Does Naproxen Elevate Fecal Calprotectin?
Yes, naproxen and other NSAIDs (non-steroidal anti-inflammatory drugs) are associated with elevated fecal calprotectin levels, even in patients without inflammatory bowel disease.
Evidence for NSAID-Associated Calprotectin Elevation
The use of NSAIDs, including naproxen, significantly increases fecal calprotectin levels independent of intestinal inflammation:
In patients with normal colonoscopy findings, NSAID use was independently associated with elevated fecal calprotectin >50 µg/g (adjusted OR: 2.411; 95% CI: 1.162-5.002) 1
This elevation occurs because NSAIDs cause direct mucosal injury and neutrophil infiltration into the gastrointestinal tract, leading to calprotectin release into the stool 1, 2
The effect is clinically significant enough that more than one-third of patients with normal colonoscopies had elevated fecal calprotectin levels, with NSAID use being one of the key contributing factors 1
Clinical Implications for Interpretation
When interpreting fecal calprotectin results in patients taking naproxen or other NSAIDs:
Consider discontinuing NSAIDs for at least 2-4 weeks before measuring fecal calprotectin if the goal is to assess for inflammatory bowel disease activity 1
If NSAID discontinuation is not feasible, recognize that elevated calprotectin may reflect NSAID-induced mucosal injury rather than underlying IBD activity 1, 2
Other medications that similarly elevate calprotectin include proton pump inhibitors (adjusted OR: 3.843) and aspirin (adjusted OR: 2.934), which should also be considered when interpreting results 1
Additional Confounding Factors
Beyond NSAIDs, several factors can cause false-positive calprotectin elevations:
Age independently increases calprotectin levels (adjusted OR: 1.051 per year) 1
Day-to-day variation in calprotectin levels exists, so borderline or unexpected results should prompt repeat testing 3
Calprotectin is elevated in any condition causing gastrointestinal inflammation, including infectious enteritis and colorectal cancer, not just IBD 4
Practical Recommendation
When evaluating patients for IBD or monitoring disease activity, obtain a medication history specifically asking about NSAID use (including over-the-counter naproxen, ibuprofen), aspirin, and proton pump inhibitors before ordering fecal calprotectin 1. If these medications are being used, either discontinue them temporarily before testing or interpret elevated results with caution, potentially requiring endoscopic confirmation rather than empiric treatment escalation 3, 1.