title: Creatine for neuroprotection in neurodegenerative disease: end of story?
abstract: Creatine (Cr) is a natural compound that plays an important role in cellular energy homeostasis. In addition, it ameliorates oxidative stress, glutamatergic excitotoxicity, and apoptosis in vitro as well as in vivo. Since these pathomechanisms are implicated to play a role in several neurodegenerative diseases, Cr supplementation as a neuroprotective strategy has received a lot of attention with several positive animal studies in models of Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). This has led to a number of randomized clinical trials (RCT) with oral Cr supplementation, with durations up to 5 years. In this paper, we review the evidence and consequences stemming from these trials. In the case of PD, the initial phase II RCT was promising and led to a large and well-designed phase III trial, which, however, turned out to be negative for all outcome measures. None of the RCTs that have examined effects of Cr in ALS patients showed any clinical benefit. In HD, Cr in high doses (up to 30 g/day) was shown to slow down brain atrophy in premanifest Huntingtin mutation carriers. In spite of this, proof is still lacking that Cr can also have beneficial clinical effects in this group of patients, who will go on to develop HD symptoms. Taken together, the use of Cr supplementation has so far proved disappointing in clinical studies with a number of symptomatic neurodegenerative diseases.
authors.affiliation: Department of Neurology with Friedrich-Baur-Institute, University of Munich, Marchioninistr. 15, 81377, Munich, Germany. andreas.bender@med.uni-muenchen.de.|Therapiezentrum Burgau, Kapuzinerstr. 34, 89331, Burgau, Germany. andreas.bender@med.uni-muenchen.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bender
authors.affiliation: Department of Neurology with Friedrich-Baur-Institute, University of Munich, Marchioninistr. 15, 81377, Munich, Germany.|Munich Cluster for Systems Neurology (SyNergy), 80336, Munich, Germany.|DZNE-German Center for Neurodegenerative Diseases, 80336, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
mesh_terms: D000818:Animals; D003401:Creatine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D018696:Neuroprotective Agents; D003401:Creatine
keywords: Creatine; Mitochondrial dysfunction; Neurodegenerative disease; Neuroprotection