Treatment of Vitamin B12 Deficiency
For patients with vitamin B12 deficiency, the recommended treatment is oral vitamin B12 supplementation at 1500-2000 mcg daily for 3 months, which is as effective as intramuscular administration for most patients, even those with malabsorption issues. 1
Diagnosis and Assessment
Before initiating treatment, confirm the diagnosis with 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 Approach
First-Line Treatment (Most Patients)
- Oral vitamin B12 supplementation:
Special Considerations for Pernicious Anemia
For pernicious anemia, parenteral (intramuscular) vitamin B12 is traditionally recommended:
- Initial dosing: 100 mcg daily for 6-7 days via intramuscular injection
- Followed by: 100 mcg on alternate days for seven doses
- Then: Every 3-4 days for 2-3 weeks
- Maintenance: 100 mcg monthly for life 2
However, recent evidence suggests high-dose oral therapy may be effective even in pernicious anemia 3
Alternative Administration Routes
- Sublingual B12 supplementation offers comparable efficacy to intramuscular administration
- Particularly suitable for patients on anticoagulants or those with needle phobia 1
Monitoring and Maintenance
- Assess treatment response after 3 months by measuring serum B12 levels 1
- Monitor platelet count until normalization 1
- Maintenance therapy depends on the underlying cause:
- Reversible causes: May not require long-term supplementation if the cause is addressed
- Irreversible causes (e.g., pernicious anemia): Require lifelong supplementation 1
Treatment Based on Etiology
Nutritional Deficiency
- Oral supplementation at 1500-2000 mcg daily is sufficient 1, 4
- Ensure adequate dietary intake through animal-source foods, fortified cereals 1
Malabsorption Conditions
- Traditional approach: Intramuscular therapy 2
- Current evidence: High-dose oral therapy (1500-2000 mcg daily) can be effective due to passive absorption 1, 3
- For severe cases or neurological symptoms: Consider intramuscular therapy for more rapid improvement 3
Post-Bariatric Surgery
- Oral vitamin B12 at 1 mg (1000 mcg) daily indefinitely 3
Important Caveats and Pitfalls
- Avoid intravenous administration as most of the vitamin will be lost in urine 2
- Do not delay treatment in patients with neurological symptoms, as untreated vitamin B12 deficiency may cause permanent degenerative lesions of the spinal cord 1
- Do not base treatment decisions solely on serum B12 levels without considering clinical symptoms 4
- Do not "titrate" injection frequency based solely on biomarkers like serum B12 or MMA 4
- Recognize that patients at high risk (elderly, those with intestinal diseases, metformin users, and those on long-term PPI or H2 blockers) may require more aggressive screening and treatment 3
Special Populations
Elderly Patients
- Should consume foods fortified with vitamin B12 or take supplements 3
- May benefit from higher doses due to reduced absorption with age 1
Vegetarians and Vegans
Patients with Neurological Symptoms
- Require prompt treatment to prevent irreversible damage 1, 5
- May benefit from initial intramuscular therapy for more rapid improvement 3
By following this evidence-based approach to vitamin B12 deficiency treatment, clinicians can effectively address deficiency while minimizing the risk of permanent neurological complications.