Creatine monohydrate: what it is and why it works not only in the muscles

Creatine is the most studied supplement in sports nutrition, and at the same time the one around which the most persistent misconceptions are held. It is sometimes called chemistry, sometimes a safe analogue of steroids, is attributed to water retention and kidney damage, and in recent years has been actively discussed as a substance for the brain. It is easier to understand all this than it seems if you start with the mechanism: creatine is neither a hormone nor a stimulant, but performs one specific biochemical job in the cell. Once you understand it, it is easy to see where both the real effects and the myths come from.

What is creatine and where does it come from?

Creatine is a natural substance that the body synthesizes on its own from three amino acids: glycine, arginine, and methionine. Synthesis occurs mainly in the liver, kidneys, and pancreas, after which creatine enters the bloodstream and is taken up by tissues via a special transporter.

The total body supply of creatine in an adult is approximately 120 grams, and about 95% of it is concentrated in skeletal muscle. The rest is distributed between the heart, brain, and gonads. Every day, some of the creatine is irreversibly converted to creatinine and excreted by the kidneys, which is why the supply needs to be constantly replenished.

The second source is food. Creatine is found in meat and fish, so people who do not consume them have lower initial reserves. This is not a pathology, but it explains why the response to additional intake varies from person to person.

The creatine phosphate system: the mechanism in three sentences

The cell uses ATP as fuel, but stores only a small amount of it—only enough for a few seconds of intense work. ATP then needs to be constantly replenished, and the fastest way to do this is to take a phosphate group from another molecule.

This is the role played by phosphocreatine. It donates phosphate to the ADP molecule, instantly converting it back to ATP, and itself becomes free creatine. The reaction is reversible: at rest, the process goes in the opposite direction and the phosphocreatine reserve is restored. In fact, it is a fast energy buffer that works in the first seconds of effort - until the slower systems have time to deploy.

Hence the logic of the supplement. A larger supply of creatine in the muscle means a larger buffer, and therefore a slightly longer ability to maintain maximum effort. This is not additional energy, but faster access to what is already there.

Why muscles are not the only tissue

The same mechanism works wherever a cell needs sudden surges in energy consumption. The brain is such a tissue: it consumes a disproportionate amount of energy and does not tolerate its fluctuations well, which is why the creatine phosphate system is present in neurons as well as in muscle fibers.

This has led to a separate line of research—the effect of creatine on cognitive function, sleep deprivation tolerance, and mental performance. But it is not possible to directly extrapolate from the sports literature here for one simple reason: brain creatine saturation occurs differently and much less predictably than muscle saturation. The blood-brain barrier limits the supply, and what works reliably for skeletal muscle remains a question mark for nervous tissue.

Creatine forms

Monohydrate is the simplest and cheapest form, and the one on which the vast majority of research has been conducted. When the scientific literature mentions “creatine,” it is almost always monohydrate that is being referred to.

The remaining forms—hydrochloride, malate, nitrate, ethyl ester, buffered variants—appeared as an attempt to solve the real or perceived shortcomings of the monohydrate: solubility, stomach discomfort, the need for larger quantities. Each has its own marketing argument, but none has a comparable amount of research. Comparing the forms with each other in direct experiments is a separate topic, and no one has yet shown a clear advantage.

What about the evidence base?

It's important to see the inequality that marketing usually smooths over. Creatine is well-studied, but not equally well-studied in all directions.

The position paper of the International Society of Sports Nutrition (Kreider et al., 2017) describes this picture in detail: an increase in intramuscular creatine concentration is reliably reproduced, but the subsequent effects depend on the type of load, training level, and initial level of reserves.

A separate detail that is worth knowing in advance: there are people whose muscle creatine reserves are close to maximum even without supplementation. For them, additional intake makes little difference. This is not a defect of the supplement or a defect of the person, but a normal physiological variability.

Three concerns are repeated most often, and all three are worthy of a separate conversation rather than a one-word answer.

Kidneys. The concern was not unfounded: creatine supplementation does indeed increase blood creatinine levels, a measure of kidney function. But creatinine appears here as a breakdown product of the additional creatine taken, not as a sign of damage. This is an analytical nuance, and it is discussed separately in the reviews by Antonio et al. (2021).

Water retention. Creatine is osmotically active and does increase the water content in the muscle cell. But “water in the muscle” and “a swollen appearance due to water under the skin” are different things that are conflated in everyday conversation.

Hair: The concern is based on a single small study that looked at a hormonal marker, not hair condition. The difference between a surrogate and a clinical outcome is fundamental here.

Each of these questions has its own evidence base and deserves detailed analysis — a generalized answer of “everything is safe” would be as superficial as the fears themselves.

What you should know before you start

The mechanism provides several practical guidelines that should be kept in mind before the first serving:

• The effect is cumulative, not instantaneous. It's about the gradual saturation of the tissue reserve, so it's pointless to evaluate the result based on one workout.
• Regularity is more important than the time of admission. Since the task is to maintain a full pool, consistency is important, not a specific time.
• The loading phase is not mandatory. It is a question of the rate of saturation, not the final level, and it deserves a separate analysis.
• The reaction is individual. The initial level of reserves, type of diet and training affect how noticeable the change will be.

Finally, about precautions. Creatine has been studied mainly in healthy adults, so if you have kidney, liver, or other chronic conditions, the decision to take it should be made together with your doctor — not because harm has been proven, but because this population is poorly represented in studies. For the same reason, data on use in adolescents, during pregnancy, and during lactation are insufficient to draw conclusions, and in these situations, the issue also remains with the doctor. The dosage and method of use of any supplement are determined by the manufacturer's instructions.

Frequently asked questions

What is creatine in simple words?
A natural substance that the body synthesizes from three amino acids and obtains from meat and fish. In the cell, it works as a quick energy buffer for the restoration of ATP.

How much creatine is in the body and why should you supplement it?
Approximately 120 grams, of which about 95% is in skeletal muscle. Some is converted to creatinine and excreted daily, so the supply is constantly being depleted.

Is creatine a steroid?
No. It is not a hormone and does not act on hormone receptors; its role is purely energetic - transferring a phosphate group to regenerate ATP.

Why doesn't creatine help with long-distance running?
Because the creatine phosphate system works in the first seconds of effort. For prolonged loads, energy is supplied by other, slower mechanisms.

Why is the effect noticeable in some people and not in others?
The initial level of reserves in the muscles varies. In those who have it close to maximum, additional intake changes little.

Does creatine harm the kidneys?
The increase in creatinine in the tests during the intake is explained by the breakdown of additionally taken creatine, and not by kidney damage. If you have existing kidney diseases, the issue should be discussed with your doctor.

Which form of creatine is best studied?
Monohydrate. The vast majority of studies have been conducted on it, so the other forms have a much smaller evidence base.

Sources

• Kreider RB and others. (2017). International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. Journal of the International Society of Sports Nutrition. https://pmc.ncbi.nlm.nih.gov/articles/PMC5469049/
• Antonio J. and others (2021). Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show? Journal of the International Society of Sports Nutrition. https://pubmed.ncbi.nlm.nih.gov/33557850/

Dietary supplement. Not a medicine. Consult a doctor before use.