Creatine is an organic compound with the nominal formula CNCH2CO2H. This species exists in various modifications in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate, the energy currency of the cell, primarily in muscle and brain tissue. Recycling is achieved by converting adenosine diphosphate back to ATP via donation of phosphate groups. Creatine also acts as a buffer. Studies in the 1920s showed that consumption of large amounts of creatine did not result in its excretion. This result pointed to the ability of the body to store creatine, which in turn suggested its use as a dietary supplement.
In 1912, Harvard University researchers Otto Folin and Willey Glover Denis found evidence that ingesting creatine can dramatically boost the creatine content of the muscle. In the late 1920s, after finding that the intramuscular stores of creatine can be increased by ingesting creatine in larger than normal amounts, scientists discovered creatine phosphate, and determined that creatine is a key player in the metabolism of skeletal muscle. The substance creatine is naturally formed in vertebrates.
The discovery of phosphocreatine was reported in 1927.
While creatine's influence on physical performance has been well documented since the early twentieth century, it came into public view following the 1992 Olympics in Barcelona. An August 7, 1992 article in The Times reported that Linford Christie, the gold medal winner at 100 meters, had used creatine before the Olympics. An article in Bodybuilding Monthly named Sally Gunnell, who was the gold medalist in the 400-meter hurdles, as another creatine user. In addition, The Times also noted that 100 meter-hurdler Colin Jackson began taking creatine before the Olympics.
At the time, low-potency creatine supplements were available in Britain, but creatine supplements designed for strength enhancement were not commercially available until 1993 when a company called Experimental and Applied Sciences introduced the compound to the sports nutrition market under the name Phosphagen. Research performed thereafter demonstrated that the consumption of high glycemic carbohydrates in conjunction with creatine increases creatine muscle stores.
Biosynthesis
Creatine synthesis primarily occurs in the liver and kidneys. Most of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, and other tissues. Some small studies suggest that total muscle creatine is significantly lower in vegetarians than non-vegetarians, as expected since foods of animal origin are the primary source of creatine. However, subjects happened to show the same levels after using supplements.
Creatine is not an essential nutrient as it is naturally produced in the human body from the amino acids glycine and arginine, with an additional requirement for methionine to catalyze the transformation of guanidinoacetate to creatine. In the first step of the biosynthesis these two amino acids are combined by the enzyme arginine:glycine amidinotransferase to form guanidinoacetate, which is then methylated by guanidinoacetate N-methyltransferase, using S-adenosyl methionine as the methyl donor. Creatine itself can be phosphorylated by creatine kinase to form phosphocreatine, which is used as an energy buffer in skeletal muscles and the brain.
Phosphocreatine system
Creatine, which is synthesized in the liver and kidneys, is transported through the blood and taken up by tissues with high energy demands, such as the brain and skeletal muscle, through an active transport system. The concentration of ATP in skeletal muscle is usually 2–5 mM, which would result in a muscle contraction of only a few seconds. During times of increased energy demands, the phosphagen system rapidly resynthesizes ATP from ADP with the use of phosphocreatine through a reversible reaction with the enzyme creatine kinase . In skeletal muscle, PCr concentrations may reach 20–35 mM or more. Additionally, in most muscles, the ATP regeneration capacity of CK is very high and is therefore not a limiting factor. Although the cellular concentrations of ATP are small, changes are difficult to detect because ATP is continuously and efficiently replenished from the large pools of PCr and CK.
Genetic deficiencies
Genetic deficiencies in the creatine biosynthetic pathway lead to various severe neurological defects. Clinically, there are three distinct disorders of creatine metabolism. Deficiencies in the two synthesis enzymes can cause L-arginine:glycine amidinotransferase deficiency caused by variants in GATM and guanidinoacetate methyltransferase deficiency, caused by variants in GAMT. Both biosynthetic defects are inherited in an autosomal recessive manner. A third defect, creatine transporter defect, is caused by mutations in SLC6A8 and inherited in a X-linked manner. This condition is related to the transport of creatine into the brain.
Supplement health effects
Use
Creatine use can increase maximum power and performance in high-intensity anaerobic repetitive work by 5 to 15%. Creatine has no significant effect on aerobic endurance, though it will increase power during short sessions of high-intensity aerobic exercise.
A survey of 21,000 college athletes showed that 14% of athletes take creatine supplements to improve performance. Non-athletes report taking creatine supplements to improve appearance. especially in individuals with inadequate intakes in their diet and is claimed by some sources to be a nootropic supplement.
Nutritional supplement
Creatine-monohydrate is suitable for vegetarians and vegans, as the raw materials used for the production of the supplement have no animal origin.
Therapeutic use
According to a clinical study focusing on people with various muscular dystrophies, using a pure form of creatine monohydrate can be beneficial in rehabilitation after injuries and immobilization.
Medical use
A clinical study has shown that the intake of pure, high-quality creatine alone, or in combination with exercise, may reduce and delay age-related muscle atrophy, by improving fat-free body mass, muscle strength and endurance, while simultaneously improving bone density.
