What causes B12 deficiency?

Causes of Vitamin B12 Deficiency

Vitamin B12 deficiency is primarily caused by inadequate dietary intake (especially in vegetarians and vegans), malabsorption disorders (particularly pernicious anemia and ileal disease), and medication effects (notably metformin). 1, 2

Major Causes of B12 Deficiency

Inadequate Dietary Intake

• Food sources: B12 is naturally present only in foods of animal origin 3
  • Absent in plant-based foods 3
  • Rich sources include eggs, milk, red meat, poultry, fish, and shellfish 2
• High-risk populations:
  • Strict vegetarians/vegans who consume no animal products 3, 4
  • Individuals with malnutrition 2
  • Elderly with poor nutritional intake 2, 4

Malabsorption Disorders

• Pernicious anemia: Autoimmune condition causing intrinsic factor deficiency 3
• Gastrointestinal disorders:
  • Atrophic gastritis (especially in elderly) 2, 4
  • Ileal disease or resection (>20 cm of distal ileum) 1
  • Crohn's disease with ileal involvement 1
  • Post-bariatric surgery 1
  • Malabsorption syndromes 2
  • Pancreatic insufficiency 5
  • Bacterial overgrowth 5
  • Parasitic infestations 5
  • Celiac disease 5
  • Inflammatory bowel diseases 5
  • Short bowel syndrome 5
• Helicobacter pylori infection: Causes gastric atrophy leading to food-bound cobalamin malabsorption 4

Medication-Induced

• Metformin: Long-term use associated with B12 deficiency 1, 2
• Other medications:
  • Antacids (reduce gastric acid needed for B12 release from food) 2
  • Pralatrexate 1
  • Sulfasalazine (affects folate metabolism, which interacts with B12) 1
  • Most antibiotics (can invalidate B12 diagnostic assays) 3
  • Colchicine (can cause malabsorption of B12) 3
  • Para-aminosalicylic acid 3

Genetic Factors

• Gene polymorphisms in transcobalamins affecting plasma B12 concentrations 4
• Inherited disorders:
  • Intrinsic factor deficiency 5
  • Imerslund-Gräsbeck disease (defects in cubilin/amnionless receptor) 5

Other Contributing Factors

• Alcohol: Heavy alcohol intake for >2 weeks can produce B12 malabsorption 3, 2
• Pregnancy and lactation: Increased B12 requirements 3
• Age-related factors: Gastric atrophy more common in elderly 4

Clinical Implications and Monitoring

• B12 deficiency left untreated for >3 months may cause permanent degenerative lesions of the spinal cord 1, 3
• Regular monitoring is essential for high-risk groups:
  • Patients with ileal disease or resection should be screened yearly 1
  • Metformin users require regular B12 level monitoring 1
  • Post-bariatric surgery patients need assessment for B12 deficiency 5

Prevention Strategies

• Balanced diet with adequate animal-source foods 1
• Daily multivitamin containing appropriate amounts of B12 1
• Oral B12 supplementation for vegetarians/vegans 3
• Prophylactic supplementation for patients on sulfasalazine or methotrexate 1

Common Pitfalls in Diagnosis

• Diverse and non-specific symptoms can delay diagnosis 6
• Marked differences in diagnostic assay performance 6
• Folic acid supplementation may mask B12 deficiency hematologically while allowing neurological damage to progress 3
• Normal-low B12 levels (200-500 pg/dL) may still indicate metabolic B12 deficiency 1

Understanding these causes is essential for proper prevention, early diagnosis, and effective management of vitamin B12 deficiency to avoid potentially irreversible neurological complications.