What is the treatment for vitamin B12 (cobalamin) deficiency?

Treatment of Vitamin B12 Deficiency

For vitamin B12 deficiency with neurological involvement, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then transition to maintenance with 1 mg intramuscularly every 2 months for life. 1, 2, 3

For vitamin B12 deficiency without neurological involvement, administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2-3 months for life. 1, 2, 3

Initial Treatment Algorithm

The treatment approach depends critically on whether neurological symptoms are present:

With Neurological Involvement

• Hydroxocobalamin 1 mg IM on alternate days until no further clinical improvement is observed 1, 2, 3
• Neurological symptoms include paresthesias, gait disturbances, cognitive impairment, or subacute combined degeneration of the spinal cord 1
• This aggressive dosing is essential because neurological damage can become irreversible if undertreated 4
• After maximal improvement, transition to 1 mg IM every 2 months for lifelong maintenance 1, 2, 3

Without Neurological Involvement

• Hydroxocobalamin 1 mg IM three times weekly for 2 weeks as the loading phase 1, 2, 3
• Then 1 mg IM every 2-3 months for life as maintenance 1, 2, 3

Route of Administration

Intramuscular administration is the preferred and recommended route for B12 deficiency due to malabsorption, which is the most common cause 2, 3, 5

• Parenteral therapy will be required for the remainder of the patient's life in cases of malabsorption 2, 5
• Oral therapy is not dependable in pernicious anemia and malabsorption conditions 5
• While high-dose oral B12 (1-2 mg daily) can correct deficiency in some patients, there is currently no evidence that oral/sublingual supplementation can safely and effectively replace injections in malabsorption cases 4, 6

Special Populations and Situations

Post-Bariatric Surgery

• 1 mg IM every 3 months or 1 mg daily orally 1
• Patients with >20 cm distal ileum resected require 1000 μg IM monthly for life 1, 3

Thrombocytopenia

• IM administration can be safely performed with platelet count >50 × 10⁹/L 1, 3
• For platelet count 25-50 × 10⁹/L, use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 1
• For platelet count <10 × 10⁹/L, consider platelet transfusion support before IM administration 1

Elderly Patients

• Higher risk population with 18.1% of patients over 80 years having metabolic B12 deficiency 1, 3
• Standard treatment protocols apply 1

Critical Safety Considerations

Never administer folic acid before treating vitamin B12 deficiency, as this may mask underlying B12 deficiency and precipitate subacute combined degeneration of the spinal cord 1, 2, 3

• Always check both vitamin B12 and folate levels, as deficiencies may coexist 2, 3
• Before initiating folic acid treatment, confirm and treat B12 deficiency first 2

Monitoring Protocol

• Monitor serum potassium closely in the first 48 hours of treatment and administer potassium if necessary 5
• Check serum B12 levels and homocysteine every 3 months until stabilization, then once yearly 1, 3
• Target homocysteine level is <10 μmol/L for optimal results 1
• Do not use serum B12 or methylmalonic acid levels to "titrate" injection frequency once treatment is established 4

Alternative Formulations

• Hydroxocobalamin is the preferred formulation in current guidelines 1, 2, 3
• Cyanocobalamin is also FDA-approved but hydroxocobalamin may be preferable in patients with renal dysfunction 1, 7
• Methylcobalamin or hydroxocobalamin may be superior to cyanocobalamin in renal impairment 1

Common Pitfalls to Avoid

• Do not discontinue B12 supplementation even if levels normalize, as patients with malabsorption require lifelong therapy 1
• Do not withhold treatment while awaiting diagnostic studies in seriously ill patients; both B12 and folic acid can be administered simultaneously 5
• Do not rely on oral therapy alone in confirmed malabsorption cases 5
• Up to 50% of individuals may require more frequent injections (ranging from daily to every 2-4 weeks) to remain symptom-free, based on clinical response rather than laboratory values 4