Can omeprazole (proton pump inhibitor) cause iron deficiency?

Omeprazole and Iron Deficiency

Long-term omeprazole use can cause iron deficiency, particularly after one year of continuous use and with higher doses, due to its effect on reducing gastric acid which is necessary for optimal iron absorption.

Mechanism and Evidence

Omeprazole, a proton pump inhibitor (PPI), reduces gastric acid secretion which is essential for:

• Converting dietary non-heme iron from ferric (Fe³⁺) to ferrous (Fe²⁺) form for absorption
• Solubilizing iron in food for optimal absorption

The FDA drug label for omeprazole specifically mentions that PPIs "can reduce the absorption of other drugs due to its effect on reducing intragastric acidity," including iron salts 1. This recognition in the official drug labeling highlights the clinical significance of this interaction.

A large case-control study from the UK Clinical Practice Research Datalink Database found dose-dependent associations between continuous PPI use and risk of iron deficiency, though only after ≥1 year of use 2. Similarly, a nested case-control study from the Kaiser Permanente Northern California healthcare system found that ≥2 years of PPI use was strongly associated with iron deficiency, with higher doses (≥1.5 PPI pills/day) showing a stronger association (adjusted OR: 2.49; 95% CI: 2.35,2.64) 2.

Risk Factors for PPI-Induced Iron Deficiency

The risk of developing iron deficiency on omeprazole is higher in:

• Patients on long-term therapy (≥1 year)
• Those taking higher doses (>1.5 pills/day)
• Patients with pre-existing iron deficiency
• Older adults
• Women of childbearing age (due to menstrual blood loss)

Clinical Approach

Monitoring Recommendations

• Check baseline iron studies before starting long-term PPI therapy
• Monitor iron parameters (serum iron, ferritin, transferrin saturation) annually in patients on long-term omeprazole, particularly in high-risk groups
• Consider more frequent monitoring in patients with pre-existing iron deficiency or risk factors

Management of Iron Deficiency in PPI Users

1. For mild iron deficiency without anemia:

   • Consider oral iron supplementation (ferrous sulfate) on alternate days
   • Take iron supplements at least 2 hours before omeprazole for better absorption

2. For significant iron deficiency anemia in patients on omeprazole:

   • Higher doses of oral iron may be required
   • Consider intravenous iron therapy if oral supplementation fails
   • A study showed only 16% of iron-deficient patients on omeprazole had optimal hemoglobin response to oral iron 3

3. Medication adjustment:

   • Reassess the need for continued PPI therapy
   • Consider reducing PPI dose if clinically appropriate
   • If possible, switch to H2-receptor antagonists which may have less impact on iron absorption

Special Considerations

Interestingly, experimental data shows variable effects. A rat model study showed that omeprazole reduced iron absorption only in iron-deficient rats but not in those on normal diets 4. A small study in healthy volunteers found no effect of short-term omeprazole on iron absorption 5, suggesting that the effect may be more significant in long-term use or in patients with pre-existing iron deficiency.

The American Gastroenterological Association does not currently recommend routine screening for iron deficiency in all patients taking PPIs 2, but targeted monitoring in high-risk patients is prudent based on the evidence of increased risk with long-term, high-dose therapy.

Conclusion

While not all patients on omeprazole will develop iron deficiency, the risk increases with duration of therapy (particularly beyond 1 year), higher doses, and in patients with pre-existing risk factors for iron deficiency. Clinicians should be vigilant about monitoring iron status in these high-risk populations.