[Clinical trials of ultra-high-dose methylcobalamin in ALS]

Brain Nerve. 2007 Oct;59(10):1141-7.
[Article in Japanese]


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting both upper and lower motor neurons. Weakness may begin in the legs, hands, proximal arms, or pharynx. The course is relentless and progressive without remissions, relapses, or even stable plateaus. There is no effective drug therapy for ALS, although riluzole has been shown to prolong life in sufferers, without tracheostomy. A vitamin B12 analog, methylcobalamin, has a protective effect on cultured cortical neurons against glutamate-induced cytotoxicity. We have shown the ultra-high-dose methylcobalamin (25 mg/day i.m.) slows down the progressive reduction of the CMAP (compound muscle action potential) amplitudes in ALS in the short term (4 weeks). The latencies of SSR (sympathetic skin response) were shorter after treatment (50 mg/day i.v., 2 weeks). In the long-term effect of methylcobalamin (50 mg/day i.m., twice a week), the survival time (or the period to become respirator-bound) was significantly longer in the treated group than in the untreated. Larger-scale randomized double blind trial was started in Japan in order to evaluate the long-term efficacy and the safety of ultra-high-dose methylcobalamin for sporadic or familial cases of ALS.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / etiology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Disease Progression
  • Double-Blind Method
  • Glutamic Acid / toxicity
  • Humans
  • Pulse Therapy, Drug
  • Randomized Controlled Trials as Topic
  • Rats
  • Time Factors
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / analogs & derivatives*


  • Glutamic Acid
  • mecobalamin
  • Vitamin B 12