What is the recommended treatment for Vitamin B12 deficiency?

Treatment of Vitamin B12 Deficiency

For vitamin B12 deficiency with neurological symptoms, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then transition to maintenance therapy with 1 mg IM every 2 months for life; for deficiency without neurological involvement, give hydroxocobalamin 1 mg IM three times weekly for 2 weeks, followed by 1 mg IM every 2-3 months lifelong. 1

Initial Assessment and Diagnosis

Before initiating treatment, confirm the diagnosis and identify the underlying cause:

• Biochemical confirmation: Measure serum B12 (deficiency confirmed when <150 pmol/L or 203 ng/L), with methylmalonic acid >271 nmol/L or homocysteine >15 μmol/L confirming functional deficiency in borderline cases 1, 2
• Identify the cause: Determine if deficiency is due to malabsorption (pernicious anemia, ileal resection >20 cm, bariatric surgery, Crohn's disease with ileal involvement), dietary insufficiency (vegan/vegetarian diet), or medication-induced (chronic PPI or metformin use) 1, 2
• Assess for neurological involvement: Evaluate for peripheral neuropathy, paresthesias, gait disturbances, cognitive impairment, or subacute combined degeneration of the spinal cord, as this determines treatment intensity 1

Treatment Protocol Based on Neurological Status

With Neurological Involvement (More Aggressive Protocol)

• Loading phase: Hydroxocobalamin 1 mg IM on alternate days until no further neurological improvement is observed 1, 3
• Maintenance phase: Hydroxocobalamin 1 mg IM every 2 months for life 1, 3
• Clinical monitoring: Pain and paresthesias typically improve before motor symptoms; monitor neurological status regularly rather than relying solely on laboratory values 1

Without Neurological Involvement (Standard Protocol)

• Loading phase: Hydroxocobalamin 1 mg IM three times weekly for 2 weeks 1, 2, 3
• Maintenance phase: Hydroxocobalamin 1 mg IM every 2-3 months for life 1, 2, 3
• Some patients may require monthly dosing (1000 mcg IM) to meet metabolic requirements 1, 4

Alternative Formulations and Routes

Oral Therapy Option

• High-dose oral cyanocobalamin (1000-2000 mcg daily) can be therapeutically equivalent to parenteral therapy, even in malabsorption conditions, through passive absorption 4, 5, 6, 7
• A 2024 prospective study demonstrated that oral cyanocobalamin 1000 mcg daily effectively reversed B12 deficiency in pernicious anemia patients within 1 month, with sustained improvement over 12 months 5
• However, traditional guidelines and FDA labeling state that oral forms are "not dependable" for pernicious anemia, and parenteral therapy remains the gold standard 8, 9

Formulation Selection

• Hydroxocobalamin is preferred over cyanocobalamin due to superior tissue retention and established dosing protocols in all major guidelines 1, 3
• Avoid cyanocobalamin in renal dysfunction: Use methylcobalamin or hydroxocobalamin instead, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1, 3

Special Population Considerations

Post-Bariatric Surgery Patients

• Roux-en-Y gastric bypass or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 1
• Sleeve gastrectomy or gastric banding: 250-350 mcg/day oral or 1000 mcg/week sublingual 1
• Pregnancy planning: Check B12 levels every 3 months throughout pregnancy 1, 2

Crohn's Disease with Ileal Involvement

• Ileal resection >20 cm: Prophylactic hydroxocobalamin 1000 mcg IM monthly for life, even without documented deficiency 1, 2
• Ileal involvement >30-60 cm without resection: Annual screening and prophylactic supplementation 1

Patients with Thrombocytopenia

• Moderate thrombocytopenia (platelets >50 × 10⁹/L): Standard IM administration is safe 1
• Severe thrombocytopenia (platelets 25-50 × 10⁹/L): Use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 1
• Critical thrombocytopenia (platelets <10 × 10⁹/L): Consider platelet transfusion support before IM administration 1

Monitoring Strategy

First Year of Treatment

• 3 months: Recheck serum B12, complete blood count, homocysteine, and methylmalonic acid 1, 2
• 6 months: Repeat same parameters to ensure adequate response 1
• 12 months: Final first-year assessment to confirm stabilization 1
• Target homocysteine: <10 μmol/L for optimal cardiovascular outcomes 1, 3

Long-Term Monitoring

• Annual monitoring once levels stabilize: Serum B12, complete blood count, and homocysteine 1, 2, 3
• High-risk patients (Crohn's disease with ileal involvement, post-bariatric surgery): Screen yearly even if asymptomatic 1, 2
• Clinical monitoring is paramount: Assess for recurrent neurological symptoms (paresthesias, gait disturbances, cognitive changes) and increase injection frequency if symptoms return, regardless of laboratory values 1, 10

Critical Pitfalls to Avoid

• Never administer folic acid before ensuring adequate B12 treatment: Folic acid can mask B12 deficiency anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2, 3
• Do not discontinue therapy after levels normalize: Patients with malabsorption require lifelong supplementation and will relapse if treatment is stopped 1, 2, 10
• Do not use laboratory values alone to guide injection frequency: Up to 50% of patients require individualized regimens with more frequent injections (ranging from weekly to every 2-4 weeks) to remain symptom-free, despite normal B12 levels 10
• Avoid the buttock as an injection site: Use deltoid or vastus lateralis to minimize risk of sciatic nerve injury 1, 3

Practical Administration Details

• Route: Intramuscular or deep subcutaneous injection 3, 8, 9
• Preferred sites: Deltoid or vastus lateralis muscle 1, 3
• Avoid intravenous route: IV administration results in almost all vitamin being lost in urine 8, 9
• Inspect solution: Check for particulate matter and discoloration before administration 8, 9