As creatine is predominately present in the diet from meats, vegetarians have lower resting creatine concentrations [2]. Creatine is used and researched in a clinical setting to investigate various pathologies or disorders such as myopathies [3, 4] and is also used as an ergogenic aid for improving health and sports performance in athletes [5]. As an oral supplement, the most widely used

AG-881 order and researched form is creatine monohydrate (CM). When orally ingested, CM has shown to improve exercise performance and increase fat free mass [5–9]. There is a great amount of research published on creatine supplementation; protocols of administration, forms of creatine, as well as potential side effects. Despite this, the mechanisms by which creatine acts in the human body to improve physical and cognitive performance are still not clear. The main objectives of this review are to analyze the more recent findings on the effects and mechanisms of creatine supplementation in sports and health. As a secondary purpose, we will analyze the most recommended protocols of ingestion and its potential side effects. Creatine metabolism The majority of creatine in the human body is in two forms, either the phosphorylated form making up 60%

of the stores or in the free form which makes up 40% of the stores. The average 70 kg young male has a creatine pool of around 120-140 g which LY3039478 in vivo varies between individuals [10, 11] depending on the skeletal muscle fiber type [1] and quantity of muscle mass [11]. The endogenous production and dietary intake matches the rate of creatinine production Carnitine palmitoyltransferase II from the degradation of phosphocreatine and creatine at 2.6% and 1.1%/d respectively. In general, oral creatine supplementation leads to an increase of creatine levels within the body. Creatine can

be cleared from the blood by saturation into various organs and cells or by renal filtration [1]. Three amino acids (glycine, arginine and methionine) and three enzymes (L-arginine:glycine amidinotransferase, guanidinoacetate methyltransferase and methionine adenosyltransferase) are required for creatine synthesis. The impact creatine synthesis has on glycine metabolism in adults is low, however the demand is more appreciable on the metabolism of arginine and methionine [11]. Creatine ingested through supplementation is transported into the cells Epoxomicin manufacturer exclusively by CreaT1. However, there is another creatine transporter Crea T2, which is primarily active and present in the testes [12]. Creatine uptake is regulated by various mechanisms, namely phosphorylation and glycosylation as well as extracellular and intracellular levels of creatine. Crea T1 has shown to be highly sensitive to the extracellular and intracellular levels being specifically activated when total creatine content inside the cell decreases [12].