Bender · Amino acids 2016 · narrative review · n=?

Creatine for neuroprotection in neurodegenerative disease: end of story?

Cited 97 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing preclinical mechanisms and clinical trials

PubMed 26748651 · doi:10.1007/s00726-015-2165-0 · record verified 2026-08-29

What was done

The authors reviewed preclinical evidence and human randomized clinical trials (lasting up to 5 years) evaluating oral creatine supplementation for neuroprotection in Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS).

What was found

No quantitative effect estimates or participant counts are provided in the abstract. In PD, a promising phase II randomized controlled trial was followed by a large phase III trial that proved negative across all outcome measures. In ALS, none of the randomized trials demonstrated clinical benefit. In HD, high-dose creatine (up to 30 g/day) slowed brain atrophy in premanifest mutation carriers, but evidence of functional clinical benefit is still lacking.

Why it matters

Despite strong mechanistic rationale and positive animal studies, clinical trial evidence indicates that creatine supplementation does not meaningfully alter disease progression in major symptomatic neurodegenerative diseases.

Limits

The abstract describes a narrative review rather than a systematic review with meta-analysis. It does not provide sample sizes, quantitative outcomes, or statistical metrics, and findings in Huntington's disease are limited to surrogate imaging markers in premanifest individuals rather than established clinical endpoints.

Cited by