Vitamin B12 Dosage for Deficiency Treatment
For adults with vitamin B12 deficiency due to malabsorption, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement if neurological symptoms are present, then maintain with 1 mg intramuscularly every 2 months for life; if no neurological involvement, give 1 mg intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months lifelong. 1, 2
Treatment Protocol Based on Neurological Involvement
With Neurological Symptoms (Paresthesias, Gait Disturbance, Cognitive Changes)
- Loading phase: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further clinical improvement occurs 1, 2
- Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2 months for life 1, 2
- Never delay treatment in these patients, as neurological damage can become irreversible 1
Without Neurological Symptoms
- Loading phase: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2
- Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 2
Oral Alternative for Dietary Deficiency
For patients with dietary insufficiency (not malabsorption), oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy. 1, 3, 4
- Oral therapy is effective even in most malabsorption cases, though intramuscular remains preferred for severe deficiency 1, 4
- FDA-approved dosing for oral supplementation is 1000 mcg (1 tablet) daily, preferably with a meal 3
- Oral therapy requires 1-2 mg daily to correct anemia and neurologic symptoms 4
Special Population Dosing
Post-Bariatric Surgery Patients
- Option 1: 1 mg intramuscularly every 3 months indefinitely 1
- Option 2: 1000-2000 mcg orally daily indefinitely 1, 4
- Check B12 levels every 3 months throughout pregnancy if planning conception 1
Ileal Resection >20 cm or Crohn's Disease
- Prophylactic therapy: 1000 mcg intramuscularly monthly for life, even without documented deficiency 1, 5
- Screen yearly for B12 deficiency 1, 5
Patients with Renal Dysfunction
- Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 2
- Cyanocobalamin requires renal clearance of cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1
Monitoring Strategy
First Year Protocol
- Check serum B12, homocysteine, and methylmalonic acid at 3 months, 6 months, and 12 months after initiating treatment 1, 2
- Target homocysteine <10 μmol/L for optimal outcomes 1, 2
- Assess complete blood count to evaluate resolution of megaloblastic anemia 1
Long-Term Monitoring
- After stabilization, monitor annually with serum B12 and homocysteine 1, 2
- Do not stop monitoring after one normal result, as patients with malabsorption can relapse 1
Critical Pitfalls to Avoid
Never administer folic acid before ensuring adequate B12 treatment, as it may mask B12 deficiency while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress. 1, 5
- Do not discontinue B12 supplementation even if levels normalize—patients require lifelong therapy when malabsorption is the cause 1
- Do not "titrate" injection frequency based on serum B12 or methylmalonic acid levels; instead, adjust based on clinical symptoms 6
- Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return 1
- Up to 50% of patients may require more frequent injections (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 6
Formulation Selection
Hydroxocobalamin is the preferred formulation due to superior tissue retention and established dosing protocols across all major guidelines. 1, 2
- All evidence-based dosing regimens are established for hydroxocobalamin, not methylcobalamin 1
- In patients with renal dysfunction, avoid cyanocobalamin and use hydroxocobalamin or methylcobalamin 1, 2
Injection Technique Considerations
- Preferred injection sites are deltoid or vastus lateralis 2
- Avoid buttock as routine site due to sciatic nerve injury risk; if used, only upper outer quadrant with needle directed anteriorly 1
- For patients with thrombocytopenia (platelets 25-50 × 10⁹/L), use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 5
- Consider platelet transfusion support if platelets <10 × 10⁹/L before intramuscular administration 5