A phase I, pharmacokinetic, dosage escalation study of creatine monohydrate in subjects with amyotrophic lateral sclerosis.
Study Goal
The researchers aimed to determine the effects of creatine supplementation on brain metabolites, specifically glutamate, in ALS patients.
Results Summary
Higher dosages of creatine were associated with a 17% decrease in glutamate + glutamine signals in the brain, suggesting a potential modulatory effect on glutamate levels. No safety concerns were reported at any dosage.
Population
Six participants with amyotrophic lateral sclerosis (ALS).
Effective Dosage
5, 10, and 15 g twice daily (b.i.d.).
Duration
Three weeks (escalating dosages weekly).
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
creatine monohydrate (creatine) | neutral | neuroprotective properties | - | - | has potential | #1 |
creatine | neutral | amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders | - | - | is a commonly used supplement | #2 |
creatine | increase | plasma creatine levels | Six participants with ALS | 20.3, 39.3, and 61.5 ug/ml at 5, 10, and 15 g b.i.d., respectively | increased | #3 |
creatine | increase | creatine spectra | Six participants with ALS | 8% | increased | #4 |
creatine | decrease | glutamate + glutamine signals | Six participants with ALS | 17% | decreased | #5 |
creatine | no change | safety | Six participants with ALS | - | no safety concerns | #6 |
creatine | increase | plasma concentrations | Six participants with ALS | - | increased in a dose-dependent manner | #7 |
creatine | neutral | the blood-brain barrier | - | - | appears to cross | #8 |
oral administration of 15 g b.i.d. creatine | increase | in vivo brain creatine concentrations | - | - | associated with increased | #9 |
oral administration of 15 g b.i.d. creatine | decrease | glutamate concentrations | - | - | associated with decreased | #10 |
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.