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Top Institute Food and Nutrition, Wageningen, THE NETHERLANDS; 2Department of Surgery, NUTRIM School for Nutrition,
Toxicology and Metabolism, Maastricht University Medical Center+, Maastricht, THE NETHERLANDS; and 3Department of
Human Movement Sciences, NUTRIM, Maastricht University Medical Center+, Maastricht, THE NETHERLANDS
ABSTRACT
VAN WIJCK, K., K. LENAERTS, A. A. VAN BIJNEN, B. BOONEN, L. J. C. VAN LOON, C. H. C. DEJONG, and W. A. BUURMAN.
Aggravation of Exercise-Induced Intestinal Injury by Ibuprofen in Athletes. Med. Sci. Sports Exerc., Vol. 44, No. 12, pp. 22572262, 2012.
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 T 137, 474 T 74, 507 T 103, and 352 T 44 pgImLj1, respectively, P G 0.002). In line, small
intestinal permeability increased, especially after cycling with ibuprofen (02 h urinary lactulose/rhamnose ratio, 0.08 (0.040.56)
compared with 0.04 (0.000.20), 0.05 (0.010.07), and 0.01 (0.010.03), respectively), reflecting loss of gut barrier integrity. Interestingly,
the extent of intestinal injury and barrier dysfunction correlated significantly (RS = 0.56, P G 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. Key Words:
NSAID, EXERCISE, GASTROINTESTINAL DAMAGE, PERMEABILITY
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RESULTS
Ibuprofen aggravates exercise-induced intestinal
injury. Plasma I-FABP levels were determined to assess
loss of cellular integrity within the small intestine. In line
with our previous study (33), plasma I-FABP levels gradually increased during cycling at 70% of Wmax from baseline
295 T 46 pgImLj1 to mean peak levels of 474 T 74 pgImLj1
immediately postexercise (P G 0.05, Fig. 1A). Interestingly,
cycling with ibuprofen resulted in even higher levels
of circulating I-FABP (P G 0.0001, Fig. 1A). In the latter
situation, peak I-FABP levels of 875 T 137 pgImLj1 were
observed immediately postexercise, being a significant increase from baseline (328 T 32 pgImLj1, P G 0.05; Fig. 1A).
These peak I-FABP levels were significantly higher than
I-FABP levels after cycling without ibuprofen (875 T 137 vs
474 T 74 pgImLj1, P G 0.05; Fig. 1A, C).
Ibuprofen consumption also increased levels of small intestinal injury at rest (P = 0.0003, Fig. 1B, C). Two of nine
DISCUSSION
NSAID consumption is common among athletes. Alarmingly, its prevalence among athletes has been reported to
reach 90% in specific sports (16,29,32). Especially, endurance athletes are well acquainted with the occurrence of GI
problems during or after exercise (26,31). However, these
athletes have limited awareness of the potentially hazardous
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reader at 450 nm. The detection window of the I-FABP assay was 12.5 to 800 pgImLj1.
Assessment of GI permeability. GI permeability
was determined as a measure of GI barrier integrity using
a multisugar test drink as described previously (34). The
food grade sugar probes included in the test drink were 1 g
lactulose (Centrafarm, Etten-Leur, The Netherlands), 1 g
sucralose (Brenntag, Sittard, The Netherlands), 1 g erythritol
(Danisco, Copenhagen, Denmark), 1 g sucrose (Van Gilse,
Dinteloord, The Netherlands), and 0.5 g L-rhamnose (Danisco)
dissolved in 150 mL of tap water. GI permeability was
assessed by determination of the 02 h urinary excretion
of these orally ingested sugar probes using a combined
high-performance liquid chromatography (model PU-1980
pump; Jasco Benelux, Maarssen, The Netherlands) and mass
spectrometry (model LTQ-XL; Thermo Electron, Breda,
The Netherlands) approach (34). Gastroduodenal permeability was assessed by calculation of the 02 h urinary
ratio of sucrose (342 D) and L-rhamnose (164 D), whereas
the urinary 02 h ratio lactulose (342 D) and L-rhamnose,
the lactulose/rhamnose (L/R) ratio, was computed to assess
small intestinal permeability.
Statistical analysis. Statistical analysis was performed
using GraphPad Prism (version 5.00; GraphPad Software
for Windows, San Diego, CA). Normality of all data was
verified by the KolmogorovSmirnov test. All normally
distributed data are presented as mean T SEM and not normally distributed data as median and range. Continuous
data were analyzed using two-way ANOVA with Bonferroni
post hoc test for multiple comparisons. Correlations
were determined by calculating the Spearman correlation
coefficient (rS). Linear regression was used to visualize the
correlation. Correlations between small intestinal injury and
small intestinal permeability were computed using individually normalized I-FABP levels, and P G 0.05 was deemed
statistically significant.
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REFERENCES
1. Alaranta A, Alaranta H, Heliovaara M, Airaksinen M, Helenius I.
Ample use of physician-prescribed medications in Finnish elite
athletes. Int J Sports Med. 2006;27(11):91925.
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