Treatment of Vitamin B12 Deficiency
For patients with vitamin B12 deficiency and neurological symptoms, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then transition to maintenance therapy with 1 mg intramuscularly every 2 months for life. 1, 2, 3
Initial Assessment
Confirm the diagnosis by measuring serum B12 levels, with deficiency confirmed when levels are <150 pmol/L (203 pg/mL), though treatment should be initiated for levels between 140-200 pmol/L if clinical symptoms are present 2. If B12 levels are borderline (140-200 pmol/L), measure methylmalonic acid—levels >271 nmol/L confirm functional B12 deficiency and warrant treatment 2.
Identify the underlying cause by evaluating for:
- Malabsorption conditions: pernicious anemia, ileal resection >20 cm, Crohn's disease with ileal involvement, bariatric surgery (especially Roux-en-Y gastric bypass or biliopancreatic diversion) 1, 2
- Dietary insufficiency: strict vegetarian or vegan diets 4
- Medication-induced deficiency: metformin use >4 months, proton pump inhibitors or H2 blockers >12 months 4, 5
- Age-related: adults >75 years 4
Treatment Protocol Based on Neurological Involvement
With Neurological Symptoms (Neuropathy, Paresthesias, Gait Disturbances, Cognitive Changes)
Loading phase: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement in symptoms 1, 2, 3
Maintenance phase: Hydroxocobalamin 1 mg intramuscularly every 2 months for life 1, 2, 3
Without Neurological Symptoms
Loading phase: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2, 3
Maintenance phase: Hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 2, 3
Special Population Considerations
Post-bariatric surgery patients require modified dosing: either 1 mg intramuscularly every 3 months OR 1000-2000 mcg orally daily indefinitely 2, 3. For those planning pregnancy after bariatric surgery, check B12 levels every 3 months throughout pregnancy 2.
Patients with ileal resection >20 cm should receive prophylactic hydroxocobalamin 1000 mcg intramuscularly monthly for life, even without documented deficiency 2, 6, 3.
Patients with Crohn's disease involving >30-60 cm of ileum require annual screening and prophylactic supplementation with either hydroxocobalamin 1000 mcg intramuscularly monthly or oral B12 1000-2000 mcg daily 2, 3.
Patients with renal dysfunction should receive methylcobalamin or hydroxocobalamin instead of cyanocobalamin, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in diabetic nephropathy 2, 6, 3.
Oral Therapy Alternative
For patients with dietary insufficiency (not malabsorption), oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy 2, 4. However, parenteral therapy is mandatory for malabsorption conditions including pernicious anemia, ileal resection, and bariatric surgery 3, 7.
Monitoring Strategy
First year monitoring: Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months after initiating treatment 2, 3. Target homocysteine <10 μmol/L for optimal outcomes 2, 3.
Long-term monitoring: After stabilization (typically by 6-12 months with two consecutive normal results), transition to annual monitoring of B12 levels and homocysteine 2, 3.
Do not use B12 levels or methylmalonic acid to titrate injection frequency—base treatment adjustments solely on clinical symptoms 8. Up to 50% of patients require more frequent injections (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 8.
Critical Pitfalls to Avoid
Never administer folic acid before treating B12 deficiency, as folic acid can mask the anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2, 6, 3.
Do not discontinue therapy even if levels normalize—patients with malabsorption require lifelong treatment, and stopping injections can lead to irreversible peripheral neuropathy 2, 6.
Do not delay treatment in patients with neurological symptoms—irreversible neurological consequences can occur if treatment is not initiated promptly 8, 9, 10.
Avoid using the buttock as an injection site due to risk of sciatic nerve injury; use the deltoid or vastus lateralis instead 2.
Formulation Selection
Hydroxocobalamin is the preferred formulation due to its longer tissue retention compared to cyanocobalamin and established dosing protocols across all major guidelines 2, 6, 3. Methylcobalamin is an acceptable alternative, particularly in patients with renal dysfunction 2, 3.