Aggravation of exercise-induced intestinal injury by Ibuprofen in athletes

Med Sci Sports Exerc. 2012 Dec;44(12):2257-62. doi: 10.1249/MSS.0b013e318265dd3d.


Introduction: Nonsteroidal anti-inflammatory drugs are commonly used by athletes to prevent anticipated exercise-induced pain, thereby putatively improving physical performance. However, these drugs may have potentially hazardous effects on the gastrointestinal (GI) mucosa during strenuous physical exercise. The aim of the current study was to determine the effect of oral ibuprofen administration before exercise on GI integrity and barrier function in healthy individuals.

Methods: Nine healthy, trained men were studied on four different occasions: 1) 400 mg ibuprofen twice before cycling, 2) cycling without ibuprofen, 3) 400 mg ibuprofen twice at rest, and 4) rest without ibuprofen intake. To assess small intestinal injury, plasma intestinal fatty acid binding protein (I-FABP) levels were determined, whereas urinary excretion of orally ingested multisugar test probes was measured using liquid chromatography and mass spectrometry to assess GI permeability.

Results: Both ibuprofen consumption and cycling resulted in increased I-FABP levels, reflecting small intestinal injury. Levels were higher after cycling with ibuprofen than after cycling without ibuprofen, rest with ibuprofen, or rest without ibuprofen (peak I-FABP, 875 ± 137, 474 ± 74, 507 ± 103, and 352 ± 44 pg·mL, respectively, P < 0.002). In line, small intestinal permeability increased, especially after cycling with ibuprofen (0-2 h urinary lactulose/rhamnose ratio, 0.08 (0.04-0.56) compared with 0.04 (0.00-0.20), 0.05 (0.01-0.07), and 0.01 (0.01-0.03), respectively), reflecting loss of gut barrier integrity. Interestingly, the extent of intestinal injury and barrier dysfunction correlated significantly (RS = 0.56, P < 0.001).

Conclusion: This is the first study to reveal that ibuprofen aggravates exercise-induced small intestinal injury and induces gut barrier dysfunction in healthy individuals. We conclude that nonsteroidal anti-inflammatory drugs consumption by athletes is not harmless and should be discouraged.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Athletes*
  • Bicycling / physiology*
  • Biomarkers / blood
  • Fatty Acid-Binding Proteins / blood
  • Humans
  • Ibuprofen / adverse effects*
  • Ibuprofen / pharmacology
  • Intestinal Mucosa / drug effects*
  • Intestine, Small / injuries*
  • Intestine, Small / metabolism
  • Male
  • Netherlands
  • Pain / prevention & control
  • Permeability


  • Anti-Inflammatory Agents, Non-Steroidal
  • Biomarkers
  • Fatty Acid-Binding Proteins
  • Ibuprofen