What is the recommended adult dose of vitamin B12 (cobalamin) for treatment of deficiency and for prophylaxis?

Vitamin B12 Dosing Guidelines

For adults with confirmed B12 deficiency due to malabsorption (pernicious anemia, post-bariatric surgery, ileal resection), administer hydroxocobalamin 1000 µg intramuscularly three times weekly for 2 weeks if no neurological symptoms are present, then maintain with 1000 µg IM every 2–3 months for life. 1, 2, 3

Treatment Based on Cause and Neurological Status

Malabsorption WITH Neurological Symptoms

• Start hydroxocobalamin 1000 µg IM on alternate days until neurological improvement plateaus (typically weeks to months) 1, 2, 3
• Neurological manifestations include paresthesias, numbness, gait disturbance, cognitive difficulties, memory problems, glossitis, or tongue tingling 1, 2
• After neurological recovery plateaus, continue hydroxocobalamin 1000 µg IM every 2 months for life 1, 2, 3
• Up to 50% of patients require more frequent dosing (weekly to monthly) to remain symptom-free, despite guideline recommendations 4

Malabsorption WITHOUT Neurological Symptoms

• Hydroxocobalamin 1000 µg IM three times weekly for 2 weeks 1, 2, 3
• Maintenance: 1000 µg IM every 2–3 months for life 1, 2, 3
• Some patients with persistent symptoms require monthly 1000 µg IM 2, 3, 4

Dietary Deficiency (Intact Absorption)

• Oral cyanocobalamin 1000–2000 µg daily until serum B12 normalizes, then continue as maintenance 1, 3, 5, 6
• This dose is >200 times the RDA (2.4 µg/day) because high oral doses are needed for adequate passive absorption 3, 7
• At least 1000 µg/day oral is required for pernicious anemia, and 250 µg/day for food-cobalamin malabsorption 5, 8

Special Population Dosing

Post-Bariatric Surgery

• Roux-en-Y or biliopancreatic diversion: 1000–2000 µg oral daily OR 1000 µg IM monthly indefinitely 1, 2, 3
• Sleeve gastrectomy or gastric banding: 250–350 µg oral daily OR 1000 µg weekly sublingual 2, 3
• Women planning pregnancy require B12 monitoring every 3 months throughout conception and gestation 2, 3

Ileal Resection or Crohn's Disease

• Ileal resection >20 cm: prophylactic hydroxocobalamin 1000 µg IM monthly for life, even without documented deficiency 1, 2, 3
• Ileal Crohn's disease >30–60 cm involvement: annual screening plus prophylactic supplementation 1, 2, 3
• Resection <20 cm typically does not cause deficiency 1, 2

Pregnancy and Lactation

• Adequate intake: 5 µg/day during pregnancy and 4.5 µg/day during lactation 1, 3
• Women with permanent malabsorption need lifelong IM injections (typically monthly) with more frequent monitoring during pregnancy 2, 3
• Never start high-dose folic acid (5 mg) until B12 status is confirmed, as folic acid masks anemia while permitting irreversible neurological damage 1, 2, 3

Renal Impairment

• Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin 1, 2, 3
• Cyanocobalamin requires renal clearance and is associated with a 2-fold increase in cardiovascular events in diabetic nephropathy 2, 3
• Dialysis patients should receive routine B-vitamin supplementation to replace dialysis losses 2, 3

Prophylactic Treatment for High-Risk Groups

Monthly hydroxocobalamin 1000 µg IM indefinitely for individuals without documented deficiency who have: 1, 3

• Ileal resection >20 cm
• Crohn's disease with ileal involvement
• Post-bariatric surgery
• Chronic PPI or metformin use >4 months
• Strict vegetarian/vegan diet
• Age >75 years

Monitoring Schedule

• First year: recheck serum B12 at 3,6, and 12 months 2, 3
• At each visit: serum B12, complete blood count, methylmalonic acid (if B12 borderline 180–350 pg/mL), and homocysteine 1, 2, 3
• Target homocysteine <10 µmol/L for optimal cardiovascular outcomes 1, 2, 3
• Include iron studies (ferritin, transferrin saturation) at every monitoring visit 1, 3
• After stabilization (6–12 months), perform annual monitoring 2, 3
• Draw serum B12 samples prior to the next scheduled IM injection (trough level) 2, 3

Critical Pitfalls to Avoid

• Never give folic acid before correcting B12 deficiency—it masks anemia while allowing irreversible subacute combined degeneration of the spinal cord 1, 2, 3
• After B12 repletion, add folic acid 5 mg daily only if folate deficiency is documented 1, 2, 3
• Do not stop treatment after levels normalize—patients with malabsorption require lifelong supplementation 1, 3, 4
• Standard serum B12 testing misses functional deficiency in up to 50% of cases; measure methylmalonic acid (>271 nmol/L confirms deficiency) when B12 is borderline 1, 3
• Do not "titrate" injection frequency based on serum B12 or MMA levels—base dosing on clinical symptom control 4
• Avoid cyanocobalamin in renal dysfunction due to increased cardiovascular risk 2, 3

Route and Formulation Selection

• Hydroxocobalamin IM is the preferred formulation for all malabsorption causes and any neurological involvement due to superior tissue retention 1, 2, 3
• Oral cyanocobalamin 1000–2000 µg daily is acceptable for dietary insufficiency with intact absorption 1, 3, 5, 6
• Subcutaneous administration can substitute for IM with the same dosing regimen 3
• Vitamin B12 has no established upper toxicity limit; excess is excreted in urine without adverse effects 1, 3