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The CREST-E study of creatine for Huntington disease: A randomized controlled trial
Steven M Hersch1, Giovanni Schifitto2, David Oakes2
1From the Department of Neurology (S.M.H., H.D.R.), Massachusetts General Hospital and Harvard Medical School, Boston; Departments of Neurology and Biostatistics (G.S., D.O.), University of Rochester Medical Center, NY; Department of Pediatrics (A.-L.B.), Medical University of South Carolina, Charleston; and NIH (C.M.M., R.N.), National Center for Complementary and Integrative Health, Bethesda, MD. hersch@helix.mgh.harvard.edu.
Insights
Creatine supplementation did not slow functional decline in early Huntington disease (HD). This study found no benefit and increased gastrointestinal issues in patients taking creatine. Further research may explore sex-based differences.
Area of Science:
- Neuroscience
- Clinical Neurology
- Pharmacology
Background:
- Huntington disease (HD) is a progressive neurodegenerative disorder.
- Early symptomatic stages of HD involve functional decline.
- Creatine is investigated for potential neuroprotective effects.
Purpose of the Study:
- To evaluate if creatine monohydrate administration can slow functional decline in adults with early Huntington disease.
- To assess the safety and tolerability of creatine in HD patients.
Main Methods:
- A multicenter, randomized, double-blind, placebo-controlled trial involving 553 participants with early HD (stages I and II).
- Participants received up to 40g of creatine monohydrate daily for up to 48 months.
- Primary outcome was the rate of change in Total Functional Capacity (TFC); secondary outcomes included clinical scores, tolerability, and quality of life.
Main Results:
- The study was halted early for futility. Creatine did not slow the rate of functional decline compared to placebo (0.82 vs 0.70 points/year decline in TFC).
- Gastrointestinal adverse events were more frequent in the creatine group. Serious adverse events, including deaths, were more frequent in the placebo group.
- Subgroup analyses indicated potential sex-based differences in response to creatine.
Conclusions:
- Creatine monohydrate is not beneficial for delaying functional decline in individuals with early manifest Huntington disease.
- The findings do not support the use of creatine for this indication.
- Class II evidence suggests creatine is not beneficial for slowing functional decline in early symptomatic HD.
Objective:
To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease.
Methods:
We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies.
Results:
At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits -0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment.
Conclusions:
Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD.
Clinicaltrialsgov Identifier:
NCT00712426.
Classification Of Evidence:
This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline.
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