Vitamin B12 Dosage for Confirmed Deficiency
For adults with confirmed Vitamin B12 deficiency, the recommended treatment is hydroxocobalamin 1000 mcg (1 mg) intramuscularly, with the dosing frequency determined by the presence or absence of neurological symptoms. 1, 2, 3
Treatment Protocol Based on Neurological Involvement
With Neurological Symptoms (including glossitis, peripheral neuropathy, cognitive changes, or paresthesias)
Aggressive initial treatment is essential to prevent irreversible nerve damage: 1, 2, 3
- Loading phase: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further neurological improvement occurs 1, 2, 3
- Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2 months for life 1, 2, 3
- Some patients may require monthly dosing (1000 mcg IM monthly) to meet metabolic requirements, particularly those with persistent symptoms despite standard dosing 2, 4
Without Neurological Symptoms
Standard loading followed by maintenance therapy: 1, 2, 3
- Loading phase: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2, 3
- Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 2, 3
Oral Alternative for Most Patients
Oral vitamin B12 is equally effective as intramuscular administration for most patients, including those with malabsorption, and costs significantly less: 1, 5, 6
- Dose: 1000-2000 mcg daily orally 1, 5, 6
- Duration: Continue until levels normalize, then maintenance therapy 1
- This approach works even in pernicious anemia because high oral doses allow passive absorption (1-2% of dose) independent of intrinsic factor 5, 6
Intramuscular administration should be prioritized if: 1, 5
- Severe neurologic manifestations are present 1
- Malabsorption is confirmed and rapid correction is needed 1
- Oral therapy fails to normalize levels 1
Special Population Dosing
Post-Bariatric Surgery
Ileal Resection >20 cm or Crohn's Disease with Ileal Involvement
- Prophylactic treatment: 1000 mcg IM monthly for life, even without documented deficiency 1, 2, 3
- Resection <20 cm typically does not cause deficiency 1
Renal Dysfunction
- Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 2, 3
- Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1, 2
Monitoring Strategy
First year monitoring schedule: 2, 3
- Recheck serum B12, complete blood count, and homocysteine at 3,6, and 12 months 2, 3
- Target homocysteine <10 μmol/L for optimal outcomes 1, 2, 3
- After stabilization, transition to annual monitoring 2, 3
What to measure at follow-up: 2
- Serum B12 levels as primary marker 2
- Complete blood count to evaluate resolution of megaloblastic anemia 2
- Methylmalonic acid (MMA) if B12 levels remain borderline or symptoms persist (target <271 nmol/L) 2
- Homocysteine as additional functional marker 2
Critical Pitfalls to Avoid
Never administer folic acid before ensuring adequate B12 treatment – folic acid can mask the anemia while allowing irreversible neurological damage (subacute combined degeneration) to progress 1, 2, 3, 5
Do not stop monitoring after one normal result – patients with malabsorption or dietary insufficiency often require ongoing supplementation and can relapse 2
Do not rely solely on serum B12 to assess treatment adequacy – up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by MMA 1
Do not discontinue B12 supplementation even if levels normalize – patients with malabsorption conditions require lifelong therapy 2
Formulation Preference
Hydroxocobalamin is preferred over cyanocobalamin due to longer tissue retention and superior safety profile, particularly in renal dysfunction 1, 2, 3
Injection sites: Deltoid or vastus lateralis preferred; avoid buttock due to sciatic nerve injury risk 2