CMT 1A: Poor tolerability of high dose ascorbic acid in a population of genetica

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Acta Neurol Scand. 2008 Dec 8. [Epub ahead of print]

Poor tolerability of high dose ascorbic acid in a population of

genetically confirmed adult Charcot-Marie-Tooth 1A patients.

Toth C.

Department of Clinical Neurosciences, University of Calgary, Calgary,

AB, Canada.

Background - Preclinical studies have suggested that ascorbic acid

(AA) treatment in a mouse model of Charcot-Marie-Tooth type 1A

(CMT1A) improves motor function and prolongs lifespan.

Aims - I sought to determine the safety and tolerability of AA in

adult patients with CMT1A.

Methods - An open-label cohort-controlled 2-year pilot study was used

to evaluate the tolerability of 5 g of AA daily. Secondary

measurements consisted of clinical and electrophysiological

measurements at 0, 12, and 24 months in CMT1A patients.

Results - Twelve CMT1A patients received AA and 10 CMT1A patients

formed a cohort group followed in identical manner. Five (42%)

patients tolerated this dose of AA for the entire 2-year span, with

six patients (50%) developing intolerable gastrointestinal side

effects. No significant differences in clinical, disability, or

electrophysiological measurements occurred between baseline and final

follow-up in patients receiving AA when compared with cohorts.

Conclusions - High dose AA was not well tolerated in all adult CMT1A

patients who may be susceptible to gastrointestinal adverse effects

of AA. Studies with greater powers to detect efficacy will be

required to test the validity of AA as a therapy in CMT1A patients.

Doses lower than 5 g of AA daily may be required for maintenance of

tolerability in the CMT1A population.