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  • Active Voice: Oral Citrulline to Circumvent Splanchnic Hypoperfusion and Gut Injury in Athletes

    by Guest Blogger | Mar 30, 2015
    By Karolina A.P. Wijnands, M.D., and Kaatje Lenaerts, Ph.D.


    Kaatje Lenaerts, Ph.D.

    Karolina A.P. Wijnands, M.D.

    In that work, we studied athletes on two occasions in which they performed a one-hour cycling protocol at 70 percent of their maximal workload capacity. In one of these cycling bouts, they ingested L-citrulline 30 minutes prior to exercise and, in the other, they ingested L-alanine as a placebo 30 minutes in advance. Oral citrulline intake significantly increased plasma citrulline and arginine in healthy athletes, resulting in prolonged increased arginine availability for NO synthesis?without causing GI discomfort, as has been reported for arginine. To assess the effect on splanchnic perfusion, we used gastric air tonometry and side-stream dark field sublingual imaging procedures (for more on gastric air tonometry, see van Wijck et al., 2012). Data revealed that citrulline intake prior to exercise resulted in preserved splanchnic perfusion and improved sublingual microcirculation. Importantly, these improvements were associated with significantly reduced enterocyte damage during exercise compared with placebo.

    These findings encourage further studies on the effects of citrulline in symptomatic athletes aimed at relieving ischemia-related abdominal complaints. Furthermore, our data may be of interest for asymptomatic athletes as well. Preserving enterocyte integrity during exercise by citrulline supplementation is expected to improve nutrient uptake during and after exercise, and in this way contribute to enhanced recovery. Furthermore, clinical studies are ongoing to determine whether citrulline supplementation exhibits similar beneficial effects in patients suffering from splanchnic-hypoperfusion, such as in sepsis.

    Viewpoints presented on the ACSM Blog reflect opinions of the authors and do not necessarily reflect positions or policies of ACSM.

    Karolina A.P. Wijnands, M.D., is in the final phase of writing her Ph.D. thesis. Her research seeks to understand the effects of L-citrulline supplementation on arginine-NO metabolism and microcirculation, employing conditions that reduce splanchnic perfusion such as (experimental) sepsis and strenuous exercise in healthy athletes. Karolina currently is an orthopedic surgery resident with the Maastricht University Hospital in The Netherlands, where she will be continuing her research on arginine-NO metabolism in inflammatory conditions, bone healing and exercise.

    Kaatje Lenaerts, Ph.D., is an assistant professor in the Department of Surgery at Maastricht University, The Netherlands. Trained as a biomedical scientist, she studies several facets of gut wall integrity loss, from unraveling the molecular basis of intestinal ischemia to developing models and tools to assess the impact of stressors on the gastrointestinal tract. Her translational research focuses on the interplay between intestinal compromise, innate immunity and nutrition to enhance intestinal mucosal homeostasis.

    This commentary presents Drs. Wijnands’ and Lenaerts’ views on the topic related to a research article that they authored with colleagues. Their article appears in the November 2014 issue of Medicine & Science in Sports & Exercise® (MSSE).

    Up to 70 percent of endurance athletes suffer from abdominal complaints during or after performing strenuous exercise. Gastrointestinal (GI) symptoms include nausea, vomiting, flatulence, cramps, diarrhea and rectal bleeding. The incidence and type of GI symptoms depend on factors including exercise type, intensity, duration and food/fluid intake, and these symptoms can vary from mild to severe.

    Splanchnic blood flow reduction and concomitant intestinal ischemia are considered important factors in the development of exercise-induced GI discomfort. This decrease in intestinal perfusion is a result of blood flow redistribution, directing the blood toward the active muscles, heart and lungs, and away from the GI system. Formation of intestinal nitric oxide (NO), a potent vasodilator, is impaired during splanchnic hypoperfusion. NO is produced from amino acid L-arginine via NO synthase and has an important role in vasoregulation of the splanchnic bed. Hence, increasing the local availability of NO is a potential means to enhance the intestinal microcirculation.

    Logically, L-arginine was one of the first agents studied in this respect and, while its administration has been shown to increase plasma arginine availability, the results have not been unequivocally positive. In addition, arginine supplementation in man may induce adverse GI effects, such as nausea, vomiting and diarrhea, thus limiting its practical application. Another means to increase NO availability is by supplying L-citrulline, a precursor of L-arginine. Importantly, in a previous study we showed that, compared with arginine, citrulline is a more suitable substrate to enhance intestinal perfusion and microcirculation in endotoxemic mice. To translate these findings to humans, we applied our strenuous exercise model, which is characterized by splanchnic hypoperfusion, intestinal injury and intestinal barrier loss in healthy athletes, to study the protective effects of citrulline in our current study, recently reported in MSSE.

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