What are the recommended vitamin B12 (cobalamin) dosing regimens for adults with deficiency (e.g., pernicious anemia, malabsorption, post‑bariatric surgery), for patients who can absorb oral cobalamin, for pregnant or lactating women, and for infants and children, including route (intramuscular, oral, subcutaneous) and adjustments for severe renal impairment?

Vitamin B12 Dosing Recommendations

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

Treatment Algorithm Based on Clinical Presentation

Malabsorption WITH Neurological Symptoms

• Initiate hydroxocobalamin 1000 mcg IM on alternate days until neurological improvement plateaus (may require weeks to months) 1, 3, 2
• Neurological manifestations include paresthesias, numbness, gait disturbances, cognitive difficulties, memory problems, glossitis, or tongue tingling 1, 2
• After neurological recovery, maintain with hydroxocobalamin 1000 mcg IM every 2 months for life 1, 3, 2
• Some patients require monthly dosing (1000 mcg IM) to remain symptom-free, particularly those with persistent symptoms despite standard dosing, post-bariatric surgery patients, or extensive ileal disease 3, 2, 4

Malabsorption WITHOUT Neurological Symptoms

• Begin hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks 1, 3, 2
• Continue maintenance with hydroxocobalamin 1000 mcg IM every 2–3 months for life 1, 3, 2

Dietary Deficiency (Intact Absorption)

• Oral cyanocobalamin 1000–2000 mcg daily until levels normalize, then continue as maintenance 1, 3
• The required dose is more than 200 times the recommended dietary allowance of 2.4 mcg/day because even with intact absorption, high doses are needed to ensure adequate uptake 1, 5
• Oral doses of 647–1032 mcg daily produce 80–90% of maximal reduction in methylmalonic acid 5

Special Populations

Post-Bariatric Surgery

• Roux-en-Y gastric bypass or biliopancreatic diversion: 1000–2000 mcg/day oral OR 1000 mcg/month IM indefinitely 1, 3
• Sleeve gastrectomy or gastric banding: 250–350 mcg/day oral OR 1000 mcg/week sublingual 3
• Women planning pregnancy after bariatric surgery require B12 monitoring every 3 months throughout conception and gestation 1, 3, 2

Ileal Resection or Crohn's Disease

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

Pregnant and Lactating Women

• Adequate intake: 5 mcg/day during pregnancy, 4.5 mcg/day during lactation 6
• Women with permanent malabsorption (pernicious anemia, ileal resection >20 cm, post-bariatric surgery) require lifelong IM injections (typically monthly), with increased monitoring frequency during pregnancy 2
• Do not start high-dose folic acid (5 mg) until adequate B12 status is confirmed, as folic acid can mask B12-related anemia while allowing irreversible neurological damage 2

Infants and Children on Parenteral Nutrition

• Preterm and term infants up to 12 months: 0.3 mcg/kg/day 3
• Children >12 months: 1 mcg/day 3

Renal Impairment

• Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin in patients with renal dysfunction 1, 3, 2
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (hazard ratio 2.0) in diabetic nephropathy 1, 3, 2
• Dialysis patients benefit from routine B vitamin supplementation including B12 to replace dialysis losses, though B12 may not completely normalize homocysteine in this population 3, 2

Route Selection

When to Use Intramuscular (IM) Route

• All malabsorption causes: pernicious anemia, gastrectomy, ileal resection >20 cm, post-bariatric surgery, ileal Crohn's disease 1, 2, 4
• Any neurological involvement regardless of cause 1, 3, 2
• Preferred formulation: hydroxocobalamin due to superior tissue retention and established dosing protocols across all major guidelines 2, 4

When Oral Route Is Acceptable

• Dietary insufficiency with intact gastrointestinal absorption 1, 4, 7
• Vegetarians, vegans, older adults with inadequate intake 8, 7
• Dose: 1000–2000 mcg daily of cyanocobalamin 1, 5, 7
• At least 1000 mcg/day is needed for pernicious anemia if oral route is attempted, though IM is preferred 7

Subcutaneous Administration

• Can be used as alternative to IM with same dosing regimen 1

Monitoring Schedule

First Year

• Recheck serum B12 at 3 months, 6 months, and 12 months 1, 2
• At each visit, measure serum B12, complete blood count, methylmalonic acid (if available and B12 remains borderline), and homocysteine 1, 2
• Target homocysteine <10 μmol/L for optimal cardiovascular outcomes 3, 2
• Include iron studies (ferritin, transferrin saturation) at every monitoring visit, as iron deficiency frequently coexists and can blunt hematologic response 2

After Stabilization

• Annual monitoring once levels stabilize (typically by 6–12 months) 1, 2
• Post-bariatric surgery patients planning pregnancy require more frequent monitoring every 3 months 3, 2

Timing of Lab Draw After IM Injection

• Serum B12 sampling should be timed prior to the next scheduled IM injection 6
• Clinical monitoring of neurological symptoms is more important than laboratory values in patients with neurological involvement 2

Critical Pitfalls to Avoid

Never Give Folic Acid Before B12 Correction

• Folic acid can mask megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress 1, 3, 2
• After B12 repletion, add folic acid 5 mg daily only if folate deficiency is also documented 2

Do Not Stop Treatment After One Normal Result

• Patients with malabsorption or dietary insufficiency require lifelong supplementation and can relapse 1, 2
• Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy 2

Do Not Use Serum B12 Alone to Rule Out Deficiency

• Standard serum B12 testing misses functional deficiency in up to 50% of cases 1
• Measure methylmalonic acid (>271 nmol/L confirms functional deficiency) and homocysteine when B12 is borderline (140–200 pmol/L or 180–350 pg/mL) 1, 2

Do Not "Titrate" Injection Frequency Based on Biomarkers

• Up to 50% of individuals require individualized injection regimens with more frequent administration (ranging from daily to every 2–4 weeks) to remain symptom-free 4
• Clinical response and symptom resolution guide frequency adjustments, not serum B12 or MMA levels 4

Avoid Cyanocobalamin in Renal Dysfunction

• Associated with increased cardiovascular events and requires renal clearance 1, 3, 2

High-Risk Populations Requiring Prophylactic Treatment

Even without documented deficiency, start prophylactic hydroxocobalamin 1000 mcg IM monthly indefinitely for: 2

• 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

Safety Profile

• Vitamin B12 has no established upper toxicity limit and excess amounts are readily excreted in urine without toxicity 1
• High-dose oral supplementation (1000–2000 mcg daily) is safe for long-term use 1
• Both oral and IM formulations are well tolerated at studied doses 9