A 52-year-old man from Delhi presents with a 6-week history of epigastric pain, heartburn, and regurgitation. Upper endoscopy reveals erosive esophagitis (Los Angeles Grade C) and a gastric ulcer. He is started on omeprazole 40 mg once daily. After 4 weeks of therapy, repeat endoscopy shows complete healing of the esophagitis and ulcer. However, the patient develops chronic diarrhea, and serum vitamin B₁₂ level is found to be 180 pg/mL (normal 200–900). Which of the following best explains the vitamin B₁₂ deficiency in this patient?

Explanation

## Mechanism of PPI-Induced B₁₂ Deficiency **Key Point:** Proton pump inhibitors (PPIs) cause vitamin B₁₂ deficiency by reducing gastric acid secretion, not by affecting intrinsic factor production. ### Pathophysiology Vitamin B₁₂ in food exists bound to proteins. Gastric acid and pepsin are required to release B₁₂ from these protein-bound complexes in the stomach. Once released, B₁₂ binds to R-protein (haptocorrin) in the stomach, and later to intrinsic factor in the small intestine for absorption in the terminal ileum. **High-Yield:** PPIs suppress gastric acid production, preventing the release of B₁₂ from food proteins. This impairs the bioavailability of dietary B₁₂, even though intrinsic factor production remains normal. ### Clinical Correlation B₁₂ deficiency from PPI use typically develops after 2–3 years of continuous therapy. The patient in this case shows early biochemical evidence (low B₁₂) after 4 weeks, which is consistent with reduced absorption of food-bound B₁₂. **Clinical Pearl:** Patients on long-term PPI therapy (>1 year) should have annual B₁₂ monitoring. Crystalline B₁₂ (not food-bound) is still absorbed via intrinsic factor and does not require gastric acid. ### Comparison of B₁₂ Absorption Defects | Cause | Mechanism | Intrinsic Factor | Gastric Acid | Site of Defect | |-------|-----------|------------------|--------------|----------------| | **PPI use** | ↓ Acid → ↓ B₁₂ release from food | Normal | ↓ Severely | Stomach | | **Pernicious anemia** | Autoimmune destruction of parietal cells | ↓ Absent | Normal | Stomach | | **Gastrectomy** | Loss of parietal cells | ↓ Reduced | ↓ Reduced | Stomach | | **Ileal disease** | Malabsorption (Crohn's, TB) | Normal | Normal | Terminal ileum | **Mnemonic:** **ACID-BOUND B₁₂** — Acid is required to Detach B₁₂ from food proteins; Intrinsic factor is needed later; Cobalamin absorption occurs in the terminal ileum; Deficiency develops after prolonged PPI use.