What is the treatment for vitamin B12 deficiency?

Treatment of Vitamin B12 Deficiency

For vitamin B12 deficiency without neurological involvement, administer hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks, then transition to maintenance therapy with 1 mg intramuscularly every 2-3 months for life. 1, 2

Initial Treatment Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1, 2
• After maximum improvement, transition to maintenance with hydroxocobalamin 1 mg intramuscularly every 2 months (not 2-3 months as in non-neurological cases) 1, 2
• This more aggressive approach is critical because neurological damage can become irreversible if undertreated 1

Without Neurological Involvement

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2
• Then maintenance: 1 mg intramuscularly every 2-3 months lifelong 1, 2

FDA-Approved Alternative Dosing

• The FDA label provides an alternative regimen: 30 mcg daily for 5-10 days, followed by 100-200 mcg monthly 3
• However, current guideline consensus favors the higher-dose protocols above for more reliable outcomes 1, 2

Maintenance Therapy

Monthly administration of 1000 mcg intramuscularly is more effective than 3-monthly injections and should be considered standard practice. 4

• Standard maintenance: Hydroxocobalamin 1 mg every 2-3 months for life 1, 2
• Some patients require more frequent dosing (monthly or even weekly) to remain symptom-free, with up to 50% needing individualized regimens 5
• Do not use serum B12 or methylmalonic acid levels to "titrate" injection frequency—base adjustments on clinical symptoms only 5

Oral Therapy Considerations

Oral vitamin B12 can be effective only after initial intramuscular loading and only in patients without malabsorption or neurological symptoms: 4, 6

• Dose: 1000-2000 mcg daily orally 1, 4, 6
• Oral therapy is as effective as intramuscular for correcting anemia in patients with adequate absorption 6, 7
• However, intramuscular therapy remains preferred for malabsorption conditions (pernicious anemia, ileal resection, bariatric surgery) where lifelong parenteral therapy is required 2, 3

Special Populations

Post-Bariatric Surgery

• 1 mg intramuscularly every 3 months or 1 mg daily orally indefinitely 1, 6
• For pregnancy planning: check B12 levels every 3 months 1

Ileal Resection

• If >20 cm of distal ileum resected: prophylactic 1000 mcg intramuscularly monthly for life 1, 2
• Even 30-60 cm of ileal Crohn's disease without resection requires annual screening 1

Elderly Patients (>80 years)

• Higher risk population with 18.1% prevalence of metabolic B12 deficiency 1, 2
• Consider methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 4

Renal Dysfunction

• Avoid cyanocobalamin—it requires renal clearance of cyanide and is associated with doubled cardiovascular risk (HR 2.0) 1
• Use methylcobalamin or hydroxocobalamin instead 1, 4

Thrombocytopenia

• Intramuscular administration is safe with platelet count >50 × 10⁹/L 1, 2
• For platelets 25-50 × 10⁹/L: use 25-27 gauge needles and apply pressure for 5-10 minutes 1
• For platelets <10 × 10⁹/L: consider platelet transfusion support before injection 1

Critical Pitfalls to Avoid

Never administer folic acid before treating vitamin B12 deficiency—this can mask the deficiency and precipitate subacute combined degeneration of the spinal cord, causing irreversible neurological damage. 1, 4, 2

• Always check both B12 and folate levels, as deficiencies may coexist 2
• In critically ill patients, it is acceptable to administer both B12 and folic acid simultaneously while awaiting confirmatory studies 3
• Do not discontinue B12 supplementation even if levels normalize—patients with malabsorption require lifelong therapy 1

Monitoring

• Check serum B12 and homocysteine every 3 months until stabilization, then annually 1, 4
• Target homocysteine <10 μmol/L for optimal outcomes 1
• Monitor serum potassium closely in the first 48 hours of treatment and supplement if necessary 3
• Reticulocytosis typically occurs between days 3-10, confirming the diagnosis 3
• Monitor for neurological symptoms (paresthesias, gait disturbances, cognitive changes) and increase injection frequency if symptoms recur 1

Choice of Formulation

• Hydroxocobalamin is preferred over cyanocobalamin for most patients 1, 4
• Methylcobalamin is an acceptable alternative, especially in renal dysfunction 1, 4
• Cyanocobalamin should be avoided in patients with kidney disease due to cyanide accumulation risk 1