Treatment of Confirmed Vitamin B12 Deficiency
For patients with confirmed vitamin B12 deficiency, the recommended treatment is 1000-2000 μg daily oral supplementation or 1000 μg intramuscular injection monthly, with the specific regimen determined by the underlying cause of deficiency. 1
Diagnosis Confirmation
Before initiating treatment, confirm the diagnosis using 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 (requires MMA measurement)
- Unlikely deficiency: Total B12 >350 ng/L or active B12 >70 pmol/L 1
Treatment Algorithm Based on Cause of Deficiency
1. Pernicious Anemia
- Traditional approach: Intramuscular injection of 100 mcg daily for 6-7 days, then alternate days for 7 doses, then every 3-4 days for 2-3 weeks, followed by 100 mcg monthly for life 2, 3
- Emerging evidence: Oral supplementation with 1000 μg/day of cyanocobalamin has been shown effective even in pernicious anemia 4
2. Normal Intestinal Absorption (Dietary Deficiency)
- Recommended: 1000-2000 μg daily oral supplementation 1
- Alternative: Initial treatment similar to pernicious anemia if deficiency is severe, followed by oral maintenance therapy 2, 3
3. Malabsorption Conditions
- Ileal resection >20 cm: 1000 mcg vitamin B12 monthly indefinitely 1
- Post-bariatric surgery: 1000 μg oral B12 daily indefinitely 1
- Crohn's disease with ileal involvement/resection: 1000 μg monthly if >20 cm of distal ileum is resected 1
4. Special Populations
- Vegans/vegetarians: 250-350 μg daily or 1000 μg weekly 1
- Breastfeeding mothers: At least 2.8 mg cyanocobalamin per day orally 1
- Patients on metformin: Regular monitoring and supplementation as needed 1
Route of Administration Considerations
Intramuscular Administration
- Advantages: Rapid correction, bypasses absorption issues
- Indications: Severe deficiency, severe neurological symptoms, malabsorption disorders 1, 5
- Caution: Avoid intravenous route as most vitamin will be lost in urine 2, 3
Oral/Sublingual Administration
- Advantages: Comparable efficacy to IM in many cases, better compliance, cost-effective, suitable for patients on anticoagulants 1
- Dosage: 1000-2000 μg daily 1
- Note: High-dose oral therapy (1000 μg daily) can be effective even in conditions previously thought to require parenteral therapy 1, 4
Monitoring and Follow-up
- Check B12 levels after 3 months of supplementation 1
- For indeterminate results (180-350 ng/L), measure MMA levels 1
- Monitor for co-existing deficiencies, particularly folate 1
Important Caveats
- Timing is critical: B12 deficiency left untreated for more than 3 months may cause permanent degenerative lesions of the spinal cord 1
- Form matters: Both methylcobalamin and adenosylcobalamin are essential with distinct metabolic functions 6
- Individual response varies: Up to 50% of individuals with malabsorption may require more frequent administration than standard protocols to remain symptom-free 5
- Avoid titration based on biomarkers: Frequency should be based on clinical response rather than serum B12 or MMA levels 5