Vitamin C for Charcot-Marie-Tooth Disease: Not Recommended
High-quality evidence from multiple randomized controlled trials demonstrates that ascorbic acid (vitamin C) does not improve the course of Charcot-Marie-Tooth disease type 1A (CMT1A) in adults or children and should not be used as treatment. 1
Evidence Against Vitamin C Treatment
Adult Studies Show No Benefit
Five randomized controlled trials involving 622 adults with CMT1A found no improvement in the CMT neuropathy score (0-36 scale) at 12 months (mean difference -0.37) or 24 months (mean difference -0.21) with ascorbic acid doses of 1-4 grams daily compared to placebo. 1
While one meta-analysis showed a statistically significant improvement in the nine-hole peg test (1.16 seconds faster), this difference is clinically insignificant and does not translate to meaningful functional improvement. 1
Meta-analyses of other secondary outcome parameters including muscle strength, walking speed, quality of life measures, and electrophysiology showed no relevant benefit of ascorbic acid treatment. 1
Pediatric Studies Also Negative
- One trial of 80 children with CMT1A receiving ascorbic acid versus placebo showed no clinical benefit of treatment. 1
Important Caveat About Vitamin Combinations
- If ascorbic acid is being considered despite the negative evidence, vitamins A and E should NOT be combined with it, as they counteract ascorbic acid's theoretical mechanism of action on PMP22 expression in Schwann cells. 2
Why the Initial Promise Didn't Pan Out
Early animal studies in CMT1A transgenic mice showed improvement with high-dose ascorbic acid, which led to human trials. 3, 4
However, the translation from mouse models to human disease failed, demonstrating the limitations of animal models in predicting human therapeutic response. 1
The trials were well-designed with low risk of bias, making the negative results highly reliable. 1
Current Management Approach
Since no pharmacological treatment is effective for CMT, focus on:
Rehabilitation therapy and physical therapy to maintain function and mobility 4
Orthopedic surgical procedures for skeletal deformities when indicated 4
Pain management strategies for neuropathic pain symptoms 3
Avoiding medications that may exacerbate peripheral neuropathy 3
Critical Clinical Pitfall
Do not recommend vitamin C supplementation to patients with CMT1A based on outdated information or animal studies. The high-quality human trial evidence is definitive that it does not work, and recommending ineffective treatments wastes resources and may give false hope. 1