l-Citrulline supplementation improves O₂ uptake kinetics and high-intensity exercise performance in humans

Abstract

Bailey SJ, Blackwell JR, Lord T, Vanhatalo A, Winyard PG, Jones AM. L-Citrulline supplementation improves O2 uptake kinetics and high-intensity exercise performance in humans. J Appl Physiol 119: 385-395, 2015. First published May 28, 2015 doi:10.1152/japplphysiol.00192.2014.-The purpose of this study was to compare the effects of L-citrulline (Cit) and L-arginine (Arg) supplementation on nitric oxide (NO) biomarkers, pulmonary O2 uptake (V O2) kinetics, and exercise performance. In a randomized, placebo (Pla)-controlled, crossover study, 10 healthy adult men completed moderate-and severe-intensity cycling exercise on days 6 and 7 of a 7-day supplementation period with Pla, Arg (6 g/day), and Cit (6 g/day). Compared with Pla, plasma Arg concentration was increased by a similar magnitude with Arg and Cit supplementation, but plasma Cit concentration was only increased (P Ͻ 0.001) with Cit supplementation. Plasma nitrite (NO 2 Ϫ ) concentration was increased with Arg supplementation (P Ͻ 0.05) and tended to increase with Cit supplementation (P ϭ 0.08) compared with Pla (83 Ϯ 25, 106 Ϯ 41, and 100 Ϯ 38 nM with Pla, Arg, and Cit, respectively); however, mean arterial blood pressure was only lower (P Ͻ 0.05) after Cit supplementation. The steady-state V O2 amplitude during moderateintensity cycle exercise was not significantly different between supplements, but Cit lowered the V O2 mean response time (59 Ϯ 8 and 53 Ϯ 5 s with Pla and Cit, respectively, P Ͻ 0.05) during severe-intensity exercise, improved tolerance to severe-intensity exercise (589 Ϯ 101 and 661 Ϯ 107 s with Pla and Cit, respectively), and increased the total amount of work completed in the exercise performance test (123 Ϯ 18 and 125 Ϯ 19 kJ with Pla and Cit, respectively, P Ͻ 0.05). These variables were not altered by Arg supplementation (P Ͼ 0.05).In conclusion, these results suggest that short-term Cit, but not Arg, supplementation can improve blood pressure, V O2 kinetics, and exercise performance in healthy adults. nitric oxide; blood pressure; near-infrared spectroscopy; metabolism; fatigue THE MULTIFACETED PHYSIOLOGICAL signaling molecule nitric oxide (NO) can be synthesized endogenously through the nitratenitrite (NO 2 Ϫ )-NO pathway (37) and through the five-electron oxidation of L-arginine (Arg) in a reaction catalyzed by the NO synthase (NOS) enzymes (55). While studies have shown that dietary nitrate supplementation can increase NO biomarkers, reduce blood pressure, and improve exercise economy/efficiency and exercise tolerance in healthy adults (see Ref. 4 for review), the extent to which these variables are impacted by dietary Arg supplementation is less clear (see Ref. 1 for review). However, when Arg treatment increases NO biomarkers, exercise economy and exercise performance are improved (5, 52), whereas exercise economy and exercise performance are not improved when Arg treatment does not influence NO synthesis (9,31,35,60). Therefore, while there is some evidence to suggest that Arg treatment might improve physiological responses ...

Two weeks of watermelon juice supplementation improves nitric oxide bioavailability but not endurance exercise performance in humans

“…[nitrite], but the 21% increase did approach statistical significance [22]. However, when a similar total L-citrulline dose was administered as concentrated watermelon juice in this study, plasma [nitrite] was increased by 90% in spite of a lower increase in plasma [Larginine] (+42%) compared to our previous study (+137%) [22].…”

“…However, while the O 2 cost of moderateintensity exercise was not altered after watermelon juice supplementation, muscle oxygenation during moderate-intensity was greater following watermelon juice supplementation. Indices of muscle oxygenation were also improved in our recent study after L-citrulline supplementation [22]. Taken together, these findings suggest that supplementation with watermelon juice or L-citrulline may improve the balance between muscle O 2 supply and muscle O 2 demand during moderate-intensity exercise.…”

“…However, when a similar total L-citrulline dose was administered as concentrated watermelon juice in this study, plasma [nitrite] was increased by 90% in spite of a lower increase in plasma [Larginine] (+42%) compared to our previous study (+137%) [22]. The greater potential for nitric oxide synthesis after watermelon juice supplementation might be linked to a synergistic effect between L-citrulline and other constituents of watermelon juice.…”

“…Consequently, watermelon juice ingestion has been reported to increase plasma L-citrulline [29] and L-arginine [29,30], and may also increase nitric oxide biomarkers [31]. We recently reported that seven days of supplementation with 6 g Lcitrulline·day -1 tended to, but did not significantly, increase plasma [nitrite] [22], a sensitive marker of nitric oxide synthase activity [32]. It has been suggested that concurrently supplementing with L-citrulline and glutathione is more effective at increasing plasma nitric oxide markers than L-citrulline alone [33].…”

“…It has also been reported that L-citrulline supplementation can increase the activity of nitric oxide synthase [20] and increase nitric oxide biomarkers [19,21], and there is accumulating evidence to suggest that short term supplementation with L-citrulline can improve skeletal muscle oxygenation [22], metabolism [23][24], force production [23] and fatigue resistance [22]. Therefore, short-term supplementation with L-citrulline might represent an effective dietary intervention to increase nitric oxide synthase-derived nitric oxide and to improve skeletal muscle perfusion, metabolism and exercise performance.…”