What is the recommended management for vitamin B12 deficiency in adults?

Management of Vitamin B12 Deficiency in Adults

For adults with confirmed B12 deficiency, initiate hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks if no neurological symptoms are present, or on alternate days until no further improvement if neurological involvement exists, followed by lifelong maintenance therapy of 1 mg intramuscularly every 2-3 months. 1, 2

Diagnostic Confirmation

Before initiating treatment, confirm the diagnosis appropriately:

• Measure serum B12 as the first-line test: Levels <150 pmol/L (<203 pg/mL) confirm deficiency and require immediate treatment 1, 3
• For borderline results (180-350 pg/mL or 133-258 pmol/L): Measure methylmalonic acid (MMA) to confirm functional deficiency, as MMA has 98.4% sensitivity and detects an additional 5-10% of patients with B12 deficiency who have low-normal B12 levels 3, 4
• Active B12 (holotranscobalamin) is more accurate than total B12, measuring the biologically active form available for cells, though it costs more (£18 vs £2 per test) 1, 3

Identify the Underlying Cause

The cause determines whether lifelong therapy is required:

• Malabsorption causes (requiring lifelong treatment): Pernicious anemia, atrophic gastritis (affecting up to 20% of older adults), ileal resection >20 cm, bariatric surgery, Crohn's disease with ileal involvement, chronic PPI use >12 months, chronic metformin use >4 months 5, 1, 4, 6
• Dietary causes: Vegan/vegetarian diets, inadequate intake in adults >75 years 5, 4
• Screen high-risk patients yearly for B12 deficiency, particularly those with gastrointestinal conditions or on long-term medications 1, 2

Treatment Protocol

Initial Loading Phase

Without neurological involvement:

• Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks 1, 2
• Alternative FDA-approved regimen: Cyanocobalamin 100 mcg daily for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks 7

With neurological involvement (paresthesias, gait disturbances, cognitive impairment, peripheral neuropathy):

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement 1, 2
• Never delay treatment in patients with neurological symptoms, as damage can become irreversible 1, 8

Maintenance Therapy

• Standard maintenance: Hydroxocobalamin 1 mg intramuscularly every 2-3 months for life 1, 2, 8
• For patients with neurological involvement: Hydroxocobalamin 1 mg intramuscularly every 2 months 1, 2
• Some patients require more frequent dosing (monthly or even more often) to remain symptom-free; up to 50% of individuals need individualized injection regimens based on symptom recurrence, not laboratory values 8

Oral Therapy Alternative

• Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 1, 4, 9, 6
• However, intramuscular therapy is preferred for severe deficiency, neurological symptoms, or confirmed malabsorption 1, 4, 8
• Oral therapy requires excellent adherence and may not be reliable in pernicious anemia 7, 8

Special Populations

Post-bariatric surgery patients:

• 1 mg intramuscularly every 3 months OR 1000-2000 mcg daily orally indefinitely 1, 2
• Check B12 levels every 3 months throughout pregnancy 1

Patients with renal dysfunction:

• Use hydroxocobalamin or methylcobalamin instead of cyanocobalamin, as cyanocobalamin requires renal clearance and is associated with increased cardiovascular events (HR 2.0) in diabetic nephropathy 3, 2

Patients on metformin:

• Periodic testing of B12 levels should be considered, particularly in those with anemia 5

Ileal resection >20 cm or Crohn's disease with ileal involvement:

• Prophylactic hydroxocobalamin 1000 mcg intramuscularly monthly for life, even without documented deficiency 1, 2

Monitoring Strategy

• Check serum B12, homocysteine, and MMA every 3 months until stabilization, then monitor once yearly 1, 2
• Target homocysteine <10 μmol/L for optimal cardiovascular outcomes 3, 2
• Monitor for neurological symptom improvement rather than relying solely on laboratory values for dose adjustments 1, 8
• Do not use serum B12 or MMA levels to "titrate" injection frequency; base adjustments on clinical symptoms 8

Critical Pitfalls to Avoid

• Never administer folic acid before treating B12 deficiency, as it may mask anemia while allowing irreversible neurological damage to progress (subacute combined degeneration of the spinal cord) 1, 3, 2
• Do not discontinue therapy even if levels normalize when malabsorption is the cause; patients require lifelong treatment 1, 8
• Do not rely solely on serum B12 to rule out deficiency, especially in patients >60 years, where metabolic deficiency is common despite normal serum levels (affecting 18.1% of those >80 years) 3
• Increase injection frequency if neurological symptoms recur during maintenance therapy, rather than accepting persistent symptoms 1, 8
• Avoid the intravenous route, as almost all vitamin will be lost in urine 7