L-citrulline improves splanchnic perfusion and reduces gut injury during exercise

Med Sci Sports Exerc. 2014 Nov;46(11):2039-46. doi: 10.1249/MSS.0000000000000332.


Purpose: Splanchnic hypoperfusion is a physiological phenomenon during strenuous exercise. It has been associated with gastrointestinal symptoms and intestinal injury and may hamper athletic performance. We hypothesized that L-citrulline supplementation improves splanchnic perfusion and decreases intestinal injury by enhancing arginine availability. The aim of this study was to determine the effect of L-citrulline intake on splanchnic perfusion, intestinal injury, and barrier function during exercise.

Methods: In this randomized, double-blind crossover study, 10 men cycled for 60 min at 70% of their maximum workload after L-citrulline (10 g) or placebo (L-alanine) intake. Splanchnic perfusion was assessed using gastric air tonometry. Sublingual microcirculation was evaluated by sidestream dark field imaging. Plasma amino acid levels and intestinal fatty acid binding protein concentrations, reflecting enterocyte damage, were assessed every 10 min. Urinary excretion of sugar probes was measured to evaluate intestinal permeability changes.

Results: Oral L-citrulline supplementation enhanced plasma citrulline (1840.3 ± 142.3 µM) and arginine levels (238.5 ± 9.1 µM) compared with that in placebo (45.7 ± 4.8 µM and 101.5 ± 6.1 µM, respectively, P < 0.0001), resulting in increased arginine availability. Splanchnic hypoperfusion was prevented during exercise after L-citrulline ingestion (reflected by unaltered gapg-apCO2 levels), whereas gapg-apCO2 increased with placebo treatment (P < 0.01). Accordingly, L-citrulline intake resulted in an increased number of perfused small sublingual vessels compared with that in placebo (7.8 ± 6.0 vs -2.0 ± 2.4, P = 0.06). Furthermore, plasma intestinal fatty acid binding protein levels were attenuated during exercise after L-citrulline supplementation compared with that in placebo (AUC0-60 min, -185% ± 506% vs 1318% ± 553%, P < 0.01). No significant differences were observed for intestinal permeability.

Conclusions: Pre-exercise L-citrulline intake preserves splanchnic perfusion and attenuates intestinal injury during exercise in athletes compared with placebo, probably by enhancing arginine availability. These results suggest that oral L-citrulline supplementation is a promising intervention to combat splanchnic hypoperfusion-induced intestinal compromise.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Arginine / blood
  • Bicycling / physiology
  • Citrulline / administration & dosage*
  • Citrulline / blood
  • Cross-Over Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Enterocytes / pathology
  • Exercise / physiology*
  • Fatty Acid-Binding Proteins / blood
  • Humans
  • Intestine, Small / blood supply*
  • Intestine, Small / pathology*
  • Male
  • Microcirculation
  • Splanchnic Circulation / physiology*
  • Young Adult


  • Fatty Acid-Binding Proteins
  • Citrulline
  • Arginine