What is the recommended 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, then transition to maintenance with 1 mg intramuscularly every 2 months for life. 1, 2, 3

Initial Treatment Protocol

With Neurological Symptoms

• Neurological involvement includes unexplained sensory/motor symptoms, gait disturbances, paresthesias, or cognitive changes 1
• Give hydroxocobalamin 1 mg IM on alternate days until symptoms stop improving 1, 2, 3
• This aggressive approach is critical because neurological damage can become irreversible if treatment is delayed 1
• Seek urgent specialist consultation from both neurology and hematology 1

Without Neurological Symptoms

• Administer hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2, 3
• This loading phase ensures rapid repletion of body stores 3

Maintenance Therapy

Standard Maintenance

• Hydroxocobalamin 1 mg IM every 2-3 months for life for patients without neurological involvement 1, 2, 3
• Hydroxocobalamin 1 mg IM every 2 months for life for patients who had neurological involvement 1, 2
• The FDA-approved cyanocobalamin alternative is 100 mcg monthly for life, though 1000 mcg monthly may be necessary to meet metabolic requirements in many patients 4, 5

Special Populations

• Post-bariatric surgery patients: 1 mg IM every 3 months OR 1000-2000 mcg daily orally indefinitely 2
• Ileal resection >20 cm: prophylactic 1000 mcg IM monthly for life 2, 3
• Pregnancy after bariatric surgery: check B12 levels every 3 months throughout pregnancy 2

Critical Treatment Considerations

Folate Administration Warning

• Never give folic acid before treating B12 deficiency - this may mask underlying B12 deficiency and precipitate subacute combined degeneration of the spinal cord 1, 2, 3
• Always check both B12 and folate levels, as deficiencies may coexist 3
• If folate deficiency is confirmed after excluding B12 deficiency, give oral folic acid 5 mg daily for minimum 4 months 1

Formulation Selection

• Hydroxocobalamin is preferred over cyanocobalamin in patients with renal dysfunction, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 2
• Methylcobalamin is also acceptable in renal dysfunction 2

Monitoring Strategy

• Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization, then once yearly 2, 3
• Target homocysteine <10 μmol/L for optimal outcomes 2
• Do not discontinue therapy even if levels normalize - patients with malabsorption require lifelong treatment 2, 3
• Monitor for recurrent neurological symptoms and increase injection frequency if symptoms return 2

Oral Therapy Alternative

• Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 2, 6
• However, intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms 6
• Oral therapy may be insufficient in true malabsorption states, where parenteral administration is preferred 7

Common Pitfalls to Avoid

• Injection site: avoid the buttock as a routine site due to sciatic nerve injury risk; if used, only the upper outer quadrant with needle directed anteriorly 2
• Thrombocytopenia: IM administration can be safely performed with platelet count >50 × 10⁹/L; use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) if platelets 25-50 × 10⁹/L 2, 3
• Avoid IV route: intravenous administration results in almost all vitamin being lost in urine 4
• Patients require lifelong therapy when malabsorption is the cause - treatment cannot be discontinued 2, 3