How can Gastroesophageal Reflux Disease (GERD) lead to iron deficiency anemia?

Iron Deficiency Anemia in GERD: Mechanisms and Clinical Approach

GERD causes iron deficiency anemia through three primary mechanisms: chronic occult blood loss from erosive esophagitis, impaired iron absorption due to acid suppression from proton pump inhibitors (PPIs), and reduced dietary iron intake from food aversions related to reflux symptoms. 1, 2

Primary Mechanisms

1. Chronic Gastrointestinal Blood Loss

• Erosive esophagitis from chronic acid exposure creates mucosal ulcerations that bleed chronically, even when not clinically apparent 3, 1
• Hiatal hernia, commonly associated with GERD, independently increases the risk of iron deficiency anemia with a hazard ratio of 2.9 (95% CI: 1.5-5.5) compared to those without hiatal hernia 4
• The bleeding is typically occult rather than overt, making it difficult to detect without specific investigation 3, 5
• A moderate correlation (r = -0.35, p = 0.025) exists between GERD severity and anemia development in pediatric populations, with lower serum iron levels found in GERD patients (F = 8.46, p = 0.012) 1

2. PPI-Induced Malabsorption

• Chronic PPI use (the mainstay treatment for GERD) causes hypo- or achlorhydria, which impairs iron absorption in the duodenum where acidic pH is required for ferrous iron solubility 6, 2
• The FDA explicitly warns that daily acid-suppressing medications used for longer than 3 years may lead to iron malabsorption 6
• Cyanocobalamin (vitamin B-12) deficiency also occurs through the same mechanism, compounding anemia 6
• Case reports document that severe iron deficiency anemia from omeprazole may require up to 8 months after PPI discontinuation to correct, even with supplementation 2

3. Malabsorption from Associated Conditions

• Atrophic gastritis (often coexisting with chronic GERD) reduces gastric acid production and intrinsic factor, impairing both iron and B-12 absorption 5, 7
• H. pylori infection, a common cause of both gastritis and GERD symptoms, contributes to iron malabsorption through chronic inflammation 5

Diagnostic Approach

Initial Laboratory Assessment

• Measure complete blood count, ferritin, transferrin saturation, and inflammatory markers (CRP) 8
• In the presence of inflammation, ferritin levels up to 100 μg/L may still reflect iron deficiency despite appearing "normal" 3, 8
• Transferrin saturation <20% with ferritin 30-100 μg/L suggests combined true iron deficiency and anemia of chronic disease 3

Endoscopic Evaluation

• Bidirectional endoscopy (gastroscopy and colonoscopy) is recommended to exclude other sources of bleeding and assess for erosive esophagitis, hiatal hernia, and gastric pathology 5
• Esophagitis shows a trend toward increased iron deficiency anemia risk (HRR 2.2,95% CI: 0.79-6.0), though not as strong as hiatal hernia 4
• Rule out celiac disease with transglutaminase antibody (IgA type) and total IgA testing, as this commonly coexists with GERD and causes malabsorption 5

Critical Pitfall to Avoid

• Do not attribute iron deficiency solely to GERD/PPI use without excluding gastrointestinal malignancy, particularly in patients over 40 years or with alarm symptoms (weight loss, dysphagia, persistent vomiting) 5, 7

Treatment Strategy

Iron Replacement

• Oral iron supplementation often fails in GERD patients on chronic PPIs due to impaired absorption 8, 2
• Consider intravenous iron as first-line therapy in patients with moderate-to-severe anemia (Hb <100 g/L) or those with documented malabsorption 3, 8
• Target ferritin levels of at least 50-100 μg/L, recognizing that inflammation may mask true deficiency 8
• If oral iron is attempted, use no more than 100-200 mg elemental iron daily and expect 3-6 months of therapy to replenish stores 5

PPI Management

• Reassess the necessity of continued PPI therapy and use the lowest effective dose for the shortest duration needed 6
• The FDA recommends using PPIs "at the lowest dose possible and for the shortest time needed" to minimize complications 6
• Consider discontinuing the PPI entirely if iron deficiency persists despite supplementation, as anemia may resolve spontaneously within 2-8 months after cessation 2
• Alternative GERD management strategies (lifestyle modifications, H2-receptor antagonists for milder disease) should be explored 2

Monitoring Protocol

• Check CBC, ferritin, and transferrin saturation every 3 months during initial treatment 8
• After normalization, continue monitoring every 6 months for at least one year to detect recurrence 8
• Do not accept "improved" iron levels as adequate—ferritin must be optimized to prevent symptom recurrence 8

Address Underlying GERD

• Optimize medical or surgical management of GERD to reduce esophageal inflammation and bleeding 3
• Treat H. pylori infection if present, as eradication improves both GERD symptoms and iron absorption 5
• Evaluate and repair hiatal hernias in refractory cases, given their strong independent association with iron deficiency 4