A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis

Neurology Clinical Trials Unit (NCTU), Massachusetts General Hospital, 13th Street, Charlestown, MA 02129, USA.
Amyotrophic Lateral Sclerosis (Impact Factor: 2.37). 12/2010; 11(6):508-13. DOI: 10.3109/17482961003797130
Source: PubMed


Creatine monohydrate (creatine) has potential neuroprotective properties and is a commonly used supplement in amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Minimum therapeutic and maximum tolerated dosages of creatine are not yet known, nor is it known what systemic plasma concentrations result from specific dosage regimens. The objectives of this study were to establish steady-state plasma pharmacokinetics of creatine at several dosages, and to evaluate the effects of creatine on brain metabolites using proton magnetic resonance spectroscopy ((1)H-MRS). Six participants with ALS received creatine at three weekly escalating oral dosages (5, 10, and 15 g b.i.d.). Plasma creatine levels and MR spectra were obtained at baseline and with each dosage increase. Mean pre-dose steady-state creatine plasma concentrations were 20.3, 39.3, and 61.5 ug/ml at 5, 10, and 15 g b.i.d., respectively. Creatine spectra increased by 8% (p = 0.06) and glutamate + glutamine signals decreased by 17% (p = 0.039) at higher dosages. There were no safety concerns at any of the dosages. In conclusion, creatine plasma concentrations increased in a dose-dependent manner. Creatine appears to cross the blood-brain barrier, and oral administration of 15 g b.i.d. is associated with increased in vivo brain creatine concentrations and decreased glutamate concentrations.

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Available from: Eva-Maria Ratai, Sep 27, 2014
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    • "Chronic creatine supplementation has been shown to address certain aspects of sleep deprivation linked and other pathophysiology linked cognitive deficits [8,9,11,13,14,19], although very low dose chronic supplementation does not appear to improve function in non-sleep deprived healthy subjects [28]. Sleep deprivation is associated with a reduction in brain stores of phosphocreatine [10] and certainly in some disease states depletion of high energy phosphate stores has been measured, associated with cognitive deficit, and alleviated to some extent by creatine supplementation [13,14,29]. Interestingly, if there is an energy deficit associated with sleep deprivation then it seems logical to contend that repeat trials would be more susceptible than one off tasks. "
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