What is the approach to managing low vitamin B12 (cobalamin) levels?

Approach to Vitamin B12 Deficiency

Initial Assessment and Testing

When vitamin B12 deficiency is suspected based on symptoms or risk factors, measure either active B12 (serum holotranscobalamin) or total B12 (serum cobalamin) as first-line testing. 1

• Active B12 is more accurate as it measures the biologically active form available for cellular use, but total B12 is acceptable and more cost-effective (£2 vs £18 per test) 1
• Either test is preferable to not testing when clinical suspicion exists 1
• Biochemical B12 deficiency is confirmed when serum cobalamin is <148 pmol/L combined with elevated functional biomarkers: homocysteine >15 μmol/L or methylmalonic acid >270 μmol/L 1
• Clinical B12 deficiency requires biochemical deficiency plus macrocytosis and/or neurological symptoms 1

Risk Factors to Identify

Screen for these high-risk conditions: 1

• Dietary: Vegan/vegetarian diets, food allergies (eggs, milk, fish), eating disorders, low income limiting food access
• Gastrointestinal: Atrophic gastritis, celiac disease, >20 cm distal ileum resection, bariatric surgery 1, 2
• Medications: Metformin, H2 receptor antagonists, colchicine, phenobarbital, pregabalin, primidone
• Autoimmune: Pernicious anemia, thyroid disease, Sjögren syndrome, type 1 diabetes

Treatment Protocol

For Deficiency WITH Neurological Involvement

Administer hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then transition to maintenance with 1 mg intramuscularly every 2 months for life. 2

• Neurological symptoms include: pins and needles, numbness, balance issues, falls, impaired gait, impaired proprioception, cognitive difficulties ("brain fog"), blurred vision, optic atrophy 1
• Critical pitfall: Never administer folic acid before treating B12 deficiency, as it may mask the deficiency and precipitate subacute combined degeneration of the spinal cord 2

For Deficiency WITHOUT Neurological Involvement

Give hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance of 1 mg intramuscularly every 2-3 months lifelong. 2

For Malabsorption Causes (Pernicious Anemia, Ileal Resection >20 cm)

Use intramuscular hydroxocobalamin 1000 μg monthly for life as prophylactic therapy. 1, 2

• Patients with >20 cm distal ileum resection require prophylactic monthly injections indefinitely 1, 2
• Resection <20 cm does not typically cause deficiency 1
• Ileal Crohn's disease involving >30-60 cm puts patients at risk even without resection 1, 2

Oral Therapy Option

For dietary deficiency or when malabsorption is not the cause, oral cyanocobalamin 1000-2000 μg daily is effective. 3, 4

• Recent high-quality evidence shows oral cyanocobalamin 1000 μg/day corrects B12 deficiency in pernicious anemia within 1 month in 88.5% of patients 3
• Oral therapy normalized plasma B12, homocysteine, and methylmalonic acid concentrations and maintained correction over 12 months 3
• In Crohn's disease patients, oral cyanocobalamin 1 mg/day was effective for acute treatment in 94.7% and maintenance in 81.7% over 3 years 4
• However, parenteral supplementation remains the reference standard for malabsorption, particularly when neurological symptoms are present 1, 2

Monitoring Strategy

Screen high-risk patients (ileal involvement/resection, medications, dietary restrictions) yearly for B12 deficiency. 1

• During active treatment: Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization 2
• After stabilization: Monitor once yearly 2
• Target homocysteine level: <10 μmol/L for optimal cardiovascular health 2
• Do not "titrate" injection frequency based on serum B12 or MMA levels—base frequency on clinical symptom resolution 5

Special Populations

Post-Bariatric Surgery

Administer 1 mg intramuscularly every 3 months or 1000-2000 μg daily orally indefinitely. 2

Pregnancy After Bariatric Surgery

Check B12 levels every 3 months throughout pregnancy. 2

Thrombocytopenia

• Platelet count >50 × 10⁹/L: Standard intramuscular administration is safe 2
• Platelet count 25-50 × 10⁹/L: Use smaller gauge needles (25-27G) and apply prolonged pressure (5-10 minutes) at injection site 2
• Platelet count <25 × 10⁹/L with neurological symptoms: Prioritize treatment despite low platelets 2
• Platelet count <10 × 10⁹/L: Consider platelet transfusion support before intramuscular administration 2

Renal Dysfunction

Methylcobalamin or hydroxocobalamin may be preferable to cyanocobalamin in patients with renal impairment. 2

Common Pitfalls

• Up to 50% of patients require more frequent injections than standard protocols (ranging from twice weekly to every 2-4 weeks) to remain symptom-free 5
• Treatment adherence failure accounts for 46.6% of oral therapy failures 4
• Do not discontinue B12 supplementation even if levels normalize—patients require lifelong therapy when malabsorption is the cause 2
• Monitor for recurrent neurological symptoms (paresthesias, gait disturbances, cognitive changes) and increase injection frequency if symptoms return 2