What is the recommended dosing regimen for oral vs intramuscular (IM) vitamin B12 supplementation in patients with vitamin B12 deficiency?

Oral vs Intramuscular Vitamin B12 Dosing

For most patients with vitamin B12 deficiency, oral supplementation with 1000-2000 mcg daily is as effective as intramuscular therapy and should be the first-line treatment, except in patients with severe neurological symptoms or critical illness who require intramuscular administration. 1, 2

Initial Treatment Protocol

Patients WITHOUT Neurological Involvement

• Oral route: 1000-2000 mcg daily indefinitely is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 3, 1, 2
• IM route (if preferred): Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance of 1 mg every 2-3 months for life 3, 4

Patients WITH Neurological Involvement

• IM route is mandatory: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg every 2 months for life 3, 4
• Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms 2

Evidence Supporting Oral Equivalence

• High-quality RCTs demonstrate that 1000-2000 mcg oral doses are as effective as intramuscular administration in achieving hematological and neurological responses 5
• Oral vitamin B12 supplementation can be used in most patients and is noninferior to intramuscular supplementation 1
• A retrospective study of 36 Crohn's disease patients showed oral therapy (1200 mg daily) to be effective in treating vitamin B12 deficiency 6

Special Population Dosing

Post-Bariatric Surgery

• Option 1: 1 mg intramuscularly every 3 months indefinitely 3, 7
• Option 2: 1000-2000 mcg orally daily indefinitely 3, 7

Crohn's Disease with Ileal Resection >20 cm

• 1000 mcg intramuscularly every month indefinitely for prophylaxis 6, 7
• Patients with ileal involvement/resection should be screened yearly for B12 deficiency 6

Pernicious Anemia

• Parenteral therapy is required for life; oral form is not dependable 8, 9
• FDA-approved regimen: 30 mcg daily for 5-10 days, followed by 100-200 mcg monthly intramuscularly 8

Monitoring Strategy

• First year: Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months 3, 7
• After stabilization: Annual monitoring of B12 levels and homocysteine 3, 4
• Target homocysteine: <10 μmol/L for optimal outcomes 3, 4

Critical Pitfalls to Avoid

• Never administer folic acid before treating B12 deficiency - this can mask anemia while allowing irreversible neurological damage to progress 3, 7
• Do not discontinue B12 supplementation even if levels normalize; patients with malabsorption require lifelong therapy 3
• Do not use cyanocobalamin in patients with renal dysfunction; use methylcobalamin or hydroxocobalamin instead due to risk of cyanide accumulation and cardiovascular complications 4, 7
• Titration of injection frequency based on measuring biomarkers such as serum B12 or MMA should not be practiced 10

When to Choose IM Over Oral

• Severe neurological symptoms (paresthesias, ataxia, cognitive impairment) 3, 2
• Critically ill patients 8
• Pernicious anemia (malabsorption is absolute) 8, 9
• Patient preference or concerns about oral adherence 10
• Up to 50% of patients may require individualized injection regimens with more frequent administration (ranging from daily to every 2-4 weeks) to remain symptom-free 10

Practical Considerations

• Hydroxocobalamin is preferred over cyanocobalamin due to longer tissue retention 4
• Oral therapy requires daily adherence but avoids injection-related complications 1, 2
• IM injections should be administered in the deltoid or vastus lateralis, avoiding the buttock due to sciatic nerve injury risk 7
• In patients with thrombocytopenia (platelets >50 × 10⁹/L), IM administration can be safely performed 7