Creatine

Most researched sports supplement: no clinically significant side effects (due to a limit on absorption), and healthy as well as potent. Creatine is a storage form of energy (known as ATP) released quicker than glucose, and greatly helps cell function under high intensity conditions.

This page features 379 unique references to scientific papers.

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Creatine (monohydrate) supplementation, according to the International Society of Sports Nutrition, is the most effective ergogenic (performance enhancing) nutritional supplement currently available to athletes in terms of increasing high-intensity exercise capacity and lean body mass during training.[1] Many forms are available and discussed in the complete summary, but have not been shown to exert significant benefits over basic monohydrate supplementation.

Creatine's main action in the body is to store high-energy phosphate groups in the form of phosphocreatine. During periods of stress, phosphocreatine releases this energy to aid the cell's functions. This mechanism of action is what causes creatine to increase strength, but can benefit almost every body system, including the brain, bones, muscles, and liver. Most benefits of creatine occur through this energy mechanism.

Creatine is produced naturally in the body, and it is also found in foods (mostly meats, eggs, and fish; some in dairy).

Creatine supplementation at normal dosages and with adequate hydration has been shown to have no harmful effects in any population tested (more info in Complete Summary under General Safety Profile). The only observed side effects are stomach cramping if consumed with insufficient water, and diarrhea if too much is consumed at once. Controlled usage of creatine with adequate water may actually reduce cramping over the long term.

Full details in our detailed summary.


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Things to Note

  • Creatine has been reported (anecdotally) to have a subtle stimulatory (or at least noticeable) effect on cognition. Less potent than classical stimulants like Caffeine, these may be placebo.
  • Creatine is known for causing water weight gains after starting usage of supplements. Gaining 5lbs or so the day after beginning usage of a creatine-containing product is relatively common and harmless.
  • Caffeine may adversely interact with creatine's actions on muscle contraction, and should be controlled before somebody judges how creatine 'works for them'.
  • Some people report to be 'non-responders' to creatine supplementation. Although caffeine co-ingestion can explain some persons, there seems to be some literature suggesting that non-responders may exist independent of caffeine. The mechanism is not known.
  • There have been some reports (see: anecdotes) of restlessness when creatine is taken within an hour of sleep

Caution Notice

If too much creatine is taken without proper liquid, an upset stomach may be the result.

Anecdotally, some people are known to be 'non-responders'. Although the cause has not been ascertained, it may be due to a diet high in meat in which the body is saturated with dietary creatine stores prior to supplementation.

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Also Known As

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

Do Not Confuse With

Creatinine (metabolite) Cyclocreatine (Analogue)

Is a Form of

Goes Well With

Does Not Go Well With

  • Caffeine (Under certain conditions; see complete summary)

I honestly see no reason why somebody shouldn't supplement creatine, nor do I see any logical basis for the seeming 'fear' of this compound in society.

Its safe, it healthy, its cheap, and for most people it just works. Get some Creatine Monohydrate, take 5g a day, and you're good to go.

If humans didn't make any in the body, this thing would be a vitamin. There do exist deficiency symptoms that result in mental retardation.[2] They're rare, but they pretty much establish the importance of this molecule as a vitamin-like compound.


Kurtis "Silverhydra" Frank

Most studies use a "loading protocol" of 0.3g/kg bodyweight for 5-7 days followed by 5g of creatine monohydrate afterwards. For a 200lb individual, this correlates to 27g a day for 5-7 days, followed by a period of time with 5g a day. Loading is used for quicker saturated of cells with creatine, and it should be noted that 5g is simply what is used traditionally and in studies, whereas 2g daily may suffice to maintain average stores.

Saturation can also be achieved at a slower rate with a constant dose of 3-10g creatine monohydrate for an extended period of time.

Most benefits associated with creatine supplementation come secondary to the state of saturation, so you can feel free to use a loading protocol or a constant maintenance dose to just 'keep the tank full'

Creatine is not a highly water soluble compound in general, so buying powders may be slightly unappetizing. Using warm water can increase the rate of dissolving or buying micronized creatine can aid in solubility; micronized is basically crushing the creatine molecules into smaller particulate size so they dissolve better, and has the same activity as basic creatine monohydrate

Below is a collection of human-only studies looking at various effects of Creatine usage. Detailed explanation and citations can be retrieved by clicking on "Show Studies"

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ConfidenceAttributeStudies Showing DecreaseStudies No ChangeStudies Showing IncreaseDetails on Studies
APower Output (Novice Athletes)--2Show All 36 Studies
AAnaerobic Running Capacity-611Show All 22 Studies
APower Output (Experienced Athletes)--2Show All 20 Studies
ALean Mass--1Show All 18 Studies
AWeight--1Show All 19 Studies
AMuscle Creatine Content--8Show All 10 Studies
AHydration--1Show All 10 Studies
AMuscular Endurance-12Show All 3 Studies
AMuscle Damage21-Show All 4 Studies
ASubjective Well-being-43Show All 9 Studies
AKidney function-7-Show All 10 Studies
AExercise Capacity in COPD-1-Show All 4 Studies
AAerobic exercise-4-Show All 4 Studies
ACognition (Omnivores)-23Show All 5 Studies
AGlycemic control--3Show All 3 Studies
AVO2 max-31Show All 6 Studies
ABlood Pressure-3-Show All 3 Studies
AFatigue Resistance-23Show All 6 Studies
BGlycogen Resynthesis--1Show Study
BTreatment of Huntington's Disease-1-Show All 2 Studies
BCognition (Vegetarians)--2Show All 2 Studies
BIGF-1-2-Show All 4 Studies
BTestosterone--2Show All 4 Studies
BSymptoms of Duchenne Muscular Dystrophy1--Show All 2 Studies
BHomocysteine1--Show Study
BTreatment of Amyotrophic lateral sclerosis (ALS)-1-Show Study
BFunctionality in Elderly or Injured-11Show All 2 Studies
BBone Mineral Density--1Show Study
BSatellite Cell Recruitment--1Show Study
BMyonuclei proliferation--1Show Study
BBody Cell Mass--1Show Study
BTreatment of Parkinsons-1-Show Study
BSchizophrenia-1-Show Study
BUric Acid2--Show All 2 Studies
BDepression1--Show All 3 Studies
BTotal Cholesterol-1-Show Study
BLipid Peroxidation11-Show All 2 Studies
BSymptoms of Osteoarthritis1--Show Study
BDNA methylation--1Show Study
BDNA damage1--Show Study
CTreatment of Cystic Fibrosis--1Show Study
CAlertness--2Show All 2 Studies
CCatabolism1--Show Study
CRange of Motion1--Show Study
CHemodynamics--1Show Study

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Table of Contents:

  1. Role of Creatine
    1. Primary Role: Energy Macronutrient
    2. Properties and Structure
    3. Synthesis of Creatine in vivo
    4. Creatine-Kinase System Overview
    5. Creatine Kinase System notables
  2. Sources of Creatine
    1. Foods
    2. Comparison to Supplementation
    3. Food bound creatine during cooking and processing
    4. Consideration to Vegetarian and Veganism
  3. Pharmacology
    1. Stomach
    2. Intestines and Absorption
    3. Liver (Hepatic)
    4. Systemic
    5. Neural
    6. Depletion
  4. Creatine Responders and Non-response
    1. Non-Response
    2. Role of the muscle creatine transporter
    3. Response and Neurology
  5. Non-Bioenergetic effects of Creatine
    1. Cytoprotection
    2. Anti-cancer effects
  6. Longevity and Life Extension
  7. Creatine and Exercise
    1. Resistance Exercise
    2. Anaerobic cardiovascular exercise
    3. Aerobic exercise
  8. Interactions with carbohydrate metabolism
    1. Glucose Oxidation
    2. Insulin
  9. Creatine and Hormones
    1. Androgens
  10. Interactions with Neurology
    1. Neuron Interactions
    2. Depression
    3. Serotonergic Interactions
    4. Parkinson's Disease and Dopamine
    5. Drug Abuse
    6. Interventions on Cognition
  11. Interactions with Skeletal Muscle Metabolism
    1. Muscle Hypertrophy and Size
    2. Aging and Sarcopenia
  12. Nutrient-Nutrient Interactions
    1. Creatine with Carbohydrates
    2. Creatine with Caffeine
    3. Creatine with Beta-alanine
    4. Creatine and HMB
    5. Creatine and Alpha-Lipoic Acid
    6. Cyclooxygenase Inhibitors
  13. Different forms of creatine and creatine supplements
    1. Creatine Monohydrate
    2. Creatine Anhydrous
    3. Liquid (Serum) Creatine
    4. Buffered Creatine
    5. Creatine Ethyl Ester
    6. Creatine-Magnesium Chelate
    7. Creatine Nitrate
    8. Creatine Malate
    9. Creatine Citrate
    10. Creatine Pyruvate
    11. Creatine a-ketoglutarate
    12. Sodium creatine phosphate
    13. Polyethylene Glycosylated Creatine
    14. Cyclocreatine
  14. Safety, toxicology, and common side effects
    1. General Safety Profile
    2. Creatine and Creatinine; Clarification
    3. Water weight gain


Edit1. Role of Creatine

1.1. Primary Role: Energy Macronutrient

Creatine is an energy intermediate. It exists in cells to donate a phosphate (energy) group to adenosine diphosphate (ADP) molecules to turn them into adenosine triphosphate (ATP). ATP is seen as the cellular energy 'currency' and is the molecule that is synthesized after breakdown of any energy substrate (carbohydrates, fatty acids, ketones) for metabolizable energy.[150][151] Whereas carbohydrates are able to provide quick energy in an anaerobic environment (high intensity exercise) and fats are mobilized to provide energy during periods of high oxygen availability at a slower rate (low intensity exercise or rest). In both cases, available creatine is used to rapidly replenish ATP.[152][153]

Creatine storage in the body is limited. Over 95% of the body's creatine is stored in muscle at a maximum cellular concentration of 30uM cellular concentration. As such, creatine storage capacity increases with increasing muscle mass[154] and, if were are to assume a 70kg male with an average physique, whole body creatine stores are about 120g.[155] In contrast to creatine, one can accumulate dozens of pounds of body fat, and glycogen is only stored in the liver, brain, and muscles[156][157].

Creatine is an energy substrate. Creatine, glucose (carbohydrate) and fatty acids (dietary fat) all serve to replenish ATP which is the energy 'currency' of the cell. Creatine exerts ATP replenishment at a faster rate than both glucose and fatty acids, and is the first line of cellular ATP replenishment; stores are limited, however, and glucose or fatty acids quickly take over energy replenishment. Creatine serves a vital role in the very first stages of energy replenishment, preventing a depletion of ATP

1.2. Properties and Structure

Creatine is a peptide compound, made of the two amino acids known as glycine and Arginine that combine to form the backbone know as guanidinoacetate; its (creatine's) skeleton structure is depicted below.

1.3. Synthesis of Creatine in vivo

Without supplementation, creatine is formed primarily in the liver, with minor contribution from the pancreas and kidneys. The two amino acids glycine and Arginine combine via the enzyme Arginine:Glycine amidinotransferase (AGAT) to form Ornithine and guanidoacetate. This is the first of two steps in creatine synthesis, and although rare any deficiency of this enzyme can result in mild mental retardation and muscular weakness.[158] AGAT is also the primary regulatory step, and an excess of dietary creatine can suppress activity of AGAT to reduce creatine synthesis[159] via reducing AGAT mRNA levels, rather than competitive inhibition.[160]

Guanidoacetate (made by AGAT) then receives a methyl donation from S-adenylmethionine via the enzyme guanidinoacetate methyltransferase (GAMT) which produces S-adenylhomocysteine and Creatine. Deficiencies in GAMT are a bit more severe (although equally rare) relative to AGAT, resulting in severe mental retardation and autism-like symptoms.[161]

For the most part, the above reactions occur in the liver[162] (where most systemic creatine is synthesized) but the AGAT and GAMT enzymes have been located to lesser amounts in kidney and pancreatic tissue (the extrahepatic synthesis locales[163]); neurons also possess the capability to create their own creatine.[164]

A binding of two amino acids yields guanidoacetate, and then methylation of this molecule results in creatine; two enzymes mediate this process, ornithine is formed, and S-adenylmethione (a methyl donor) is used up. Any error in synthesis of creatine results in mental retardation

As mentioned before, S-adenylmethionine must be converted to S-adenylhomocysteine in order for guanidoacetate to convert into creatine during a process known as methylation.[165] It has been suggested that the production of creatine accounts for up to 40% of the S-adenylmethionine used in the body for methylation processes.[165][166]

Creatine supplementation alleviates the intrinsic burden of producing creatine. Supplementation reduces the expected increase in homocysteine[167] after intense exercise and may be a reason why creatine is seen as cardioprotective around the time of exercise.

After supplementation of creatine monohydrate (loading phase, followed by 19 weeks maintenance) creatine precursors are decreased by up to 50% (loading) or 30% (maintenance), which suggests a decrease in endogenous creatine synthesis during supplementation.[129] This appears to be through creatine's own positive feedback and suppression of the l-arginine:glycine amidinotransferase enzyme, the rate limiting step in creatine synthesis, as levels of intermediates before this stage are typically elevated by up to 75%.[129]

A suppression of creatine synthesis is seen when creatine is supplemented enough to cover all vital needs (approximately 4g daily, 2g of which would have been synthesized). This suppression may be beneficial to health, due to inherent costs associated with creatine synthesis

References

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  2. Creatine Deficiency Syndrome
  3. Bogdanis GC, et al. Recovery of power output and muscle metabolites following 30 s of maximal sprint cycling in man. J Physiol. (1995)
  4. Branch JD. Effect of creatine supplementation on body composition and performance: a meta-analysis. Int J Sport Nutr Exerc Metab. (2003)
  5. Brilla LR, et al. Magnesium-creatine supplementation effects on body water. Metabolism. (2003)
  6. Burke DG, et al. Effect of creatine and weight training on muscle creatine and performance in vegetarians. Med Sci Sports Exerc. (2003)
  7. Rawson ES, Volek JS. Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance. J Strength Cond Res. (2003)
  8. Volek JS, et al. The effects of creatine supplementation on muscular performance and body composition responses to short-term resistance training overreaching. Eur J Appl Physiol. (2004)
  9. Kilduff LP, et al. Effects of creatine on body composition and strength gains after 4 weeks of resistance training in previously nonresistance-trained humans. Int J Sport Nutr Exerc Metab. (2003)
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  12. Carter JM, et al. Does nutritional supplementation influence adaptability of muscle to resistance training in men aged 48 to 72 years. J Geriatr Phys Ther. (2005)
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  16. Poortmans JR, Francaux M. Adverse effects of creatine supplementation: fact or fiction. Sports Med. (2000)
  17. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc. (1999)
  18. Farquhar WB, Zambraski EJ. Effects of creatine use on the athlete's kidney. Curr Sports Med Rep. (2002)
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