Creatine is part of the guanidine-phosphate family, a protein-free amino acid compound naturally present in several foods, including mainly red meat and fish. Most of the creatine is deposited in skeletal muscle (95%), the rest divided between the brain and testicles. Approximately 2/3 of intramuscular creatine occurs in the form of phospho-creatine (Pcr), the rest as free creatine. It was identified for the first time in 1832 by the French chemist Chevreul but its presence in the flesh was confirmed by the well-known German chemist Von Liebig only in 1847, to which followed in the decade's numerous studies, which do not end yet to produce surprises, studies that saw among the protagonists the Italian school of Margaria.

Of course, a proportion of creatine, chemically "methyl guanidino acetic acid", can be synthesized at the liver level, partly also in the kidneys and pancreas, starting from arginine, S-adenosyl-methionine and glycine, Its most well-known physiological functions include the ability to rapidly provide a phosphate molecule in ATP resynthesis from ADP in the known cyclic reaction and thus in energy management in the first seconds of muscle activity.

It is therefore evident that the availability of Pcr is able to manage muscle energy flows for intense efforts of short duration, the availability of Pcr depends mainly on the activity of the enzyme creatine kinase (CK), muscle stocks (and therefore by total mass) and endogenous synthesis capacity considering that the amount assimilable by food is extremely small. The primary role of creatine, as well as its pleiotropic effect, is linked to the CK/Pcr system, schematically reported in Figure 2.

Figure 2

The amount of Cr used daily depends on various factors, including the duration and intensity of exercise, the bioavailability of sources of Cr, muscle mass of the athlete, In fact, it has been reported that large athletes are able to consume amounts of Cr equal to 5-10 g/day; in some clinical conditions, it is even 10-30 g/day (Braissant, Wyss et. All).


For several years it has been hypothesized that increasing the amount of Cr ingested could lead to the advantages caused by the greater availability and therefore an increase in the storage capacity of the same in the muscles given also the demonstration that when the concentration of Cr decreases with the continuation of the exercise, therefore, decreases the ability to keep the intensity constant.

With a normal diet, it is possible to provide 1-2 g of Cr per day which means saturating the deposits for 60-70%, clearly, a supplementation would not only allow to saturate the deposits at 100% but even increase the capacity of 20-40% also as a result of various strategies of supplementation (Candow, Kreider et all.)

Is Cr’s supplementation really able to improve athletic performance? 

Cr and its supplementation have been the subject of at least 25 years of a very long and copious series of studies that have led to know many aspects of the biochemistry of the substance and how this is able to accompany and modify metabolic adaptations that follow the exercises, often of very high intensity and load and of particular duration, without considering the very interesting perspectives that are opening in the clinical field but which we will not write on this occasion.

Recommended quantities

The amount of Cr to be ingested to increase deposits is about 5 g/day for 5-7 days, we speak of CREATINE MONOHYDRATE, the most studied form.

The quantities of Cr to be administered able to maintain constant maximum quantities of muscle Cr now see a decided sharing indicating 3-5 g/day even for long periods; it is considered a greater need for athletes of large tonnage for which 5-10 g/day. In some studies, it was recommended to start with a short period of loading (in any case not less than 0.3 g/kg bodyweight for 4-5 days) followed by the doses previously recommended.

Administering Cr monohydrate together with carbohydrates or a mixture of carbohydrates and proteins increases the ability to retain and increase deposits (Steenge, Greenwood). Alternative protocol sees a quantity of 3 g/day for at least 28 consecutive days but the increase in deposits is slow and gradual. It should be considered that once the maximum quantity of deposits has been obtained in case of cessation of supplementation, the return to the starting quantity would take place after 4-6 weeks.

Creatine monohydrate, as mentioned above, the most widely used and studied form, is very stable in solid form, less in aqueous solution in which it remains stable for several hours (the instability manifests with creatinine cyclization which would make it little or nothing assimilatable), the stability increases to the increase of the pH and to the decrease of the temperature of the solution; once ingested the peak of absorption occurs after about 60 minutes. In addition to Creatine Monohydrate, several other forms have been proposed (citrate, ethyl ester, nitrate, buffered and others) but none has been shown to have better properties both in the final result and in the kinetics of absorption.

When to take it

Regarding the timing, however, several studies state with a determination that taking Cr post-workout determines better results than pre-workout by analyzing the values of strength and body composition.

Advantages of supplementation

A copious series of studies has led to having strong evidence in relation to the ability of Cr to provide an energy supplement in a wide range of exercises; clearly different sports disciplines benefit in view of the presence of the different stages in the table that makes up the characteristics of the discipline to be considered.

Next is a summary table that takes into account sports disciplines that bring an advantage from the supplementation of Cr and why prevalent.

As you can see, several disciplines are involved confirming that the supplementation of Cr is able to increase performance in all athletic conditions and that is both in pure strength and high intensity, continuous and intermittent, as well as in long-term tests.

In a recent overview of the additional benefits derived from the use of Cr there is a schematic description:

  • Improvement of recovery
  • Prevention of accidents
  • Increase in heat tolerance
  • Improvement of rehabilitation from injury
  • Brain and column neuroprotection


One of the most interesting aspects is the safety reported after massive doses of Cr taken for long periods without having any particular side effects. In particular, it is reported that the intake for several years of doses of 0.3-0.8 g per kg/ body weight (equal to 21-56 g for a subject of 70 kg) daily did not result in clinical events or serious side effects.

Beliefs and false myths

The remarkable fame assumed by the abilities of the Cr has also led, as often happens, to the diffusion of both elements of amazing advantage, never confirmed in such proportions, whereas, on the contrary, alarming data on side effects are likely to compromise certain salient features of specific disciplines, such as the worrying condition of weight gain due to water retention obviously problematic in the disciplines where weight loss is crucial.

Necessary for this purpose to report the final conclusions of a study that has analyzed many scientific publications published on the supplementation of Cr, very illuminating study in this regard:

  1. Cr does not lead to water retention
  2. Cr is not an anabolic steroid
  3. If taken in the recommended dosages does not result in kidney damage or dysfunction
  4. Most evidence shows no correlation between Cr use and hair loss
  5. Cr does not cause dehydration and cramps
  6. The CR is able to bring the benefits reported safely even in teenagers
  7. Cr does not increase fat mass
  8. Small doses of Cr (3-5 g per day) are sufficient to maintain constant maximum amounts of muscle Cr deposits so the load (25 g/day) is usually not useful
  9. The supplementation of Cr in combination with counter-resistance training brings considerable advantages to the elderly population; note that in these subjects even the only Cr (without training) is able to bring advantages
  10. Cr is able to bring benefits in a wide variety of sports disciplines
  11. The CR is able to bring the same benefits to the female sex throughout life
  12. No alternative form of Cr has advantages over creatine monohydrate.

In conclusion, the Cr is becoming increasingly important as a substance of considerable interest for the most varied aspects in the various sports disciplines not excluded clinical aspects which, increasingly, go beyond the sporting needs and for which, However, scientific evidence is now assuming unequivocal proportions.


Braissant O, et al. Creatine deficiency syndromes and the importance of creatine synthesis in the brain. Amino Acids.

Wyss M, et al. Creatine and creatine kinase in health and disease–a bright future ahead? Subcell Biochem. 2007;46:309–34.2011;40(5):1315–24.

Candow DG, Chilibeck PD. Potential of creatine supplementation for improving aging bone health. J Nutr Health Aging. 2010;14(2):149–53.

Kreider RB. Effects of creatine supplementation on performance and training adaptations. Mol Cell Biochem. 2003;244(1–2):89–94.

Steenge GR, Simpson EJ, Greenhaff PL. Protein- and carbohydrate-induced augmentation of whole body creatine retention in humans. J Appl Physiol (1985). 2000;89(3):1165–71.

Greenwood M, et al. Differences in creatine retention among three nutritional formulations of oral creatine supplements. J Exerc Physiol Online. 2003;6(2):37–43.

Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J. Int. Soc. Sports Nutr. 2017;14:18-z eCollection 2017.

Antonio, J., Candow, D.G., Forbes, S.C. et al. Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?. J Int Soc Sports Nutr 18, 13 (2021)