What treatment is used for vitamin B12 deficiency?

Treatment for Vitamin B12 Deficiency

For vitamin B12 deficiency, use hydroxocobalamin 1 mg intramuscularly—either three times weekly for 2 weeks followed by maintenance every 2-3 months for life (if no neurological symptoms), or on alternate days until no further improvement then every 2 months for life (if neurological involvement is present). 1, 2, 3

Treatment Protocol Based on Neurological Involvement

With Neurological Symptoms

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement in symptoms 1, 2, 3
• After the loading phase, transition to maintenance with hydroxocobalamin 1 mg intramuscularly every 2 months for life 1, 2, 3
• Neurological symptoms include unexplained sensory/motor symptoms, gait disturbances, paresthesias, or cognitive changes 1, 2
• Seek urgent specialist advice from neurology and hematology when neurological involvement is suspected 1

Without Neurological Symptoms

• Administer hydroxocobalamin 1 mg intramuscularly three times per week for 2 weeks 1, 2, 3
• Follow with maintenance treatment of 1 mg intramuscularly every 2-3 months for life 1, 2, 3

Oral vs. Intramuscular Therapy

Intramuscular therapy is preferred for malabsorption-related deficiency (pernicious anemia, post-bariatric surgery, ileal resection, inflammatory bowel disease) because oral absorption is unreliable in these conditions 2, 3, 4. The FDA label explicitly states that oral forms are "not dependable" for pernicious anemia and parenteral B12 is required for life 4.

For dietary deficiency without malabsorption, oral supplementation with 1-2 mg daily can be effective 5. However, up to 50% of patients with malabsorption require individualized injection frequencies ranging from twice weekly to every 2-4 weeks to remain symptom-free, despite guidelines suggesting every 2-3 months 6.

Choice of Formulation

Hydroxocobalamin is the preferred formulation due to superior tissue retention and established dosing protocols across all major guidelines 2, 3.

Avoid cyanocobalamin in patients with renal dysfunction—use methylcobalamin or hydroxocobalamin instead, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in diabetic nephropathy 2, 3.

Critical Safety Considerations

Never administer folic acid before treating B12 deficiency—this may mask the anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2, 3. If folate deficiency coexists, treat B12 first, then add folic acid 5 mg daily for minimum 4 months 1.

Special Populations

Post-Bariatric Surgery

• 1000 mcg intramuscularly monthly for life OR 1000-2000 mcg oral daily 2, 3, 5
• Prophylactic treatment is recommended even without documented deficiency 2

Ileal Resection

• Patients with >20 cm of distal ileum resected require prophylactic B12 injections (1000 mcg) monthly for life 2, 3

Crohn's Disease

• Annual screening for B12 deficiency if ileal involvement or resection present 2
• Prophylactic supplementation with 1000 mcg IM monthly or 1000-2000 mcg oral daily if >30-60 cm ileal involvement 2

Monitoring Strategy

First year monitoring schedule: 2, 3

• Check serum B12, complete blood count, and homocysteine at 3 months, 6 months, and 12 months
• Target homocysteine <10 μmol/L for optimal outcomes 2, 3

After stabilization: 2, 3

• Annual monitoring of B12 levels and homocysteine once levels stabilize for two consecutive checks

Do not stop monitoring after one normal result—patients with malabsorption often require lifelong supplementation and can relapse 2.

Administration Details

• Route: Intramuscular or deep subcutaneous injection 3, 4
• Preferred sites: Deltoid or vastus lateralis 3
• Avoid the buttock due to potential sciatic nerve injury risk; if used, only the upper outer quadrant with needle directed anteriorly 2
• Avoid intravenous route—almost all vitamin will be lost in urine 4

Common Pitfalls

• Do not discontinue B12 supplementation even if levels normalize—patients will likely require lifelong therapy 2
• Do not "titrate" injection frequency based on serum B12 or methylmalonic acid levels—base frequency on clinical symptoms and whether the patient remains symptom-free 6
• Do not assume standard every-2-3-month dosing works for everyone—clinical experience shows up to 50% require more frequent injections to maintain quality of life 6