Vitamin C and Charcot-Marie-Tooth 1A: Pharmacokinetic considerations

Highlights ► Charcot-Marie-Tooth 1A cannot rely on effective pharmacological treatment. ► Several human trials failed to provide evidence of a therapeutic role of vitamin C. ► Human vitamin C's pharmacokinetics are tightly regulated. ► Ascorbic acid should not be given in excess of its transport system capacity.
Charcot–Marie–Tooth 1A disease (CMT1A) is a disease for which no drug treatments are available. In 2004, it was reported that ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing PMP22, an animal model of human CMT1A, compared with untreated mice. Based on those results, clinical trials were undertaken at different centers worldwide and four of them have been completed, but none of them resulted in significant improvements. Based on the pharmacokinetics of ascorbic acid, we propose that the randomized clinical trial carried out thus far confirmed the tight control of ascorbic acid's absorption and proved its tolerability at one and two years. The pharmacokinetic considerations discussed in this article might largely explain the disappointing results of the recent CMT1A trials.