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1 Neurosurgery, Yale University School of Medicine, New haven, Connecticut, United States
2 Anesthesiology, University of Florida, Gainsville, Florida, United States
* To whom correspondence should be addressed. E-mail: jullie.pan{at}yale.edu.
There has been considerable interest in the use of creatine supplementation to treat neurological disorders. However in contrast to muscle physiology, there are relatively few studies of creatine supplementation in the brain. In this report we use high field MR 31P and 1H spectroscopic imaging of human brain with a 7 day protocol of oral creatine supplementation to examine its effects on cerebral energetics (phosphocreatine PCr, ATP) and mitochondrial metabolism (N-acetyl aspartate NAA, and creatine Cr). We find an increased ratio of PCr/ATP (Day0 0.80±0.10; Day7 0.85±0.09) with this change largely due to decreased ATP, from 2.7±0.3mM to 2.5±0.3mM. The ratio of NAA/Cr also decreased (Day0 1.32±0.17; Day7 1.18±0.13), primarily from increased Cr (9.6±1.9 to 10.1±2.0mM). The creatine-induced changes significantly correlated with the basal state, with the fractional increase in PCr/ATP negatively correlating with the basal PCr/ATP value (R=-0.74, p<0.001). As NAA is a measure of mitochondrial function, there was also a significant negative correlation between basal NAA concentrations with the fractional change in PCr and ATP. Thus, healthy human brain energetics is malleable, and shifts with 7 days of creatine supplementation, with the regions of initially low PCr showing the largest increments in PCr. Overall, creatine supplementation appears to improve high energy phosphate turnover and in healthy brain, and can result in either a decrease or increase in high energy phosphate concentrations.
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