What is the treatment for Vitamin B12 deficiency?

Treatment of Vitamin B12 Deficiency

For patients 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

For patients without neurological involvement, give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance of 1 mg intramuscularly every 2-3 months lifelong. 1, 2

Treatment Algorithm Based on Clinical Presentation

Step 1: Assess for Neurological Involvement

• Neurological symptoms present (paresthesias, gait disturbances, cognitive changes, subacute combined degeneration): 1

  • Hydroxocobalamin 1 mg IM on alternate days until no further improvement 1, 2
  • Then maintenance: 1 mg IM every 2 months for life 1, 2

• No neurological symptoms: 1

  • Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2
  • Then maintenance: 1 mg IM every 2-3 months for life 1, 2

Step 2: Identify the Underlying Cause

• Malabsorption conditions (pernicious anemia, ileal resection >20 cm, bariatric surgery, atrophic gastritis, celiac disease): 1, 3

  • Parenteral therapy required for life 2
  • Never discontinue treatment even if levels normalize 1

• Dietary deficiency (vegan/vegetarian diet): 1

  • Oral supplementation may be sufficient if absorption is intact 4
  • Consider 1000-2000 mcg daily orally 1

Special Population Considerations

Post-Bariatric Surgery Patients

• Roux-en-Y gastric bypass or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 3
• Sleeve gastrectomy or gastric banding: 250-350 mcg/day oral or 1000 mcg/week sublingual 3
• Check B12 levels every 3 months if planning pregnancy 1

Patients with Renal Dysfunction

• Avoid cyanocobalamin in patients with renal impairment due to potential cyanide accumulation and increased cardiovascular risk (HR 2.0) 3
• Use methylcobalamin or hydroxocobalamin instead, as cyanocobalamin requires renal clearance of the cyanide moiety 3

Patients with Thrombocytopenia

• Platelet count >50 × 10⁹/L: Standard IM administration is safe 3, 2
• Platelet count 25-50 × 10⁹/L: Use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 3
• Platelet count <25 × 10⁹/L with neurological symptoms: Prioritize treatment despite low platelets 3
• Platelet count <10 × 10⁹/L: Consider platelet transfusion support before IM administration 3

Monitoring Strategy

• Initial phase: Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization 1
• Long-term: Monitor once yearly after stabilization 1
• Target homocysteine: <10 μmol/L for optimal cardiovascular outcomes 1, 3
• Do not titrate injection frequency based on serum B12 or MMA levels - base adjustments on clinical symptoms only 5

Critical Pitfalls to Avoid

Never Give Folic Acid Before B12 Treatment

• Folic acid may mask B12 deficiency anemia while allowing irreversible neurological damage to progress (subacute combined degeneration of the spinal cord) 3, 2, 6
• Always check both B12 and folate levels, as deficiencies may coexist 2
• If folate is also low, treat B12 first, then add folic acid 6

Do Not Discontinue Therapy Prematurely

• Patients with malabsorption require lifelong therapy regardless of normalized laboratory values 1
• Vitamin B12 deficiency allowed to progress >3 months may produce permanent degenerative spinal cord lesions 6
• Patients with pernicious anemia must understand they require monthly injections for life 6

Recognize When More Frequent Dosing is Needed

• Up to 50% of patients require individualized injection regimens with more frequent administration (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 5
• If neurological symptoms recur, increase injection frequency rather than measuring biomarkers 1
• Monthly dosing (1000 mcg IM) may be necessary to meet metabolic requirements in some patients 3, 7

Alternative Oral Therapy

• High-dose oral cyanocobalamin (1000-2000 mcg daily) is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 7, 4
• However, parenteral therapy remains the first choice for patients with acute and severe manifestations or neurological involvement 8
• Oral therapy may be considered for long-term maintenance after initial parenteral loading in selected patients without neurological symptoms 8