What oral vitamin B12 (cobalamin) dosing regimen is recommended for a patient with documented or suspected deficiency and intact gastrointestinal absorption?

Oral Vitamin B12 Supplementation for Deficiency with Intact GI Absorption

For patients with documented vitamin B12 deficiency and intact gastrointestinal absorption, oral cyanocobalamin 1000–2000 µg daily is as effective as intramuscular therapy and should be the first-line treatment. 1, 2, 3

Initial Treatment Regimen

• Start oral cyanocobalamin 1000 µg daily for patients with biochemical deficiency (serum B12 <180 pg/mL or <133 pmol/L) who have intact GI absorption. 1, 3

• Use 2000 µg daily if the deficiency is more severe (B12 <150 pmol/L) or if symptoms are prominent, as higher doses ensure adequate passive absorption even without intrinsic factor. 1, 3

• Continue daily dosing for at least 3–4 months until serum B12 normalizes and functional markers (methylmalonic acid, homocysteine) return to target ranges. 2

When Oral Therapy Is Appropriate

Oral supplementation works through passive diffusion (1–2% absorption) independent of intrinsic factor, making it effective when:

• Dietary insufficiency is the cause (vegetarians, vegans, elderly with poor intake). 1

• Food-cobalamin malabsorption is present (atrophic gastritis, PPI use >12 months, metformin >4 months) but intrinsic factor secretion remains intact. 1, 3

• Mild-to-moderate deficiency without neurological involvement is documented, as oral therapy normalizes B12 levels within 1–3 months in these cases. 2, 3

When Intramuscular Therapy Is Mandatory

Switch to hydroxocobalamin 1000 µg IM if:

• Severe neurological symptoms are present (subacute combined degeneration, peripheral neuropathy, cognitive impairment), because IM therapy achieves faster tissue saturation. 4, 5

• Pernicious anemia is confirmed by positive anti-intrinsic factor antibodies, though recent evidence shows oral 1000 µg daily can normalize B12 even in PA. 2

• Malabsorption is anatomic (ileal resection >20 cm, total gastrectomy, Roux-en-Y gastric bypass), as these patients lack the absorptive surface for passive uptake. 4, 6

• Oral therapy fails after 3 months, defined as persistent low B12 or elevated MMA despite adherence. 7, 1

Monitoring Schedule

• Recheck serum B12 at 1 month to confirm rising levels; 88.5% of patients normalize by this point on oral therapy. 2

• Measure B12, MMA, and homocysteine at 3 months to assess functional adequacy; target homocysteine <10 µmol/L and MMA <271 nmol/L. 4, 2

• Repeat at 6 and 12 months in the first year, then annually thereafter if levels remain stable. 4

• Check complete blood count at 1 and 3 months to document resolution of macrocytosis (MCV should normalize within 2–4 months). 2

Maintenance Dosing

• After normalization, continue 1000 µg daily indefinitely if the underlying cause persists (e.g., veganism, chronic PPI use, atrophic gastritis). 1, 3

• Reduce to 250–350 µg daily only if the cause was transient (e.g., short-term dietary insufficiency) and repeat testing at 6 months confirms stable levels. 3

• Never discontinue supplementation in patients with permanent malabsorption risk factors, as deficiency will recur within 2–3 years once body stores deplete. 4

Critical Pitfalls to Avoid

• Do not give folic acid before correcting B12 deficiency, as folate masks megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress. 4, 8

• Do not rely on serum B12 alone to guide therapy; up to 50% of patients with "normal" B12 have functional deficiency confirmed by elevated MMA. 8, 7

• Do not use cyanocobalamin in renal dysfunction (eGFR <50 mL/min); switch to methylcobalamin or hydroxocobalamin, as cyanocobalamin doubles cardiovascular event risk in diabetic nephropathy (HR 2.0). 4

• Do not assume oral therapy is inadequate for pernicious anemia; a 2024 prospective cohort showed 1000 µg daily oral cyanocobalamin normalized B12 in 88.5% of PA patients by 1 month. 2

Formulation Selection

• Cyanocobalamin is the preferred oral form for patients with normal renal function, as it has established dosing protocols, costs £2 per month, and demonstrates superior stability during storage. 4, 1, 3

• Methylcobalamin or hydroxocobalamin should replace cyanocobalamin in patients with eGFR <50 mL/min, as cyanocobalamin requires renal clearance of its cyanide moiety. 4

Evidence Strength

The recommendation for oral therapy is based on:

• Four randomized controlled trials comparing oral vs. IM B12, showing equivalent normalization of serum B12 and functional markers. 1

• A 2024 prospective cohort (n=26) demonstrating 88.5% of pernicious anemia patients normalized B12 within 1 month on oral 1000 µg daily, with sustained improvement at 12 months. 2

• Cochrane systematic review confirming oral cyanocobalamin 1000 µg daily is as effective as IM therapy for correcting biochemical and hematological abnormalities. 1, 3