Recommended Vitamin B12 Supplement
For confirmed vitamin B12 deficiency, administer hydroxocobalamin 1000 mcg intramuscularly three times weekly for 2 weeks if no neurological symptoms are present, followed by maintenance therapy of 1000 mcg intramuscularly every 2-3 months for life. 1
Initial Treatment Protocol
Without Neurological Involvement
- Hydroxocobalamin 1 mg (1000 mcg) intramuscularly three times weekly for 2 weeks is the standard loading regimen 1, 2
- After loading, transition to maintenance therapy of 1 mg intramuscularly every 2-3 months lifelong 1, 2
- Some patients may require monthly dosing (1000 mcg IM monthly) to meet metabolic requirements 1, 3
With Neurological Involvement
- Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement is required for patients with neurological symptoms 1, 2
- After neurological improvement plateaus, transition to maintenance of 1 mg intramuscularly every 2 months for life 1, 2
- Never delay treatment in patients with neurological symptoms, as damage can become irreversible 1
Oral Alternative
High-dose oral vitamin B12 (1000-2000 mcg daily) is therapeutically equivalent to intramuscular therapy for most patients, including those with malabsorption. 2, 4, 5, 6
- Oral therapy at 1000-2000 mcg daily achieves similar hematological and neurological responses as intramuscular administration 4, 5
- This route is effective even in pernicious anemia and malabsorption states due to passive diffusion 4, 5
- However, intramuscular therapy should be prioritized in patients with severe neurological symptoms or severe deficiency to ensure more rapid improvement 5
Special Population Dosing
Post-Bariatric Surgery
- 1000 mcg intramuscularly every 3 months OR 1000-2000 mcg orally daily indefinitely 1, 5
- Patients planning pregnancy require B12 level checks every 3 months 1
Ileal Resection >20 cm
- Prophylactic hydroxocobalamin 1000 mcg intramuscularly monthly for life, even without documented deficiency 1
Crohn's Disease with Ileal Involvement
- Annual screening recommended 1
- If deficient: 1000 mcg intramuscularly monthly or 1200 mcg orally daily 2
Critical Formulation Considerations
Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin in patients with renal dysfunction, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in diabetic nephropathy 1
Monitoring Schedule
- Recheck serum B12 levels at 3 months after initiating supplementation 1
- Second recheck at 6 months 1
- Third recheck at 12 months 1
- Once stabilized, transition to annual monitoring 1, 2
- Measure homocysteine (target <10 μmol/L) and methylmalonic acid as functional markers 1
Common Pitfalls to Avoid
- Never administer folic acid before treating B12 deficiency, as it may mask anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2
- Do not discontinue supplementation even if levels normalize—patients with malabsorption require lifelong therapy 1, 2
- Do not rely on serum B12 levels alone to guide injection frequency; up to 50% of patients require individualized regimens with more frequent dosing (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 7
- Avoid using cyanocobalamin in renal dysfunction 1
Treatment Duration
Treatment must continue for life in patients with irreversible causes (pernicious anemia, ileal resection, post-bariatric surgery) 1, 2. Even after symptom resolution and laboratory normalization, maintenance therapy is mandatory as the underlying malabsorption persists 1.