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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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.
Examine.com Disclaimera-methylguanidinoacetic acid, creatine monohydrate, creatine 2-oxopropanoate
Creatinine (metabolite) Cyclocreatine (Analogue)
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"
Questions/comments/concerns? Join the Creatine Discussion
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
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.
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
