What is the recommended dosing for Vitamin B12 (Cobalamin) in adults with a deficiency?

Vitamin B12 Dosing for Deficiency in Adults

For adults with confirmed B12 deficiency, use hydroxocobalamin 1000 mcg (1 mg) intramuscularly: if neurological symptoms are present, give on alternate days until no further improvement, then every 2 months for life; if no neurological symptoms, give three times weekly for 2 weeks, then every 2-3 months for life. 1, 2, 3

Treatment Protocol Based on Neurological Involvement

With Neurological Symptoms (paresthesias, gait disturbance, cognitive changes)

• Loading phase: Hydroxocobalamin 1000 mcg IM on alternate days until no further improvement occurs 1, 2, 3
• Maintenance: Hydroxocobalamin 1000 mcg IM every 2 months for life 1, 2, 3
• This aggressive approach is critical because neurological damage can become irreversible if treatment is delayed beyond 3 months 4

Without Neurological Symptoms

• Loading phase: Hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks 1, 2, 3
• Maintenance: Hydroxocobalamin 1000 mcg IM every 2-3 months for life 1, 2, 3
• Monthly dosing (every 4 weeks) is more effective than every 3 months and may be necessary to meet metabolic requirements in up to 50% of patients 1, 5, 6

Alternative: High-Dose Oral Therapy

Oral vitamin B12 can be used ONLY in patients without neurological symptoms and after the initial loading phase. 1, 7

• Dose: 1000-2000 mcg daily 1, 7, 8, 9
• Oral therapy at these doses is as effective as IM for correcting anemia and biochemical markers in patients with adequate absorption 7, 9
• However, IM therapy leads to more rapid improvement and remains preferred for severe deficiency 7

Special Population Adjustments

Post-Bariatric Surgery

• Roux-en-Y or biliopancreatic diversion: 1000 mcg IM monthly OR 1000-2000 mcg oral daily 1
• Sleeve gastrectomy or gastric banding: 250-350 mcg oral daily OR 1000 mcg sublingual weekly 1
• Pregnant women after bariatric surgery: 1000 mcg IM every 3 months or 1000 mcg oral daily 1

Ileal Resection or Crohn's Disease

• >20 cm distal ileum resected: 1000 mcg IM monthly for life (prophylactic) 1, 2
• Ileal Crohn's disease (>30-60 cm involvement): Annual screening and prophylactic supplementation with 1000 mcg IM monthly or 1000-2000 mcg oral daily 1, 2

Renal Dysfunction

• Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 2
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with a 2-fold increased risk of cardiovascular events in patients with diabetic nephropathy 1, 2
• Dialysis patients require routine supplementation to replace dialysis losses 2

Monitoring Strategy

First Year

• Check serum B12, complete blood count, and homocysteine at 3,6, and 12 months 1, 2, 3
• Target homocysteine <10 μmol/L for optimal outcomes 1, 2, 3
• Evaluate for resolution of symptoms (fatigue, paresthesias, cognitive changes) 2

After Stabilization

• Annual monitoring of B12 levels and homocysteine once levels stabilize for two consecutive checks 1, 2
• Do not stop monitoring after one normal result—patients with malabsorption can relapse 1

During Loading Phase

• Monitor serum potassium closely in the first 48 hours, especially in patients with severe anemia 4
• Check hematocrit and reticulocyte count daily from days 5-7, then frequently until hematocrit normalizes 4
• If reticulocytes do not increase or remain elevated, reevaluate diagnosis or consider complicating conditions (iron deficiency, folate deficiency) 4

Critical Pitfalls to Avoid

Never Give Folic Acid Before B12 Treatment

• Folic acid can mask the anemia of B12 deficiency while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 1, 2, 4
• Always check B12 status before initiating folic acid supplementation 1

Do Not Discontinue Treatment Prematurely

• Patients with malabsorption require lifelong therapy 2, 3, 4
• Stopping injections after symptoms improve will result in recurrence of anemia and irreversible nerve damage 2, 4

Recognize Functional Deficiency

• Patients with borderline B12 levels (140-200 pmol/L or 180-350 pg/mL) and elevated methylmalonic acid (>271 nmol/L) or homocysteine (>15 μmol/L) have functional deficiency and require treatment 1, 2

Formulation Preference

Hydroxocobalamin is preferred over cyanocobalamin due to superior tissue retention and established dosing protocols in all major guidelines. 2, 3

• Hydroxocobalamin has longer tissue retention compared to cyanocobalamin 2, 3
• All guideline-based dosing regimens are established for hydroxocobalamin 2
• Cyanocobalamin 1000 mcg IM monthly is an acceptable alternative if hydroxocobalamin is unavailable 1, 5

Administration Details

• Route: Intramuscular or deep subcutaneous injection 3
• Preferred sites: Deltoid or vastus lateralis 3
• Avoid buttock injections due to risk of sciatic nerve injury; if used, only the upper outer quadrant with needle directed anteriorly 1
• In patients with severe thrombocytopenia (platelets <50 × 10⁹/L), use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 2
• Consider platelet transfusion if platelets <10 × 10⁹/L before IM administration 2