What is the recommended dose of vitamin B12 (cobalamin) for adults with a deficiency?

Recommended Dose of Vitamin B12

For adults with B12 deficiency, the recommended dose depends on whether neurological symptoms are present: if neurological involvement exists, administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement occurs, then 1 mg every 2 months for life; if no neurological symptoms, give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, then 1 mg every 2-3 months for life. 1, 2

Initial Treatment Protocol

With Neurological Involvement

• Administer hydroxocobalamin 1 mg IM on alternate days until neurological symptoms plateau and no further improvement is observed 1, 3, 2
• This aggressive initial regimen is critical because neurological complications can become irreversible if undertreated 3
• After improvement plateaus, transition to maintenance dosing 3

Without Neurological Involvement

• Give hydroxocobalamin 1 mg IM three times per week for 2 weeks 1, 2
• This loading phase ensures adequate tissue stores are replenished 2
• Then proceed to maintenance therapy 2

Maintenance Therapy

After initial treatment, lifelong maintenance with hydroxocobalamin 1 mg IM every 2-3 months is required for patients with malabsorption-related deficiency 1, 2

• Monthly dosing of 1000 mcg IM is an acceptable alternative that may be necessary to meet metabolic requirements in some patients 1, 4
• Never discontinue therapy even if symptoms resolve or B12 levels normalize, as deficiency will recur without ongoing supplementation 3
• Up to 50% of individuals may require more frequent administration (ranging from every 2-4 weeks) to remain symptom-free 5

Oral Supplementation Alternative

For patients without malabsorption issues, oral supplementation with 1000-2000 mcg daily is as effective as intramuscular administration 1, 6

• Oral doses of 647-1032 mcg daily are required to normalize biochemical markers in mild deficiency 7
• The lowest effective oral dose is more than 200 times the recommended dietary allowance 7
• Oral therapy should not replace injections in patients with documented malabsorption 5, 6

Special Populations

Post-Bariatric Surgery

• Administer 1 mg IM every 3 months OR 1000-2000 mcg daily orally 1
• After Roux-en-Y gastric bypass 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

Patients with Ileal Resection

• Patients with >20 cm of distal ileum resected require prophylactic B12 injections (1000 mcg) monthly for life 1

Renal Dysfunction

• Use methylcobalamin or hydroxocobalamin instead of cyanocobalamin in patients with renal impairment 1, 3
• Cyanocobalamin requires renal clearance of the cyanide moiety and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 1

Monitoring Recommendations

• Check serum B12 and homocysteine every 3 months until stabilization, then annually 1, 3
• Target homocysteine level <10 μmol/L for optimal outcomes 1, 3
• During initial treatment, monitor serum potassium closely in the first 48 hours and replace if necessary 8, 9
• Hematocrit and reticulocyte counts should be repeated daily from days 5-7 of therapy, then frequently until hematocrit normalizes 8, 9

Critical Pitfalls to Avoid

Never administer folic acid before treating B12 deficiency, as it may mask the deficiency while allowing neurological damage to progress, potentially precipitating subacute combined degeneration of the spinal cord 1, 3, 2, 8, 9

• Doses of folic acid >0.1 mg/day may result in hematologic remission while neurologic manifestations continue to worsen 8, 9
• Always check and treat B12 deficiency before initiating folic acid 2
• Do not use biomarkers like serum B12 or MMA to "titrate" injection frequency—base treatment on clinical response 5
• Vitamin B12 deficiency allowed to progress for >3 months may produce permanent degenerative spinal cord lesions 8, 9

Form Selection

• Hydroxocobalamin or methylcobalamin are preferred over cyanocobalamin, particularly in patients with renal dysfunction 1, 3
• Cyanocobalamin is the only B12 preparation available in the United States for parenteral use 4
• Both hydroxocobalamin and methylcobalamin are effective; choice depends on availability and patient-specific factors 3