L-Citrulline Improves Splanchnic Perfusion and Reduces Gut Injury during Exercise

van Wijck, Kim1,2; Wijnands, Karolina A. P.2; Meesters, Dennis M.2; Boonen, Bas2; van Loon, Luc J. C.1,3; Buurman, Wim A.2; Dejong, Cornelis H. C.1,2; Lenaerts, Kaatje1,2; Poeze, Martijn2

Medicine & Science in Sports & Exercise:
doi: 10.1249/MSS.0000000000000332
Clinical Sciences
Abstract

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.

Author Information

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

Address for correspondence: Kaatje Lenaerts, Ph.D., Department of General Surgery, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands; E-mail: Kaatje.lenaerts@maastrichtuniversity.nl.

K.V.W. and K. A. P. W. contributed equally to this article.

Submitted for publication October 2013.

Accepted for publication March 2014.

© 2014 American College of Sports Medicine