title: Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study.
abstract: The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.
authors.affiliation: Department of Neurology, University of Bonn, Bonn, Germany. cornelia.kornblum@ukb.uni-bonn.de
authors.forename: C
authors.initials: C
authors.lastname: Kornblum
authors.forename: R
authors.initials: R
authors.lastname: Schröder
authors.forename: K
authors.initials: K
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Vorgerd
authors.forename: J
authors.initials: J
authors.lastname: Eggers
authors.forename: M
authors.initials: M
authors.lastname: Bogdanow
authors.forename: A
authors.initials: A
authors.lastname: Papassotiropoulos
authors.forename: K
authors.initials: K
authors.lastname: Fabian
authors.forename: T
authors.initials: T
authors.lastname: Klockgether
authors.forename: J
authors.initials: J
authors.lastname: Zange
mesh_terms: D000328:Adult; D016001:Confidence Intervals; D003401:Creatine / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004272:DNA, Mitochondrial / Q000235:genetics; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010759:Phosphorus Isotopes / Q000627:therapeutic use; D010919:Placebos; D017384:Sequence Deletion / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D004272:DNA, Mitochondrial; D010759:Phosphorus Isotopes; D010919:Placebos; D003401:Creatine