What are the causes of Vitamin B12 deficiency?

Causes of Vitamin B12 Deficiency

Vitamin B12 deficiency results from inadequate dietary intake, malabsorption disorders, or conditions affecting the stomach and small intestine, with food-cobalamin malabsorption now recognized as the most common cause in adults. 1, 2

Malabsorption Disorders

Gastric Causes

• Pernicious anemia (autoimmune destruction of gastric parietal cells leading to intrinsic factor deficiency) remains a classic but now less common cause 3, 2
• Atrophic gastritis affecting the gastric body impairs B12 absorption by reducing intrinsic factor secretion and gastric acid production 4, 5
• Total or partial gastrectomy always produces B12 deficiency due to loss of intrinsic factor-producing cells 3
• Gastric lesions from corrosive ingestion or extensive neoplasia that destroy gastric mucosa 3

Small Intestinal Causes

• Ileal resection >20 cm requires lifelong prophylactic B12 supplementation due to loss of the primary absorption site 6, 5
• Inflammatory bowel disease, particularly Crohn's disease with ileal involvement >30-60 cm, causes malabsorption even without resection 6, 7
• Tropical and nontropical sprue (including celiac disease and gluten-induced enteropathy) damage the ileal mucosa 3, 5
• Bacterial overgrowth in blind-loop syndrome competes for B12 absorption 3, 5
• Parasitic infestations, especially fish tapeworm (Diphyllobothrium latum), which absorbs large quantities of B12 3, 5

Bariatric Surgery

• Roux-en-Y gastric bypass and biliopancreatic diversion cause B12 deficiency through reduced gastric acid production and decreased intrinsic factor availability 8, 6
• Post-bariatric surgery patients require routine supplementation (1 mg daily orally or 1 mg every 3 months intramuscularly) indefinitely 8, 7

Dietary Deficiency

• Strict vegetarian or vegan diets lack animal-derived B12 sources, leading to deficiency over months to years as body stores deplete 3, 7
• Breast-fed infants of B12-deficient mothers (particularly strict vegetarians) can develop isolated B12 deficiency 3
• Dietary deficiency is rare in non-vegetarians due to adequate B12 in animal products 3

Medication-Induced Deficiency

• Metformin use >4 months interferes with B12 absorption and warrants screening 8, 9, 7
• Proton pump inhibitors or H2 receptor antagonists >12 months reduce gastric acid needed to release B12 from food proteins 4, 9, 7
• Anticonvulsants, sulfasalazine, and methotrexate affect folate and B12 metabolism 8, 4
• Colchicine impairs B12 absorption 4, 10

Food-Cobalamin Malabsorption

• Failure to separate B12 from food carrier proteins is now the most common cause in older adults, resulting from reduced gastric acid secretion 1, 2
• This condition differs from pernicious anemia as intrinsic factor remains present but B12 cannot be released from dietary proteins 2

Pancreatic Insufficiency

• Inadequate pancreatic protease secretion prevents degradation of haptocorrin, blocking transfer of B12 to intrinsic factor in the duodenum 5
• Obstructive jaundice can impair B12 absorption through similar mechanisms 3, 5

Other Causes

• Zollinger-Ellison syndrome with excessive gastric acid secretion paradoxically impairs B12 absorption 5
• Chronic radiation enteritis of the distal ileum damages the absorption site 5
• Short bowel syndrome from extensive intestinal resection 5
• Inadequate utilization when antimetabolites are used in cancer treatment 3
• Advanced age >75 years increases risk through multiple mechanisms including atrophic gastritis and medication use 9, 7

Associated Autoimmune Conditions

• Autoimmune thyroid disease, type 1 diabetes, and other autoimmune disorders frequently coexist with autoimmune gastritis and pernicious anemia, with B12 deficiency prevalence of 28-68% in these populations 4

Common Pitfall

Never assume normal serum B12 excludes deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid, particularly in elderly patients and those with neurological symptoms 4, 9. Always measure MMA when B12 levels are borderline (180-350 pg/mL) and clinical suspicion remains high 8, 9.