Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate

In Kyoon Lyoo, Sek Won Kong, Seung Mo Sung, Fuyuki Hirashima, Aimee Parow, John Hennen, Bruce M. Cohen, Perry F. Renshaw

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110 Scopus citations


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 β-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×2 cm×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 β-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.

Original languageEnglish
Pages (from-to)87-100
Number of pages14
JournalPsychiatry Research - Neuroimaging
Issue number2
StatePublished - 30 Jun 2003

Bibliographical note

Funding Information:
The research reported was supported, in part, by grants from the National Institute on Drug Abuse (DA09448), the National Institute of Mental Health (MH58681), the Stanley Foundation Bipolar Disorders Research Center at McLean Hospital, the NARSAD Young Investigator Award (I.K.L.) and Independent Investigator Award (P.F.R.), the Harvard-MIT CITP (I.K.L.) and the postdoctoral fellowship program from the Korea Science and Engineering Foundation (KOSEF) (I.K.L.).


  • Adenosine triphosphate
  • Brain chemistry
  • Depression
  • Frontal lobe
  • Phosphocreatine


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