Vitamin B12 Dosage Recommendations
For vitamin B12 deficiency treatment, use hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months for life if no neurological symptoms are present; if neurological symptoms exist, give 1 mg on alternate days until improvement stops, then 1 mg every 2 months for life. 1, 2
Initial Treatment Protocol
Without Neurological Involvement
- Hydroxocobalamin 1 mg IM three times per week for 2 weeks 1, 2
- Then transition to maintenance dosing 1, 2
With Neurological Involvement
- Hydroxocobalamin 1 mg IM on alternate days until no further improvement 1, 2
- This more aggressive approach is critical to prevent irreversible neurological damage 1
- After maximum improvement achieved, switch to maintenance 1, 2
Maintenance Therapy
The standard maintenance regimen is hydroxocobalamin 1 mg IM every 2-3 months for life 1, 3, 2
However, important nuances exist:
- Monthly dosing (1000 mcg IM) may be more effective than every 2-3 months and is necessary to meet metabolic requirements in many patients 3, 4
- For neurological involvement cases specifically, use 1 mg every 2 months (more frequent than standard) 1, 2
- Up to 50% of patients require individualized injection frequencies ranging from every 2-4 weeks to remain symptom-free 5
Special Population Dosing
Post-Bariatric Surgery
- 1 mg every 3 months IM OR 1 mg (1000 mcg) daily orally 1, 3
- After Roux-en-Y or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 1
- After sleeve gastrectomy or gastric banding: 250-350 mcg/day oral OR 1000 mcg/week sublingual 1
Ileal Resection
Thrombocytopenia
- Platelet count >50 × 10⁹/L: Standard IM dosing safe 1
- Platelet count 25-50 × 10⁹/L: Use 25-27G needles with 5-10 minutes pressure post-injection 1
- Platelet count <10 × 10⁹/L: Consider platelet transfusion before IM administration 1
Renal Dysfunction
- Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin 1, 3
- Cyanocobalamin requires renal clearance and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1
Alternative: Oral High-Dose Therapy
Oral vitamin B12 1000-2000 mcg daily is as effective as IM therapy for correcting deficiency 3, 6, 7
Key considerations:
- Only appropriate after initial IM loading phase if no neurological symptoms present 3
- Requires intact absorption capacity (not suitable for pernicious anemia or malabsorption) 8, 6
- Studies show 2000 mcg oral daily achieves similar serum levels and neurological responses as IM 7
FDA-Approved Cyanocobalamin Dosing (Alternative to Hydroxocobalamin)
If using cyanocobalamin instead of hydroxocobalamin:
- 100 mcg IM daily for 6-7 days 8
- Then 100 mcg on alternate days for 7 doses 8
- Then 100 mcg every 3-4 days for 2-3 weeks 8
- Maintenance: 100 mcg monthly for life 8
However, 1000 mcg cyanocobalamin is superior to 100 mcg with greater retention, no increased toxicity, and may be necessary for metabolic requirements 4
Critical Pitfalls to Avoid
- Never administer folic acid before treating B12 deficiency - this masks deficiency and can precipitate subacute combined degeneration of the spinal cord 1, 3, 2
- Avoid IV route - results in almost all vitamin being lost in urine 8
- Do not use cyanocobalamin in renal dysfunction - use methylcobalamin or hydroxocobalamin instead 1, 3
- Do not discontinue therapy even if levels normalize - lifelong treatment required for malabsorption causes 1
- Do not titrate injection frequency based on serum B12 or MMA levels - base frequency on symptom control 5
Monitoring Parameters
- Check serum B12 and homocysteine every 3 months until stabilization, then yearly 1, 3
- Target homocysteine <10 μmol/L for optimal cardiovascular outcomes 1
- Monitor for neurological symptom improvement (paresthesias, gait disturbances, cognitive changes) 1
- For post-bariatric surgery patients planning pregnancy: check B12 every 3 months 1