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This study investigated the effects of combined L -arginine (Arg) and citrulline-malate (CM) supplementation on aerobic, anaerobic, and high-intensity interval training in healthy, trained men. Both Arg and CM are widely marketed for their potential ergogenic effects, as Arg serves as a precursor to nitric oxide (NO), which may support vasodilation, muscle contractility, and exercise performance. Arg and CM are hypothesized to exert synergistic effects due to their complementary roles in NO synthesis. Citrulline can potentially enhance and prolong Arg availability, thereby amplifying NO-mediated vasodilation, nutrient delivery, and muscle performance during exercise. In this randomized, double-blind, placebo-controlled trial, 46 healthy, trained men aged 24.8 ± 5.0 years were divided into 3 exercise groups subjected to consuming 0.15 g/kg bodyweight of Arg and 0.1 g/kg bodyweight of CM prior. The participants were then randomly divided into three groups based on the exercise protocol:: the Wingate Anaerobic Test ( n  = 16), a 20 min CrossFit workout ‘Cindy’ ( n  = 16) consisting of continuous rounds of pull-ups, push-ups, and air squats to measure functional fitness and muscular endurance, or the Harvard Step Test ( n  = 14) a measurement of cardiovascular endurance and recovery. This design allowed for the evaluation of supplementation effects across multiple exercise modalities . The results revealed no significant improvement in performance with supplementation in comparison to placebo, except for a shorter time to reach peak power in the Wingate test. Findings suggest that the combined acute supplementation of Arg and CM, at the given dosages, may not provide substantial benefits for aerobic and anaerobic or CrossFit performance in active individuals. Future research with larger sample sizes and higher dosages, potentially adjusted for muscle mass, is recommended to determine whether chronic supplementation might yield greater ergogenic effects.

Purpose Citrulline malate (CM) is a nonessential amino acid that increases exercise performance in males. However, based on physiological differences between genders, these results cannot be extrapolated to females. Therefore, the purpose of this investigation was to evaluate effects of acute CM supplementation on upper- and lower-body weightlifting performance in resistance-trained females. Methods Fifteen females (23 ± 3 years) completed two randomized, double-blind trials consuming either CM (8 g dextrose + 8 g CM) or a placebo (8 g dextrose). One hour after supplement consumption, participants performed six sets each of upper- (i.e., bench press) and lower-body (i.e., leg press) exercises to failure at 80 % of previously established one-repetition maximum. Immediately after each set, repetitions completed, heart rate and rating of perceived exertion (RPE) were recorded. Results Repeated-measures analysis of variance indicated that subjects completed significantly ( p  = .045) more repetitions throughout upper-body exercise when consuming CM versus placebo (34.1 ± 5.7 vs. 32.9 ± 6.0, respectively). When consuming CM, similar significant ( p  = .03) improvements in total repetitions completed were observed for lower-body exercise (66.7 ± 30.5 vs. 55.13 ± 20.64, respectively). Overall RPE score was significantly lower ( p  = .02) in upper-body exercise when subjects consumed CM versus placebo (7.9 ± 0.3 and 8.6 ± 0.2, respectively). The supplement consumed exhibited no significant effects on heart rate at any time point. Conclusions Acute CM supplementation in females increased upper- and lower-body resistance exercise performance and decreased RPE during upper-body exercise. These data indicate that athletes competing in sports with muscular endurance-based requirements may potentially improve performance by acutely supplementing CM.

Given the increasing popularity of CrossFit® as a high-intensity functional training program and the potential benefits of citrulline malate (CM) in enhancing exercise performance through its role as a precursor to L-arginine and nitric oxide production, this study aimed to investigate the acute effects of CM supplementation on CrossFit® performance and cardiovascular function. Using a randomized, double-blind, placebo-controlled, cross-over design, 21 recreationally active participants (mean age 22.2 ± 2.6 years, mean body weight 75.9 ± 10.4 kg) with CrossFit® experience completed the “Cindy” workout under CM and placebo conditions. Participants consumed 4.4 g of CM or a placebo 60 min before the workout, and the performance was measured by the number of rounds completed. Secondary outcomes included heart rate response, time spent in different heart rate intensity zones, and post-exercise recovery time. The results indicated no significant difference in the number of rounds completed between the CM and placebo conditions (13.5 ± 5.2 vs. 13.8 ± 6.7 rounds, respectively; p = 0.587). However, the time spent in zone 4 (80–90% of HR max) was significantly increased in the CM condition (527 ± 395 s vs. 453 ± 334 s; p = 0.017), suggesting a potential benefit for aerobic capacity and anaerobic threshold. No significant differences in post-exercise recovery time were observed (6.6 ± 4.7 h vs. 6.9 ± 4.7 h; p = 0.475). This study highlights the need for further research with larger sample sizes, both genders, and different CM dosages to clarify these findings and better understand CM’s role in enhancing athletic performance.

Nitric-oxide-stimulating dietary supplements are widely available and marketed to strength athletes and weightlifters seeking to increase muscle performance and augment training adaptations. These supplements contain ingredients classified as nitric oxide (NO) precursors (i.e., “NO boosters”). Endogenous NO is generated via a nitric oxide synthase (NOS)-dependent pathway and a NOS-independent pathway that rely on precursors including L-arginine and nitrates, with L-citrulline serving as an effective precursor of L-arginine. Nitric oxide plays a critical role in endothelial function, promoting relaxation of vascular smooth muscle and subsequent dilation which may favorably impact blood flow and augment mechanisms contributing to skeletal muscle performance, hypertrophy, and strength adaptations. The aim of this review is to describe the NO production pathways and summarize the current literature on the effects of supplementation with NO precursors for strength and power performance. The information will allow for an informed decision when considering the use of L-arginine, L-citrulline, and nitrates to improve muscular function by increasing NO bioavailability.

Background Many human studies report that nitric oxide (NO) improves sport performance. This is because NO is a potential modulator of blood flow, muscle energy metabolism, and mitochondrial respiration during exercise. L-Citrulline is an amino acid present in the body and is a potent endogenous precursor of L-arginine, which is a substrate for NO synthase. Here, we investigated the effect of oral L-citrulline supplementation on cycling time trial performance in humans. Methods A double-blind randomized placebo-controlled 2-way crossover study was employed. Twenty-two trained males consumed 2.4 g/day of L-citrulline or placebo orally for 7 days. On Day 8 they took 2.4 g of L-citrulline or placebo 1 h before a 4-km cycling time trial. Time taken to complete the 4 km cycle, along with power output/VO 2 ratio (PO/VO 2 ), plasma nitrite and nitrate (NOx) and amino acid levels, and visual analog scale (VAS) scores, was evaluated. Results L-Citrulline supplementation significantly increased plasma L-arginine levels and reduced completion time by 1.5 % ( p  < 0.05) compared with placebo. Moreover, L-citrulline significantly improved subjective feelings of muscle fatigue and concentration immediately after exercise. Conclusions Oral L-citrulline supplementation reduced the time take to complete a cycle ergometer exercise trial. Trial registration Current Controlled Trials UMIN000014278 .

Background: Pre-season training is critical for developing tolerance to high physical demands in professional soccer, and nitric oxide (NO) precursors such as dietary nitrate (NO3−) and citrulline malate (CM) can support performance and recovery during this demanding phase. This study aimed to examine the effects of a four-week supplementation protocol combining 500 mg of NO3− from amaranth extract and 8 g of CM (NIT + CM) on external training load and post-match recovery in professional female soccer players during pre-season. Methods: A randomized, double-blind, placebo-controlled trial was conducted with 34 female soccer players who received either the NIT + CM product or a placebo for four weeks during pre-season. Global positioning system (GPS)-derived external load was recorded throughout the intervention. Performance tests—a countermovement jump (CMJ) test and the Wingate anaerobic test (WAnT)—and blood sampling for plasma NO3− and nitrite (NO2−) concentrations were conducted at baseline and the day after a competitive match. Results: The supplementation with NIT + CM increased maximal speed (Vmax) throughout training and match play. During post-match testing, the NIT + CM group exhibited a significantly smaller decline in mean (Pmean) and minimum (Pmin) power during the WAnT, along with reduced power loss in both the first (0–15 s) and second (15–30 s) intervals. Plasma NO3− concentrations significantly increased from baseline in the NIT + CM group and remained elevated 24 h after the final dose, confirming sustained systemic exposure. Conclusions: Chronic NIT + CM supplementation may enhance Vmax and help preserve anaerobic performance the day after a match. These effects could reflect improved tolerance to high training loads and sustained NO3− availability during recovery.

Citrulline malate (CM) is purported to be an ergogenic aid during various types of exercise performance. However, the effects of CM on repeated sprint performance (RSP) are under‐explored. In a placebo‐controlled, double‐blind, counterbalanced cross‐over design, male university‐level team sport athletes (n = 13) performed two familiarization trials, after which CM or placebo (PLA) (8 × 1 g tablets each day) were taken on the 2 days prior to, and with breakfast on the morning of, each main experimental trial. The main experimental trials employed a RSP protocol consisting of 10 repetitions of 40 m maximal shuttle run test (MST) with a 30 s interval between the start of each sprint. Sprint times and heart rate were recorded throughout the MST, and blood lactate concentrations were measured before, immediately after, and 5 min after completing the MST. CM resulted in better RSP compared to PLA, as indicated by a lower sprint performance decrement (Sdec: CM, 4.68% ± 1.82% vs. PLA, 6.10% ± 1.83%; p = 0.03; ES = 0.77), which was possibly influenced by the fastest sprint time being faster in CM (CM, 8.16 ± 0.34 s vs. PLA, 8.29 ± 0.39 s; p = 0.011; ES = 0.34). There were no differences between CM and PLA in average sprint time (p = 0.54), slowest sprint time (p = 0.48), blood lactate concentrations (p = 0.73) or heart rate (p = 0.18), nor was there a condition × time interaction effect across the 10 sprints (p = 0.166). Three days of CM supplementation (8 g daily) attenuated the sprint performance decrement during short‐duration high‐intensity exercise in the form of running RSP in male university‐level team sport athletes. Highlights This study addresses a knowledge gap around the ergogenic potential of citrulline malate (CM) in repeated sprint running performance. Three days of CM supplementation (8 g daily) was observed to improve short‐duration (5 min) high‐intensity exercise performance in male university‐level team sport athletes when measured by the sprint performance decrement in a 10 repetition 40 m maximal shuttle run test. The attenuation in the sprint performance decrement was not associated with any differences compared to the placebo condition in heart rate or blood lactate concentrations. The outcomes of this study suggest that short‐term CM supplementation could be beneficial for team sport athletes who perform short‐duration high‐intensity efforts, such as soccer, Gaelic games, field hockey, and rugby.

Background Ankle-brachial index (ABI) and ankle blood pressure (BP) are associated with increased carotid wave reflection (augmentation index, AIx). Oral L-citrulline and L-arginine from synthetic or watermelon sources have reduced brachial BP, aortic BP, and aortic AIx. A directly measured carotid AIx (cAIx) rather than aortic AIx has been proposed as a better measurement of central AIx. We evaluated the effects of watermelon extract on ankle BP and cAIx in individuals with normal ABI and prehypertension or stage 1 hypertension. Methods Ankle and brachial systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), cAIx, ABI, and heart rate (HR) were evaluated in the supine position in 14 adults (11 women/3 men, age 58 ± 1 years) with prehypertension or stage 1 hypertension (153 ± 4 mm Hg). Subjects were randomly assigned to 6 weeks of watermelon extract supplementation (L-citrulline/L-arginine, 6 g daily) or placebo followed by a 2-week washout period and then crossover. Results Ankle and brachial SBP (−11.5 ± 3.8 and −15.1 ± 2.8 mm Hg), DBP (−7.8 ± 2.3 and −7.6 ± 1.8 mm Hg), and MAP (−9.8 ± 2.6 and −7.3 ± 1.8 mm Hg), and cAIx (−8.8 ± 2.6 %) decreased significantly (P < 0.05) after watermelon supplementation compared to placebo. Watermelon supplementation had no significant effect (P > 0.05) on ABI and HR. Conclusions This study shows that watermelon extract supplementation reduces ankle BP, brachial BP, and carotid wave reflection in obese middle-aged adults with prehypertension or stage 1 hypertension and normal ABI, which may reflect improved arterial function.

Background: The dietary supplement citrulline might increase nitric oxide levels, leading to vasodilation and improved blood flow, potentially benefiting athletes’ aerobic exercise performance. However, rapid oxidative impairment of the L-arginine/nitric oxide (NO) pathway limits these effects. This is countered by Bergamot Polyphenolic Fraction Gold® (BPFG), a strong natural antioxidant. To investigate L-citrulline + BPFG supplementation’s effects, we performed a randomized, double-blind, placebo-controlled pilot trial on athletic performance and blood flow in trained athletes (cyclists). Methods: Random assignment of 90 male athletes resulted in nine different groups: placebo for Group 1, BPFG at 500 and 1000 mg daily for Groups 2 and 3, L-citrulline at 1000 and 2000 mg/daily for Groups 4 and 5, and the combination product of BPFG plus citrulline (N.O. Max) for Groups 6–9. Baseline and 3-month pre- and post-exercise biochemical, reactive vasodilation (RHI), and maximal oxygen consumption measurements were taken for all subjects. Results: Three months of the combination of BPFG and L-citrulline (N.O. Max) produced a significant synergistic effect, markedly increasing NO (p < 0.001 vs. placebo) release and RHI (p < 0.001 vs. placebo). Cardiorespiratory fitness improved significantly with the BPFG and L-citrulline combination, resulting in substantially higher VO2 max, VT1, VT2, and peak power and a significantly lower heart rate (p < 0.01 vs. placebo). No harmful adverse effects were observed. Conclusions: N.O. Max supplementation, providing beneficial effects on the antioxidant state and preserving the vascular endothelium might be a supplementation strategy to improve athletic performance and potentiate results. Given the small sample size, this study serves as a pilot, and further research is needed to validate these findings on a larger scale.

The effects of citrulline malate (CM) on muscle recovery from resistance exercise remains unknown. We aimed to determine if citrulline malate supplementation improves muscle recovery after a single session of high-intensity resistance exercise (RE) in untrained young adult men. Nine young adult men (24.0 ± 3.3 years) participated in a double-blind crossover study in which they received 6 g of CM and placebo (PL) on two occasions, separated by a seven-day washout period. Each occasion consisted of a single session of high-intensity RE (0 h) and three subsequent fatigue tests sessions (at 24, 48, and 72 h) to assess the time course of muscle recovery. During the tests sessions, we assessed the following variables: number of maximum repetitions, electromyographic signal (i.e., root mean square (RMS) and median frequency (MF)), muscle soreness and perceived exertion, as well as blood levels of creatine kinase (CK), lactate, insulin, and testosterone:cortisol ratio. CK levels increased at 24 h post-exercise and remained elevate at 48 and 72 h, with no difference between CM and PL conditions. Muscle soreness increased at 24 h post-exercise, which progressively returned to baseline at 72 h in both conditions. Lactate levels increased immediately post-exercise and remained elevated at 24, 48, and 72 h in both conditions. No significant treatment × time interaction was found for all dependents variables (maximum repetitions, perceived exertion, CK, lactate, RMS, MF, and testosterone:cortisol ratio) during the recovery period. In conclusion, our data indicate that CM supplementation (single 6 g dose pre-workout) does not improve the muscle recovery process following a high-intensity RE session in untrained young adult men.