Causes of Vitamin B12 Deficiency
Malabsorption Disorders
The most common cause of vitamin B12 deficiency in the 21st century is food-cobalamin malabsorption, not pernicious anemia. 1
- Atrophic gastritis affecting the gastric body impairs B12 absorption by reducing gastric acid production needed to separate B12 from food proteins 2, 3
- Pernicious anemia (autoimmune gastritis with intrinsic factor deficiency) causes classic malabsorption and requires lifelong treatment, though it now accounts for a minority of cases 2, 1
- Celiac disease is a significant autoimmune condition that impairs B12 absorption in the terminal ileum 2
- Ileal resection >20 cm (with or without ileocecal valve) in Crohn's disease patients causes permanent malabsorption requiring lifelong monthly IM supplementation 2
- Post-bariatric surgery (sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch) reduces both intrinsic factor and gastric acid production 2, 3
Dietary Insufficiency
- Vegan or strict vegetarian diets lacking all animal products (including milk, eggs, fish) provide no dietary B12 since it is absent from plant-based foods 2, 4
- Limited consumption of fortified foods in at-risk populations contributes to deficiency 2
- Food allergies to eggs, milk, or fish may restrict B12-containing foods 2
- Eating disorders with severely restricted diets lead to inadequate intake 2
Medication-Induced Deficiency
- Metformin use, especially for >4 months, significantly increases deficiency risk 2, 3, 5
- Proton pump inhibitors and H2 receptor antagonists used for >12 months impair B12 absorption by reducing gastric acid 2, 3, 6
- Colchicine interferes with B12 absorption 2, 3, 7
- Anticonvulsants (phenobarbital, primidone) contribute to deficiency 2, 3
- Pregabalin use is associated with B12 deficiency 2, 3
- Methotrexate and sulfasalazine can contribute to deficiency 3
Autoimmune Associations
- Autoimmune thyroid disease (Hashimoto's, Graves') has a 28-68% prevalence of B12 deficiency, strongly associated with positive thyroid antibodies 3
- Type 1 diabetes increases risk through autoimmune mechanisms 2, 3
- Sjögren syndrome is associated with increased B12 deficiency risk 2
Age-Related Factors
- Age ≥60 years carries significantly higher risk, with 18.1% having metabolic deficiency and 25% of those ≥85 years having low B12 levels 3
- Atrophic gastritis prevalence increases with age, making food-cobalamin malabsorption the dominant mechanism in elderly populations 1, 8
Physiologic Increased Demand
- Pregnancy and lactation increase B12 requirements, and deficiency can occur in breastfed infants of vegetarian mothers even when mothers are asymptomatic 4
Critical Clinical Pitfall
Never administer folic acid before treating B12 deficiency - folic acid doses >0.1 mg daily may mask the anemia while allowing irreversible neurological damage (subacute combined degeneration of the spinal cord) to progress 3, 4