Cyanocobalamin Dosing for Vitamin B12 Deficiency
For treating vitamin B12 deficiency in adults, oral cyanocobalamin 1000-2000 mcg daily is as effective as intramuscular therapy for most patients, but intramuscular hydroxocobalamin 1000 mcg three times weekly for 2 weeks followed by maintenance every 2-3 months is required for severe malabsorption or neurological involvement. 1
Standard Maintenance Requirements
Healthy Adults and Pregnancy
- Healthy adults require 4 mcg/day for maintenance 2
- Pregnant women need 5 mcg/day 2
- Breastfeeding mothers require at least 2.8 mcg/day orally 2
Treatment of Established Deficiency
Oral Therapy (First-Line for Most Patients)
Oral cyanocobalamin 1000-2000 mcg daily effectively treats B12 deficiency in patients without severe neurological symptoms, including those with pernicious anemia. 1, 3, 4
- The minimum effective dose is 647-1032 mcg daily to achieve 80-90% maximal reduction in methylmalonic acid 5
- Daily doses of 1000 mcg are effective even in pernicious anemia patients lacking intrinsic factor, as passive diffusion bypasses the need for intrinsic factor-mediated absorption 3, 4
- For food-cobalamin malabsorption without pernicious anemia, 250 mcg daily may suffice 4
- Oral therapy is effective in Crohn's disease patients, even with ileal resection, with 94.7% achieving normalization 6
Intramuscular Therapy (Required for Specific Situations)
Intramuscular hydroxocobalamin is mandatory for patients with neurological involvement or when oral therapy fails. 1, 7
Initial Loading Phase
- With neurological symptoms: Hydroxocobalamin 1000 mcg IM on alternate days until no further improvement 1, 7
- Without neurological symptoms: Hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks 1, 7
Maintenance Phase
- Hydroxocobalamin 1000 mcg IM every 2-3 months for life 1, 7
- Monthly dosing (1000 mcg IM) is an acceptable alternative that may better meet metabolic requirements in some patients 1, 7
Special Populations and Malabsorption
Post-Bariatric Surgery
- After Roux-en-Y gastric bypass or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 7
- After sleeve gastrectomy or gastric banding: 250-350 mcg/day oral or 1000 mcg/week sublingual 7
Ileal Resection or Crohn's Disease
- Prophylactic treatment with hydroxocobalamin 1000 mcg IM monthly for life is required for ileal resection >20 cm, even without documented deficiency 7, 6
- Ileal Crohn's disease involving >30-60 cm requires annual screening and prophylactic supplementation 7
- Oral cyanocobalamin 1000 mcg daily is effective for both acute treatment and maintenance in Crohn's disease patients, with 81.7% maintaining adequate levels over 3 years 6
Renal Dysfunction
In patients with renal impairment, use methylcobalamin or hydroxocobalamin instead of cyanocobalamin, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy. 1, 7, 8
Monitoring Strategy
Initial Follow-Up
- Recheck serum B12 at 3 months after initiating supplementation 7
- Second recheck at 6 months 7
- Third recheck at 12 months 7
- Transition to annual monitoring once levels stabilize for two consecutive checks 7
Laboratory Targets
- Serum B12 should normalize to >258 pmol/L (>350 ng/L) 7
- Target homocysteine <10 μmol/L for optimal outcomes 7
- Methylmalonic acid should decrease to <271 nmol/L 7
What to Measure
- Serum B12 as primary marker 7
- Complete blood count to evaluate resolution of megaloblastic anemia 7
- Methylmalonic acid if B12 levels remain borderline or symptoms persist 7
- Homocysteine as additional functional marker 7
Critical Pitfalls to Avoid
Never Give Folic Acid Before B12 Treatment
Administering folic acid before or without adequate B12 treatment can mask the anemia while allowing irreversible neurological damage to progress, including subacute combined degeneration of the spinal cord. 7
Do Not Stop Treatment Prematurely
- Patients with malabsorption require lifelong supplementation 7
- Do not discontinue B12 even if levels normalize, as patients will likely require ongoing therapy 7
- Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy 7
Recognize Inadequate Dosing
- The recommended dietary allowance of 2.4 mcg/day is insufficient for treating deficiency 5
- Treatment requires doses more than 200 times the RDA 5
- For oral therapy, doses <500 mcg daily are often inadequate 5, 4
Formulation Considerations
Hydroxocobalamin is the preferred intramuscular formulation due to superior tissue retention and established dosing protocols across all major guidelines. 7