What is the recommended starting dose of vitamin B12 (cobalamin) supplements?

Starting Dose of Vitamin B12 Supplementation

For oral supplementation in deficiency states, start with 1000-2000 mcg daily, which is as effective as intramuscular therapy for most patients; for intramuscular therapy, use 1000 mcg (1 mg) as the standard dose. 1, 2, 3

Oral Supplementation Dosing

High-dose oral vitamin B12 (1000-2000 mcg daily) is therapeutically equivalent to intramuscular administration for correcting both anemia and neurologic symptoms, even in patients with malabsorption. 2, 3, 4

• The evidence from randomized controlled trials demonstrates that 2000 mcg daily or 1000 mcg daily (initially daily, then weekly, then monthly) achieves the same hematological and neurological responses as intramuscular therapy 3
• Oral therapy at 300-1000 mcg per day may be therapeutically equivalent to parenteral therapy, though higher doses (1000-2000 mcg) are preferred for reliability 4
• Post-bariatric surgery patients specifically require 1000-2000 mcg daily orally or 1 mg intramuscular monthly indefinitely 1, 5

Intramuscular Dosing Protocol

For Patients WITH Neurological Involvement:

• Start with hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs 1, 6
• Then transition to maintenance: 1 mg intramuscularly every 2 months for life 1, 6

For Patients WITHOUT Neurological Involvement:

• Give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 6
• Then transition to maintenance: 1 mg intramuscularly every 2-3 months lifelong 1, 6

When to Choose Intramuscular Over Oral

Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe neurologic symptoms. 2

• Use IM therapy when neurological symptoms are present (paresthesias, gait disturbances, cognitive changes) 1
• Consider IM for patients with critical deficiency levels or symptomatic anemia requiring rapid correction 2
• After initial IM loading, many patients can transition to high-dose oral maintenance 3, 4

Special Population Considerations

Post-Bariatric Surgery:

• 1000-2000 mcg daily orally OR 1 mg intramuscularly every 3 months indefinitely 1, 5
• 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 (>20 cm):

• Prophylactic 1000 mcg intramuscularly monthly for life 1, 6

Pregnancy and Lactation:

• 4 mcg daily minimum (Food and Nutrition Board recommendation) 7, 8
• Higher doses may be needed if deficiency is present 7, 8

Pediatric:

• 0.5-3 mcg daily per Food and Nutrition Board recommendations 7, 8

Choice of B12 Formulation

Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin in patients with renal dysfunction, as cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy. 1

• Hydroxocobalamin is the preferred formulation for intramuscular therapy in guidelines 1, 6
• Cyanocobalamin is acceptable for oral therapy in patients with normal renal function 2, 3

Monitoring After Initiation

• First recheck at 3 months after starting supplementation 1
• Second recheck at 6 months 1
• Third recheck at 12 months 1
• Then annual monitoring once levels stabilize 1, 6
• Measure serum B12, complete blood count, and consider homocysteine (target <10 μmol/L) and methylmalonic acid 1, 2

Critical Pitfalls to Avoid

Never administer folic acid before or without ensuring adequate B12 treatment, as folic acid can mask B12 deficiency anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress. 1, 7, 8

• Do not stop supplementation even if levels normalize—patients with malabsorption require lifelong therapy 1, 6
• Do not use inadequate doses thinking "some is enough"—1000 mcg retains far more vitamin than 100 mcg with no disadvantage in cost or toxicity 4
• Medications like metformin, proton pump inhibitors, and H2 blockers interfere with B12 absorption and require higher supplementation doses 5, 2

Safety Profile

Vitamin B12 has no established upper tolerable limit because excess amounts are readily excreted in urine without toxicity. 5

• High doses (1000-2000 mcg) are safe and routinely used without adverse effects 5, 3
• There is no evidence that cyanocobalamin is carcinogenic from long-term use 7, 8