, , ,

What is MeCbl

  • Discovered in 1962 (1) as a conezyme form of vitamin B12, MeCbl (methylcobalamin) acts as a methyltransferase cofactor.
  • Methyltransferases are B12-dependent enzymes.
  • They play important roles in amino acid metabolism.
  • MeCbl helps covert homocysteine to methionine, important for DNA and protein methylation.

MeCbl uses in therapy
Other than to correct vitamin B12 deficiency, two important functions postulated: reduces circulating homocysteine (non-protein amino acid) and improves/restores nerve function.

  • Too much homocysteine in circulation, hyperhomocysteinaemia, causes vascular problems (e.g. thickening of arteries), coronary artery disease and stroke.
    • MeCbl increases homocysteine consumption and lowers its circulating concentration to the normal range (4-15micromol/liter).
  • Compared to other B12 analogs, MeCbl is most effectively taken up by neurons.
    • In rat studies, MeCbl helped myelin sheath regeneration and restored nerve function in neuropathy (2, 3).
    • Led to the idea that such effective delivery may make MeCbl more effective in human nervous system disorders.

How could MeCbl reduce pain?
No definite answers, only hypothesis. MeCbl may inhibit pain perception by increasing the availability of noradrenaline and 5-hydroxytryptamine.

Human study data for MeCbl therapy

  • Cochrane reviews conducted under the auspices of the Cochrane Collaboration are systematic reviews of randomised controlled clinical trials.
  • Cochrane reviews are considered the best quality reviews of clinical trials.
  • What does a 2008 Cochrane review conclude about MeCbl for treating peripheral nerve pain (4)?
    • Total of 13 trials (n=741) on alcoholic or diabetic neuropathy.
    • Of these 13 trials, only one trial passed muster as being properly conducted and controlled.
    • See details in the following 2 figures.

This Cochrane review (4) excluded majority of MeCbl trials for diabetic neuropathy because they had methodological errors: either they weren’t randomised or they relied on improper diagnosis of neuropathy. Here is my summary of the excluded trials and Cochrane’s reasons for exclusion.

A more recent review (5) examined MeCbl for diabetic, and nonsepcific lower back and neck pain.

  • It concludes that MeCbl Rx reduced diabetic neuropathy in some studies.
  • However, my own analysis shows that this conclusion is incorrect.
  • Rather, studies were either too small, not properly controlled or relied on self-reported symptoms for pain diagnosis.
  • Cross-study comparisons not possible because they used different routes, doses, formulations and durations of Rx.
  • Studies also relied on different methods for pain diagnosis and for assessing symptom reduction/changes.
  • See details in the figure below.

Finally, another meta-analysis of MeCbl Rx for diabetic neuropathy (6) concluded that combination of MeCbl with prostaglandin E1 (PGE1) might work better. Qualified their conclusion by emphasizing that most studies were too small or had methodological problems (weren’t randomised/used improper diagnostic criteria/improper/inadequate outcomes measured). In other words, MeCbl+PGE1 might work for diabetic and other neuropathies but bigger and better designed studies are needed.

Review (5) of MeCbl trials for nonspecific lower back and neck pain suggests

  • Oral MeCbl may not be effective.
  • Injection MeCbl (either into skin or intramuscularly) may more effectively reduce pain compared to oral MeCbl.
  • See details in the figure below.

One study on herpes-associated local neuralgia (nerve pain) (7):

  • Compared skin (subcutaneous) injection versus oral MeCbl.
  • Also compared to injection Lidocaine (a local anesthetic).
  • Injections were 6 times a week/4 weeks.
  • MeCbl injection was 1mg/2ml, Lidocaine injection was 2ml.
  • Oral MeCbl was 0.5mg 3 times a day.
  • Patients were also on antivirals (oral acyclovir or valaciclovir).
  • Greater pain reduction with injection MeCbl.
  • Patients on injection MeCbl took less oral analegsics (gabapentin/pregabalin/amititriptyline/oxycodone/tramadol) for their pain.
  • See details in the figure below.

Another study (8) on intramuscular MeCbl for nonspecific lower back pain:

  • Placebo controlled.
  • Patients got 6 intramuscular injections over 2 weeks (on days 1, 3, 5 of each week).
  • Got either 500micrograms of MeCbl or saline.
  • Patients also took paracetamol as needed, up to a maximum of 3mg/day.
  • Followed-up for 2 months after Rx start.
  • Injection MeCbl worked best to reduce pain.
    • Self-reported pain responses and scores reduced most.
    • Paracetamol use reduced most.
    • OTOH, injection MeCbl also had greater injection site pain and hematoma (local swelling from bleeding).
  • See details in the figure below.

Bottomline on MeCbl for pain reduction.

  • Too few well-designed and controlled studies.
  • Small study sizes are another limitation.
  • More recent, better designed studies with better measured outcomes suggest
    • Injection MeCbl may be more effective compared to oral.
    • Little or no adverse effects from injection itself.
    • Combination regimens with other agents such as prostaglandin E1 (PGE1) might be more effective.


  1. Guest, J. R., et al. “A methyl analogue of cobamide coenzyme in relation to methionine synthesis by bacteria.” (1962): 340-342.
  2. Okada, Kiyoshi, et al. “Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model.” Experimental neurology 222.2 (2010): 191-203.
  3. Yamatsu, K., et al. “[Pharmacological studies on degeneration and regeneration of the peripheral nerves.(2) Effects of methylcobalamin on mitosis of Schwann cells and incorporation of labeled amino acid into protein fractions of crushed sciatic nerve in rats].” Nihon yakurigaku zasshi. Folia pharmacologica Japonica 72.2 (1976): 269-278.
  4. Ang, Cynthia D., et al. “Vitamin B for treating peripheral neuropathy.” The Cochrane Library (2008). Page on update-software.com
  5. Zhang, Ming, et al. “Methylcobalamin: a potential vitamin of pain killer.” Neural plasticity 2013 (2013). Methylcobalamin: A Potential Vitamin of Pain Killer
  6. Deng, Houliang, et al. “Meta-analysis of methylcobalamin alone and in combination with prostaglandin E1 in the treatment of diabetic peripheral neuropathy.” Endocrine 46.3 (2014): 445-454.
  7. Xu, Gang, et al. “A Single‐Center Randomized Controlled Trial of Local Methylcobalamin Injection for Subacute Herpetic Neuralgia.” Pain Medicine 14.6 (2013): 884-894. Page on painmuse.org
  8. Chiu, C. K., et al. “The efficacy and safety of intramuscular injections of methylcobalamin in patients with chronic nonspecific low back pain: a randomised controlled trial.” Singapore medical journal 52.12 (2011): 868-873. Page on apamedcentral.org