Treatment of Vitamin B12 Deficiency
For vitamin B12 deficiency with neurological involvement, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then transition to maintenance with 1 mg intramuscularly every 2 months for life. 1, 2, 3
Initial Treatment Protocol
The treatment approach depends critically on whether neurological symptoms are present:
With Neurological Involvement
- Loading phase: Hydroxocobalamin 1 mg IM on alternate days until no further improvement occurs 1, 2, 3
- Maintenance: Hydroxocobalamin 1 mg IM every 2 months for life 1, 2, 3
- Neurological symptoms include paresthesias, gait disturbances, cognitive impairment, or peripheral neuropathy 1
Without Neurological Involvement
- Loading phase: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2, 3
- Maintenance: Hydroxocobalamin 1 mg IM every 2-3 months for life 1, 2, 3
Formulation Selection
Hydroxocobalamin is the preferred formulation over cyanocobalamin due to superior tissue retention and established dosing protocols. 2, 3
Critical Caveat for Renal Dysfunction
- In patients with renal impairment, avoid cyanocobalamin as it requires renal clearance of the cyanide moiety and is associated with a 2-fold increased risk of cardiovascular events (HR 2.0) 1, 2
- Use methylcobalamin or hydroxocobalamin instead in this population 1, 2, 3
Oral Alternative
High-dose oral therapy (1000-2000 mcg daily) is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 4. However, guidelines consistently recommend parenteral therapy for malabsorption conditions such as pernicious anemia, ileal resection, or bariatric surgery 3, 5, 6.
Special Populations Requiring Modified Dosing
Post-Bariatric Surgery
- 1 mg IM every 3 months OR 1000-2000 mcg oral daily indefinitely 1, 2
- If planning pregnancy: check B12 levels every 3 months throughout pregnancy 1
Ileal Resection >20 cm or Crohn's Disease
- Prophylactic treatment: 1000 mcg IM monthly for life, even without documented deficiency 1, 2
- Screen yearly for B12 deficiency 1, 2
Dietary Deficiency (Vegans/Vegetarians)
- Oral supplementation 1000-2000 mcg daily is sufficient 1
- Parenteral therapy not required unless malabsorption develops 3
Monitoring Strategy
First Year
- Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months after initiating treatment 1, 2
- Target homocysteine <10 μmol/L for optimal outcomes 1, 2
- If B12 remains borderline or symptoms persist, measure methylmalonic acid (target <271 nmol/L) 1, 2
After Stabilization
- Annual monitoring of B12 levels and homocysteine once levels stabilize 1, 2, 3
- Do not stop monitoring after one normal result - patients with malabsorption can relapse 2
Clinical Monitoring
- Monitor for improvement in neurological symptoms (pain, paresthesias, numbness, motor weakness) 2
- Pain and paresthesias typically improve before motor symptoms 2
- If symptoms recur despite normal B12 levels, increase injection frequency 1, 2
Critical Pitfalls to Avoid
Never Give Folic Acid Before B12 Treatment
Administering folic acid before or without adequate B12 treatment can mask the anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress. 1, 2, 3 This is the most dangerous error in B12 deficiency management.
Lifelong Therapy Required for Malabsorption
- Do not discontinue B12 supplementation even if levels normalize when malabsorption is the cause 1, 2
- Patients with pernicious anemia, ileal resection, or bariatric surgery require lifelong therapy 1, 2, 3
Individual Variation in Requirements
- Up to 50% of patients require more frequent injections than standard protocols (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 7
- Do not titrate injection frequency based solely on serum B12 or MMA levels - clinical response is more important 7
- If neurological symptoms recur, increase injection frequency regardless of laboratory values 1, 2