What is the recommended dose and frequency of vitamin B12 (cobalamin)?

Vitamin B12 Dosing and Frequency

For treatment of vitamin B12 deficiency, administer hydroxocobalamin 1000 mcg (1 mg) intramuscularly three times weekly for 2 weeks as initial loading, followed by maintenance therapy of 1000 mcg intramuscularly every 2-3 months for life, with monthly injections being more effective than every 3 months. 1, 2

Initial Treatment (Loading Phase)

For patients with confirmed B12 deficiency:

• Hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks is the standard loading protocol 1, 2
• If neurological symptoms are present: Administer 1000 mcg IM on alternate days until symptoms stop improving, then transition to maintenance 1, 2
• The FDA-approved cyanocobalamin regimen is 30 mcg daily for 5-10 days, followed by 100-200 mcg monthly, though this is less commonly used in current practice 3

Critical caveat: Never administer folic acid before treating B12 deficiency, as it may mask the deficiency while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 2, 4, 5

Maintenance Therapy

Standard maintenance dosing:

• Hydroxocobalamin 1000 mcg IM every 2-3 months for life is the baseline recommendation 1, 2
• Monthly administration of 1000 mcg IM is more effective than every 3 months and may be necessary to meet metabolic requirements in up to 50% of patients 1, 6, 7
• Treatment must continue indefinitely if the underlying cause cannot be corrected 2

Alternative oral therapy:

• Oral supplementation with 1000-2000 mcg daily may be considered after the initial IM loading phase if the patient has no neurological symptoms 1
• Oral therapy can be as effective as parenteral administration even in pernicious anemia, though IM is preferred for malabsorption 8, 7, 9

Special Populations

Post-bariatric surgery patients:

• 1000 mcg IM every 3 months OR 1000 mcg orally daily 1, 2
• For Roux-en-Y or biliopancreatic diversion: 1000-2000 mcg/day sublingual OR 1000 mcg/month IM 2

Patients with ileal resection (>20 cm):

• 1000 mcg IM monthly for life as prophylaxis 1, 2

Patients with renal dysfunction:

• 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 10, 1, 2

Elderly patients:

• Higher risk of deficiency (18.1% metabolic B12 deficiency in patients >80 years) 1, 2
• Same dosing as general population, but consider more frequent monitoring 9

Monitoring and Targets

Laboratory monitoring:

• Check serum B12 and homocysteine every 3 months until stabilization, then annually 1, 2, 4
• Target homocysteine <10 μmol/L for optimal cardiovascular outcomes 10, 1
• Do not use serum B12 or MMA levels to "titrate" injection frequency once on maintenance therapy 7

Clinical monitoring:

• Evaluate for resolution of fatigue, neurological symptoms (paresthesias, gait disturbances), and cognitive symptoms 4
• If symptoms recur on standard maintenance, increase injection frequency rather than measuring levels 7

Stroke Prevention Context

For patients with ischemic stroke or elevated homocysteine:

• All patients with ischemic stroke should have serum B12 and homocysteine measured 10
• Treat if B12 is abnormal or homocysteine >14-15 μmol/L 10
• Doses of 400-1000 mcg daily cyanocobalamin were used in stroke prevention trials, with better outcomes at higher doses and in patients with baseline B12 >322 pmol/L 10
• A 34% reduction in cardiovascular events was observed with 400 mcg daily in appropriate patients 10

Common Pitfalls to Avoid

• Never discontinue B12 supplementation even if levels normalize—patients require lifelong therapy if the underlying cause persists 2, 4
• Do not give folic acid before checking and treating B12 status—this can precipitate irreversible spinal cord damage 1, 2, 4, 5
• Do not use cyanocobalamin in renal dysfunction—use hydroxocobalamin or methylcobalamin instead 1, 2
• Do not rely solely on serum B12 levels for diagnosis—use clinical symptoms plus elevated homocysteine or methylmalonic acid for confirmation 7, 9
• Up to 50% of patients require more frequent injections than standard guidelines suggest—individualize based on symptom resolution, not lab values 7