Vitamin B12 Dosing for Deficiency Treatment
Initial Treatment Protocol
For patients with neurological involvement (paresthesias, gait disturbance, cognitive changes), administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then transition to maintenance therapy with 1 mg intramuscularly every 2 months for life. 1, 2, 3
For patients without neurological involvement, give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance therapy of 1 mg intramuscularly every 2-3 months lifelong. 1, 2, 3
Key Distinction in Treatment Approach
The presence or absence of neurological symptoms fundamentally changes the treatment regimen 1, 2:
- With neurological symptoms: More aggressive loading (alternate days until plateau) + more frequent maintenance (every 2 months) 1, 2
- Without neurological symptoms: Standard loading (3x weekly for 2 weeks) + standard maintenance (every 2-3 months) 1, 2, 3
FDA-Approved Cyanocobalamin Dosing (Alternative)
The FDA label for intramuscular cyanocobalamin provides an alternative regimen 4:
- Loading phase: 100 mcg daily for 6-7 days intramuscularly, then alternate days for 7 doses, then every 3-4 days for 2-3 weeks 4
- Maintenance: 100 mcg monthly for life 4
However, 1000 mcg (1 mg) dosing is superior to 100 mcg dosing because significantly more vitamin is retained with the higher dose, with no disadvantage in cost or toxicity 5. The 100 mcg FDA regimen is outdated and may be insufficient to meet metabolic requirements in many patients 5.
Oral Therapy as Alternative
Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption. 1, 6, 7
- Oral therapy at 1000 mcg daily normalizes B12 levels in 94.7% of Crohn's disease patients with malabsorption 7
- Effective even in food-cobalamin malabsorption and nutritional deficiency 8
- Exception: Pernicious anemia requires parenteral therapy as oral is not dependable 4
Special Population Dosing
Post-Bariatric Surgery
- 1 mg intramuscularly every 3 months OR 1000-2000 mcg orally daily indefinitely 1, 2, 3
- Check B12 levels every 3 months throughout pregnancy in post-bariatric patients 1
Ileal Resection >20 cm or Crohn's Disease with Ileal Involvement
- Prophylactic 1000 mcg intramuscularly monthly for life, even without documented deficiency 1, 2
- Screen yearly for B12 deficiency 1, 2
Renal Dysfunction
- Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 2, 3
- Cyanocobalamin requires renal clearance of cyanide moiety and is associated with doubled cardiovascular risk (HR 2.0) in diabetic nephropathy 2
Monitoring Strategy
First Year
- Check serum B12, homocysteine, and methylmalonic acid at 3 months, 6 months, and 12 months 1, 2, 3
- Target homocysteine <10 μmol/L for optimal outcomes 1, 2, 3
- Assess complete blood count for resolution of megaloblastic anemia 2
After Stabilization
Critical Pitfalls to Avoid
Never administer folic acid before ensuring adequate B12 treatment - this can mask anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 2, 3
Never discontinue therapy even if levels normalize - patients with malabsorption require lifelong therapy 1, 2
Do not use serum B12 levels to titrate injection frequency - clinical symptoms should guide treatment adjustments, not biomarker levels 9
Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return, as up to 50% of patients require more frequent dosing than standard protocols (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 9
Preferred Formulation
Hydroxocobalamin is preferred over cyanocobalamin due to superior tissue retention and established dosing protocols across all major guidelines 2, 3