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

Treatment for Vitamin B12 (Cobalamin) Deficiency

The recommended treatment for vitamin B12 deficiency is hydroxocobalamin 1 mg intramuscularly, with frequency based on the presence of neurological symptoms: for those with neurological involvement, administer on alternate days until no further improvement, then every 2 months; for those without neurological symptoms, administer three times weekly for 2 weeks, followed by maintenance treatment of 1 mg intramuscularly every 2-3 months lifelong. 1, 2

Diagnosis of B12 Deficiency

Before initiating treatment, confirm the diagnosis:

• Test either total B12 (serum cobalamin) or active B12 (serum holotranscobalamin) 2
• Consider methylmalonic acid (MMA) testing for confirmatory diagnosis when initial results are indeterminate 2
• Never administer folic acid before treating vitamin B12 deficiency, as it may mask B12 deficiency and precipitate subacute combined degeneration of the spinal cord 2

Treatment Protocol Based on Clinical Presentation

For Patients with Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 2, 1
• Then transition to maintenance with hydroxocobalamin 1 mg intramuscularly every 2 months 2, 1
• Seek urgent specialist advice from neurologist and hematologist for patients with unexplained sensory, motor, or gait symptoms 2

For Patients without Neurological Involvement

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

Alternative Treatment Option (Cyanocobalamin)

• For pernicious anemia: 100 mcg daily for 6-7 days by intramuscular injection, then every 3-4 days for 2-3 weeks if clinical improvement occurs, followed by 100 mcg monthly for life 3
• Folic acid should be administered concomitantly if needed, but only after B12 treatment has begun 3

Special Considerations

Route of Administration

• Intramuscular administration is preferred for patients with malabsorption issues 1, 3
• Oral high-dose vitamin B12 (1-2 mg daily) can be effective for patients with normal intestinal absorption 4, 5
• Avoid intravenous administration as most of the vitamin will be lost in urine 3

Specific Patient Populations

• Patients with ileal resection (>20 cm of distal ileum): prophylactic vitamin B12 injections (1000 μg) monthly for life 1
• Post-bariatric surgery patients: regular vitamin B12 injections, especially after procedures affecting the ileum 1
• Patients with pernicious anemia: lifelong treatment required 3

Monitoring and Follow-up

• Clinical response should guide treatment frequency, as up to 50% of individuals may require more frequent administration (ranging from daily to every 2-4 weeks) to remain symptom-free 4
• Do not use serum B12 or MMA levels to "titrate" injection frequency 4

Common Pitfalls to Avoid

• Failing to rule out B12 deficiency before treating folate deficiency 2
• Discontinuing treatment prematurely - maintenance therapy is typically lifelong for patients with malabsorption 2, 1
• Assuming oral supplementation can replace injections in all cases - patients with malabsorption often require parenteral therapy 1, 4
• Overlooking neurological symptoms, which require more aggressive initial treatment 2, 1
• Neglecting to consider the cause of B12 deficiency, which may require additional treatment (e.g., H. pylori eradication, gluten-free diet) 3, 6