Safety and Efficacy of Intravenous Ultra-high Dose Methylcobalamin Treatment for Peripheral Neuropathy: A Phase I/II Open Label Clinical Trial

Abstract

Objective No clinically effective treatment for promoting peripheral axonal regeneration has yet been established. Several experimental studies in vitro and in vivo have shown that a high dose of methylcobalamin (MeCbl), an analogue of vitamin B12, promotes axonal growth in peripheral nerve injury. We herein assessed the safety and efficacy of an ultra-high dose MeCbl treatment for patients with peripheral neuropathy and chronic axonal degeneration. Methods Fourteen patients with immune-mediated or hereditary neuropathy in the chronic progressive or stable phase were enrolled. MeCbl, 25 mg/day for 10 days followed by monthly 25 mg for 5 months, was intravenously administered. The patients were evaluated before and 1 year following treatment. The primary endpoints were safety and improvement in the Medical Research Council (MRC) sum score in at least two muscles of the 20 muscles. This trial is registered with the University Hospital Medical Information Network (UMIN) Center in Japan under the ID: UMIN000009359. Results There were no adverse effects in twelve of the patients, whereas treatment was discontinued in two patients who had seborrheic dermatitis at 3 months and respiratory tract infection at 2 months, respectively. Therefore, twelve patients were evaluated for the primary outcomes; the MRC sum score was improved in seven of the patients and unchanged or worsened in the remaining five patients. Conclusion Intravenous ultra-high dose MeCbl treatment is a safe and potentially efficacious therapy for patients with peripheral neuropathy and chronic axonal degeneration.

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

“…An accumulation and an excess of absorption are highly unlikely, in fact Cbl is a water-soluble molecule that requires a specific transport system which is easily saturated [19,149]. Its safety has been demonstrated through the use of an ultra-high parenteral dose of 25 mg daily for 10 days followed by 25 mg monthly for five months [150]. Cn-Cbl is the most common form used in the literature and in supplement formulation.…”

An In Vitro Model of Gastric Inflammation and Treatment with Cobalamin

“…These data confirm the lack of gastric epithelial cell toxicity of methylcobalamin which was used up to values five times greater than the upper limit of cobalamin (5000 pg/ml). This high concentration and lack of toxicity are supported by clinical trials in Japan, where patients with peripheral neuropathy were treated with 25 mg/day IV methylcobalamin [20] over 10 days for five months. This is 2.5 × 10 10 times greater than the recommended dose for patients with PA who are given 1 mg/ml every 8–12 weeks.…”

Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis

“…In clinical practice, intravenous administration of methylcobalamin (0.5 mg/day) has long been performed in patients with vitamin B12 deficiency. In addition, intravenous administration of ultra-high dose methylcobalamin improved motor deficits in patients with peripheral neuropathy [1]. High-dose methylcobalamin was also reported to protect cortical neurons against glutamate toxicity [24].…”

“…On the other hand, ultra-high dose (25 mg/day i.v.) has been shown to improve muscle weakness in patients with peripheral neuropathy [1]. Methylcobalamin promotes nerve regeneration in rat peripheral neuropathy or injury models [2][3][4][5].…”