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

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

doi:10.1016/s0925-4927(03)00046-5

Cited by 118 publications

(89 citation statements)

References 41 publications

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“…Our result fits nicely to the known effect of oral creatine supplementation: there is evidence from preclinical and human studies that excessive oral creatine supplementation increases regionally dependent brain tCr levels (Michaelis et al, 1999;Dechent et al, 1999;Lyoo et al, 2003;Pan and Takahashi, 2007). In those studies supplementation usually took place for at least 1 week, sometimes several weeks, which may suggest an upregulation of the CrT under constant excessive creatine supply.…”

Section: Discussionsupporting

confidence: 85%

Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain

Sartorius

Lugenbiel

Mahlstedt

et al. 2008

Journal of Neuroscience Methods

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Section: Discussionsupporting

confidence: 85%

Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain

Sartorius

Lugenbiel

Mahlstedt

et al. 2008

Journal of Neuroscience Methods

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“…First, the relatively small sample size may have limited our ability to detect small changes in metabolite concentrations after lithium administration. Nonetheless, as suggested by the reported effect sizes from studies that examined possible medication changes on brain 1 H MRS metabolites (Brambilla et al, 2002a, b;Deicken et al, 1992;Lyoo et al, 2003), our study with 12 subjects had adequate statistical power. Second, only the DLPFC was investigated in this study.…”

Section: Discussionmentioning

confidence: 85%

1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

Brambilla

Stanley

Sassi

et al. 2004

Neuropsychopharmacol

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The mechanism of action of lithium is still largely unknown. However, recent animal and human studies suggested the possible neuroprotective effects of this medication. In particular, a recent magnetic resonance spectroscopy (MRS) study showed the increase of cortical brain levels of N-acetyl-aspartate (NAA), a putative marker of neuronal integrity/functioning, in both bipolar patients and normal controls after 4 weeks of lithium administration. We investigated the effects of lithium on NAA levels in a sample of healthy individuals using in vivo 1 H MRS in dorsolateral prefrontal cortex (DLPFC), a region likely implicated in the pathophysiology of bipolar disorder. In vivo short echo-time 1 H-MRS measurements of 8 cm 3 single voxels placed bilaterally in the DLPFC were conducted at baseline and after 4 weeks of lithium administration on 12 healthy individuals (mean age7SD ¼ 25.079.8 years; six males). After lithium administration, no significant differences in NAA, phosphocreatine plus creatine, glycerophosphocholine plus phosphocholine (or choline-containing molecules), and myo-inositol absolute levels or ratios were found in DLPFC (paired t-tests, p40.05). Contrary to prior MRS reports in bipolar patients, we found that lithium administration did not significantly increase NAA levels in the DLPFC of healthy individuals. Future longitudinal studies will be needed to further investigate whether chronic lithium treatment increases NAA levels in other brain regions in healthy individuals, and whether it promotes changes in these levels in specific brain regions in bipolar patients.

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“…SEVERAL GROUPS HAVE SHOWN that oral creatine (Cr) supplementation can affect energy dynamics and performance in muscle (4,17,22) and brain (7,12,16,24). In both of these tissues where energy demand and ATP consumption may be temporally dynamic, relatively higher concentrations of creatine and phosphocreatine are found, presumably for its physiological role as a buffer for ATP.…”

mentioning

confidence: 99%

Cerebral energetic effects of creatine supplementation in humans

Pan¹,

Takahashi²

2007

American Journal of Physiology-Regulatory, Integrative and Comp

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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 Ϯ 0.10; day 7, 0.85 Ϯ 09), with this change largely due to decreased ATP, from 2.7 Ϯ 0.3 mM to 2.5 Ϯ 0.3 mM. The ratio of NAA/Cr also decreased (day 0, 1.32 Ϯ 0.17; day 7 1.18 Ϯ 0.13), primarily from increased Cr (9.6 Ϯ 1.9 to 10.1 Ϯ 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 ϭ Ϫ0.74, P Ͻ 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. high-energy phosphates; brain; N-acetyl aspartate; metabolism SEVERAL GROUPS HAVE SHOWN that oral creatine (Cr) supplementation can affect energy dynamics and performance in muscle (4,17,22) and brain (7,12,16,24). In both of these tissues where energy demand and ATP consumption may be temporally dynamic, relatively higher concentrations of creatine and phosphocreatine are found, presumably for its physiological role as a buffer for ATP. Also found in these tissues are mitochondrial and cytosolic creatine kinase isoforms that serve to transfer high-energy phosphate equivalents between the sites of production and consumption. Thus, as suggested in muscle (3, 18), Cr supplementation may enhance both the spatial and chemical buffering of high-energy phosphates, and this effect may contribute to the functional consequences of supplementation. For example, Watanabe et al. (24) used a double-blind placebo-controlled study of short-period creatine supplementation (5 days) to affect cognitive performance, finding that the cognitive decline associated with mental fatigue was reduced with a brief period of creatine supplementation (8 g/day for 5 days). Although these considerations have contributed to the therapeutic use of creatine in neurological diseases in which metabolic and mitochondrial dysfunction is pertinent [e.g

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

Cited by 118 publications

References 41 publications

Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain

Proton magnetic resonance spectroscopic creatine correlates with creatine transporter protein density in rat brain

1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

Cerebral energetic effects of creatine supplementation in humans

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