What effect does omeprazole (proton pump inhibitor) have on fecal calprotectin levels in patients with inflammatory bowel disease (IBD) or gastrointestinal conditions?

Omeprazole Elevates Fecal Calprotectin Levels

Omeprazole and other proton pump inhibitors (PPIs) cause false elevations in fecal calprotectin levels, with 53% of healthy individuals on omeprazole developing elevated calprotectin (median 85.3 μg/g, range 51.1-249 μg/g) during short-term use. 1

Direct Effect on Calprotectin Measurement

• A randomized clinical trial in 32 healthy volunteers demonstrated that 20 mg omeprazole daily for 2 weeks elevated fecal calprotectin above normal (>50 μg/g) in 53% of participants 1
• When omeprazole was combined with diclofenac, 69% of participants had elevated calprotectin (median 101.5 μg/g, range 51.5-532 μg/g), suggesting an additive effect 1
• After omeprazole cessation, calprotectin levels normalized within 3 weeks in all participants 1

Clinical Implications for IBD Monitoring

• The British Society of Gastroenterology and American Gastroenterological Association guidelines do not specifically mention PPI use as a confounder when interpreting calprotectin, but they do emphasize that NSAID use within 6 weeks can affect levels 2, 3
• In patients with known IBD on omeprazole, distinguishing true disease activity from PPI-induced elevation becomes challenging, particularly when calprotectin falls in the intermediate range (50-250 μg/g) 2
• If a patient on omeprazole has mildly elevated calprotectin (50-250 μg/g) without corresponding clinical symptoms, consider repeating the test at least 3 weeks after PPI cessation before escalating IBD therapy 1

Mechanism and Additional Considerations

• PPIs alter intestinal microbiome composition and may increase intestinal permeability through disruption of tight junction barriers, which could theoretically contribute to both false elevation of calprotectin and worsening of underlying IBD 4
• Long-term PPI use in IBD patients has been associated with worse clinical outcomes, including increased risk of new biologic initiation (OR 1.11), IBD-related hospitalizations (OR 1.95), and surgeries (OR 1.46) 5
• A dose-response relationship exists between number of PPI prescriptions and risk of IBD-related complications 5

Practical Recommendations

• When interpreting elevated calprotectin in patients on omeprazole, document PPI use duration and consider temporary discontinuation (if clinically appropriate) with repeat testing 3 weeks later 1
• For patients with moderate-to-severe IBD symptoms and calprotectin >150 μg/g, the PPI effect is less clinically relevant as these levels reliably indicate endoscopic inflammation regardless of PPI use 2, 6
• In asymptomatic IBD patients on omeprazole with calprotectin 50-250 μg/g, the false positive rate may be higher, warranting either PPI cessation with repeat testing or proceeding directly to endoscopic assessment 2, 1
• Review necessity of PPI therapy in all IBD patients, as inappropriate long-term use may contribute to disease progression independent of its effect on calprotectin measurement 5