Can iron supplements cause reactive gastropathy?

Iron Supplements and Reactive Gastropathy

Yes, oral iron supplements can cause reactive gastropathy, a well-documented complication that occurs in approximately 16% of patients taking oral iron tablets. 1

Mechanism and Pathology

Oral iron supplementation, particularly ferrous sulfate, causes direct mucosal injury to the upper gastrointestinal tract through local tissue damage and iron deposition. 2, 3 The pathologic findings include:

• Reactive gastritis with mucosal erosion occurring in 80% of cases with gastric iron deposition 1
• Iron accumulation in lamina propria macrophages, parietal cells, and chief cells 2
• Crystalline iron deposits with surrounding inflammation and tissue injury 4
• Mitochondrial iron accumulation in gastric epithelial cells, particularly after gastric surgery 2

Clinical Recognition

The diagnosis is often underrecognized because symptoms are vague and nonspecific. 5 Key features include:

• Endoscopic findings: Erythematous, violaceous, or erosive mucosa, particularly at sites of pill contact 2, 3
• Histopathologic confirmation: Iron deposits visible on routine H&E staining, confirmed with Prussian blue iron stain 1
• Temporal relationship: Symptoms develop after initiating oral iron therapy and resolve with cessation 3

Clinical Implications from Guidelines

The gastrointestinal side effects of oral iron are well-established in clinical guidelines:

• Common adverse effects include nausea, flatulence, diarrhea, constipation, and gastric erosion 6
• FDA labeling specifically warns that "occasional gastrointestinal discomfort may be minimized by taking with meals" 7
• Frequency of GI side effects is significantly higher with oral iron compared to placebo (OR 2.32) or parenteral iron (OR 3.05) 6

Risk Factors

Certain populations face higher risk:

• Patients with prior gastric surgery (e.g., Billroth II) show enhanced iron absorption in gastric remnant tissue 2
• Patients with active GI pathology are at increased risk for severe gastritis when starting iron supplementation 3
• Inflammatory bowel disease patients may experience disease exacerbation from reactive oxygen species generated by unabsorbed iron 6

Management Recommendations

When iron pill gastritis is suspected or confirmed, immediately discontinue oral iron and switch to intravenous formulations. 6 The guidelines provide clear direction:

• Intravenous iron should be used when patients do not tolerate oral iron or have conditions affecting absorption 6
• For IBD patients with active inflammation, IV iron is preferred as oral iron can worsen inflammation through oxidative stress 6
• Modern IV preparations (ferric carboxymaltose, iron isomaltoside) allow complete iron repletion in 1-2 infusions 6

Prevention Strategies

To minimize gastropathy risk while treating iron deficiency:

• Use alternate-day dosing rather than daily dosing, which improves absorption and reduces side effects 6
• Lower doses (one tablet daily or every other day) are as effective as higher doses with fewer adverse effects 6
• Add vitamin C to enhance absorption and potentially reduce required iron dose 6
• Consider IV iron first-line in patients with known GI pathology, prior gastric surgery, or inflammatory conditions 6

Important Caveats

While reactive gastropathy from oral iron is common, it must be distinguished from other causes of gastritis. The key distinguishing feature is histologic demonstration of iron deposits in the gastric mucosa, which is pathognomonic for iron pill injury. 1 Simply having gastritis while taking iron is insufficient for diagnosis—the iron deposition must be documented. 5

Continued follow-up is essential for all patients receiving oral iron supplementation, particularly in the weeks following treatment initiation, regardless of age or comorbidity. 3 This allows early detection and management of iron-induced mucosal injury before severe complications develop.