Methylcobalamin: clinical application and safety

General Description

Methylcobalamin, a form of vitamin B12, has shown promising therapeutic effects in treating various conditions. In patients with diabetic neuropathy, methylcobalamin supplementation resulted in significant improvements in neurological parameters such as sural nerve conduction velocity, vibration perception threshold, and sudomotor function, as well as pain score and quality of life. It may also be effective in slowing functional decline in patients with amyotrophic lateral sclerosis (ALS) and as an analgesic for patients with low back pain, neuralgia, and other conditions. Methylcobalamin exhibits anti-inflammatory and antiapoptotic activities, providing neuroprotection against cerebral ischemia injuries and the potential to be developed as a novel neuroprotective therapy for stroke patients. Safety trials have shown that it is safe to use with no notable differences in laboratory measurements, electrocardiogram parameters, and vital signs observed between methylcobalamin and placebo groups. Methylcobalamin shows great potential as a safe and effective alternative treatment option for these conditions.

Figure 1. Methylcobalamin Injections

Clinical application

Diabetic Neuropathy

Methylcobalamin is a form of vitamin B12 that has been found to have beneficial effects on patients with diabetic neuropathy. In a study where patients were given 1000 µg/day for one year, the normalization of B12 levels was associated with improvements in various neurological parameters such as sural nerve conduction velocity, vibration perception threshold, and sudomotor function, as well as pain score and quality of life. However, it did not significantly improve cardiovascular autonomic reflex tests and Michigan Neuropathy Screening Instrument Examination. The results suggest that methylcobalamin supplementation may be a useful treatment option for patients with diabetic neuropathy who have lower levels of B12. ¹

Amyotrophic lateral sclerosis

Methylcobalamin has been found to be a promising agent for the treatment of amyotrophic lateral sclerosis (ALS). This double-blind, randomized phase 3 clinical trial evaluated the efficacy and safety of ultrahigh-dose methylcobalamin in patients with ALS who were enrolled within one year of onset. Patients received intramuscular injections of methylcobalamin or placebo twice weekly for 16 weeks. The primary endpoint was the change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale total score from baseline to week 16. A total of 129 patients were eligible for the full analysis set and the results showed that ultrahigh-dose methylcobalamin was efficacious in slowing functional decline in patients with early-stage ALS and with moderate progression rate. It was also found to be safe to use during the 16-week treatment period. ²

Pain killer

Methylcobalamin has been used clinically to treat various nutritional deficiencies and diseases such as Alzheimer's disease and rheumatoid arthritis. As an adjuvant, it acts as a neuroprotective agent by promoting nerve regeneration and antagonizing glutamate-induced neurotoxicity. In recent years, there is growing evidence from both experimental and clinical studies suggesting potential analgesic effects of methylcobalamin. For example, it has been shown to relieve pain behavior in patients with diabetic neuropathy, low back pain, and neuralgia. Methylcobalamin improves nerve conduction, promotes nerve regeneration, and inhibits ectopic spontaneous discharges of injured primary sensory neurons. This article provides a review of the analgesic effects and mechanisms of methylcobalamin. ³

Cerebral stroke

Methylcobalamin exhibits anti-inflammatory and antiapoptotic activities in various diseases. In vitro and in vivo models were used to simulate cerebral ischemic injury, and various measurements were taken to determine its effect. Results showed that methylcobalamin improved cell viability, reduced lactate dehydrogenase release, attenuated inflammatory cytokine expression, decreased the apoptotic proportion, and enhanced autophagy flux after  oxygen and glucose deprivation/reperfusion treatment. In addition, it increased levels of Bcl-2 and Beclin1 expression as well as the LC3 II/I ratio while decreasing levels of Bax and cleaved caspase-3. In vivo, methylcobalamin significantly reduced cerebral infarction volume and neurological deficits in rats. Furthermore, it activated the ERK1/2 pathway, which was shown to be a significant factor in its protective effects. Overall, methylcobalamin can provide neuroprotection against cerebral ischemia injuries and may have the potential to be developed as a novel neuroprotective therapy for stroke patients. ⁴

Safety

In a safety trial of ultrahigh-dose methylcobalamin, adverse events were reported in both the methylcobalamin and placebo groups with a similar incidence. Serious adverse events were experienced by three patients, but they were not causally related to the investigational drugs. The details of adverse events reported by at least 5% of patients in either group are found, and no notable differences in changes of laboratory measurements, electrocardiogram parameters, and vital signs were observed between the two groups. No adverse events led to discontinuation of treatment. ²

Reference

1. Didangelos T, Karlafti E, Kotzakioulafi E, et al. Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 2021, 13(2):395.

2. Oki R, Izumi Y, Fujita K, et al. Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol, 2022, 79(6):575-583.

3. Zhang M, Han W, Hu S, Xu H. Methylcobalamin: a potential vitamin of pain killer. Neural Plast, 2013, 2013:424651.

4. Li Y, Zheng J, Zhu Y, Qu Y, Suo R, Zhu Y. Neuroprotective effects of methylcobalamin in cerebral ischemia/reperfusion injury through activation of the ERK1/2 signaling pathway. Int Immunopharmacol, 2021, 99:108040.