title: Ascorbic acid for the treatment of Charcot-Marie-Tooth disease.
abstract: BACKGROUND
  Charcot-Marie-Tooth disease (CMT) comprises a large group of different forms of hereditary motor and sensory neuropathy. The molecular basis of several CMT subtypes has been clarified during the last 20 years. Since slowly progressive muscle weakness and sensory disturbances are the main features of these syndromes, treatments aim to improve motor impairment and sensory disturbances to improve abilities. Pharmacological treatment trials in CMT are rare. This review was derived from a Cochrane review, Treatment for Charcot Marie Tooth disease, which will be updated via this review and a forthcoming title, Treatments other than ascorbic acid for Charcot-Marie-Tooth disease.
  
  
  OBJECTIVE
  To assess the effects of ascorbic acid (vitamin C) treatment for CMT.
  
  
  METHODS
  On 21 September 2015, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS for randomised controlled trials (RCTs) of treatment for CMT. We also checked clinical trials registries for ongoing studies.
  
  
  METHODS
  We included RCTs and quasi-RCTs of any ascorbic acid treatment for people with CMT. Where a study aimed to evaluate the treatment of general neuromuscular symptoms of people with peripheral neuropathy including CMT, we included the study if we were able to identify the effect of treatment in the CMT group. We did not include observational studies or case reports of ascorbic acid treatment in people with CMT.
  
  
  METHODS
  Two review authors (BG and JB) independently extracted the data and assessed study quality.
  
  
  RESULTS
  Six RCTs compared the effect of oral ascorbic acid (1 to 4 grams) and placebo treatment in CMT1A. In five trials involving adults with CMT1A, a total of 622 participants received ascorbic acid or placebo. Trials were largely at low risk of bias. There is high-quality evidence that ascorbic acid does not improve the course of CMT1A in adults as measured by the CMT neuropathy score (0 to 36 scale) at 12 months (mean difference (MD) -0.37; 95% confidence intervals (CI) -0.83 to 0.09; five studies; N = 533), or at 24 months (MD -0.21; 95% CI -0.81 to 0.39; three studies; N = 388). Ascorbic acid treatment showed a positive effect on the nine-hole peg test versus placebo (MD -1.16 seconds; 95% CI -1.96 to -0.37), but the clinical significance of this result is probably small. Meta-analyses of other secondary outcome parameters showed no relevant benefit of ascorbic acid. In one trial, 80 children with CMT1A received ascorbic acid or placebo. The trial showed no clinical benefit of ascorbic acid treatment. Adverse effects did not differ in their nature or abundance between ascorbic acid and placebo.
  
  
  CONCLUSIONS
  High-quality evidence indicates that ascorbic acid does not improve the course of CMT1A in adults in terms of the outcome parameters used. According to low-quality evidence, ascorbic acid does not improve the course of CMT1A in children. However, CMT1A is slowly progressive and the outcome parameters show only small change over time. Longer study durations should be considered, and outcome parameters more sensitive to change over time should be designed and validated for future studies.
authors.affiliation: Department of Neurology, University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, Germany, 52074.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Gess
authors.forename: Jonathan
authors.initials: J
authors.lastname: Baets
authors.forename: Peter
authors.initials: P
authors.lastname: De Jonghe
authors.forename: Mary M
authors.initials: MM
authors.lastname: Reilly
authors.forename: Davide
authors.initials: D
authors.lastname: Pareyson
authors.forename: Peter
authors.initials: P
authors.lastname: Young
mesh_terms: D000328:Adult; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002607:Charcot-Marie-Tooth Disease / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D001205:Ascorbic Acid