Important limitations
- Individual claims and source links have not yet completed editorial verification.
- Evidence level, applicable study model, formulation, route and population remain unassigned.
B12 Methylcobalamin
Methylcobalamin (MeCbl) is a biologically active coenzyme form of Vitamin B12.
Reported protocols for B12 Methylcobalamin
What published studies and recent community write-ups report about amounts, timing and course length. 5 clinical, 1 preclinical and 3 community-reported rows, each linked to its source. These are descriptions of what others report, not instructions, and nothing here is medical advice.
| Context | Dose | Frequency | Route | Course | Source |
|---|---|---|---|---|---|
| Clinical5 rows | |||||
| Japanese prescription label (Methycobal Injection 500 mcg/mL), peripheral neuropathyAdults with peripheral neuropathies | 500 mcg (one 1 mL ampoule) | Three times a week | Intramuscular or intravenous | Reviewed after about a monthThe label says not to continue aimlessly beyond one month if there is no effect | National Drug Formulary, Singapore (Eisai label)2026 |
| The Eisai label registered in Singapore gives 500 mcg three times a week, adjusted for age and symptoms, and lists hypersensitivity to any B12 form or to D-mannitol as the only contraindication. The product is light-sensitive and the label asks that ampoules be used immediately after opening. | |||||
| Japanese prescription label, megaloblastic anemia from B12 deficiencyAdults with megaloblastic anemia caused by vitamin B12 deficiency | 500 mcg (one ampoule) | Three times a week for about 2 months, then once every 1-3 months | Intramuscular or intravenous | About 2 months of loading, then open-ended maintenanceMaintenance spaced to one injection every 1-3 months | National Drug Formulary, Singapore (Eisai label)2026 |
| This is the only labelled loading-and-maintenance schedule for methylcobalamin specifically; Western guidelines for B12 replacement are written for cyanocobalamin or hydroxocobalamin and compounding pharmacies extrapolate from them. The label does not address use in people without a documented deficiency. | |||||
| Randomised comparison of two injection schedules in peripheral neuropathy24 adults with peripheral neuropathy at a Kolkata neurology clinic, plus 10 healthy volunteers | 500 mcg three times a week, or 1,500 mcg once a week | Three times weekly versus once weekly | Intramuscular | 2 weeksNot applicable | Korean Journal of Pain (PubMed Central)2018 |
| Serum cobalamin at the end of treatment was higher with 500 mcg three times a week (about 1,892 pg/mL) than with a single weekly 1,500 mcg injection (about 1,439 pg/mL), while two neuropathic pain questionnaires changed similarly in both groups. The study was open-label, lasted only two weeks and was funded by a manufacturer of the 500 mcg ampoule. | |||||
| Phase 3 ultra-high-dose trial in early amyotrophic lateral sclerosis (JETALS)130 Japanese adults with ALS diagnosed within a year of onset and a 1-2 point ALSFRS-R decline over a 12-week run-in | 50 mg | Twice weekly | Intramuscular | 16 weeks double-blind, then open-label continuationNone | JAMA Neurology (PubMed)2022 |
| The ALSFRS-R score fell 1.97 points less on methylcobalamin than on placebo over 16 weeks (a decline of 2.66 versus 4.63 points), with adverse event rates similar between groups. This is 100 times the labelled neuropathy dose, was tested in a narrowly selected population, and an earlier 373-patient trial at 25 and 50 mg had missed its primary endpoint overall. | |||||
| Oral methylcobalamin in metformin-treated diabetic neuropathy90 adults with type 2 diabetes on metformin for at least 4 years, peripheral and autonomic neuropathy, and B12 below 400 pmol/L | 1,000 mcg | Once daily | Oral dispersible tablet | 12 monthsNone | Nutrients (PubMed)2021 |
| Plasma B12 rose from about 232 to 777 pmol/L and sural nerve conduction, vibration perception, sudomotor function, pain scores and quality of life improved against a placebo group that deteriorated on several measures. Cardiovascular autonomic tests did not improve significantly, and all participants had low or borderline B12 at entry. | |||||
| Preclinical1 row | |||||
| Rat demyelination model, continuous infusionMale Wistar rats with lysophosphatidylcholine-induced demyelination of the sciatic nerve | 1 mg/kg per day | Continuous | Subcutaneous osmotic minipump | 1 weekNot applicable | Frontiers in Cellular Neuroscience (PubMed Central)2015 |
| Continuous methylcobalamin promoted Schwann cell differentiation and remyelination in the injured nerve, following the same delivery method the Osaka group used in its 2010 sciatic nerve injury study. These are high, continuous rodent exposures that do not translate to an intermittent human injection schedule. | |||||
| Community-reported3 rows | |||||
| Compounding pharmacy reference regimen | 1,000 mcg | Once weekly for 4-8 weeks, then once every 1-3 months | Subcutaneous | 4-8 week loading phase, then indefinite maintenance where the cause of deficiency is irreversibleMaintenance spacing of 1-3 months | Community resource2026 |
| A compounding pharmacy's 2026 monograph gives 1,000 mcg subcutaneously weekly for 4-8 weeks then every 1-3 months, and states that these methylcobalamin schedules are extrapolated from British haematology guidance for cyanocobalamin and hydroxocobalamin rather than from methylcobalamin dose-finding trials. It lists compounded strengths of 1,000, 5,000 and 10,000 mcg/mL and stresses that the 25-50 mg ALS regimens are not appropriate for B12 replacement. | |||||
| Telehealth loading and maintenance schedule | 1 mg (1,000 mcg) | Daily or every other day for 1-2 weeks, then weekly for 4-8 weeks, then monthly; 1 mg weekly or every two weeks for people without deficiency | Intramuscular or subcutaneous self-injection | About 2-3 months to reach maintenanceMonthly or twice-monthly maintenance | Community resource2026 |
| A telehealth prescriber describes a classic deficiency loading pattern followed by monthly maintenance, and a more conservative weekly or biweekly 1 mg schedule for members without a documented deficiency. It notes that neurological symptoms resolve more slowly than fatigue and may not fully reverse after a long deficiency. | |||||
| Telehealth dosage table by use | 1,000 mcg for deficiency or maintenance; 2,000-5,000 mcg for neuropathy or metabolic support | 1-3 times a week for deficiency; every 1-4 weeks for maintenance; neuropathy doses as directed | Intramuscular or intravenous | Open-endedMaintenance spaced to every 1-4 weeks | Community resource2026 |
| A hormone-clinic telehealth page tabulates 1,000 mcg one to three times weekly for deficiency, higher 2,000-5,000 mcg amounts for neuropathy, and 1,000 mcg every one to four weeks for maintenance, while saying there is no universal dose. These figures are practice patterns from a compounded product, not trial-derived. | |||||
How a course is commonly described
- Weeks 1-2: loadingCommunity-reported
For a documented deficiency, telehealth prescribers describe 1 mg injected daily or every other day for one to two weeks. The Japanese label instead uses 500 mcg three times a week from the start, with no daily phase.
- Weeks 2-8: weeklyCommunity-reported
The compounding reference regimen runs 1,000 mcg subcutaneously once a week for four to eight weeks, which is also the schedule the legacy page for this product described (1 mL once a week). Energy changes are reported by week three to four, while nerve symptoms take months.
- Month 3 onward: maintenanceClinical
The Methycobal label drops to one 500 mcg ampoule every one to three months after about two months of treatment for anemia, and compounding and telehealth schedules likewise thin to monthly or every one to three months. Maintenance is lifelong when the cause of deficiency cannot be fixed.
- Clinical comparisonClinical
The only large randomised methylcobalamin program used 50 mg intramuscularly twice weekly for 16 weeks in early ALS, a dose 50 to 100 times anything used for B12 replacement, and a two-week comparison found 500 mcg three times a week raised serum B12 more than 1,500 mcg once a week. Neither tells you what weekly 1 mg does in a person with normal B12.
- Methylcobalamin dosing for B12 replacement is borrowed from cyanocobalamin and hydroxocobalamin guidance; no dose-finding trial has established that the methyl form needs a different amount or schedule, and head-to-head outcome trials against cyanocobalamin are lacking.
- The Japanese label and the Kolkata comparison both favour 500 mcg three times a week over less frequent larger injections for raising serum B12, while the Western weekly 1 mg pattern is a convenience schedule. B12 is water-soluble and excess is excreted, so the main risks of high doses are injection-site reactions and rare hypersensitivity.
- Methylcobalamin is photosensitive and compounded vials are stored protected from light. In the United States it is available only as a compounded or research product; compounded medications are not evaluated by the FDA for safety, efficacy or quality.
Sources for this section (12)
- METHYCOBAL INJECTION 500 MCG/ML (SIN06349P): product information
- A randomized, open labeled study comparing the serum levels of cobalamin after three doses of 500 mcg vs. a single dose methylcobalamin of 1500 mcg in patients with peripheral neuropathy
- Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial
- Eisai initiates preparation for new drug application based on the results of an investigator-initiated clinical trial of ultrahigh-dose mecobalamin for amyotrophic lateral sclerosis in Japan
- Vitamin B12 Supplementation in Diabetic Neuropathy: A 1-Year, Randomized, Double-Blind, Placebo-Controlled Trial
- Methylcobalamin promotes the differentiation of Schwann cells and remyelination in lysophosphatidylcholine-induced demyelination of the rat sciatic nerve
- Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model
Plus 5 community resources (dosing guides, forum threads and vendor write-ups), reported above but not linked.
Overview
Methylcobalamin is one of the two coenzyme forms of vitamin B12 in human cells, where it serves methionine synthase in the methylation cycle; the other, adenosylcobalamin, works inside mitochondria. It is sold as a prescription injectable in Japan and much of Asia (Eisai's Methycobal, 500 mcg per 1 mL ampoule) for peripheral neuropathy and B12-deficiency anemia, but there is no FDA-approved standalone methylcobalamin product in the United States, where cyanocobalamin and hydroxocobalamin are the approved injectable forms and methylcobalamin is prepared by 503A compounding pharmacies, usually at 1,000 to 5,000 mcg/mL. A Japanese phase 3 trial of 50 mg intramuscularly twice weekly slowed functional decline in early amyotrophic lateral sclerosis, and Eisai moved toward a Japanese approval on that basis. Research vendors sell it as a ready-to-use 20 mL liquid (one reseller lists the vendor version at 2,500 mcg/mL), and the legacy page for this product gave 1 mL once a week.
What researchers are exploring
These themes organize the educational information currently available. Individual claims remain under source review and are not treatment claims.
- 1
Absorption & Transport
Causes of malabsorption include pernicious anemia (autoimmune loss of IF), gastric surgery, achlorhydria, pancreatic insufficiency, and ileal disease.
- 2
FAQs
It’s one of the active forms of Vitamin B12. The other active coenzyme is adenosylcobalamin; cyanocobalamin/hydroxocobalamin are common supplemental/parent forms that convert to active forms in vivo.…
What is known and what still needs verification
Available context is organized without assigning unsupported study models or evidence grades.
- Not graded
Absorption & Transport
Causes of malabsorption include pernicious anemia (autoimmune loss of IF), gastric surgery, achlorhydria, pancreatic insufficiency, and ileal disease.
- Not graded
FAQs
It’s one of the active forms of Vitamin B12. The other active coenzyme is adenosylcobalamin; cyanocobalamin/hydroxocobalamin are common supplemental/parent forms that convert to active forms in vivo. Adenosylcobalamin (AdoCbl), not methylcobalamin.…
Chemistry identifiers
Sequence, synonyms and registry identifiers as recorded in PubChem, the National Library of Medicine's open chemistry database. Formula, mass and CAS number are summarized at the top of the page.
Also listed as
Mecobalamin (INN, JAN), Methycobal (Eisai brand), MeCbl, Methyl-B12, Co-Methylcobalamin, Methylcobalamin, USP Reference Standard, CHEBI:28115, DrugBank DB03614
InChIKey
ZFLASALABLFSNM-WYVZQNDMSA-L
IUPAC name
carbanide;cobalt(3+);[(2R,3S,4R,5S)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] 1-[3-[(1R,2R,3R,5Z,7S,10Z,12S,13S,15Z,17S,18S,19R)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7,12,17-tetrahydro-1H-corrin-24-id-3-yl]propanoylamino]propan-2-yl phosphate
Limitations and unknowns
Sources
1 link carried over from the earlier page, awaiting verification.