Alterations in brain high-energy
phosphate metabolism, determined by in vivo magnetic resonance spectroscopy (MRS), have been reported in subjects with a number of
brain disorders including major depression,
schizophrenia, and
substance abuse. It is not clear to what extent these changes can be modified by pharmacological or nutritional means. To address this possibility, we evaluated changes in brain chemistry that were associated with oral
creatine (Cr) administration. We hypothesized that oral Cr supplementation, by increasing brain
creatine and high-energy
phosphate stored in
phosphocreatine, would result in an increase in the
creatine resonance, as measured using
proton 1H-MRS, and a decrease in the beta-
nucleoside triphosphate (NTP) peak and an increase in the
phosphocreatine (PCr) peak, as measured by
phosphorus 31P-MRS, in brain of healthy human subjects. Fifteen healthy male subjects (age=22.9+/-2.2; body mass index=22.9+/-1.7), who were without any axis I disorders or physical or neurological illness, were recruited. Ten subjects took
creatine-monohydrate, 0.3 g/kg/day for the first 7 days and 0.03 g/kg/day for the next 7 days (
creatine group). Five comparison subjects took equivalent amounts of
sucrose as placebo (placebo group). Both 1H- and 31P-MRS scans were acquired at baseline, as well as at day 7 and day 14 of oral supplementation. 1H-MRS: Water suppressed localized spectra were acquired using a single-voxel (1.5 cm x 2 cm x 2 cm)
proton MRS PRESS sequence in the left frontal lobe. 31P-MRS:
Phosphorus spectral data were recorded from a 5-cm-thick axial brain slice using a short-TE slice selective spin-echo pulse sequence. The
creatine group had significantly increased brain
creatine levels (8.1% and 9.3%, in
creatine/
N-acetyl aspartate and
creatine/
choline ratios, respectively) compared to the placebo group over the 2-week period. The
creatine group had significantly decreased beta-NTP levels (7.8%) and marginally increased PCr (3.4%) over the same period. In addition, the brain
inorganic phosphate level increased over the same period in the
creatine group (9.8%). The current study is the first multinuclear (1H and 31P) MRS study to evaluate changes in brain high-energy
phosphate metabolism following oral
creatine supplementation in healthy human subjects. These findings suggest the possibility of using oral
creatine supplementation to modify brain high-energy
phosphate metabolism in subjects with various
brain disorders, including major depression,
schizophrenia,
cocaine and
opiate abuse, where alterations in brain high-energy
phosphate metabolism have been reported.