Creatine enters the brain via a specialized sodium dependent transporter. Dechent et al (1999) studied the effect of oral creatine supplementation of 20g/day for 4 wk demonstrating a significant increase of mean concentration of total creatine across brain regions (8.7% corresponding to 0.6mM, P < 0.001). Lyoo et al (2003) studied magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine reporting that creatine (0.3 g/kg/day for the first 7 days and 0.03 g/kg/day for the next 7 days) significantly increased brain creatine levels. These findings suggest the possibility of using oral creatine supplementation to modify brain high-energy phosphate metabolism in subjects with various brain disorders, including schizophrenia and major depression, where alterations in brain high-energy phosphate metabolism have been reported.