title: L-citrulline improves splanchnic perfusion and reduces gut injury during exercise.
abstract: OBJECTIVE
  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.
authors.affiliation: 1Top Institute Food and Nutrition, Wageningen, The NETHERLANDS; 2Department of General Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, The NETHERLANDS; and 3Department of Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, The NETHERLANDS.
authors.forename: Kim
authors.initials: K
authors.lastname: van Wijck
authors.forename: Karolina A P
authors.initials: KA
authors.lastname: Wijnands
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Meesters
authors.forename: Bas
authors.initials: B
authors.lastname: Boonen
authors.forename: Luc J C
authors.initials: LJ
authors.lastname: van Loon
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Cornelis H C
authors.initials: CH
authors.lastname: Dejong
authors.forename: Kaatje
authors.initials: K
authors.lastname: Lenaerts
authors.forename: Martijn
authors.initials: M
authors.lastname: Poeze
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001120:Arginine / Q000097:blood; D001642:Bicycling / Q000502:physiology; D002956:Citrulline / Q000008:administration & dosage* / Q000097:blood; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D020895:Enterocytes / Q000473:pathology; D015444:Exercise / Q000502:physiology*; D050556:Fatty Acid-Binding Proteins / Q000097:blood; D006801:Humans; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology*; D008297:Male; D008833:Microcirculation; D013152:Splanchnic Circulation / Q000502:physiology*; D055815:Young Adult
chemical_list: D050556:Fatty Acid-Binding Proteins; D002956:Citrulline; D001120:Arginine