Guanidinoacetic Acid (GAA) Administration in Physically Active Men and Women

For the last two decades, top athletes first, then sport professionals and amateur sports participants have been using oral creatine supplementation on regular basis as an ergogenic aid to improve performance (Poortmans & Francaux 2000). Up to 90% of team-game athletes are regular consumers of creatine (Striegel et al. 2006), with nearly 60% of recreational athletes have tried creatine (Froiland et al. 2004). Supplementation with oral creatine, that currently is viewed to be safe, augments skeletal muscle creatine concentrations in most individuals, which has been shown to promote gains in lean body mass when used in conjunction with resistance training, to enhance power and strength, and to improve performance in intense exercise, especially during repeated bouts (Racette 2003; Ostojic 2004). Yet, creatine is not stable in solution and as such is only offered in a variety of non-liquid forms including powder, tablets, gel, chewing gum, and candy (Benzi & Ceci 2001). Although creatine synthesis is a proprietary process among manufacturers, it is quite common to use another muscle-related compounds (i.e. sarcosine, cyanamide), as the principal starting materials for the commercial synthesis of creatine (Williams & Branch 1998). Glycocyamine (guanidinoacetic acid - GAA) along with L-ornithine is formed from arginine and glycine in the kidney, with this reaction is believed to be the regulated step of creatine biosynthesis (Edison et al. 2007). The second enzyme in the pathway is GAA N-methyltransferaze which catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to GAA to form S-adenosylhomocysteine (SAH) and creatine (Walker 1979). It has been estimated that about 75% of labile methyl groups is used to synthetize creatine by a reaction catalyzed by GAA N-methyltransferaze (Mudd et al. 1975). It seems that creatine synthesis is an interorgan process whereby GAA, produced by the kindey, is released into the circulation and is methylated to creatine in the liver. Creatine is then released from the liver and into the circulation where it can be taken up, via a specific transporter, by various tissues. According to previous studies in animals (da Silva et al. 2009) and preliminary research in humans (AlzChem 2009), short-term oral intake of GAA increases serum level of creatine, with level of increase interrelated with GAA dose supplemented. GAA is the biochemical presursor of creatine, which is phosphorylated and plays an important role as a high-energy carrier in the muscle (Edison et al. 2007). Since GAA can be administred in liquid solutions, such as sports drinks, it could be hypothesised that GAA could easily enhance creatine biosynthesis with clear physiological effects yet to be determined. Moreover, it seems that GAA has a significantly better bioavailability than creatine, developing maximal activity at a dosage at which creatine leads to no observable effects (AlzChem 2009). Several human studies (Borsook & Borsook 1951; Graybiel & Patterson 1951; Higgins et al. 1952; Dixon et al. 1954) found beneficial effects of creatine precursors oral administration on cardiac decompensation, arthritis, anxiety and depression patients. Authors speculated that benefical effects of GAA intake could be due to boosting energy levels and/or increased availability of dimethylglycine for incorporation into tissue proteins, providing repair of damaged muscle cells. Yet, no single study has examined the influence of additive-free GAA (e.g. without betaine or choline) on health, human performance or body composition indices. The amount taken of this supplementation ranges typically from a few grams to tens of grams per day for weeks or months in previous research in humans. Although, the most effective dose is yet to be find. Finally, the adverse effects of GAA supplementation in both animals and humans are yet to be determined. Several studies showed moderate hyperhomocysteinemia (Stead et al. 2001; Fukada et al. 2006; Setoue et al. 2008; AlzChem 2009), disturbances in antioxidant system (Zugno et al. 2008), modulation of inflammatory responses (Glorieux et al. 2004) after GAA supplementation. If GAA have ergogenic properties it could become new effective performance-enhancing substance for both professional and recreational athletes, stable in water solutions, where creatine at neutral to slightly acidic pH-values is rapidly being metabolised to creatinine, which is meaningless for the energy production (AlzChem 2009).