Creatine supplementation lowers brain glutamate levels in Huntington’s disease

  title={Creatine supplementation lowers brain glutamate levels in Huntington’s disease},
  author={Andreas Bender and Dorothee P. Auer and Thomas Merl and Ralf Reilmann and P. Saemann and Alexander Yassouridis and J Bender and Adolf Weindl and Matthias Dose and Thomas Gasser and Thomas Klopstock},
  journal={Journal of Neurology},
AbstractThere is evidence from in vitro and animal experiments that oral creatine (Cr) supplementation might prevent or slow down neurodegeneration in Huntington’s disease (HD). However, this neuroprotective effect could not be replicated in clinical trials, possibly owing to treatment periods being too short to impact on clinical endpoints. We used proton magnetic resonance spectroscopy (1H-MRS) as a surrogate marker to evaluate the effect of Cr supplementation on brain metabolite levels in HD… 

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Magnetic resonance spectroscopy biomarkers in premanifest and early Huntington disease

It is concluded that putaminal MRS measurements of NAA and mI are promising potential biomarkers of HD onset and progression and resolve disagreement in the literature about the role of MRS as an HD biomarker.

Brain metabolite alterations and cognitive dysfunction in early Huntington's disease

  • P. UnschuldR. Edden C. Ross
  • Medicine, Biology
    Movement disorders : official journal of the Movement Disorder Society
  • 2012
N‐acetylaspartate and glutamate magnetic resonance spectroscopy signals of the posterior cingulate cortex region may serve as potential biomarkers of disease progression or treatment outcome in HD and other neurodegenerative disorders with early cognitive dysfunction, when structural brain changes are still minor.

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Three months of creatine administration failed to detect any efficacy in treating symptoms of schizophrenia, but further research is suggested.

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Investigating the effect of oral creatine supplementation on aging in 162 aged wild-type C57Bl/6J mice showed that creatine improves health and longevity in mice, and may be a promising food supplement to promote healthy human aging.

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The findings of MRS of the brain suggest disordered striatal glutamate metabolism and may support the theory of glutamate excitotoxicity in HD.

Effect of Creatine Supplementation on Metabolite Levels in ALS Motor Cortices

The effects of a 1-month oral administration of creatine on (1)H NMR-visible metabolites in the motor cortices of 15 controls and 15 patients with sporadic ALS, most of whom had mitochondrial pathology in skeletal muscle can be explained by a deficiency of enzymes of mitochondrial respiratory chain in the ALS motor cortex.

Neuroprotective Effects of Creatine in a Transgenic Mouse Model of Huntington's Disease

Nuclear magnetic resonance spectroscopy showed that creatine supplementation significantly increased brain creatine concentrations and delayed decreases in N-acetylaspartate concentrations, supporting a role of metabolic dysfunction in a transgenic mouse model of HD and suggesting a novel therapeutic strategy to slow the pathological process.

Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy.

Lactate concentrations were increased in the occipital cortex of symptomatic HD patients when compared with normal controls, and the lactate level correlated with duration of illness, consistent with a possible defect in energy metabolism in HD.

Creatine therapy for Huntington’s disease: Clinical and MRS findings in a 1-year pilot study

Correlation of the muscle bioenergetic defect and CAG repeat length provides a link between this biochemical abnormality and the HD molecular defect, supporting the role of calcium-mediated excitotoxicity and mitochondrial dysfunction.

Creatine supplementation in Huntington’s disease

One year of Cr intake, at a rate that can improve muscle functional capacity in healthy subjects and patients with neuromuscular disease (5 g/day), did not improve functional, neuromUScular, and cognitive status in patients with stage I to III HD.

Creatine Increases Survival and Delays Motor Symptoms in a Transgenic Animal Model of Huntington's Disease

The effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss.

Evidence for irnnairment of energy metabofism in vivo in Huntington's disease using localized 1H NMR spectroscopy

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1H NMR spectroscopy studies of Huntington's disease

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Oral supplementation with creatine or cyclocreatine results in neuroprotective effects in vivo, which may represent a novel therapeutic strategy for HD and other neurodegenerative diseases.