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

Abstract

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.

• Authors: Nazem Atassi, Eva-Maria Ratai, David J Greenblatt, Darlene Pulley, Yanli Zhao, Jeffery Bombardier, Stuart Wallace, Joanna Eckenrode, Merit Cudkowicz, Allitia Dibernardo
• Journal: Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases (Amyotroph Lateral Scler) Vol. 11 Issue 6 Pg. 508-13 (Dec 2010) ISSN: 1471-180X [Electronic] England
• PMID: 20698808 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• Glutamine
• Glutamic Acid
• Creatine

Topics

• Adult
• Aged
• Amyotrophic Lateral Sclerosis (drug therapy)
• Brain (anatomy & histology, metabolism)
• Creatine (blood, pharmacokinetics, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Glutamic Acid (metabolism)
• Glutamine (metabolism)
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Neuroprotective Agents (therapeutic use)