Cerebral energetic effects of creatine supplementation in humans

Abstract

There has been considerable interest in the use of creatine (Cr) 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 (31)P and (1)H spectroscopic imaging of human brain with a 7-day protocol of oral Cr supplementation to examine its effects on cerebral energetics (phosphocreatine, PCr; ATP) and mitochondrial metabolism (N-acetyl aspartate, NAA; and Cr). We find an increased ratio of PCr/ATP (day 0, 0.80 +/- 0.10; day 7, 0.85 +/- 09), with this change largely due to decreased ATP, from 2.7 +/- 0.3 mM to 2.5 +/- 0.3 mM. The ratio of NAA/Cr also decreased (day 0, 1.32 +/- 0.17; day 7 1.18 +/- 0.13), primarily from increased Cr (9.6 +/- 1.9 to 10.1 +/- 2.0 mM). The Cr-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 Cr supplementation, with the regions of initially low PCr showing the largest increments in PCr. Overall, Cr supplementation appears to improve high-energy phosphate turnover in healthy brain and can result in either a decrease or an increase in high-energy phosphate concentrations.

Fig. 1

Scout showing the location of the right ¹H hippocampal measurement (A), ¹H spectra (B) and ³¹P spectra (C) are shown from a single volunteer. The baseline data set (top spectra) are compared with the day 7 data set (bottom spectra) for both ¹H and ³¹P acquisitions. From the same volunteer, scouts (D) are shown with the locations of the ³¹P data, striatum (left), medial temporal lobe (middle) and parasagittal occipital lobe (right). PCr, phosphocreatine; Cr, creatine; NAA, N-acetyl asparate; and Ch, choline.

Fig. 2

Basal PCr/ATP correlates well with creatine-induced changes in PCr/ATP (R = − 0.74, P < 0.001; A), with the individual components ATP (B) and PCr (C) show similar correlations, ATP, R = −0.71, P < 0.001; PCr R = −0.72, P < 0.001. Shown are the linear regressions with 95% confidence intervals on the predicted changes in PCr/ATP or NAA/Cr. All of these data were acquired from the medial temporal lobe.

Fig. 3

Basal NAA/Cr correlates with fractional change in NAA/Cr (A), R = −0.73 P < 0.001. Basal NAA correlates with fractional changes in ATP R = −0.42 P < 0.05 (B) and with PCr R = −0.41 P < 0.05 (C). Shown are the linear regression lines with the 95% confidence intervals with the predicted changes.

Fig. 4

The changes in NAA and ADP induced by the 7-ay protocol correlate positively at R = +0.49, P < 0.02.