with other agents.
Functionality in Elderly or Injured Minor Moderate See 2 studies
Possibly an effect, but the less reliable effects of creatine in the older population (which seem to respond less) seems to manifest here.
Glycemic Control Minor Very High See 2 studies
Appears to be somewhat effective in diabetics for improving glycemic control.
Homocysteine Minor Very High See study
Decrease in homocysteine (biomarker of inflammatory cardiovascular disease) was present, but not to a remarkable magnitude
Myonuclei proliferation Minor Very High See study
Creatine supplementation appears to induce myonuclei proliferation, to a degree unknown relative to other agents.
Satellite Cell Recruitment Minor Very High See study
Compared to reference drugs, creatine had no significant effect.
Symptoms of Duchenne Muscular Dystrophy Minor Very High See 2 studies
There appears to be a mild therapeutic effect of creatine supplementation (2-5g) to boys with DMD, mostly related to an improvement in handgrip strength and body composition with some parent-rated improvements.
Symptoms of McArdles Disease
Minor
Low See 2 studies
Two trials have shown differing effects, for reasons currently unknown.
Symptoms of Osteoarthritis Minor Very High See study
Functionality seems to improve, although not to a remarkable degree.
Symptoms of Sleep Deprivation Minor Very High See 2 studies
The cognitive dysfunction associated with prolonged sleep deprivation can be attenuated, to a small degree, with prior creatine loading.
Uric Acid Minor Very High See 2 studies
A minor reduction has been observed.
Adrenaline - Very High See study
No significant alterations in plasma adrenaline are seen with creatine supplementation during sleep deprivation.
Aldosterone Low See 2 studies
Anti-Oxidant Enzyme Profile
Low See study
Attention - Very High See study
No effect on attention during sleep deprivation.
Bilirubin - Low See all 3 studies
C-Reactive Protein
Low See study
Cerebral Oxygenation Low See study
DNA damage Low See study
Dopamine - Very High See study
No significant alterations in plasma dopamine are seen with creatine supplementation during sleep deprivation.
Fat Oxidation Low See 2 studies
Food Intake - Very High See 2 studies
No effect on food intake.
General Oxidation
Low See study
Glycogen content Low See 2 studies
HDL-C Low See 2 studies
Injury Rehabilitation Rate - Low See study
Insulin Secretion - Very High See study
No effect on the insulin secretion in response to a test meal.
Insulin Sensitivity - Very High See study
No effect on insulin sensitivity.
LDL-C Low See 2 studies
Memory - Very High See 2 studies
No effect on short-term recall during sleep deprivation.
Muscle Oxygenation Low See study
Noradrenaline - Very High See study
No significant alterations in plasma noradrenaline are seen with creatine supplementation during sleep deprivation.
Proteinuria - Very High See study
There is no significant influence on protein losses in the urine (proteinuria).
Schizophrenia - Very High See study
Insufficient evidence to support a role in schizophrenia.
Skeletal Muscle Atrophy - Very High See 2 studies
The study that noted a prevention of lean mass loss did not distinguish between water and muscle, while the study that measured muscle mass specifically failed to find a protective effect during limb immobilization.
Sprint performance Low See study
Symptoms of Mitochondrial Cytopathies Low See all 3 studies
TNF-Alpha
Low See study
Training Volume - Very High See 2 studies
No effect on the training volume of swimmers.
Treatment of Huntington's Disease - Low See 2 studies
Treatment of Parkinsons - Low See study
Triglycerides Low See all 3 studies
Urea Low See all 4 studies
vLDL-C Low See study
Dizziness Notable Very High See study
Dizziness as a side-effect of traumatic brain injury is reduced with 400 mg/kg/day.
Treatment of Headaches Notable Very High See study
400 mg/kg/day in children and adolescents subject to traumatic brain injury reduces headache frequency from around 90% down to near 10%.
Alertness Minor Very High See 2 studies
Increases in alertness tend to be during sleep deprivation or stress, rather than outright increases in alertness. Not overly potent
Blood Flow Minor Very High See 2 studies
One study has found that creatine can increase blood flow to the calf and leg when combined with resistance training in healthy men. Creatine alone was found to have no effect.
Range of Motion Minor Very High See study
One study, that needs to be replicated, noted a reduction in range of motion.
Metabolic Rate
Low See study
Subjective Well-being Low See study
Symptoms of Cystic Fibrosis - Very High See study
An increase in well-being and muscular strength has been noted in youth, but the main parameters under investigation (lung and chest symptoms) seemed unaffected.

Studies Excluded from Consideration

  • Confounded with the inclusion of CoQ10[1]

  • Confounded with glycerol[2]


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Scientific Support & Reference Citations

References

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