Treatment of Vitamin B12 Deficiency
For confirmed vitamin B12 deficiency, treatment should consist of 1000-2000 μg daily oral supplementation for patients with normal intestinal absorption, or 1000 mcg intramuscular injections monthly for those with malabsorption conditions such as pernicious anemia. 1
Diagnosis Confirmation
Before initiating treatment, confirm B12 deficiency using these thresholds:
- Total B12 <180 ng/L or active B12 <25 pmol/L: Confirmed deficiency
- Total B12 180-350 ng/L or active B12 25-70 pmol/L: Indeterminate (requires additional testing)
- Total B12 >350 ng/L or active B12 >70 pmol/L: Unlikely deficiency 1
For indeterminate results, measure serum methylmalonic acid (MMA), homocysteine, complete blood count, and folate levels to confirm diagnosis.
Treatment Algorithm Based on Cause
1. Pernicious Anemia
- Initial treatment: 100 mcg intramuscular (IM) injection daily for 6-7 days
- Continuation: If clinical improvement occurs, give 100 mcg IM on alternate days for seven doses, then every 3-4 days for 2-3 weeks
- Maintenance: 100 mcg IM monthly for life 2
- Important: While recent research suggests oral supplementation at 1000 μg/day may be effective even in pernicious anemia 3, the FDA label specifically states that "oral form is not dependable" for pernicious anemia 2
2. Normal Intestinal Absorption (dietary deficiency, vegetarians/vegans)
- 1000-2000 μg daily oral supplementation 1
- Sublingual B12 supplementation is equally effective as IM and offers better patient compliance 1
3. Malabsorption Conditions (ileal disease/resection, inflammatory bowel disease)
- For ileal resection >20 cm: Lifelong B12 supplementation is mandatory 1
- Treatment approach similar to pernicious anemia with IM injections 2
4. Medication-Induced Deficiency (metformin, PPIs)
- 1000-2000 μg daily oral supplementation 1
- Regular monitoring of B12 levels, especially in high-risk patients 1
Route of Administration Considerations
Intramuscular Route
- Preferred for:
- Leads to more rapid improvement in severe cases 4
- Caution: Avoid intravenous administration as most vitamin will be lost in urine 2
Oral Route
- Comparable to IM for correcting anemia and neurologic symptoms in patients with normal absorption 4, 6
- More convenient, cost-effective, and suitable for patients on anticoagulants or with needle phobia 1
- Recent evidence suggests effectiveness even in pernicious anemia at 1000 μg/day dosage 3, though this contradicts traditional guidance 2
Monitoring and Follow-up
- Monitor platelet count until normalization 1
- Assess B12 levels periodically during maintenance therapy 1
- Screen for neurological manifestations and hyperhomocysteinemia 1
- Treatment response may vary considerably between individuals 5
Important Caveats
- Untreated B12 deficiency for more than 3 months may cause permanent degenerative lesions of the spinal cord 1
- 'Titration' of injection frequency based solely on measuring biomarkers should not be practiced; clinical response is important 5
- Concomitant folic acid should be administered if needed 2
- Patients who have had bariatric surgery should receive 1 mg of oral vitamin B12 per day indefinitely 4