What is the recommended dose of Vitamin B12 (Cobalamin) for an adult patient with a diagnosed Vitamin B12 deficiency?

Vitamin B12 Dosing for Deficiency

For adults with confirmed Vitamin B12 deficiency, the recommended dose is hydroxocobalamin 1000 mcg (1 mg) intramuscularly, with the frequency depending on whether neurological symptoms are present: alternate days until no further improvement if neurological involvement exists, or three times weekly for 2 weeks if no neurological symptoms, followed by maintenance therapy every 2-3 months for life. 1, 2

Initial Treatment Protocol

With Neurological Symptoms

• Loading phase: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further neurological improvement occurs 1, 2
• Maintenance: 1 mg intramuscularly every 2 months for life 1, 2
• Neurological symptoms include cognitive difficulties, peripheral neuropathy, paresthesias, gait disturbances, glossitis, or visual problems 3
• Critical warning: Neurological damage can become irreversible if treatment is delayed beyond 3 months 4

Without Neurological Symptoms

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

Oral vs. Intramuscular Administration

Oral vitamin B12 (1000-2000 mcg daily) is as effective as intramuscular administration for most patients without malabsorption and costs less. 3 However, parenteral therapy is required for:

• Pernicious anemia (intrinsic factor deficiency) 3, 1
• Ileal resection >20 cm 1
• Post-bariatric surgery patients 1
• Severe neurological manifestations 3
• Confirmed malabsorption 3

The evidence shows that oral high-dose B12 (1-2 mg daily) corrects anemia and neurologic symptoms as effectively as injections in patients with intact absorption 5, but intramuscular therapy leads to more rapid improvement 5.

Special Population Dosing

Post-Bariatric Surgery

• Roux-en-Y 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
• Lifelong supplementation required due to permanent malabsorption 3, 1

Ileal Resection or Crohn's Disease

• Resection >20 cm: Prophylactic 1000 mcg IM monthly for life, even without documented deficiency 1
• Ileal involvement >30-60 cm: Annual screening and prophylactic supplementation 1
• Resection <20 cm typically does not cause deficiency 3

Renal Dysfunction

• Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 2
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1

Maintenance Therapy Considerations

Up to 50% of patients require more frequent injections than the standard every 2-3 months to remain symptom-free. 6 Monthly dosing (1000 mcg IM monthly) is an acceptable alternative that may better meet metabolic requirements in:

• Patients with persistent symptoms despite standard dosing 1, 6
• Post-bariatric surgery patients 1
• Patients with extensive ileal disease or resection 1

The 1000 mcg dose is preferred over 100 mcg because much greater amounts are retained with no disadvantage in cost or toxicity 7.

Monitoring Strategy

First Year

• Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months 1, 2
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2
• Monitor for resolution of neurological symptoms and normalization of MCV 3

After Stabilization

• Annual monitoring of B12 levels and homocysteine once levels stabilize 1, 2
• Continue lifelong for patients with malabsorption conditions 1, 4

Critical Pitfalls to Avoid

Never administer folic acid before or without adequate B12 treatment. 1, 2, 4 Folic acid doses >0.1 mg/day may produce hematologic remission while allowing irreversible neurological damage to progress (subacute combined degeneration of the spinal cord) 4. This is the most dangerous error in B12 deficiency management.

Additional warnings:

• Do not rely solely on serum B12 to rule out deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid 3
• Do not stop monitoring after one normal result—patients with malabsorption often relapse 1
• Do not discontinue injections after symptoms improve in patients with permanent malabsorption 1
• Titration of injection frequency based on measuring biomarkers should not be practiced—base frequency on symptom control 6

Formulation Preference

Hydroxocobalamin is preferred over cyanocobalamin due to longer tissue retention 2, 6 and established dosing protocols across all major guidelines 1. Methylcobalamin is an acceptable alternative, particularly in renal dysfunction 1, 2.