Introduction
1.1 Definition and discovery
1.1.1 Definition
Creatine has the chemical formula NH2-C(NH)-NCH2(COOH)-CH3
Creatine is recognised as an ergogenic substance that can enhance muscle performance and has become very popular amongst athletes over the last two decades. It is produced naturally in the body, either directly from food or synthesised by the liver, kidneys and pancreas from amino acids.
1.1.2 History
Creatine, or N-methylguanidinoacetic acid, was discovered by the French chemist Michel Eugène Chevreul in 1832. Initially isolated from skeletal muscle, Chevreul named it ‘kreas’, which means ‘meat’ in Greek. However, it would take several years to fully understand its role in cellular energy production and to apply this knowledge to nutritional supplementation in elite athletes. (1)
In the early 20th century, papers began to be published on the effects of oral creatine administration and its storage in skeletal muscle. At the same time, the idea was put forward that creatine, in its free or phosphorylated form (phosphocreatine or creatine phosphate), played an essential role in muscle metabolism. (2)
1.2 Sources
Creatine is found mainly in foods of animal origin:
- Red meat (beef, lamb): approximately 4 to 5 grams per kilogram.
- Fish (salmon, tuna, herring): approximately 4 to 7 grams per kilogram.
- Poultry (chicken, turkey): approximately 3 to 4 grams per kilogram.
Please note that cooking can reduce the creatine content of food due to thermal degradation. Creatine may be lost in the cooking water or degraded at high temperatures.
1.2.1 Supplementation
Legislation in force in 2023 clearly stipulates that creatine is not included on the list of prohibited substances for athletes, as defined by the World Anti-Doping Agency. This lack of classification as a doping substance is explained by the fact that creatine is a protein naturally present in common foods.
Creatine requirements may vary according to age, gender, physical activity and state of health.
Athletes may benefit from supplementing with 3 grams of creatine per day to improve muscle performance.
As dietary sources of creatine are mainly of animal origin, vegetarians and vegans may wish to consider creatine supplements to maintain optimal levels. Vegetarians and vegans are advised to consult a nutritionist or dietitian regularly to ensure that all their nutritional needs, including creatine levels, are met.
Ensuring an adequate intake of protein from a variety of plant-based sources (pulses, cereals, nuts, seeds, soya products) is crucial, as creatine in the body is also synthesised from certain amino acids. One study (3) demonstrates, in particular, the benefit of supplementation for people following ovo-lacto-vegetarian diets.
1.3 Absorption and excretion
Absorption: Creatine from food is almost completely absorbed in the intestine, as it is resistant to the acidic and enzymatic secretions of the digestive system. It therefore has very high bioavailability and is transported throughout the body via the bloodstream. In fact, approximately 80% of the creatine consumed is effectively absorbed in the intestine. (4)
Distribution: Once in the bloodstream, creatine is transported to various target tissues via a sodium- and chloride-dependent transmembrane transporter called CRTR (Creatine Transporter). The presence of insulin can also influence muscle uptake of creatine, particularly following the consumption of glucose, which promotes an increase in plasma insulin levels and, consequently, greater muscle uptake of creatine. (5) (6)
Storage: In humans and animals, most creatine (95%) is stored in skeletal muscle, whilst the remainder (5%) is found in other tissues such as the heart, brain, testicles or the photoreceptor cells of the retina. In muscle, 40% of creatine is stored in its free form and the remainder in its phosphorylated form, known as phosphocreatine. An adult has between 80 and 130 g of creatine.
Elimination: Our body eliminates approximately 1% to 2% of stored creatine daily. Creatine is broken down via a non-enzymatic process that results in its cyclisation to creatinine. Creatinine diffuses passively out of the cells, enters the systemic circulation and is excreted in the urine. Urinary creatinine excretion is frequently used as an indicator of muscle mass and a marker of kidney function. (7)
2 Structure and properties
2.1 Chemical structure and endogenous production
Endogenous synthesis takes place in two steps involving three amino acids: arginine, glycine and methionine (Figure 1). Firstly, L-arginine glycine amidinotransferase (AGAT) catalyses the transfer of the amino group from arginine to glycine, leading to the biosynthesis of ornithine and guanidinoacetic acid (or GAA).
In a second step, GAA is methylated via a reaction mediated by guanidinoacetate methyltransferase (GAMT). This enzyme transfers a methyl group from S-adenosylmethionine (SAM) to creatine, producing S-adenosylhomocysteine. (8)
2.2 Physicochemical properties
2.2.1 Buffering function in the regulation of intramuscular pH
This function is essential for optimal muscle function during intense exercise. This process is detailed below:
1. Release of protons during muscle contraction:
During exercise, contracting muscles utilise ATP (adenosine triphosphate) as an energy source. The hydrolysis of ATP into ADP (adenosine diphosphate) and inorganic phosphate releases energy for muscle contraction. This process also produces protons (H+), which contributes to the acidification of the intracellular environment.