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Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness
Abstract
The purpose of the present study was to determine the effects of a single dose of citrulline malate (CM) on the performance of flat barbell bench presses as an anaerobic exercise and in terms of decreasing muscle soreness after exercise. Forty-one men performed 2 consecutive pectoral training session protocols (16 sets). The study was performed as a randomized, double-blind, 2-period crossover design. Eight grams of CM was used in 1 of the 2 training sessions, and a placebo was used in the other. The subjects' resistance was tested using the repetitions to fatigue test, at 80% of their predetermined 1 repetition maximum (RM), in the 8 sets of flat barbell bench presses during the pectoral training session (S1-4 and S1'-4'). The p-value was 0.05. The number of repetitions showed a significant increase from placebo treatment to CM treatment from the third set evaluated (p <0.0001). This increase was positively correlated with the number of sets, achieving 52.92% more repetitions and the 100% of response in the last set (S4'). A significant decrease of 40% in muscle soreness at 24 hours and 48 hours after the pectoral training session and a higher percentage response than 90% was achieved with CM supplementation. The only side effect reported was a feeling of stomach discomfort in 14.63% of the subjects. We conclude that the use of CM might be useful to increase athletic performance in high-intensity anaerobic exercises with short rest times and to relieve postexercise muscle soreness. Thus, athletes undergoing intensive preparation involving a high level of training or in competitive events might profit from CM.
... Investigations into CM on exercise performance have noted positive effects on both aerobic and anaerobic exercise outcomes including reduced muscle damage markers, improved fatigue resistance, improved exercise performance and reduced muscle soreness [2,8,11,13,14,16,19,20,27,32,35]. Moreover, two recent meta-analysis investigating the effects of Citrulline supplementation [32,34] reported a small but significant effect in overall performance when used with resistance trained subjects. ...
... Finally, there was some indication CM may reduce muscle soreness, at specific sites (Tensor Fasciae), this might be specific to the type of exercise challenge, however no difference was seen in total muscle soreness overall. A reduction in muscle soreness with CM has been previously noted by Pérez-Guisado [27]. This could be attributed to L-citrulline mechanisms i.e. clearing the ammonia. ...
... Differences between studies might be explained by the exercise challenge, and CM dosing. Pérez-Guisado [27] for example focused on an upper body exercise regime of bench pressing, while da Silva et al. [28] and Chappell et al. [5], both utilised a lower body training challenge and Chappell et al. [6] utilised a bicep curl challenge. The contrasting results suggest more work is needed to clarify if CM influences lactate and CK, presumably via ammonia clearance or increased NOS production. ...
The use of supplements to enhance performance is popular amongst gym enthusiasts. Citrulline-malate (CM) has been suggested as an effective ergogenic aid via the purported mechanisms of augmented ammonia metabolism, lactate buffering and increased vasodilation. The present investigation aimed to assess whether an 8 g loading dose of CM over 4-days improves anaerobic muscular endurance, strength, and rate of force development (RFD) recovery and muscle soreness. A counterbalanced randomised double-blind placebo cross-over trial was implemented over a 3-week period. Eleven resistance-trained males were recruited to take part in a German Volume Training (GVT) protocol. Maximum isometric, concentric and eccentric strength, RFD and muscle soreness scores were assessed using an isokinetic chair and a visual analogue scale (VAS). There was no difference (P > 0.05) in blood arginine and citrulline under the CM condition 38.9 ± 11.4 µmol/L and 45.7 ± 34 µmol/L respectively, compared to the placebo 27.3 ± 12.6 µmol/L and 9.9 ± 26.9 µmol/L. A repeated measure analysis of variance identified no significant difference (P = 0.71) in reps across sets (treatment x time). Post hoc analysis however found the absolute number of repetitions achieved was greater in the treatment group (P = 0.001), CM: 68.1 ± 19.0, vs. placebo: 54.9 ± 18.1. There were no differences (P > 0.05) in any strength and RFD measurements or muscle soreness between treatment arms. A loading dose of CM increase total repetitions but not muscular endurance across sets, more research is suggested to corroborate these findings.
... L-citrulline is commonly known as a non-essential amino acid involved in the urea cycle, while malate is a tricarboxylic acid (TCA) cycle intermediate. CM sold as a pharmaceutical agent (brand name: Stimol) was originally developed to enhance muscle performance and to mitigate muscle recovery time in humans with asthenia after acute disease (Creff, 1982;Dauverchain, 1982), for which the recommended dose was 1 g taken 3 times a day (Bendahan et al., 2002;Pérez-Guisado & Jakeman, 2010). ...
... The potential efficacy of CM as an ergogenic aid is based on three hypothetical mechanisms of action: (1) via the L-arginine nitric oxide (NO) pathway, which may improve the delivery of blood (and oxygen) to and from the active musculature during exercise (Wax et al., 2015); (2) via ammonia detoxification through the urea cycle, which may decrease lactate production and enhance the erobic utilization of pyruvate, thereby improving muscle function and attenuating fatigue (Gonzalez & Trexler, 2020); and (3) via the malate component, which has been proposed to augment energy production and increase the rate of adenosine triphosphate (ATP) production (Bendahan et al., 2002;Gonzalez & Trexler, 2020). Additionally, CM supplementation is well-tolerated, with studies using 12 g (Cunniffe et al., 2016), 8 g (Chappell et al., 2020(Chappell et al., , 2018Farney et al., 2019;Glenn et al., 2016Glenn et al., , 2017Gonzalez et al., 2018;Pérez-Guisado & Jakeman, 2010;Wax et al., 2015;Wax et al., 2016), 6 g (Da Silva et al., 2017;Figueroa et al., 2015), and 2 g (Hwang et al., 2018). As an ergogenic aid, the most frequently used dosage has been a single dose of 8 g consumed 1 h before the exercise session (Gonzalez & Trexler, 2020), yet the optimal dosing strategy remains to be established. ...
... L-citrulline is a popular ingredient in multi-ingredient preworkout supplement formulations (Jagim et al., 2019). For more than a decade, CM has been purported to be an ergogenic aid during various types of exercise, such as resistance exercise (Chappell et al., 2020(Chappell et al., , 2018Da Silva et al., 2017;Farney et al., 2019;Glenn et al., 2016Glenn et al., , 2017Gonzalez et al., 2018;Hwang et al., 2018;Pérez-Guisado & Jakeman, 2010;Trexler, Keith, et al., 2019;Wax et al., 2015Wax et al., , 2016, cycling (Cunniffe et al., 2016;Glenn et al., 2016), and running (Bezuglov et al., 2022). However, assessing physical fitness and performance in tests that are representative of the physiological demands of the sport is essential (Charron et al., 2020). ...
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.
... Bei einer Einnahme von 8 g L-Citrullin-Malat konnte eine Erhöhung der Arbeitskapazität um 19% festgestellt werden, gemessen an den ausgeführten Wiederholungen bis zum Versagen bei einem Langhantel-Flachbankdrücken mit 80% 1-RM [98] . Eine weitere Studie konnte ebenfalls einen Anstieg der ausgeführten Wiederholung von 10% bis 53% dokumentieren. ...
... Eine weitere Studie konnte ebenfalls einen Anstieg der ausgeführten Wiederholung von 10% bis 53% dokumentieren. Trainings-induzierter Muskelkater war gegenüber einem Placebo nach 24 Stunden um 39,7% und nach 48 Stunden um 41,7% reduziert [98] . ...
... Die -in Form von verbesserter genereller Leistungsfähigkeit, erhöhter Sauerstoffaufnahme, verlängerter Zeit bis Erschöpfung sowie verringerter wahrgenommener Erschöpfung -messbaren Effekte auf die Ausdauerkapazität können hierbei insbesondere im Rahmen eines Ausdauer-basierten Fitnesstrainings eine Leistungssteigerung ermöglichen [95,96,97] . Ebenso kann L-Citrullin bei einem Fitnesstraining mit Gewichten eine Erhöhung der, sich an den ausgeführten Wiederholungen bemessenden Arbeitskapazität bewirken und somit zu einem Kraftanstieg beitragen [98] . Zudem kann L-Citrullin nach einer Belastung zu einer verbesserten Regeneration Trainings-induzierter Muskelschmerzen -durch Verringerung dieser -beitragen [98] . ...
Consumption of pre-workout supplements (PWS) has increased substantially in recent years. However, dosages of ingredients vary between manufacturers. Therefore, the aim of this study was to analyze ingredients from various products and to survey past and present (4 weeks) consumption behavior. Analysis of ingredients was performed in 30 products according to manufacturer's specifications. Subsequently, online questionnaire was used to assess reasons for taking, timing and dosing of PWS in 39 recreational athletes (4 females; 35 males; 25.15 ± 3.67 years). Most prevalent ingredients in PWS were caffeine, beta-alanine, L-citrulline, L-arginine, L-tyrosine, taurine and creatine. Average dosing per serving were 254mg caffeine (125-410 mg), 2513 mg beta-alanine (500-4000 mg), L-citrulline 3506 mg (500-8000 mg), L-arginine 2726 mg (500-8000 mg), L-tyrosine 1227 mg (150-3000 mg), taurine 1211 mg (90-2500 mg) and creatine 3031 mg (1000-5000 mg). Average values were in (63%) or below (36%) the recommended ergogenic dosage. Major motives for PWS use were improved concentration, increased blood flow and delayed onset of fatigue. Most subjects consumed PWS 1-3 times per month. In most cases consumption took place 15-30 min before training. Manufacturers' recommendations for consumption were generally followed. A large number of subjects (82%) reported minor side effects from PWS consumption (e. g. paresthesia, insomnia, headache). Based on current research only caffeine, L-citrulline, L-arginine and taurine show relevant direct performance-enhancing effects, while the benefit of beta-alanine, L-tyrosine and creatine in PWS seems highly questionable. Dosages of ingredients were safe, but often too low to increase performance.
... Contrasting with L-arginine, L-citrulline bypasses hepatic metabolism, maintaining bioavailability, and converted to Larginine via kidneys (13). Moreover, for L-citrulline to have an ergogenic effect on resistance training, it must be paired with malate, intermediate of the tricarboxylic acid cycle, which augments the amount of adenosine triphosphate production (ATP) and may impact acid-base balance by stimulating systemic alkalosis (5,24). Mechanistically, the combination of L-citrulline and malate has potential to increase exercise performance. ...
... In addition, no significant performance differences were found between trials during the 50RP test for any variables examined. The physiological mechanisms behind our findings include enhanced circulating NO increasing contractile properties through an increase in cellular calcium handling, skeletal muscle glucose uptake, and an increase in ATP production (4,8,24). Through the conversion of L-citrulline, NO has shown to improve muscle mechanical and metabolic capability while improving glucose oxidation (4,24). ...
... The physiological mechanisms behind our findings include enhanced circulating NO increasing contractile properties through an increase in cellular calcium handling, skeletal muscle glucose uptake, and an increase in ATP production (4,8,24). Through the conversion of L-citrulline, NO has shown to improve muscle mechanical and metabolic capability while improving glucose oxidation (4,24). Because the ATP-PCr system is the main form of energy that produced these results, such mechanisms are likely in play. ...
Gills, JL, Spliker, B, Glenn, JM, Szymanski, D, Romer, B, Lu, H-C, and Gray, M. Acute citrulline-malate supplementation increases total work in short lower-body isokinetic tasks for recreationally active females during menstruation. J Strength Cond Res XX(X): 000-000, 2021-Citrulline-Malate (CM) exhibits acute ergogenic benefits through nitric oxide production (NO) and augmentation of vasodilatory properties. Nitric oxide is upregulated by estrogen and may influence CM's ergogenic efficacy in women. Therefore, the objective of this study was to evaluate the acute effects of CM supplementation on lower-body isokinetic performance in recreationally active women. Nineteen women (23.5 ± 3.1 years; 164.8 ± 7.0 cm; 61.9 ± 27.4 kg; 28.8 ± 8.1% body fat) completed 2 randomized, double-blind, crossover trials consuming CM (8 g CM + 12 g dextrose) or placebo (12 g dextrose). For testing trials, subjects were in the menstruating portion of the follicular phase of their menstrual cycle. Subjects performed a 5-repetition isokinetic leg extension protocol (5RP) followed by a 50-repetition isokinetic leg extension protocol (50RP), 60 minutes after supplement consumption. Repeated measures analysis of variance analysis showed that CM significantly increased total work completed, relative total work, and total work during maximum repetition compared with placebo (p < 0.05); but no significant performance differences existed between trials for peak torque production (p = 0.14) for the 5RP. No significant differences were identified between trials for peak torque production (p = 0.69) or total work (p = 0.33) completed during the 50RP. CM increased total work completed during the 5RP, but provided no ergogenic benefit during the 50RP in recreationally active menstruating women. Citrulline-Malate amplifies power-based resistance exercise performance in women during the follicular phase of the menstrual cycle, potentially because of depressed estrogen levels. Additional research is needed to identify timing efficacy of CM to increase sport performance during each phase of the menstrual cycle.
... At the end of each session during this six weeks (Watermelon juice or placebo), the subjects selfreported their soreness 24 and 48 h after the physical exertion on a scale questionnaire from 1 to 5 as follows: 1, no soreness; 2, minimal soreness with no impact on immediate training; 3, medium soreness with minimal impact on immediate training; 4, high soreness with negative impact on immediate training; 5, maximum soreness with physical disability for immediate training(27, 28). ...
... Taekwondo training included a 15minute dynamic warm-up (stretching exercises of the upper and lower limbs, dynamic movements like marching, pelvis and leg and waist movements, and jumping movements including jumping and hopping), and the dedicated exercise held up for subjects during 90 minutes in each session, diversely.At the end of each exercise session, the participants performed a 10-minute cooldown including stretching exercises. Subjects' dietary's plan and daily energy intake were calculated by the software (N4) during this research(27). The macronutrients intake is presented in the table2. ...
Introduction and objective:The natural product watermelon contains a high concentration of antioxidants that have the potential to mitigate the oxidative damage resulting from the generation of free radicals post-exercise. As such, this study aims to explore the impact of six weeks of watermelon juice supplementation on the antioxidant capacity of elite female taekwondo athletes.
Methods: In a study involving twenty-five young female elite taekwondo players with a mean age of 21.84±2.26 years, participants were randomly assigned to either the watermelon juice group (n=15) or the placebo group (n=10). Over six weeks, subjects consumed 500 ml of watermelon juice or placebo 45 minutes before each of their three weekly training sessions. The Total Antioxidant Capacity (TAC) index was measured in selected athletes undergoing training at the Taekwondo House in Kermanshah, located in western Iran.
Results: The study found that following six weeks of intervention, watermelon juice supplementation led to a significant increase in total antioxidant capacity (TAC) (p=0.001), while the TAC levels in the placebo (PLA) group remained relatively unchanged (p=0.490). Moreover, participants in the watermelon juice group demonstrated higher VO2max compared to the placebo group, and experienced significantly lower levels of muscle soreness at 24 and 48 hours post-exercise (p>0.05).
Conclusions: A six-week regimen of watermelon juice supplementation has been found to enhance overall antioxidant capacity and alleviate muscle soreness.
... It plays a role in the body's ammonia excretion and energy production 22 . Malate salt is a crucial mediator in the Krebs cycle, also known as the citric acid cycle 23 . Its use as a supplement can aid athletes in various ways, including enhancing endurance and reducing fatigue 24 . ...
... Its use as a supplement can aid athletes in various ways, including enhancing endurance and reducing fatigue 24 . Citrulline malate supplementation improves ATP production by enhancing ammonia, arginine, and lactic acid buffering mechanisms, reducing fatigue 23,24 . ...
Purpose: This research aimed to investigate the impact of active and passive recovery strategies as well as Citrulline-Malate (CM) supplementation, on the performance and biomarkers, i.e., hypoxanthine and hypoxanthine-guanine phosphoribosyl transferase (HGPRT) of young, trained wrestlers during the first day of a simulated Free-Style wrestling tournament. Methods: A total of 12 professional freestyle wrestlers (aged 19.2 ± 1.0 years) participated in the study. In a counterbalanced crossover design, twelve wrestlers ingested either a placebo or CM (8g) one hour before the initiation of the tournament. They then completed four consecutive simulated wrestling standard performance tests, each consisting of 6-minute wrestling simulations followed by a 30-minute recovery period, alternating between active and passive recovery. Results: The results showed no significant effects of active versus passive recovery or CM supplementation versus placebo for various performance tests and biomarkers in trained wrestlers across multiple wrestling simulations. However, significant differences were observed in the active vs. passive recovery group for the HGPRT biomarker, burpee agility test, and RPE in the third simulated wrestling session. Other tests, such as hand grip strength, back-leg-chest, and Wrestling-Specific Performance Tests, did not show significant differences among the groups. Conclusions: The findings revealed that there were no significant differences in performance tests or biomarkers between active and passive recovery strategies. Similarly, CM supplementation and placebo groups have not been equally effective in all events, during the simulated wrestling conducted on trained wrestlers. Individual responses to these strategies may vary among trained wrestlers and the recovery requirements can also differ between different events.
... Our study found that the addition of GIK increased the levels of L-citrulline, L-asparagine, L-aspartic acid, and DL-3-phenyllactic acid in the uterine tissue of mice, compared to those in mice treated with oxytocin alone. These amino acids have been shown to improve tissue microcirculation [20][21][22][23][24].L-citrulline functions similarly to a nitric oxide (NO) supplement and can be converted to L-arginine in the body. L-arginine primarily acts through the arginine-NO pathway and generates citrulline and NO [20] in vivo. ...
... Morphological results of the uteri also suggest that group G exhibited more intact uterine muscle fibers and reduced interstitial edema, which may also be related to GIK's improvement of uterine energy metabolism and mitigation of ischemic injury. However, this study did not find any differences in LDH levels among the three groups, indicating that the process by which GIK promotes glycolysis may occur upstream of citrulline supplements can enhance athletic performance, increase exercise tolerance, and even alleviate post-exercise muscle soreness [22].The increase in L-citrulline levels in this study, after GIK administration, suggests that GIK may expand uterine blood vessels through the arginine-NO pathway, thereby increasing the tolerance of the uterus to ischemia and hypoxia. Ornithine can combine with carbamoyl phosphate to produce citrulline, thereby ameliorating uterine ischemia and hypoxia through the same pathway as that of citrulline. ...
This study aimed to explore the effect of glucose-insulin-potassium (GIK) on postpartum uterine cramping pain(UCP) in mice and the possible underlying mechanisms. Thirty full-term pregnancy C57BL/6 mice, within 6 h after spontaneous labor, the mice were randomly assigned into the following three groups: the control group (group C), the oxytocin group (group O), and the GIK plus oxytocin group (group G). Group G and group O were administered GIK and normal saline, respectively, and 10 min later, oxytocin was injected intraperitoneally; group C received normal saline twice. The pain scores of the mice were assessed after establishment of the postpartum UCP model. The differential expressions of energy metabolism and oxidized lipid metabolites in the uterus were analyzed. The behavioral scores in group G were significantly lower than those in group O ( P < 0.05).When compared to group O, group G showed a significant increase in ATP levels ( P = 0.046), and group G exhibited elevated levels of amino acids, including L-glutamine, L-aspartic acid, and ornithine. Additionally, phosphate compounds (2-phosphoglyceric acid and 3-phosphoglyceric acid) showed elevated levels. When compared to group O, group G exhibited a decrease in 19R-hydroxy PGF 2α , an increase in 9,10-EpOME and 12,13-EpOME, and a decrease in trans-EKODE-E-Ib. Additionally, group G showed an elevation in 16,17-EpDPE and 8-HDoHE. This study confirms the analgesic effect of GIK during postpartum oxytocin infusion. Metabolomics and glycolysis product analysis suggest that GIK’s alleviation of UCP is associated with its enhancement of glycolysis and the influence of phenylalanine synthesis, aspartate metabolism, and arginine synthesis pathways. Additionally, the effects of GIK appears to be linked to its influence on the linoleic acid metabolic pathway.
... Citrulline malate is typically provided as an acute 8 g (g) dose in a 1:1 or 2:1 ratio which would yield approximately 4.0 to 5.3 g of L-citrulline and 3.7 to 4.0 g of malate. Some studies have shown that 8 g of citrulline malate could delay fatigue, improve power output, and increase the work performed during resistance exercise [8][9][10][11][12][13]. However, others have failed to demonstrate an ergogenic benefit following 8 g of citrulline malate [14][15][16][17][18][19]. ...
... Studies from Wax and colleagues have shown that 8 g of citrulline malate could improve the repetitions performed during a protocol consisting of five sets of leg presses, hack squats, and leg extensions at 60% 1RM [13] and during a protocol consisting of three sets of bodyweight chin-ups, reverse chin-ups, and push-ups [12]. An acute 8 g dose of citrulline malate was also reported to improve repetitions of failure during eight sets of bench press at 80% 1RM [11] and during six sets of bench press and leg press exercises at 80% 1RM [10]. Therefore, the current state of evidence is mixed, yet a recent meta-analysis [20] showed how citrulline malate could significantly increase repetitions to failure during high-intensity strength training. ...
L-citrulline serves as a nitric oxide precursor with the potential to increase blood flow and improve resistance exercise performance, yet more research is needed to examine its ergogenic potential. To examine the effect of L-citrulline supplementation on resistance exercise performance, muscle oxygenation, and the subjective perception of effort, energy, focus, fatigue, and muscle pump, eighteen resistance-trained men (n = 11) and women (n = 7) (21.4 ± 1.8 years; 172.3 ± 7.5 cm; 76.9 ± 10.8 kg) were randomly assigned for supplementation with 8 g of L-citrulline (CIT) or a placebo (PL) in a cross-over fashion one hour prior to testing. Participants completed an isometric mid-thigh pull test (IMTP), a ballistic bench press protocol [two sets of two repetitions at 75% 1-repetition maximum (1 RM) with maximum ballistic intent], and a strength-endurance bench press protocol [five repetition-maximum sets at 75% 1RM]. Barbell velocity and power were measured via a linear position transducer during the ballistic protocol, while the repetitions completed, volume load and muscle oxygenation were quantified during the strength-endurance protocol. Subjective measures were assessed at the baseline and immediately pre- and post-exercise. Repeated measures of the analysis of variance and Bayesian equivalents revealed no significant interactions, providing evidence favoring the null hypothesis (BF10 < 1) for IMTP (PL 497.5 ± 133.6 vs. CIT 492.5 ± 129.4 N), barbell velocity, and power, and repetitions completed (PL 36.7 ± 7.2 vs. CIT 36.9 ± 8.1 repetitions). There were also no significant interactions for muscle oxygenation parameters or subjective measures except perceived fatigue. Women reported greater fatigue across all time points compared to men (~1.88 au, p = 0.045, BF10 = 0.2). The results indicate that a single 8 g dose of L-citrulline did not enhance isometric force production, muscle endurance, or muscle oxygenation parameters during the protocol implemented in this study.
... L-citrulline is sometimes combined with malate, and at oral doses of 6-8g administered 60 min before exercise, has been shown to acutely improve muscular endurance (i.e., repetitions to failure) and reduce perceived exertion and subjective muscle soreness in men [7][8][9] and in women 10 , albeit with some inconsistent findings [11][12][13] . As a result, Lcitrulline has been the topic of several recent reviews in an attempt to develop a consensus of the literature [4][5][6][14][15][16] . ...
... Lastly, fewer adverse events occurred under the 3DPump condition. Previous investigations commonly examined 8g of citrulline to stimulate vasodilatory and performance effects within the muscle [7][8][9]13 . Notably both conditions in this study had a similar effect on appendicular girth pre to post workout along with subjective ratings of a muscle pump despite a lower citrulline dose in the 3D PUMP condition. ...
Introduction: Citrulline is a non-essential amino acid that has previously been shown to improve athletic performance, reduce fatigue, and increase blood flow. The purpose of this study was to examine the efficacy of a novel dietary supplement blend (3D PUMP BREAKTHROUGH®, 3DPump) vs. citrulline alone on changes in muscle volume, fluid shifts, markers of hydration, inflammation, recovery, affect, and muscular endurance. Methods: Twenty-eight recreationally active subjects (6 women, 22 men) participated in a randomized, positive-controlled, single-blind, crossover study which involved 4 testing visits (2 workout visits each with a 24-hr follow-up visit). Participants ingested 3DPump (containing 3g L-citrulline, 1.2g glycerol, 165mg Amla fruit extract) or 8g of L-citrulline alone 45min before an aerobic and resistance training workout. Assessments of body fluid shifts (via BIA), markers of hydration (urine and serum osmolality, USG, hemoglobin), and appendicular girth were taken before and after exercise while markers of damage and inflammation (neutrophils, CK, ESR, MCP-1, CRP) were taken before and 24 hours after exercise, muscular endurance (reps to failure) was assessed during resistance exercises, and subjective measures of affect and recovery were taken before, after and 24 hours after exercise. Mixed factorial ANOVAs with dependent t-tests were used to compare treatments. Results: A significant interaction occurred for right thigh circumference; however post hoc testing indicated both groups increased similarly in post workout girth (p<0.05). A significant interaction occurred for ECF/TBW indicating post workout was greater than pre workout in 3DPump only (p=0.002). An interaction trend (p≤0.010) occurred for SBP and DBP indicating that 3DPump was uniquely able to significantly lower blood pressure (SBP and DBP) post workout compared to baseline and 24 hours after exercise (p<0.001). Conclusions: 3DPump, which contains 3g L-citrulline was able to provide similar effects in muscular endurance, muscle pump and other subjective feelings of affect, hydration, damage and inflammation markers, and body fluid shifts as an 8g dose of L-citrulline alone. 3DPump may have unique benefits on improving post exercise vascular tone and ECF/TBW.
... However, the relationship between improved athletic performance and increased NO production in response to Cit supplementation is unclear [30]. Furthermore, previous studies that reported improved athletic performance with Cit supplementation used it in combination with malates and other components [30,[49][50][51][52]. Most studies have reported that supplementation of Cit and malate is done in combination due to their synergistic coupling at the intramuscular level [52][53][54]. ...
... According to a review study, taking a single acute dose of 8 g of CitMal 1 h prior to exercise in resistance-trained men and women may improve dynamic muscle endurance and strength performance [53]. In a study involving resistance-trained men, the iteration of failure was improved in all sets of barbell bench presses (except for the first two sets) after ingestion of 8 g of CitMal 1 h before exercise [50]. Similar results were observed in a study of resistance-trained females, with improved performance responses during six sets of plate-loaded leg press and bench press exercises at 80% 1RM [132]. ...
The global market for nutritional supplements (NS) is growing rapidly, and the use of L-arginine (Arg), L-citrulline (Cit), and citrulline malate (CitMal) supplements has been shown to enhance cardiovascular health and athletic performance. Over the past decade, Arg, Cit, and CitMal supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on hemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance. Previous studies were reviewed to determine the potential impact of Arg, Cit, and CitMal supplements on cardiovascular health and exercise performance. By synthesizing the existing literature, the study aimed to provide insight into the possible uses and limitations of these supplements for these purposes. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis with 0.075 g or 6 g doses of Arg supplement per body weight. However, 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion. The effects of an 8 g acute dose of CitMal supplement were inconsistent, and more research is needed to determine its impact on muscle endurance performance. Based on the positive effects reported in previous studies, further testing is warranted in various populations that may benefit from nutritional supplements, including aerobic and anaerobic athletes, resistance-trained individuals, elderly people, and clinical populations, to determine the impact of different doses, timing of ingestion, and long-term and acute effects of Arg, Cit, and CitMal supplements on cardiovascular health and athletic performance.
... The association of CM supplementation (3 g/day) for six weeks, associated with a programmed protocol of physical activity adapted to elders, resulted in a general tendency to improve in terms of adaptation to exercise and optimal recovery. Several authors, using higher doses of CM (8 g/day) showed a clear improvement in strength [39,40]. However, these data were not reproduced in a study with a similar design carried out on women [41]. ...
... This disparity leads us to hypothesise that lowering the dose to 6 g/day may be the reason why Cutrufello et al. [41] did not find the performance benefits cited in other studies with male volunteers using higher doses (8 g/day). We did not observe significant increases either, only slight increases (a tendency), but the dose used was the lower (3 g/day) compared to other studies [39][40][41]. Glen et al. [42] carried out a study only with young (23 ± 3 years) trained female volunteers, who were supplemented with 8 g/day of CM and performed a submaximal bench press test until exhaustion. These authors observed similar results to those obtained in groups of men. ...
Sarcopenia is a process associated to aging. Persistent inflammation and oxidative stress in muscle favour muscle wasting and decreased ability to perform physical activity. Controlled exercise can optimize blood flux and moderate the production of reactive oxygen species. Therefore, supplements that can work as a vasodilators and control oxidative stress, might be beneficial for active elders. In this context, we have tested citrulline supplementation in a group of 44 participants aged from 60–73 years that followed a physical activity program adapted to their age and capacities. Volunteers were divided in two groups: placebo (n = 22) and citrullline supplemented (n = 22). Different physical tests and blood extractions were performed at the beginning and at the end of intervention (six weeks). Strength and endurance showed a tendency to increase in the citrulline supplemented group, with no significant differences respect to placebo. However, walking speed in the citrulline supplemented group improved significantly compared to placebo. Markers of muscle damage as well as circulating levels of testosterone, cortisol and vitamin D showed no significant changes, but a tendency to improve at the end of intervention in the supplemented group compared to placebo. Additional studies are necessary to confirm the effect of citrulline supplementation in sarcopenia delay.
... This could be important for either subsequent performance when recovery between bouts is limited (i.e., track and field) and/ or overall quality and quantity of chronic training. In a large study of forty-one men, ingestion of 8 g CM 1 h before a resistance training bout led to decreases in muscle soreness at both 24 h (-40%) and 48 h (-41%), respectively, compared to a placebo (Perez-Guisado et al. 2010). However, there was no subsequent performance bout to substantiate whether the reduction in soreness translates to improved performance. ...
... However, there was no subsequent performance bout to substantiate whether the reduction in soreness translates to improved performance. In a more thorough study (da Silva et al. 2017), CM supplementation (6 g, 1 h before exercise) failed to improve muscle soreness when more reporting points (24, 48, and 72 h) were used compared to Perez-Guisado et al. (2010). Importantly, da Silva et al. (2017) also reported no improvement in subsequent performance for neither leg press exercise, nor hack squat to exhaustion. ...
As a nitric oxide (NO) enhancer, citrulline malate (CM) has recently been touted as a potential ergogenic aid to both resistance and high-intensity exercise performance, as well as the recovery of muscular performance. The mechanism has been associated with enhanced blood flow to active musculature, however, it might be more far-reaching as either ammonia homeostasis could be improved, or ATP production could be increased via greater availability of malate. Moreover, CM might improve muscle recovery via increased nutrient delivery and/or removal of waste products. To date, a single acute 8 g dose of CM on either resistance exercise performance or cycling has been supplemented, which has produced equivocal results. This makes the effectiveness of CM to improve exercise performance difficult to determine. Reasons for the disparity in conclusions seem to be due to methodological discrepancies such as the testing protocols and the associated test-retest reliability, dosing strategy (i.e. amount and timing), and the recent discovery of quality control issues with some manufacturers stated (i.e. citrulline:malate ratios). Further exploration of the optimal dose is therefore required including quantification of the bioavailability of NO, citrulline, and malate following ingestion of a range of CM doses. Similarly, further well-controlled studies using highly repeatable exercise protocols with a large aerobic component are required to assess the mechanisms associated with this supplement appropriately. Until such studies are completed, the efficacy of CM supplementation to improve exercise performance remains ambiguous.
... Moreover, a meta-analysis reported a significant decrease on VO 2 uptake, thus in EE, during exercise performed at moderate and heavy intensity domains, but no effects at maximal intensity (Pawlak-Chaouch et al. 2016). On the other hand, CIT supplementation has been associated to the improvement of physiological outcomes (e.g., maximal strength, anaerobic performance, VO 2 uptake at submaximal intensities) (Ashley et al. 2018;Glenn et al. 2016;Pérez-Guisado & Jakeman 2010), following the CIT recycle step into arginine for subsequent NO production (Kim et al. 2015). For instance, 7 days of supplementation with CIT (6 g per day) improved VO 2 kinetics during severeintensity exercise (Bailey et al. 2015a, b). ...
Purpose
Citrulline (CIT) and beetroot extract (BR) supplements positively impacts exercise performance in elite rowers. However, its influence on metabolic outcomes such as whole-body volumes of oxygen consumption (VO2) and carbon dioxide production (VCO2), substrate oxidation, energy expenditure (EE), and gross efficiency remains unknown. We studied the effects of 1 week of daily co-supplementation of 3.5 g BR (500 mg NO3⁻) plus 6 g CIT on VO2 and VCO2 kinetics, substrate utilization, EE, and gross efficiency in elite male rowers compared to a placebo and to a BR supplementation.
Methods
Twenty elite rowers participated in this randomized, double-blind, placebo-controlled crossover trial completing 1 week of supplementation in each group of study: Placebo (PLAG); BRG; and BR-CITG. Efficiency (70% VO2max) and performance (incremental maximal) tests were performed, and gas-exchange data were collected via indirect calorimetry.
Results
Analysis of covariance (ANCOVA) showed no mean between-condition differences on respiratory exchange ratio (RER), EE, and gross efficiency in the efficiency test (all P > 0.06), and in the performance test (all P > 0.28). Moreover, in both tests no interaction Time × Supplement effects were observed for VO2, VCO2, RER, EE, substrate oxidation, and, gross efficiency (all P > 0.12).
Conclusion
After 1 week, no effects on energy metabolism and substrate utilization were observed after the daily co-ingestion of BR extract plus CIT supplement, therefore longer (> 7 days) and higher doses of supplementation might be needed to influence metabolism.
... They concluded that the use of CM may be beneficial in improving athletic performance in high-intensity anaerobic exercises with short rest periods and in relieving post-exercise muscle fatigue. Thus, athletes who are in an intense preparation phase with high-level training or competition activities stated that they can gain from CM [9]. In today's studies, reducing fatigue during exercise has become extremely important in terms of making ongoing exercises healthier. ...
This research is to determine the effect of citrulline malate supplement applied in addition to fitness training on the hormonal metabolism of athletes. 30 male athletes (15 Control group, 15 Experimental group) who are in the fitness branch and regularly participate in the research group voluntarily participated. A four-week, ninety-minute fitness training program three days a week was applied to the research group. Blood samples were taken from the athletes in the research group twice, before the start of the training program and at the end of the training. ACTH, Cortisol and Total Testosterone levels were determined in the blood samples taken. SPSS package program was used in the analysis of the data. Significance was accepted as p<0.05. According to the research results; It was determined that there was a statistically significant difference between the pretest-posttest values of the experimental group's ACTH, cortisol and total testosterone levels (p<0.05), while it was determined that there was a statistically significant difference between the pretest-posttest values of the control group's total testosterone levels (p<0.05), there was no statistically significant difference between the pretest-posttest values of ACTH and cortisol levels (p>0.05). According to the comparisons between the groups; It was seen that there was a significant difference between the cortisol and total testosterone levels post-test values of the control and experimental groups (p<0.05), there was no significant difference between the pre-test values of ACTH pre-post-test, cortisol and total testosterone levels (p>0.05).. In conclusion; It has been observed that the citrulline malate supplement group applied in addition to the fitness training has a significant effect on the hormone metabolism and provides a greater increase compared to the group in which the fitness training is applied. In this context, we believe that the supplements to be applied in addition to routine training will contribute positively to the performance of the athletes.
... The main finding of this trial was that short-term consumption of CM did not have significant effects in terms of oxidative stress and muscle damage markers in trained soccer players. In spite of some studies on the beneficial effects of CM [27,28], the findings of our study were in accordance with previous studies which show acute or short-term CM supplementation fails to improve performance [29]. ...
... Equivocal results have been found when L-citrulline is supplemented prior to endurance exercise performance [9][10][11]; therefore, co-ingestion with malate could provide the missing link to a consistent ergogenic benefit. However, CM research to date has primarily focused on resistance training following early work by Pérez-Guisado and Jakeman [12]. The authors found that ingesting 8 g CM an hour before exercise increased bench press repetitions to failure when performed both before (+18%) and after (+53%) a chest-based workout; yet, subsequent similar research has since yielded equivocal findings [13,14]. ...
Citrulline malate (CM) has been touted as a nutritional ergogenic aid for sports performance, with purported mechanisms of increased muscle blood flow, ammonia clearance, and adenosine triphosphate resynthesis. Combined, these physiological benefits may be best applied to whole-body endurance exercises, such as swimming, though this postulate has not yet been explored. In a double-blind, randomised, and crossover design, 11 national-level swimmers (age: 17 ± 3 years, height: 1.71 ± 0.05 m, body mass: 60.6 ± 8.3 kg) from a high-performance swimming club ingested either 15 g CM or a placebo (PLA) 60 min before six × 300 m freestyle bouts (at 4.5 min intervals). Blood lactate, blood pressure, and ratings of perceived exertion were measured at baseline, 60 min post-ingestion, and immediately post-exercise. Neither mean 300 m swimming time (CM: 212.0 ± 9.6 vs. PLA: 212.8 ± 7.7 s, p = 0.683, g = 0.09) nor any individual swimming bouts (p = 0.679, Pŋ2 = 0.02) were improved with CM ingestion. Moreover, no differences in any physiological or subjective measures were identified between conditions (all p > 0.05). Whether the proposed CM mechanisms were active was unclear as more direct physiological measures (i.e., plasma NO, ammonia) may have been required. Resultantly, these observations do not support an ergogenic effect of acute CM ingestion in highly trained swimmers.
... Citrulline malate (CM) has been found to enhance aerobic energy production and increase phosphocreatine (PCr) levels during exercise recovery [120,121]. It also improves ammonia (NH3) elimination after exhaustive exercise [122,123], reduces muscle soreness following high-intensity resistance exercise (RE), and enhances performance in repeated bouts of high-intensity RE [124]. Ultimately, da Silva and colleagues demonstrated that the administration of CM at a dosage of 6 g taken 60 min before a workout does not enhance the process of muscle recovery following a single session of high-intensity resistance exercise in young adult men who are not trained in physical fitness. ...
Citation: Martín-Rodríguez, A.; Belinchón-deMiguel, P.; Rubio-Zarapuz, A.; Tornero-Aguilera, J.F.; Martínez-Guardado, I.; Villanueva-Tobaldo, C.V.; Clemente-Suárez, V.J. Advances in Understanding the Interplay between Dietary Practices, Body Composition, and Sports Performance in Athletes. Nutrients 2024, 16, 571. Abstract: The dietary practices of athletes play a crucial role in shaping their body composition, influencing sports performance, training adaptations, and overall health. However, despite the widely acknowledged significance of dietary intake in athletic success, there exists a gap in our understanding of the intricate relationships between nutrition, body composition, and performance. Furthermore, emerging evidence suggests that many athletes fail to adopt optimal nutritional practices, which can impede their potential achievements. In response, this Special Issue seeks to gather research papers that delve into athletes' dietary practices and their potential impacts on body composition and sports performance. Additionally, studies focusing on interventions aimed at optimizing dietary habits are encouraged. This paper outlines the key aspects and points that will be developed in the ensuing articles of this Special Issue.
... This could potentially reduce the energetic cost of ATP in a muscle contraction, enhance force production, and improve calcium handling and mitochondrial efficiency [13]. CitMal may also influence ammonia clearance and delay exercise-induced fatigue resulting with performance improvements [14]. Indeed, an animal-model study reported that citrulline consumption reduced ammonia accumulation and increased endurance performance [15]. ...
Purpose
The aim of this study was to explore the isolated and combined effects of caffeine and citrulline malate (CitMal) on jumping performance, muscular strength, muscular endurance, and pain perception in resistance-trained participants.
Methods
Using a randomized and double-blind study design, 35 resistance-trained males (n = 18) and females (n = 17) completed four testing sessions following the ingestion of isolated caffeine (5 mg/kg), isolated CitMal (12 g), combined doses of caffeine and CitMal, and placebo. Supplements were ingested 60 min before performing a countermovement jump (CMJ) test (outcomes included jump height, rate of force development, peak force, and peak power), one-repetition maximum (1RM) squat and bench press, and repetitions to muscular failure in the squat and bench press with 60% of 1RM. Pain perception was evaluated following the repetitions to failure tests. The study was registered at ISRCTN (registration number: ISRCTN11694009).
Results
Compared to the placebo condition, isolated caffeine ingestion and co-ingestion of caffeine and CitMal significantly enhanced strength in 1RM bench press (Cohen’s d: 0.05–0.06; 2.5–2.7%), muscular endurance in the squat (d: 0.46–0.58; 18.6–18.7%) and bench press (d: 0.48–0.64; 9.3–9.5%). However, there was no significant difference between isolated caffeine ingestion and caffeine co-ingested with CitMal, and isolated CitMal supplementation did not have an ergogenic effect in any outcome. No main effect of condition was found in the analysis for CMJ-derived variables, 1RM squat and pain perception.
Conclusion
Caffeine ingestion appears to be ergogenic for muscular strength and muscular endurance, while adding CitMal does not seem to further enhance these effects.
... In a recent meta-analysis, it has been reported that the acute ingestion of citrulline malate, in a range of 6-8 g one hour before exercise, could increase athletes' capacity for greater training volume and lower neuromuscular-metabolic fatigue during high-intensity activities [12]. The latter could be attributed to enhanced oxygen uptake, muscles' aerobic metabolism, the delivery of nutrients to the muscles [72], muscles' buffer capacity [73], and post-exercise perceived effort and muscle soreness [74]. BCAAs, probably through the enhancement of muscle metabolism and protection against muscle damage, also positively affect anaerobic performance [11]. ...
A pre-workout supplement’s (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18–31 years, height 166–195 cm, weight 70.2–116.7 kg, body fat 10.6–26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: −2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: −2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: −7.5 ± 5.9%), and fatigue index (PWS: −25.0 ± 0.9%; PL: −4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players’ alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not.
... L-citrulline is an amino acid involved in the urea cycle and may promote the excretion of ammonia and faster recovery of creatine phosphate after exercise. Intracellular accumulation of ammonia promotes glycolysis by inhibiting aerobic pyruvate utilization [37,38] and subsequent lactate formation, which can contribute to fatigue [39,40]. Lactate is the most measurable metabolite, as its level is one of the predictors of the onset of overtraining [41]. ...
The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes (n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.
... Glenn et al. [63] reported that a single 8 g dose of CitMal significantly increased total repetitions to failure performed during both the bench press and leg press exercises over six sets for each exercise at 80% 1RM as well as decreased post-session rating of perceived exertion (RPE) in resistance-trained females. Pérez-Guisado & Jakeman [64] also reported that a single 8 g dose of CitMal significantly increased repetitions to failure during eight sets of bench press to failure at 80% 1RM in resistance-trained males. Expanding on these findings, a single 8 g dose of CitMal has also been observed to enhance repetitions to failure in a high-volume lower body resistance exercise protocol consisting of five sets of leg press, hack squat, and leg extension to failure at 60% 1RM in advanced male weightlifters [65]. ...
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.
... For example, ORN is used in dietary supplements as an agent to improve liver function (Müting et al. 1992), as a sleep enhancer (Horiuchi et al. 2013;Miyake et al. 2014), or as a precursor to polyamine production and subsequent collagen formation for bone healing (Meesters et al. 2020;Wijnands et al. 2012). CIT has been claimed to aid in recovery from fatigue or exercise (Bendahan et al. 2002;Perez-Guisado et al. 2010) and to reduce swelling (Morita et al. 2012). In recent years, some human studies of CIT supplementation have been reported about protein metabolism under malnutrition (Jourdan et al 2015;Bouillane et al. 2019) and high-intensity interval training (Marcangeli et al 2022). ...
Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers, but the safe supplementation levels of these compounds are unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults ( n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2, and 12 g/day) or citrulline (6, 12, 18, and 24 g/day) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality, and mental self-assessment. In the ornithine hydrochloride supplementation group, minor increase in plasma aspartic acid and glutamic acid concentrations was observed at the highest intake dosages. In the citrulline supplementation group, minor changes in laboratory data for serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, arginine, and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4 weeks), respectively.
... An increase in the availability of plasma arginine has also been linked to availability of substrate for NO synthesis and to the activity of polymorphonuclear neutrophils. Another current study by Perez-Guisado and Jakeman confirmed that a single 8-g dose L-citrulline with malate increased working capacity by almost 19%, as measured by the number of repetitions completed until exhaustion in a bench-press fitness test at 80% of one-repetition-maximum [16,22]. ...
Nitric oxide (NO) is an essential component of the human body, involved in blood vessel dilation, stimulation of hormone release, signaling and regulation of neurotransmission. Nitric oxide is synthesized by nitric-oxide-synthase-dependent and -independent pathways. Nitric oxide supplementation improves cardiac health, enhances performance during exercise, reduces high blood pressure during pregnancy, reduces erectile dysfunction and improves healing processes and respiratory response. Nitric-oxide-associated benefits are mostly apparent in untrained or moderately trained individuals. L-arginine and L-citrulline supplementation contributes to nitric oxide levels because L-arginine is directly involved in NO synthesis, whereas L-citrulline acts as an L-arginine precursor that is further converted to NO by a reaction catalyzed by NO synthase. L-arginine supplements increase respiratory response and enhance performance during exercise, while L-citrulline with malate and other molecules increase working capacity. Various studies involving beetroot juice have reported a significant increase in plasma nitrite levels, regarded as markers of NO, after intake of beetroot juice. Although NO supplementation may have mild to moderate side-effects, using smaller or divided doses could avoid some of these side-effects. Since nitric oxide supplementation may worsen certain health conditions and may interfere with certain medicines, it should only be taken under medical supervision.
... Specifically, EAA+ contained additional amino acids and natural botanical compounds, including: 1.20 g of citrulline, 805 mg of glutamine, 689 mg of Schisandra chinensis, 200 mg of Lycium barbarum, and 50.0 mg of ferulic acid. Citrulline has been reported to improve nitric oxidemediated vasodilation [35], enhance muscle recovery following RE in men [36], and protect skeletal muscle cells from catabolic stimuli [37] whereas glutamine, which may influence protein synthesis by modulating mammalian target of rapamycin complex 1 (mTORC1) activity in cell culture [38], has been reported to enhance muscle recovery following RE in men [39]. The inclusion of the natural botanical compounds was based on preclinical evidence that Schisandra chinensis and compounds of the Lycium family have been reported to promote myoblast differentiation and mTORC1-mediated protein synthesis, as well as inhibit ubiquitin-proteasome-mediated protein degradation in rodent [40] and skeletal muscle cell models [41]. ...
Home-based resistance exercise (RE) has become increasingly prevalent, but its effects on protein metabolism are understudied. We tested the effect of an essential amino acid formulation (EAA+: 9 g EAAs, 3 g leucine) and branched-chain amino acids (BCAAs: 6 g BCAAs, 3 g leucine), relative to a carbohydrate (CHO) placebo, on exogenous leucine retention and myofibrillar protein breakdown following dynamic bodyweight RE in a home-based setting. Twelve recreationally active adults (nine male, three female) participated in a double-blind, placebo-controlled, crossover study with four trial conditions: (i) RE and EAA+ (EX-EAA+); (ii) RE and BCAAs (EX-BCAA); (iii) RE and CHO placebo (EX-CHO); and (iv) rest and CHO placebo (REST-CHO). Total exogenous leucine oxidation and retention (estimates of whole-body anabolism) and urinary 3-methylhistidine:creatinine ratio (3MH:Cr; estimate of muscle catabolism) were assessed over 5 h post-supplement. Total exogenous leucine oxidation and retention in EX-EAA+ and EX-BCAA did not significantly differ (p = 0.116) but were greater than EX-CHO (p < 0.01). There was a main effect of condition on urinary 3MH:Cr (p = 0.034), with post hoc analysis revealing a trend (p = 0.096) for reduced urinary 3MH:Cr with EX-EAA+ (32%) compared to EX-CHO. By direct comparison, urinary 3MH:Cr was significantly lower (23%) in EX-EAA+ than EX-BCAA (p = 0.026). In summary, the ingestion of EAA+ or BCAA provided leucine that was ~60% retained for protein synthesis following home-based bodyweight RE, but EAA+ most effectively attenuated myofibrillar protein breakdown.
... However, a study by Jones (2016) reported that insufficient evidence was available to link increased exercise performance to the increased NO production in response to L-Cit supplementation [20]. Furthermore, several studies claiming that L-Cit supplementation improved exercise performance in recreationally active individuals and well-trained athletes did not use standalone L-Cit [42][43][44][45]; instead, they combined it with malate and other components [20]. Most of the available literature has combined L-Cit with malate because of its synergistic combination at the intramuscular level [45][46][47]. ...
Consumption of amino acids L-arginine (L-Arg) and L-citrulline (L-Cit) are purported to increase nitric oxide (NO) production and improve physical performance. Clinical trials have shown relatively more favorable outcomes than not after supplementing with L-Cit and combined L-Arg and L-Cit. However, in most studies, other active ingredients such as malate were included in the supplement. Therefore, the aim of this study was to determine the efficacy of consuming standalone L-Arg, L-Cit, and their combination (in the form of powder or beverage) on blood NO level and physical performance markers. A systematic review was undertaken following PRISMA 2020 guidelines (PROSPERO: CRD42021287530). Four electronic databases (PubMed, Ebscohost, Science Direct, and Google scholar) were used. An acute dose of 0.075 g/kg of L-Arg or 6 g L-Arg had no significant increase in NO biomarkers and physical performance markers (p > 0.05). Consumption of 2.4 to 6 g/day of L-Cit over 7 to 16 days significantly increased NO level and physical performance markers (p < 0.05). Combined L-Arg and L-Cit supplementation significantly increased circulating NO, improved performance, and reduced feelings of exertion (p < 0.05). Standalone L-Cit and combined L-Arg with L-Cit consumed over several days effectively increases circulating NO and improves physical performance and feelings of exertion in recreationally active and well-trained athletes.
... Among others, ornithine has been used in dietary supplements as an agent to improve liver function (Müting et al., 1992) or as a sleep enhancer (Horiuchi et al., 2013;Miyake et al., 2014). Citrulline has been claimed to aid in recovery from fatigue or exercise (Bendahan et al., 2002;Perez-Guisado et al., 2010) and to reduce swelling (Morita et al., 2012). Despite their intake from dietary supplements, chronic or subchronic dosedependent evaluations of safety are insu cient. ...
Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe intake level of ornithine or citrulline supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults (n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2 and 12 g/d) or citrulline (6, 12, 18 and 24 g/d) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality and mental self-assessment. In the ornithine hydrochloride supplementation group, minor changes in plasma aspartic acid, glutamic acid concentrations and increased its plasma concentration at highest intake dosages were observed. In the citrulline supplementation group minor changes in laboratory data of serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, as well as arginine and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4weeks), respectively.
... A 2019 review of the ingredient profiles of the top 100 selling MIPS on a commercial supplement website found that 86% of products contained caffeine, with an average dose of 254 mg per serving [7]. Investigations of other common ingredients in MIPS, such as citrulline [8,9], beta-alanine [10,11], and taurine [12,13] suggest potential ergogenic effects, which when combined in a product formulation could theoretically provide additional benefits over caffeine alone. However, due to the common conclusion that caffeine is the primary cause for any observed exercise performance improvement with MIPS ingestion, less attention has been given to formulations that do not include caffeine. ...
Background:
There is substantial consumer and practitioner interest in an emerging supplement class known as multi-ingredient pre-workout supplements (MIPS), largely due to their prevalence in resistance training communities as well as research findings demonstrating the ergogenic impact of caffeine on muscular performance. However, limited research has examined the potential efficacy of non-caffeinated MIPS, despite their growing popularity among those who are caffeine-sensitive or who train later in the day.
Methods:
Twenty-four resistance-trained college-aged males (n = 12) and females (n = 12) completed three visits in which they ingested either a caffeinated MIPS (C), an otherwise identical non-caffeinated MIPS (NC), or placebo in a double-blind, counterbalanced, crossover fashion. Squat isometric peak force (PFiso), rate of force development (RFD), and isokinetic performance were assessed. Upper and lower body maximal muscular strength and endurance were evaluated using the bench press and leg press, respectively. Visual analog scales for energy, focus, and fatigue were completed five times throughout the testing protocol. The effects of supplementation and biological sex on all variables were examined using linear mixed effects models.
Results:
Significantly greater PFiso was observed in both C (b: 0.36 transformed units [0.09, 0.62]) and NC (b: 0.32 transformed units [95% CI: 0.05, 0.58]) conditions, relative to placebo. Early RFD (RFD50) may have been higher with supplementation, particularly in females, with no effects for late RFD (RFD200) or peak RFD. In addition, increases in subjective energy after supplement ingestion were noted for C, but not NC. No effects of supplementation on traditional resistance exercise performance or isokinetic squat performance were observed, other than a lower leg press one-repetition maximum for males in the NC condition.
Conclusions:
These data indicate that acute ingestion of either a caffeinated or non-caffeinated pre-workout formulation improved maximal force production during an isometric squat test but did not provide additional benefit to leg press, bench press, or isokinetic squat performance over placebo, within the context of a laboratory environment. The consumption of a caffeinated, but not non-caffeinated, MIPS increased subjective ratings of energy over placebo when assessed as part of a testing battery.
... Sitrülin malat (SM) son zamanlarda vücut geliştiricileri arasında popüler bir takviye haline gelmiştir; fakat sağlıklı insanlarda SM takviyesi ilgili çok az bilimsel araştırma yapılmıştır. SM'ın performansı üç mekanizma ile iyileştirdiği varsayılır: 1) sitrulin, üre siklüsünün önemli bir parçasıdır ve amonyak temizlenmesine katılabilir, 2) malat, laktik asit birikimini azaltabilecek bir trikarboksilik asit döngüsü ara maddesidir ve 3) sitrülin, arjinine dönüşebilir; fakat, sitrülinin bu mekanizma ile ergojenik etki yarattığı belli değildir (55). 15 günlük SM desteğinin, egzersiz sırasında ATP üretimini %34 oranında artırdığı, egzersiz sonrası fosfokreatin geri kazanım oranını %20 artırdığı ve yorgunluk algılamalarını azalttığı gösterilmiştir. ...
Vücut geliştirme sporunun popülaritesi gün geçtikçe artmaktadır fakat buna karşılık literatüre bakıldığında kanıta dayalı beslenme önerilerinin sayısının oldukça az olduğu görülmektedir. Bu çalışmada literatürde geçen, vücut ge- liştirme sporcuları için verilen kanıta dayalı güncel beslenme önerileri derlenmiştir. Vücut geliştirme sporuyla ilgilenen bireylerde enerji ihtiyacının doğru hesaplanması, vücut ağırlığında azalma sağlamak için temel hedef olmalıdır. Vücut geliştirme sporcularında kas kaybını önlemek için haftalık en fazla %1’lik vücut ağırlığında azalma önerilmektedir. Vücut geliştirme sporcusu için gerekli enerji hesaplaması yapıldıktan sonra, vücut ağırlığında kilogram başına en az 2.3 g/kg/gün protein alımı önerilmektedir. Aynı zamanda her öğünün 0.4-0.5 g/kg protein içermesi önerilmektedir. Günlük enerji gereksiniminin %15-30’unun yağlardan, %20’sinin proteinlerden ve geri kalanın ise karbonhidratlardan gelecek şekilde beslenme programı düzenlenmelidir. Vücut geliştirme sporcuları için ideal öğün sayısında ise özellikle dayanıklılık egzersizleri süresince günlük 3 ile 6 öğün tercih edilmelidir. Yapılan araştırma sonuçlarına göre öğün saatleri ve sıklığının vücut ağırlığında azalma veya yağsız kütleyi korumak için belirgin bir pozitif etkisinin olmadığı görülmüştür. Müsabakalardan birkaç gün önce uygulanan dehidrasyon programı, elektrolit imbalansına sebep olabileceğinden dikkatli olunması gerekmektedir. Müsabakalara hazırlanılan son dönemlerde karbonhidrat alımındaki artışın olumlu etkileri olabilir, bu sebeple karbonhidrat yüklemesi sporcuya uygun olarak yapılmalıdır. Vücut geliştirme sporcularında supleman kullanımıyla ilgili de farklı tartışmalar bulunmaktadır. Kreatin monohidrat, kafein ve beta alanin alımının müsabakalara hazırlanma süresince olumlu etkileri olduğu görülmüştür. Diğer suplemanlarla ilgili daha fazla çalışmaya ihtiyaç olduğu, güncel literatür verileri dahilinde düşünülmektedir. Son olarak, estetik bir spor çeşidi olan vücut geliştirme sporcularında yeme bozuklukları ve vücut algısı bozukluklarının sık görüldüğü unutulmamalıdır.
... The participants did not present any disease, and they did not drink alcohol, smoke or consume other drugs or stimulant substances during the study period which could alter the hormone response. Likewise, to eliminate the probable interference of other nutritional aids with the different outcomes measured in this research, a 2-week washout period was included [39][40][41]. ...
Simple Summary: Recovery is one of the main elements in achieving adequate athletic performance. Various supplements have been used for this purpose. Citrulline (CIT) and Nitrate-Rich Beetroot Extract (BR) are so-called nitric oxide precursor supplements that have shown an ergogenic effect on sports performance when used on a short-term, individual basis. These supplements appear to have other pathways that may promote athletic performance. The purpose of this study was to assess the effect of a co-supplementation for 9 weeks of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates) on recovery by exercise-induced muscle damage markers (EIMD), anabolic/cat-abolic hormones and distance covered in the Cooper test (CP). Thirty-two male triathletes were randomized into 4 groups of 8 in this double-blind, placebo-controlled trial: placebo group, CIT group, BR group and CIT-BR group. Blood samples and CP were collected at baseline and after 9 weeks. The main conclusions were the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT-BR improved recovery status by preventing an increase in cortisol and showing an increase in Tes-tosterone/Cortisol ratio and distance covered in the CP. Abstract: Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors' knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and an-abolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3 −)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and Citation: Burgos, J.; Viribay, A.; Calleja-González, J.; Fernández-Lázaro, D.; Olasagasti-Ibargoien, J.; Seco-Calvo, J.; Mielgo-Ayuso, J. Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons At-tribution (CC BY) license (http://crea-tivecommons.org/licenses/by/4.0/). Biology 2022, 11, 75 2 of 17 anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triath-letes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3 −)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η 2 p = 0.418), cortisol (p = 0.044; η 2 p = 0.247) and T/C (p = 0.005; η²p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η²p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η 2 p = 0.257) and in T/C percentage change (p = 0.018; η 2 p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.
... The participants did not present any disease, and they did not drink alcohol, smoke or consume other drugs or stimulant substances during the study period which could alter the hormone response. Likewise, to eliminate the probable interference of other nutritional aids with the different outcomes measured in this research, a 2-week washout period was included [39][40][41]. ...
Simple Summary: Recovery is one of the main elements in achieving adequate athletic performance. Various supplements have been used for this purpose. Citrulline (CIT) and Nitrate-Rich Beetroot Extract (BR) are so-called nitric oxide precursor supplements that have shown an ergogenic effect on sports performance when used on a short-term, individual basis. These supplements appear to have other pathways that may promote athletic performance. The purpose of this study was to assess the effect of a co-supplementation for 9 weeks of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates) on recovery by exercise-induced muscle damage markers (EIMD), anabolic/cat-abolic hormones and distance covered in the Cooper test (CP). Thirty-two male triathletes were randomized into 4 groups of 8 in this double-blind, placebo-controlled trial: placebo group, CIT group, BR group and CIT-BR group. Blood samples and CP were collected at baseline and after 9 weeks. The main conclusions were the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT-BR improved recovery status by preventing an increase in cortisol and showing an increase in Tes-tosterone/Cortisol ratio and distance covered in the CP. Abstract: Citrulline (CIT) and nitrate-rich beetroot extract (BR) are widely studied ergogenic aids. Nevertheless, both supplements have been studied in short-term trials and separately. To the best of the authors' knowledge, the effects of combining CIT and BR supplementation on recovery status observed by distance covered in the Cooper test, exercise-induced muscle damage (EIMD) and an-abolic/catabolic hormone status have not been investigated to date. Therefore, the main purpose of this research was to assess the effect of the long-term (9 weeks) mixture of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of nitrates (NO3 −)) supplementation on recovery by distance covered in the Cooper test, EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) and Citation: Burgos, J.; Viribay, A.; Calleja-González, J.; Fernández-Lázaro, D.; Olasagasti-Ibargoien, J.; Seco-Calvo, J.; Mielgo-Ayuso, J. Publisher's Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons At-tribution (CC BY) license (http://crea-tivecommons.org/licenses/by/4.0/). Biology 2022, 11, 75 2 of 17 anabolic/catabolic hormones (testosterone, cortisol and testosterone/cortisol ratio (T/C)) in male trained triathletes. Thirty-two triathletes were randomized into four different groups of eight triath-letes in this double-blind, placebo-controlled trial: placebo group (PLG), CIT group (CITG; 3 g/day of CIT), BR group (BRG; 2.1 g/day of BR (300 mg/day of NO3 −)) and CIT-BR group (CIT-BRG; 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −)). Distance covered in the Cooper test and blood samples were collected from all participants at baseline (T1) and after 9 weeks of supplementation (T2). There were no significant differences in the interaction between group and time in EIMD markers (urea, creatinine, AST, ALT, GGT, LDH and CK) (p > 0.05). However, significant differences were observed in the group-by-time interaction in distance covered in the Cooper test (p = 0.002; η 2 p = 0.418), cortisol (p = 0.044; η 2 p = 0.247) and T/C (p = 0.005; η²p = 0.359). Concretely, significant differences were observed in distance covered in the Cooper test percentage of change (p = 0.002; η²p = 0.418) between CIT-BRG and PLG and CITG, in cortisol percentage change (p = 0.049; η 2 p = 0.257) and in T/C percentage change (p = 0.018; η 2 p = 0.297) between CIT-BRG and PLG. In conclusion, the combination of 3 g/day of CIT plus 2.1 g/day of BR (300 mg/day of NO3 −) supplementation for 9 weeks did not present any benefit for EIMD. However, CIT + BR improved recovery status by preventing an increase in cortisol and showing an increase in distance covered in the Cooper test and T/C.
... A number of different agents have been suggested to improve or augment performance and mitochondrial function in athletes. These include, but are not limited to supplementary glucose, various amino acids [6][7][8] (i.e., L-arginine [9], beta-alanine [10,11], citrulline (in the form of citrulline-malate [12,13] or citrulline alone [12,14,15], glutamine [3,16], taurine [17] among other amino acids [18] and/ or a combination of branched-chain amino acids, particularly including L-Leucine [19]. Additional ergogenic and anaplerotic agents have been investigated, including [20][21][22], pyruvate [23][24][25], citrate [26][27][28], or malate [29] alone, creatine [22,30,31] (often in the form of pyruvate-creatine or creatine citrate [32,33], carnitine [34,35], various vitamins [36,37], co-factors [38], and antioxidants [39,40], among many others, particularly plant derived extracts or natural products (for example green tea [41], Cordyceps sinensis and yohimbine [42]) or complex derivatives thereof concocted into fortified beverages with supplementary carbohydrates [28,43] or protein isolates [44]. ...
... On the other hand, and regarding endurance-strength capacity, Perez-Guisado showed a significant increase in the number of bench press repetitions performed and a reduction in fatigue at 24 and 48 h after ingestion of 8 g of CIT one hour before training [62]. Along the same lines, Wax et al. [17] obtained satisfactory results by performing a similar protocol increasing upper-body resistance performance in trained college-age males. ...
Citrulline (CIT) and nitrate-rich beetroot extract (BR) are ergogenic aids and nitric oxide
(NO) precursors. In addition, both supplements seem to have other actions at the level of muscle metabolism that can benefit strength and aerobic power performance. Both supplements have been studied in numerous investigations in isolation. However, scientific evidence combining both supplements is scarce, and to the best of the authors’ knowledge, there is no current study of endurance athletes. Therefore, the main purpose of this study was to determine the effect of 9 weeks of CIT plus BR supplementation on maximal and endurance-strength performance and aerobic power in male triathletes. This study was a randomized double-blind, placebo-controlled trial where participants (n = 32) were randomized into four different groups: placebo group (PLG; n = 8), CIT plus BR group (CIT- BRG; 3 g/kg/day of CIT plus 3 mg/kg/day of nitrates (NO3 −); n = 8), CIT group (CITG; 3 g/kg/day; n = 8) and BR group (BRG; 3 mg/kg/day of NO3−; n = 8). Before (T1) and
after 9 weeks (T2), four physical condition tests were carried out in order to assess sport performance: the horizontal jump test (HJUMP), handgrip dynamometer test, 1-min abdominal tests (1-MAT) and finally, the Cooper test. Although, no significant interactions (time × supplementation groups) were found for the strength tests (p > 0.05), the CIT- BRG supplementation presented a trend on HJUMP and 1-MAT tests confirmed by significant increase between two study moments in CIT-BRG. Likewise, CIT-BRG presented significant interactions in the aerobic power test confirmed by this group’s improve estimated VO2max during the study with respect to the other study groups (p = 0.002; η 2p = 0.418). In summary, supplementing with 3 g/day of CIT and 2.1 g/day of BR (300 mg/day of
NO3 −) for 9 weeks could increase maximal and endurance strength. Furthermore, when compared to CIT or BR supplementation alone, this combination improved performance in tests related to aerobic power.
Adult humans generally experience a 0.5-1%/year loss in whole-body skeletal muscle mass and a reduction of muscle strength by 1.5-5%/year beginning at the age of 50 years. This results in sarcopenia (aging-related progressive losses of skeletal muscle mass and strength) that affects 10-16% of adults aged ≥ 60 years worldwide. Concentrations of some amino acids (AAs) such as branched-chain AAs, arginine, glutamine, glycine, and serine are reduced in the plasma of older than young adults likely due to insufficient protein intake, reduced protein digestibility, and increased AA catabolism by the portal-drained viscera. Acute, short-term, or long-term administration of some of these AAs or a mixture of proteinogenic AAs can enhance blood flow to skeletal muscle, activate the mechanistic target of rapamycin cell signaling pathway for the initiation of muscle protein synthesis, and modulate the metabolic activity of the muscle. In addition, some AA metabolites such as taurine, β-alanine, carnosine, and creatine have similar physiological effects on improving muscle mass and function in older adults. Long-term adequate intakes of protein and the AA metabolites can aid in mitigating sarcopenia in elderly adults. Appropriate combinations of animal- and plant-sourced foods are most desirable to maintain proper dietary AA balance.
During sustained or repeated maximal voluntary efforts, muscle fatigue (acute strength loss) is not linear. After a large initial decrease, muscle strength plateaus at approximately 40% of baseline. This plateau, which likely reflects muscle strength preservation, has been observed in sustained maximal isometric and repeated maximal isokinetic contractions. Whether this pattern of fatigue occurs with traditional resistance exercise repetitions with free weights and weight stack machines has not been overviewed. Here, the aim was to determine whether the number of repetitions completed across 4 or more consecutive repetitions-to-failure tests exhibits the same nonlinear pattern of muscle fatigue. A secondary analysis was applied to data extracted as part of a recent meta-analysis on repetitions-to-failure tests. Studies were eligible if they reported mean number of repetitions completed in 4–6 consecutive repetitions-to-failure tests at a given relative load. Twenty-nine studies were included. Overall, the results show that the number of repetitions completed in consecutive repetitions-to-failure tests at a given load generally decreases curvilinearly. The numbers of repetitions completed in sets 2, 3, 4, 5, and 6 were equal to approximately 70, 55, 50, 45, and 45% of the number of repetitions completed in set 1, respectively. Longer interset rest intervals typically attenuated repetition loss, but the curvilinear pattern remained. From the results, a chart was created to predict the number of repetitions across 6 sets of resistance exercise taken to failure based on the number of repetitions completed in set 1. The chart is a general guide and educational tool. It should be used cautiously. More data from a variety of exercises, relative loads, and interset rest intervals are needed for more precise estimates of number of repetitions completed during repeated sets of fatiguing resistance exercise.
Purpose
Citrulline (CIT) and beetroot extract (BR) have separately shown benefits in rowing performance-related outcomes. However, effects of combined supplementation remain to be elucidated. The main purpose of this research was to study the effects of 1 week of daily co-supplementation of 3.5 g BR (500 mg NO3⁻) plus 6 g CIT on aerobic performance, maximal strength, and high-intensity power and peak stroke in elite male rowers compared to a placebo and to a BR supplementation.
Methods
20 elite rowers participated in this randomized, double-blind, placebo-controlled crossover trial completing 1 week of supplementation in each group of study: Placebo group (PLAG); BR group (BRG); and BR + CIT group (BR-CITG). 3 main physical tests were performed: aerobic performance, Wingate test and CMJ jump, and metabolic biomarkers and physiological outcomes were collected.
Results
The Wingate all-out test showed no between-condition differences in peak power, mean power, relative power, or fatigue index (P > 0.05), but clearance of lactate was better in BR-CITG (P < 0.05). In the performance test, peak power differed only between PLAG and BR-CITG (P = 0.036), while VO2peak and maximum heart rate remained similar. CMJ jumping test results showed no between-condition differences, and blood samples were consistent (P > 0.200).
Conclusion
Supplementation with 3.5 g of BR extract plus 6 g of CIT for 7 days improved lactate clearance after Wingate test and peak power in a performance test. No further improvements were found, suggesting longer period of supplementation might be needed to show greater benefits.
Sarcopenia is an age-related loss of muscle mass and function for which there is no approved pharmacological treatment. We tested direct efficacy by evaluating grip strength improvement in a sarcopenia mouse model rather than drug screening, which inhibits specific molecular mechanisms. Various physiological functions of ginseng berries are beneficial to the human body. The present study aimed to evaluate the efficacy and safety of steamed ginseng berry powder (SGBP). SGBP administration increased myotube diameter and suppressed the mRNA expression of sarcopenia-inducing molecules. SGBP also reduced the levels of inflammatory transcription factors and cytokines that are known to induce sarcopenia. Oral administration of SGBP improved muscle mass and physical performance in a mouse model of sarcopenia. In summary, our data suggest that SGBP is a novel therapeutic candidate for the amelioration of muscle weakness, including sarcopenia.
The maximal number of repetitions that can be completed at various percentages of the one repetition maximum (1RM) [REPS ~ %1RM relationship] is foundational knowledge in resistance exercise programming. The current REPS ~ %1RM relationship is based on few studies and has not incorporated uncertainty into estimations or accounted for between-individuals variation. Therefore, we conducted a meta-regression to estimate the mean and between-individuals standard deviation of the number of repetitions that can be completed at various percentages of 1RM. We also explored if the REPS ~ %1RM relationship is moderated by sex, age, training status, and/or exercise. A total of 952 repetitions-to-failure tests, completed by 7289 individuals in 452 groups from 269 studies, were identified. Study groups were predominantly male (66%), healthy (97%), < 59 years of age (92%), and resistance trained (60%). The bench press (42%) and leg press (14%) were the most commonly studied exercises. The REPS ~ %1RM relationship for mean repetitions and standard deviation of repetitions were best described using natural cubic splines and a linear model, respectively, with mean and standard deviation for repetitions decreasing with increasing %1RM. More repetitions were evident in the leg press than bench press across the loading spectrum , thus separate REPS ~ %1RM tables were developed for these two exercises. Analysis of moderators suggested little influences of sex, age, or training status on the REPS ~ %1RM relationship, thus the general main model REPS ~ %1RM table can be applied to all individuals and to all exercises other than the bench press and leg press. More data are needed to develop REPS ~ %1RM tables for other exercises.
Introduction: The aim of this study was to investigate the potential ergogenic properties of citrulline malate (CM) during a 300-yard shuttle run. Methods: Thirty-two recreationally active subjects (M=24; F=8) participated in a randomized, placebo-controlled, double-blind study. Participants completed baseline testing which consisted of two 300-yard shuttle runs for time. Immediately post-exercise blood lactate was taken via a finger stick. An average of the two trials (time in seconds and blood lactate in mmols/L) were recorded and used for analysis. One week later, participants were randomly assigned to one of four groups (control, placebo, 4 grams CM, or 8 grams of CM) and repeated the same exercise protocol. Data were analyzed using a two-way repeated measures analysis of variance. Results: No main effect for shuttle-run time (F=0.149; p=0.702) or shuttle run time by group interaction was observed (F=0.672; p=0.576). There was a main effect for blood lactate (F=17.079; p<0.001) with lactate accumulation during the pre-test (11.64±2.83 mmol/L) being significantly greater compared to the post-treatment lactate levels (9.65±1.94 mmol/L). There was no blood lactate by group interaction (F=0.867; p=0.47). Conclusions: These results indicated that acute CM supplementation did not improve anaerobic performance in healthy, young adults.
Background:
Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance.
Methods:
In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period.
Results:
There was a significant increase (p = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase (p = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test.
Conclusions:
The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.
Background
Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline’s effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken.
Aim
To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults.
Methods
A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane’s Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results
Nine studies (n = 158 participants) met the eligibility criteria; five reported TTE outcomes (I² = 0%, χ² = 0.37, df = 4, P = 0.99) and four reported TTC outcomes (I² = 0%, χ² = 0.46, df = 3, P = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [−0.27, 0.33]) and TTC (pooled SMD = −0.07 [−0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults.
Discussion
The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition.
Sarcopenia is a condition in which muscle mass, strength, and performance decrease with age. It is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, and contributes to an increase in mortality. Because managing sarcopenia is critical for maintaining good health and quality of life for the elderly, the condition has sparked concern among many researchers. To counteract sarcopenia, intake of protein is an important factor, while a lack of either protein or vitamin D is a major cause of sarcopenia. In addition, essential amino acids, leucine, βhydroxy β-methylbutyrate (HMB), creatine, and citrulline are used as supplements for muscle health and are suggested as alternatives for controlling sarcopenia. There are many studies on such proteins and supplements, but it is necessary to actually organize the types, amounts, and methods by which proteins and supplements should be consumed to inhibit sarcopenia. In this study, the efficacy of proteins and supplements for controlling sarcopenia according to human clinical studies is summarized to provide suggestions about how the elderly may consume proteins, amino acids, and other supplements.
Citrulline is a non-protein amino acid, which is synthesized from glutamine in the small intestinal enterocytes. It is involved in three important metabolic pathways, including the de novo synthesis of arginine in the kidney, intrahepatic transformation of ammonia to urea, and nitric oxide synthesis. Since citrulline is synthesized mainly by enterocytes, the blood levels of citrulline reflect the overall enterocyte mass. A reduction in the levels of citrulline reflects small intestinal enterocyte injury. Plasma concentration of citrulline has been considered to be a noninvasive marker of villous abnormalities and small intestinal length in short bowel syndrome. Plasma citrulline has also been explored to predict and assess the severity of rejection after small intestinal transplantation. Many inborn errors of metabolism such as deficiency of argininosuccinate synthase can lead to hyper-citrullinemia and neurological dysfunctions. Since citrulline is a source of arginine and nitric oxide, its supplementation has been used in many cardiovascular conditions, sarcopenia, and erectile dysfunction. In this chapter, we have comprehensively discussed the synthesis and metabolism of citrulline as well as its diagnostic and therapeutic importance in human health.
Citrulline malate (CM) has been shown to improve muscle performance in healthy participants during a single exercise session. Yet, within the framework of exercises repeated at close time interval, the consequences of CM ingestion on mechanical performance are controversial and the bioenergetics side remains undocumented. The aim of this double-blind placebo-controlled study was to evaluate in vivo the effect of short-term (7 doses in 48 h) oral administration of CM upon gastrocnemius muscle function and bioenergetics using non-invasive multimodal NMR techniques in healthy rats. The experimental protocol consisted of two 6-min bouts of fatiguing exercise spaced by an 8-min recovery period. CM treatment did not affect the basal bioenergetics status and increased the half-fatigue time during the first exercise bout. With exercise repetition, it prevented PCr cost alteration and decreased both the glycolytic ATP production and the contractile ATP cost in working muscle, but these changes were not associated to any improvement in mechanical performance. In addition, CM did not influence the replenishment of high-energy phosphorylated compounds during the post-exercise recovery periods. Therefore, short-term CM administration enhances muscle bioenergetics throughout fatiguing bouts of exercise repeated at close time interval but this enhancement does not benefit to mechanical performance.
Watermelon (Citrullus lanatus ) is commonly consumed by humans and widely available around the world. It has impressive nutritional properties, a rich phytochemical profile, and various claimed medicinal and health benefits. The major carotenoids in watermelon include lycopene, β-carotene, phytofluene, phytoene, lutein, and neurosporene. Lycopene (approximately 6,888 μg/152 g) is the major bioactive component in the fruit and it reportedly promotes several therapeutic effects, such as anti-cancer and anti-inflammatory activities etc. in humans and animals. Watermelon is also a good source of the amino acid citrulline, which is involved in production of arginine. Pre- and postharvest factors, including fruit sampling area, application of fertilizer, climatic factors, and genetic variability, are known to affect its bioactive compounds and nutrient concentrations. This review summarizes our current understanding of the watermelon phytochemical profile and the factors affecting its bioactivities and therapeutic effects.
ABSTRACTSarcopenia is a societal health issue owing to population density shifts and characterized by musclemass and muscle function loss due to age. Despite many efforts to develop treatment strategies forsarcopenia, exceptionally restricted therapies are still available for clinical use. Mostpharmacological drugs studied too far have been hormonal and targeting myostatin signaling.Alternatively, dietary supplements help to improve sarcopenia and recover muscular function. Asubstantial body of scientific and clinical data supports a positive outlook for the use of naturaltherapy and chemicals to manage or treat diseases. It is possible to take nutritional supplements insuch a way that will provide sufficient vital nutrients for human requirements. The purpose of thisstudy is to provide an overview of current information about the nutritional characteristics, helpfuland nutritious substances, and their application in the management and treatment of sarcopenia.
KEYWORDS: Sarcopenia, muscle mass, ageing, giant muscle, musculoskeletal system
This study compared the acute and chronic impact of citrulline malate (CM) supplementation on muscle contractile properties and fatigue rate of the quadriceps. Eighteen recreationally trained males consumed both a placebo (PL) and CM treatment for two separate dosing periods. The first experimental testing session for each dosing period was considered the baseline day, the second session the acute day, and the third session the chronic day, which followed seven consecutive days of supplementation. All testing sessions included exercising on a cycle ergometer at 50%–60% of their max power output for 30 min followed by performing the Thorstensson test on an isokinetic dynamometer. A two-way (Supplement × Time) analysis of variance with repeated measures resulted in no significant interactions ( p > .05) (PL: baseline day, acute day, chronic day vs. CM: baseline day, acute day, chronic day) for peak power (in watts) (469 ± 81, 490 ± 97, 502 ± 99 vs. 464 ± 85, 480 ± 103, 501 ± 81); peak torque (in newton meters) (150 ± 26, 157 ± 32, 161 ± 31 vs. 149 ± 27, 156 ± 33, 161 ± 26); fatigue rate (in percentage) (57 ± 9, 57 ± 10, 58 ± 9 vs. 57 ± 10, 56 ± 9, 58 ± 9); and heart rate (in beats per minute) (156 ± 17, 146 ± 13, 146 ± 9 vs. 155 ± 11, 146 ± 11, 146 ± 9). The results of this study suggest that neither acute nor chronic supplementation of CM had an effect on recovery or fatigue rate of the quadriceps.
Achieving adequate nutrition for exercising humans is especially important for improving both muscle mass and metabolic health. One of the most common misunderstandings in the fitness industry is that the human body has requirements for dietary whole protein and that exercising individuals must consume only whole protein to meet their physiological needs. This view, however, is incorrect. Instead, humans at rest or during exercise have requirements for dietary amino acids (AAs), and dietary protein is a source of AAs in the body. The requirements for AAs must be met each day to avoid a negative nitrogen balance in individuals with moderate or intense physical activity. By properly meeting increased requirements for AAs through increased intake of high-quality protein (the source of AAs) plus supplemental AAs, athletes can improve their overall athletic performance. AAs or metabolites that are of special importance for exercising individuals include arginine, branched-chain AAs, creatine, glycine, taurine, and glutamine. The AAs play vital roles as both substrates for protein synthesis and molecules for regulating blood flow and nutrient metabolism. The functional roles of AAs include the maintenance of cell and tissue integrity; stimulation of mechanistic target of rapamycin and AMP-activated protein kinase cell signaling pathways; energy sources for the small intestine, cells of the immune system, and skeletal muscle; antioxidant and anti-inflammatory reactions; production of neurotransmitters; modulation of acid–base balance in the body. All of those roles are crucial for the overall goal of improving exercise performance. Therefore, adequate intakes of proteinogenic AAs and their functional metabolites, especially those noted in this review, are essential for optimal human health (including optimum muscle mass and function) and should be a primary goal of exercising individuals.
Early in cold acclimation (1–7 days), heat is produced by shivering,while late in cold acclimation (12–45 days), skeletal muscle contributes to thermogenesis by tissue metabolism other than contractions. Given that both thermogenic phases augment skeletal muscle aerobic power and reactive species production, we aimed in this study to examine possible changes in skeletal muscle antioxidative defence (AD) during early and late cold acclimation with special emphasis on the influence of the l-arginine/nitric oxide(NO)-producing pathway on the modulation of AD in this tissue. Adult Mill Hill hybrid hooded rat males were divided into two main groups: a control group,which was kept at room temperature (22±1°C), and a group maintained at 4±1°C for 45 days. The cold-acclimated group was divided into three subgroups: untreated, l-arginine treated and Nω-nitro-l-arginine methyl ester(l-NAME) treated. The AD parameters were determined in the gastrocnemius muscle on day 1, 3, 7, 12, 21 and 45 of cold acclimation. The results showed an improvement of skeletal muscle AD in both early and late cold acclimation. Clear phase-dependent changes were seen only in copper, zinc superoxide dismutase activity, which was increased in early cold acclimation but returned to the control level in late acclimation. In contrast, there were no phase-dependent changes in manganese superoxide dismutase, catalase,glutathione peroxidase, glutathione reductase and glutathione S-transferase,the activities of which were increased during the whole cold exposure,indicating their engagement in both thermogenic phases. l-Arginine in early cold acclimation accelerated the cold-induced AD response, while in the late phase it sustained increases achieved in the early period. l-NAME affected both early and late acclimation through attenuation and a decrease in the AD response. These data strongly suggest the involvement of the l-arginine/NO pathway in the modulation of skeletal muscle AD.
Euglena gracilis can be used as a microbial model to study the effect of drugs on lactate metabolism and gluconeogenetic synthesis. The cell growth and metabolism have been characterized in a 33 mM lactate medium, non-supplemented or supplemented by dl-malate or by l-citrulline alone or by the compound formed by the stoichiometric combination of the two components: the citrulline-malate (Stimol). The malate of the complex accelerated the ammonium disappearance, while the citrulline facilitated the lactate consumption. A synergistic action of the complex, by comparison with the additive effects of the individual components, on most of the parameters studied was detected. A remarkable resistance to anoxia, and a quicker recovery under aeration of the cells supplemented with CM, were evident: after carbonation for 2 min the total nucleotides in the medium were increased by 44 per cent with an unchanged energy charge; and after a prolonged (20 min) anoxia followed by an aeration, the capacities of the cells to synthesize ATP in the presence of excesses of both ADP and phosphate were two-fold higher in Stimol treated cells than in control.
Previous studies have shown an antiasthenic effect of citrulline/malate (CM) but the mechanism of action at the muscular level remains unknown.
To investigate the effects of CM supplementation on muscle energetics.
Eighteen men complaining of fatigue but with no documented disease were included in the study. A rest-exercise (finger flexions)-recovery protocol was performed twice before (D-7 and D0), three times during (D3, D8, D15), and once after (D22) 15 days of oral supplementation with 6 g/day CM. Metabolism of the flexor digitorum superficialis was analysed by (31)P magnetic resonance spectroscopy at 4.7 T.
Metabolic variables measured twice before CM ingestion showed no differences, indicating good reproducibility of measurements and no learning effect from repeating the exercise protocol. CM ingestion resulted in a significant reduction in the sensation of fatigue, a 34% increase in the rate of oxidative ATP production during exercise, and a 20% increase in the rate of phosphocreatine recovery after exercise, indicating a larger contribution of oxidative ATP synthesis to energy production. Considering subjects individually and variables characterising aerobic function, extrema were measured after either eight or 15 days of treatment, indicating chronological heterogeneity of treatment induced changes. One way analysis of variance confirmed improved aerobic function, which may be the result of an enhanced malate supply activating ATP production from the tricarboxylic acid cycle through anaplerotic reactions.
The changes in muscle metabolism produced by CM treatment indicate that CM may promote aerobic energy production.
Arginine supplementation seems logical in situations where this amino acid becomes essential, for example after massive intestinal resection. Arginine is taken up and metabolised by the liver to a large extent and its supplementation is potentially unsafe. Citrulline is not captured by the liver and passes freely to the kidneys where it is metabolised to arginine, and so is a good candidate to generate arginine and thereby improve nutritional status.
Twenty four rats were assigned to four groups: citrulline, arginine, control, and sham. The sham group underwent transection and the three other groups resection of 80% of the small intestine. All rats were fed by enteral nutrition and its composition was as follows: supplementation with citrulline in the citrulline group, supplementation with arginine in the arginine group, and standard polymeric enteral nutrition in the control and sham groups. All groups received isonitrogenous nutrition and citrulline and arginine intakes were equimolar in their respective groups. After 10 days, the rats were sacrificed.
Arginine concentration was higher (p<0.05) in plasma and muscle in the citrulline group than in the three other groups. Plasma levels of arginine were 110 (12), 79 (7), 167 (22), and 228 (13) mumol/l in the sham, control, arginine, and citrulline groups respectively. Arginine concentrations in the gastrocnemius were: 0.15 (0.02), 0.16 (0.02), 0.40 (0.05), and 0.94 (0.20) mumol/g, respectively. Citrulline preserved nitrogen balance in resected rats but not in arginine supplemented rats (mean J10: 2.27 (0.29), 1.67 (0.15), 1.98 (0.29), and 2.43 (0.41) g/24 hours in the sham, control, arginine, and citrulline groups, respectively).
Supplementing the diet with citrulline is a very efficient means of increasing arginine levels and improving nitrogen balance after massive intestinal resection. The results of this study form a strong rationale for citrulline supplementation in these patients.
The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma [Formula] and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans.
• antioxidant
• nitric oxide
• amino acids
• endothelial nitric oxide synthase
Citrulline, a nonprotein amino acid, is an important source of endogenous arginine. The gut is the main source of citrulline in humans. Hence, citrulline is a potential biomarker of short bowel function. Conversely, citrulline uptake by the gut is important for an oral supply of this amino acid as an alternative to arginine. This review discusses these two aspects of citrulline, as well as the recent developments in the understanding of its metabolism.
Citrullinemia is such an efficient marker when the active mass of the bowel is affected that it can be used as a prognostic marker for parenteral nutrition weaning (if citrullinemia is >20 micromol/l) and as a factor for deciding between parenteral and enteral nutrition (as long as the pathology is considered). Citrullinemia should be used with care as a marker either of the intestinal absorption or following small bowel transplantation.
Citrulline is easily taken up by the gut, with a broad set of transporters that can remove it from the lumen in the enterocytes. This is confirmed by pharmacokinetic studies and the efficacy is so great that oral complementation with citrulline seems more efficient than complementation with arginine to provide arginine.
Citrulline malate is known to improve performance in weakened muscles. The present experiment was designed to test the hypothesis that citrulline malate can limit the effect of endotoxins on muscle fatigability. Endotoxemia was induced in rats by injection of lipopolysaccharides from Klebsiella pneumoniae. Resistance to fatigue was quantified by measuring tension production during repetitive electrical stimulation of the isolated epitrochlearis muscle. Oral treatment by citrulline malate was found to increase resistance to fatigue in infected rats, whereas twitch tension was not modified. This demonstrates the efficacy of citrulline malate for limiting an increase in muscle fatigue elicited with bacterial endotoxins.
1.1. Pyruvate carboxylation and citrulline synthesis were studied in rat liver mitochondria incubated in Slate 4 and State 3 in order to vary the intramitochondrial ATP/ADP ratio.2.2. 1 mM NH4Cl diminished the rate of pyruvate carboxylation in the presence and absence of fatty acids.3.3. The addition of NH4Cl resulted in a decrease of Vmax value of pyruvate carboxylation but had no effect on the Km value for ATP.4.4. In mitochondria incubated in State 4 and State 3 citrulline synthesis resulted in a decrease of pyruvate carboxylation, suggesting a competition for energy between carbamoylphosphate synthase (ammonia) and pyruvate carboxylase.5.5. When exogenous ATP was used as an energy source an inhibition of the rate of pyruvate carhoxylation by citrulline synthesis was not observed.
An experimental evaluation of citrulline malate (Stimol, CAS 54940-97-5), an anti-fatigue compound, was undertaken in man and in the animal in order to study the pharmacological activity of the substance at hepatic and renal level. In man, the protocol involved a double-blind randomized, placebo-controlled cross-over technique. The study in the animal was blind and placebo-controlled with two randomized parallel groups. Results showed that citrulline malate stimulates hepatic ureogenesis and favorizes the renal reabsorption of bicarbonates. These metabolic actions had a protective effect against acidosis and ammonia poisoning and explain the anti-fatigue properties of citrulline malate in man.
Citrulline malate is known to improve performance in weakened muscles. The present experiment was designed to test the hypothesis that citrulline malate can limit the effect of endotoxins on muscle fatigability. Endotoxemia was induced in rats by injection of lipopolysaccharides from Klebsiella pneumoniae. Resistance to fatigue was quantified by measuring tension production during repetitive electrical stimulation of the isolated epitrochlearis muscle. Oral treatment by citrulline malate was found to increase resistance to fatigue in infected rats, whereas twitch tension was not modified. This demonstrates the efficacy of citrulline malate for limiting an increase in muscle fatigue elicited with bacterial endotoxins.
Essai randomisé en double aveugle contre placebo du malate de citrulline en gériatrie
- M Carbasse
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Evaluation clinique des antiasthéniques
- R Dahan
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The role of lactate and ammonium in fatigue
- P Vanuxem
- D Vanuxem
- E Fomaris
- P Bernasconi
Vanuxem, P, Vanuxem, D, Fomaris, E, and Bernasconi, P. The role of lactate and
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