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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.

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.

This study aimed to investigate and compare the effects of chronic supplementation with L-Citrulline (LC) vs. L-Citrulline DL-malate (CM) on resistance training (RT) performance. Thirty-three resistance-trained men were randomly assigned to ingest LC (8 g), CM (12 g), or Placebo (PL) daily, along with participation in a 6-week RT protocol. Muscular strength (1-repetition maximum [1RM] for hack squat [HS] and bench press [BP]), muscular endurance (repetitions to failure [RTF] for HS, leg extension [LE], BP, and incline press [IP]), rating of perceived exertion (RPE), and blood biomarkers (lactate, urea, and nitric oxide metabolites [NO ]) were assessed before and after the intervention. This study was registered on irct.ir (IRCTID: IRCT20221128056642N1). Comparing mean ∆ scores revealed a significant difference between LC and PL (  < 0.001) and between CM and PL (  = 0.026) for total upper body (the sum of BP and IP) RTF, but only a trend for difference between LC and PL (  = 0.070) for total lower body (the sum of HS and LE) RTF. A significant time effect for NO was detected only for LC (  = 0.014) and CM (  = 0.003). In addition, a significant difference between CM and PL (  = 0.009) and a marginally significant difference between LC and PL (  = 0.057) was detected regarding post-exercise NO values at post-intervention. There were no other between-group differences for any outcome measure. Chronic citrulline supplementation seems to enhance upper body muscular endurance and post-exercise NO response to RT, but there is no apparent difference between LC and CM in these aspects.

The purpose of this study was to examine the effects of Citrulline/Malate supplementation with intensive training on blood lactate level in active handball players. The athletes were subjected to intense training for 4 weeks, 4 days a week, mainly pre-season strength and technique training. In this training period, stimol group ( n  = 11) athletes were given stimol 3 times a day as 1 g for breakfast, 1 g for lunch, and 1 g for dinner while the placebo group ( n  = 11) athletes were given only placebo in the same dosage and the same color at the same time. Blood lactate levels in athletes were measured 4 times, prior to and after a 1-month program as follows: rest (R), end effort (EE), recuperation 5 min (R5 m), and recuperation 20 min (R20 m). Blood lactate levels were compared both as intra-group and between the groups. In intra-group comparison, no change was observed in blood lactate levels in placebo group while a significant difference was found in the levels of stimol group as p  < 0.05 with a 49.8% decrease in blood lactate level. In the measurements between groups, in the post-test measurements made after the training period, significant differences as p  < 0.05 were found with a 60.7% decrease in blood lactate level EE. Considerable decline was seen especially immediately after exercise in blood lactate levels of the athletes being given stimol supplement. In this case, we can say that Citrulline/Malate supplementation may contribute positively to the performance of athletes and may help postpone fatigue at excessive or prolonged activity.

Exhaustive exercise induces disturbances in metabolic homeostasis which can result in amino acid catabolism and limited l -arginine availability. Oral l -citrulline supplementation raises plasma l -arginine concentration and augments NO-dependent signalling. Our aim was to evaluate the effects of diet supplementation with l -citrulline-malate prior to intense exercise on the metabolic handle of plasma amino acids and on the products of metabolism of arginine as creatinine, urea and nitrite and the possible effects on the hormonal levels. Seventeen voluntary male pre-professional cyclists were randomly assigned to one of two groups: control or supplemented (6 g l -citrulline-malate 2 h prior exercise) and participated in a 137-km cycling stage. Blood samples were taken in basal conditions, 15 min after the race and 3 h post race (recovery). Most essential amino acids significantly decreased their plasma concentration as a result of exercise; however, most non-essential amino acids tended to significantly increase their concentration. Citrulline-malate ingestion significantly increased the plasma concentration of citrulline, arginine, ornithine, urea, creatinine and nitrite ( p  < 0.05) and significantly decreased the isoleucine concentration from basal measures to after exercise ( p  < 0.05). Insulin levels significantly increased after exercise in both groups ( p  < 0.05) returning to basal values at recovery. Growth hormone increased after exercise in both groups, although the increase was higher in the citrulline-malate supplemented group ( p  < 0.05). l -citrulline-malate supplementation can enhance the use of amino acids, especially the branched chain amino acids during exercise and also enhance the production of arginine-derived metabolites such as nitrite, creatinine, ornithine and urea.

Background One of the most important antidepressants side effects is dry mouth. The aim of this study was to evaluate the clinical efficacy of a topical sialogogue spray containing 1% malic acid on patients affected by dry mouth caused by antidepressants drug. Materials and methods This research took the form of a double‐blind, randomized clinical trial at Faculty of Dentistry of University of Granada (Spain). Seventy participants with antidepressant‐induced dry mouth were divided into two groups: for the first “intervention group” (35 subjects) a topical sialogogue spray (1% malic acid) was applied, while for the second “control group” (35 subjects), a placebo spray was applied; for both groups, the sprays were applied on demand during 2 weeks. The Dry Mouth Questionnaire (DMQ) was used to evaluate dry mouth symptoms before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. Results Dry mouth symptoms improved after 1% malic acid topical spray application (p < .05). After 2 weeks of 1% malic acid application, unstimulated and stimulated salivary flows rates increased significantly (p < .05). Conclusions A sialogogue spray containing 1% malic acid improved dry mouth feeling of the patients suffering antidepressant‐induced dry mouth and increased unstimulated and stimulated salivary flows rates.

Background. Hand disinfection is frequently recommended for prevention of rhinovirus (RV) infection and RV-associated common colds. The effectiveness of this intervention has not been established in a natural setting. The purpose of this study was to determine the effect of hand disinfection on RV infection and RV-associated common cold illness in a natural setting. Methods. A controlled clinical trial was done in young adult volunteers during 9 weeks of the fall 2009 RV season. Volunteers were randomized to either an antiviral hand treatment containing 2% citric acid and 2% malic acid in 62% ethanol (n = 116) or to a no-treatment control group (n = 96). The hand treatment was applied every 3 hours while the subjects were awake. All volunteers kept a daily diary of symptoms and had a nasal lavage for polymerase chain reaction once each week and 2 additional lavages around the time of each common cold illness. The primary endpoint was the number of RV-associated illnesses. The incidence of RV infection and of common cold illnesses were evaluated as secondary endpoints. Results. The hand treatment did not significantly reduce RV infection or RV-related common cold illnesses. The total number of common cold illnesses was significantly reduced in the intent-to-treat analysis, but this effect was not seen in the per protocol analysis. Conclusions. In this study, hand disinfection did not reduce RV infection or RV-related common cold illnesses. Clinical Trials Registration. NCT00993759.