What is the recommended treatment for vitamin B12 deficiency?

Treatment of Vitamin B12 Deficiency

For B12 deficiency due to malabsorption (pernicious anemia, ileal resection, bariatric surgery), use hydroxocobalamin 1 mg intramuscularly with a loading phase followed by lifelong maintenance injections every 2-3 months. 1, 2

Initial Treatment Protocol

The treatment approach depends critically on whether neurological symptoms are present:

With Neurological Involvement

• Loading phase: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1, 2
• Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2 months for life 1, 2
• Neurological symptoms include paresthesias, gait disturbances, cognitive impairment, peripheral neuropathy, or visual problems 1

Without Neurological Involvement

• Loading phase: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2
• Maintenance: Hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 2

Route of Administration

Intramuscular or deep subcutaneous injection is required for malabsorption-related deficiency (pernicious anemia, ileal resection >20 cm, post-bariatric surgery), as oral supplementation is unreliable in these conditions 1, 3

For dietary deficiency without malabsorption:

• High-dose oral B12 (1000-2000 mcg daily) is as effective as intramuscular therapy 4, 5, 6
• Oral therapy may be considered in patients with normal intestinal absorption 3

Choice of B12 Formulation

Hydroxocobalamin is the preferred formulation due to superior tissue retention and established dosing protocols across all major guidelines 1, 2

Avoid cyanocobalamin in patients with renal dysfunction, as it requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in diabetic nephropathy 1

Use methylcobalamin or hydroxocobalamin instead in patients with impaired renal function 1, 5

Special Population Dosing

Post-Bariatric Surgery

• 1000 mcg intramuscularly monthly for life, OR 1
• 1000-2000 mcg oral daily indefinitely 1, 5

Ileal Resection

• Resection >20 cm: 1000 mcg intramuscularly monthly for life 1
• Resection <20 cm typically does not cause deficiency 7

Crohn's Disease with Ileal Involvement

• Annual screening required 1
• Prophylactic treatment with 1000 mcg intramuscularly monthly if >30-60 cm of ileum involved 1

Monitoring Strategy

First Year

• Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months after initiating treatment 1, 2
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2
• Methylmalonic acid (MMA) should be measured if B12 levels remain borderline or symptoms persist (target MMA <271 nmol/L) 1

After Stabilization

• Annual monitoring of B12 levels and homocysteine once levels stabilize 1, 2
• Monitor neurological symptoms clinically, as symptom improvement is more important than laboratory values 1

Critical Pitfalls to Avoid

Never administer folic acid before treating B12 deficiency, as it may mask the anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress 1, 2

Do not discontinue B12 supplementation even if levels normalize, as patients with malabsorption require lifelong therapy 1

Do not use intravenous route, as almost all vitamin will be lost in the urine 3

Do not rely on standard monthly dosing for all patients, as up to 50% may require more frequent injections (weekly to every 2-4 weeks) to remain symptom-free based on clinical response, not laboratory titration 8

Maintenance Dose Considerations

While guidelines recommend 1 mg every 2-3 months, some patients require monthly dosing (1000 mcg) to meet metabolic requirements 1, 9

The 1000 mcg dose results in greater vitamin retention compared to 100 mcg, with no disadvantage in cost or toxicity 9

Adjust injection frequency based on symptom control rather than laboratory values, as clinical and patient experience suggests significant interindividual variation in requirements 8