Vitamin B12 Supplementation: A Practical Overview
Indications for Supplementation
Vitamin B12 supplementation is primarily indicated for patients with documented deficiency (serum B12 <180 pg/mL or <133 pmol/L), those with malabsorption conditions (pernicious anemia, ileal resection >20 cm, post-bariatric surgery, Crohn's disease with ileal involvement), and individuals at high risk including vegans, adults >75 years, and those on metformin >4 months or proton pump inhibitors >12 months. 1, 2, 3
Screening is warranted in high-risk populations rather than average-risk adults, including patients with gastrointestinal surgeries, inflammatory bowel disease, chronic medication use (metformin, PPIs), strict vegetarians/vegans, and elderly adults. 3
Prophylactic supplementation is required for patients with ileal resection >20 cm (1000 μg IM monthly for life) and post-bariatric surgery patients (1000-2000 μg daily oral or 1 mg IM monthly indefinitely). 1, 4
Available Formulations and Route Selection
Hydroxocobalamin is the guideline-recommended injectable form, with superior tissue retention compared to cyanocobalamin; oral high-dose B12 (1000-2000 μg daily) is equally effective as intramuscular therapy for most patients without severe neurological symptoms. 1, 5, 6
Injectable Forms
Hydroxocobalamin is preferred over cyanocobalamin due to better tissue retention and established dosing protocols across all major guidelines. 1
Avoid cyanocobalamin in renal dysfunction (GFR <50 mL/min) because it requires renal clearance of cyanide metabolites and is associated with doubled cardiovascular risk (HR 2.0) in diabetic nephropathy. 1
Methylcobalamin or hydroxocobalamin should be used instead of cyanocobalamin in patients with impaired renal function. 1
Never use intravenous administration—the intramuscular or deep subcutaneous route is mandatory, as IV dosing results in almost complete urinary loss of the vitamin. 7
Oral Formulations
Oral B12 at 1000-2000 μg daily is as effective as intramuscular administration for correcting deficiency in patients with adequate absorption capacity. 5, 3
Sublingual dosing of 350 μg/week (50 μg/day) effectively restores adequate B12 status in vegetarians/vegans with marginal deficiency. 8
Oral therapy is not dependable for pernicious anemia or severe malabsorption—these patients require lifelong intramuscular therapy. 7
Dosing Protocols
For Neurological Involvement
Hydroxocobalamin 1 mg IM on alternate days until neurological improvement plateaus (often requiring weeks to months), then maintenance of 1 mg IM every 2 months for life. 1
Aggressive alternate-day dosing is mandatory to prevent irreversible nerve damage. 1
Without Neurological Symptoms
Hydroxocobalamin 1 mg IM three times weekly for 2 weeks, followed by maintenance of 1 mg IM every 2-3 months for life. 1
For pernicious anemia specifically: 100 μg daily IM for 6-7 days, then alternate days for seven doses, then every 3-4 days for 2-3 weeks, followed by 100 μg monthly for life. 7
Oral Supplementation
1000-2000 μg daily for dietary insufficiency or confirmed deficiency in patients without malabsorption. 4, 5, 3
Post-bariatric surgery: 1000-2000 μg daily oral OR 1 mg IM monthly indefinitely. 1, 4
Vegans/vegetarians with marginal deficiency: 350 μg/week sublingual (50 μg/day) is sufficient. 8
Prophylactic Dosing
Post-bariatric surgery: 1 mg IM every 3 months or 1000-2000 μg daily oral for life. 1
Ileal resection >20 cm: 1000 μg IM monthly for life. 1
Safety Profile
Vitamin B12 has no established upper tolerable limit because excess amounts are readily excreted in urine without toxicity—doses up to 2000 μg daily are routinely used safely. 4
High-dose oral supplementation (1000-2000 μg daily) is safe and well-tolerated with no risk of toxicity. 4, 5
Long-term B12 supplementation is effective and safe, though individual responses may vary. 6
Critical Safety Warnings
Never administer folic acid before correcting B12 deficiency—folic acid can mask megaloblastic anemia while allowing irreversible subacute combined degeneration of the spinal cord to progress. 1, 4
After successful B12 repletion, folic acid 5 mg daily may be added only if concurrent folate deficiency is documented. 1
Intramuscular therapy is contraindicated in patients with severe thrombocytopenia (<10 × 10⁹/L) without platelet transfusion support. 1
Monitoring Schedule
Recheck serum B12 at 3 months, 6 months, and 12 months in the first year, then annually thereafter. 1
Target homocysteine <10 μmol/L for optimal cardiovascular outcomes. 1
For patients on IM therapy, measure serum B12 directly before the next scheduled injection (trough level) to identify potential under-dosing. 1
Do not use serum B12 or MMA levels to "titrate" injection frequency—base dosing adjustments on clinical symptoms and quality of life, not biomarkers. 6
Special Populations
Elderly (>75 years): Higher risk of metabolic deficiency (18.1% in those >80 years); consider prophylactic supplementation of 1000 μg daily. 2
Pregnancy after bariatric surgery: Check B12 levels every 3 months throughout pregnancy and lactation. 1
Renal dysfunction: Use hydroxocobalamin or methylcobalamin exclusively; avoid cyanocobalamin. 1
Metformin users: Screen after 4 months of use; consider routine supplementation with 1000 μg daily. 2, 3