title: Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study.
abstract: BACKGROUND
  In a recent study, we showed that administration of low-dose creatine (Cr) (60 mg/kg daily) improved work capacity in patients with McArdle disease.
  
  
  OBJECTIVE
  To assess the efficacy of high-dose Cr therapy in McArdle disease.
  
  
  METHODS
  Randomized, double-blind, placebo-controlled crossover study.
  
  
  METHODS
  Nineteen patients with McArdle disease.
  
  
  METHODS
  Treatment with Cr, 150 mg/kg daily. Each treatment phase with Cr or placebo lasted 5 weeks.
  
  
  METHODS
  The patient's daily rating of symptoms of exercise intolerance. At the end of each treatment phase, serum creatine and serum creatine kinase levels, phosphorus 31 magnetic resonance spectroscopy, and surface electromyograms were assessed.
  
  
  RESULTS
  Clinical end points revealed increases in the intensity of exercise-induced pain in working muscles (mean treatment-induced difference [d], 0.30 in log(score); 95% confidence interval [CI], 0.05-0.55; P =.02), the limitation of daily activities (d, 0.59; 95% CI, 0.22-0.97;P =.005), and body mass index (d, 0.33 kg/m2, 95% CI, 0.10-0.56 kg/m2; P =.008) with Cr use. Surface electromyograms revealed a smaller increase in the electromyographic amplitude over time during muscle contraction with Cr use (d, -13.52%/min; 95% CI, -23.71%/min to -3.34%/min; P =.01). There were no significant changes in phosphorus 31 magnetic resonance spectroscopy variables.
  
  
  CONCLUSIONS
  Administration of high-dose Cr worsened the main clinical symptoms of exercise intolerance in McArdle disease. These neurologic adverse effects represent a major dose-limiting factor in Cr therapy for McArdle disease. Taken together with results of a previous study, the indication for symptomatic therapy with Cr needs to be clarified. An effective Cr dosage without adverse effects may be between 60 and 150 mg/kg daily.
authors.affiliation: Department of Neurology, Ruhr-University Bochum, Kliniken Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. matthias.vorgerd@ruhr-uni-bochum.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Vorgerd
authors.forename: Jochen
authors.initials: J
authors.lastname: Zange
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kley
authors.forename: T
authors.initials: T
authors.lastname: Grehl
authors.forename: Anika
authors.initials: A
authors.lastname: Hüsing
authors.forename: Matthias
authors.initials: M
authors.lastname: Jäger
authors.forename: Klaus
authors.initials: K
authors.lastname: Müller
authors.forename: Rolf
authors.initials: R
authors.lastname: Schröder
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Mortier
authors.forename: Klaus
authors.initials: K
authors.lastname: Fabian
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Malin
authors.forename: Alwin
authors.initials: A
authors.lastname: Luttmann
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003401:Creatine / Q000008:administration & dosage* / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D015444:Exercise; D005260:Female; D006012:Glycogen Storage Disease Type V / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018763:Muscle Fatigue / Q000187:drug effects; D010759:Phosphorus Isotopes; D017211:Treatment Failure
chemical_list: D010759:Phosphorus Isotopes; D003401:Creatine