Vitamin B12 Injection Dosing for Deficiency
For patients with low vitamin B12 levels without neurological symptoms, administer hydroxocobalamin 1000 mcg (1 mg) intramuscularly three times weekly for 2 weeks, then continue with 1000 mcg intramuscularly every 2-3 months for life. 1, 2
Initial Loading Phase
Without Neurological Involvement:
- Hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks (total of 6 injections) 1, 2, 3
- This loading phase rapidly replenishes body stores and reverses hematological abnormalities 4
With Neurological Involvement (tingling, numbness, neuropathy, cognitive changes):
- Hydroxocobalamin 1000 mcg IM on alternate days until no further improvement 1, 2, 3
- This more aggressive protocol prevents irreversible neurological damage 5
- Neurological symptoms require immediate and intensive treatment as delays beyond 3 months can cause permanent spinal cord degeneration 5
Maintenance Phase
Standard Maintenance:
- Hydroxocobalamin 1000 mcg IM every 2-3 months for life 1, 2, 3
- Some patients require monthly injections to meet metabolic requirements 2
- Never discontinue therapy even if levels normalize, as patients with malabsorption require lifelong supplementation 2, 3
With Ongoing Neurological Symptoms:
- Hydroxocobalamin 1000 mcg IM every 2 months indefinitely 1, 2
- More frequent dosing prevents symptom recurrence 2
Special Populations Requiring Modified Dosing
Post-Bariatric Surgery:
- 1000 mcg IM every 3 months for life OR 1000-2000 mcg oral daily 1, 2
- If pregnant after bariatric surgery: check B12 levels every 3 months throughout pregnancy 2
Ileal Resection >20 cm:
- 1000 mcg IM monthly for life as prophylaxis 1, 2, 3
- These patients have permanent malabsorption requiring lifelong monthly dosing 2
Crohn's Disease with Ileal Involvement:
Oral Alternative (When Appropriate)
High-dose oral vitamin B12 can be considered ONLY after the initial loading phase is complete and ONLY in patients without neurological symptoms: 1, 6
- Cyanocobalamin 1000-2000 mcg oral daily 1, 7
- Recent evidence shows oral supplementation at 1000 mcg daily can effectively treat even pernicious anemia 7
- However, intramuscular therapy remains preferred for severe deficiency, neurological symptoms, or when compliance is uncertain 6
Critical Warnings
Never administer folic acid before or without adequate B12 treatment - this can mask anemia while allowing irreversible neurological damage to progress, including subacute combined degeneration of the spinal cord 1, 2, 5
Formulation considerations:
- Hydroxocobalamin is the preferred formulation over cyanocobalamin 2, 3
- In patients with renal dysfunction, use hydroxocobalamin or methylcobalamin instead of cyanocobalamin, as cyanocobalamin requires renal clearance and is associated with increased cardiovascular events (HR 2.0) 1, 2
Monitoring Schedule
First year after starting treatment:
- Recheck serum B12 at 3 months, 6 months, and 12 months 2
- Measure complete blood count, methylmalonic acid (if B12 remains borderline), and homocysteine (target <10 μmol/L) 2
After stabilization:
- Annual monitoring once levels stabilize 2, 3
- Do not stop monitoring after one normal result - patients with malabsorption can relapse 2
Clinical monitoring is more important than laboratory values - assess for improvement in fatigue, neurological symptoms (tingling, numbness, weakness), and cognitive function 2, 4
Common Pitfalls to Avoid
- Do not use every-two-week dosing for maintenance - the standard is every 2-3 months, not every 2 weeks 2
- Do not stop injections when symptoms improve - this leads to recurrence and potential irreversible damage 2
- Do not rely solely on serum B12 levels - clinical response and symptom resolution are more important 8
- Patients with pernicious anemia must understand they require monthly or bi-monthly injections for the remainder of their lives 5