What is the recommended dosing regimen for vitamin B12 (cobalamin) deficiency?

Vitamin B12 Dosing Regimen for Deficiency

For vitamin B12 deficiency, the recommended dosing is 1000-2000 mcg daily orally for 3 months for most patients, while those with pernicious anemia require 100 mcg intramuscular injections daily for 6-7 days, followed by alternate day dosing for 7 doses, then every 3-4 days for 2-3 weeks, and finally 100 mcg monthly for life. 1, 2

Diagnosis and Assessment

Before initiating treatment, confirm vitamin B12 deficiency using appropriate testing:

• Initial testing should use either:

  • Total B12 (serum cobalamin) or
  • Active B12 (serum holotranscobalamin)

• Interpret results according to these thresholds:

  • Confirmed deficiency: Total B12 <180 ng/L or active B12 <25 pmol/L
  • Indeterminate: Total B12 180-350 ng/L or active B12 25-70 pmol/L
  • Unlikely deficiency: Total B12 >350 ng/L or active B12 >70 pmol/L 1

• For indeterminate results, measure serum methylmalonic acid (MMA) to confirm deficiency 1

Treatment Regimens Based on Cause

1. Pernicious Anemia (Malabsorption)

• Intramuscular (IM) administration is required for life 2
• Initial dosing: 100 mcg daily for 6-7 days via IM or deep subcutaneous injection
• If clinical improvement occurs:
  • Continue with 100 mcg on alternate days for 7 doses
  • Then 100 mcg every 3-4 days for 2-3 weeks
  • Maintenance: 100 mcg monthly for life 2

2. Normal Intestinal Absorption

• Oral administration: 1000-2000 mcg daily for 3 months 1, 3
• High-dose oral vitamin B12 (1000-2000 mcg daily) is as effective as IM administration for most patients 1, 4
• Even in malabsorption, 1-2% absorption occurs via passive diffusion with high oral doses 1

3. Sublingual Administration

• Sublingual B12 offers comparable efficacy to IM administration
• Benefits include better patient compliance, cost-effectiveness, and suitability for patients on anticoagulants or with needle phobia 1

Monitoring and Maintenance

• Assess response after 3 months by measuring serum B12 levels 1
• Monitor platelet count until normalization 1
• Maintenance therapy depends on underlying cause:
  • Reversible causes: May not require long-term supplementation if cause is addressed
  • Irreversible causes (like pernicious anemia): Lifelong supplementation required 1, 2

Important Clinical Considerations

• Avoid intravenous administration as most of the vitamin will be lost in urine 2
• For patients with severe deficiency or severe neurologic symptoms, IM therapy leads to more rapid improvement 4
• The most recent evidence suggests that up to 50% of individuals with malabsorption may require individualized injection regimens (ranging from daily/twice weekly to every 2-4 weeks) to remain symptom-free 5
• Untreated vitamin B12 deficiency may cause permanent degenerative lesions of the spinal cord, highlighting the importance of early and adequate treatment 1

Special Populations

• Post-bariatric surgery patients: Should receive 1 mg oral vitamin B12 daily indefinitely 4
• Adults over 50 years, vegans, or strict vegetarians: Should consume foods fortified with vitamin B12 or take supplements 4
• Patients on metformin or proton pump inhibitors: Require regular monitoring of B12 levels due to increased risk of deficiency 1

Remember that early and appropriate treatment is essential to prevent irreversible neurological complications associated with vitamin B12 deficiency 1, 5.