What should a patient with vitamin B12 deficiency take for treatment?

Treatment for Vitamin B12 Deficiency

For most patients with vitamin B12 deficiency, oral supplementation with 1000-2000 mcg daily is as effective as intramuscular injections and should be the first-line treatment, reserving IM therapy for those with severe neurological symptoms, confirmed malabsorption, or treatment failure. 1, 2

Initial Treatment Selection Algorithm

Step 1: Assess Severity and Route Selection

Choose ORAL therapy (1000-2000 mcg daily) if: 1, 2

• No neurological symptoms present
• Mild to moderate deficiency (B12 >150 pmol/L or >203 pg/mL)
• Patient can comply with daily oral medication
• Even if malabsorption is present (passive absorption still occurs at high doses) 3, 4

Choose INTRAMUSCULAR therapy if: 1, 5, 6

• Severe neurological involvement (peripheral neuropathy, cognitive impairment, subacute combined degeneration, glossitis with neurological features)
• Severe deficiency with B12 <150 pmol/L (<203 pg/mL) AND symptoms
• Oral therapy fails to normalize levels after 3 months
• Patient cannot comply with daily oral medication

Step 2: Specific Dosing Protocols

For Oral Treatment: 1, 5, 2

• Standard dose: 1000-2000 mcg cyanocobalamin daily
• Continue until levels normalize (typically 3-6 months), then transition to maintenance
• Maintenance: 1000 mcg daily indefinitely for high-risk patients (post-bariatric surgery, ileal resection >20 cm, pernicious anemia, strict vegans)

For Intramuscular Treatment WITHOUT Neurological Symptoms: 5, 6

• Loading phase: Hydroxocobalamin 1000 mcg IM three times weekly for 2 weeks
• Maintenance: 1000 mcg IM every 2-3 months for life
• Alternative: 1000 mcg IM monthly (may better meet metabolic requirements in some patients) 5, 6

For Intramuscular Treatment WITH Neurological Symptoms: 5, 6

• Intensive loading: Hydroxocobalamin 1000 mcg IM on alternate days until no further neurological improvement (typically 2-3 weeks)
• Maintenance: 1000 mcg IM every 2 months for life
• Never delay treatment—neurological damage can become irreversible if untreated beyond 3 months 7

Critical Formulation Considerations

Preferred B12 forms: 1, 5, 6

• Hydroxocobalamin (first choice for IM): Superior tissue retention, established dosing protocols, guideline-recommended
• Cyanocobalamin (acceptable for oral): Well-studied, cost-effective
• Avoid cyanocobalamin in renal dysfunction: Associated with increased cardiovascular events (HR 2.0) due to cyanide accumulation; use methylcobalamin or hydroxocobalamin instead 5, 6

Special Population Protocols

Post-Bariatric Surgery: 1, 5

• Roux-en-Y or biliopancreatic diversion: 1000-2000 mcg/day oral OR 1000 mcg/month IM indefinitely
• Sleeve gastrectomy or gastric banding: 250-350 mcg/day oral OR 1000 mcg/week sublingual

Ileal Resection or Crohn's Disease: 1, 5, 6

• Resection >20 cm: 1000 mcg IM monthly for life (prophylactic, even without documented deficiency)
• Ileal involvement >30-60 cm without resection: Annual screening + prophylactic supplementation
• Resection <20 cm: Typically does not require prophylaxis

Pernicious Anemia: 7, 3

• Traditional approach: 100 mcg IM daily for 6-7 days, then alternate days for 7 doses, then every 3-4 days for 2-3 weeks, then 100 mcg monthly for life
• Modern evidence supports oral therapy: 1000 mcg daily oral cyanocobalamin is effective even in pernicious anemia, with 88.5% of patients no longer deficient after 1 month 3

Elderly Patients (>75 years): 1

• Higher risk of metabolic deficiency (18.1% in those >80 years)
• Consider prophylactic supplementation: 500-1000 mcg daily oral
• Crystalline B12 absorption remains intact despite atrophic gastritis

Metformin Use >4 Months: 1

• Screen for deficiency
• If deficient: 1000 mcg daily oral while continuing metformin
• Consider prophylactic supplementation in long-term users

Monitoring Protocol

Initial monitoring (first year): 6

• Recheck serum B12 at 3 months, 6 months, and 12 months
• Measure complete blood count to assess megaloblastic anemia resolution
• If B12 remains borderline (180-350 pg/mL), measure methylmalonic acid (MMA >271 nmol/L confirms functional deficiency) 1
• Target homocysteine <10 μmol/L for optimal cardiovascular outcomes 1, 5

Long-term monitoring: 6

• Once levels stabilize (two consecutive normal checks), transition to annual monitoring
• Continue annual screening in high-risk populations (autoimmune thyroid disease, post-bariatric surgery, ileal disease)

What to measure at follow-up: 6

• Serum B12 (primary marker)
• Complete blood count (assess anemia resolution)
• MMA if B12 borderline or symptoms persist
• Homocysteine (target <10 μmol/L)

Critical Pitfalls to Avoid

Never give folic acid before treating B12 deficiency: 1, 5, 6, 7

• Folic acid masks megaloblastic anemia while allowing irreversible neurological damage (subacute combined degeneration) to progress
• Once B12 treatment begins, folic acid 1 mg daily for 3 months can be added if folate is also deficient

Do not rely solely on serum B12 to rule out deficiency: 1

• Standard testing misses functional deficiency in up to 50% of cases
• In elderly patients (>60 years), 18.1% have metabolic deficiency despite "normal" serum levels
• Use MMA (>271 nmol/L) to confirm functional deficiency when B12 is 180-350 pg/mL

Do not stop treatment after one normal result: 6

• Patients with malabsorption or dietary insufficiency require lifelong supplementation
• Stopping injections after symptom improvement can lead to irreversible peripheral neuropathy

Do not use cyanocobalamin in renal dysfunction: 5, 6

• Requires renal clearance of cyanide moiety
• Associated with 2-fold increased cardiovascular events in diabetic nephropathy
• Use hydroxocobalamin or methylcobalamin instead

Adjunctive Considerations

Screen for coexisting deficiencies: 1

• Iron (ferritin, though up to 100 μg/L may still indicate deficiency in inflammatory conditions)
• Folate (check concurrently with B12)
• Vitamin D, thiamin, copper (can cause similar neurological symptoms)

Investigate underlying causes: 1, 6

• Intrinsic factor antibodies (pernicious anemia)
• Gastrin levels if pernicious anemia suspected (>1000 pg/mL indicates condition)
• Celiac disease (tissue transglutaminase antibodies) in autoimmune thyroid patients
• Medication review (PPIs >12 months, metformin >4 months, colchicine, anticonvulsants)

For persistent symptoms despite normal B12: 1

• Measure MMA and homocysteine (functional markers)
• Consider genetic testing for transcobalamin deficiency (TCN2 gene) or intracellular cobalamin metabolism defects (MMACHC, MMADHC, MTRR, MTR genes) if strong family history
• Increase dose or frequency of supplementation
• Switch from oral to IM if oral therapy fails