Article

Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

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.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... 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. ...
Article
Full-text available
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.
... Durante las últimas décadas se han intentado descubrir y explicar las propiedades ergogénicas de los aminoácidos L-arg y L-citr, en todas sus formas, sobre el rendimiento deportivo, dando lugar a ensayos clínicos que tratan de confirmar estas propiedades (19)(20)(21). Sin embargo, a pesar de estas intensas y extensas investigaciones, los resultados son a menudo poco claros (22). Esto puede estar relacionado, en parte, con diferencias metodológicas entre los estudios, como la cantidad y duración de la suplementación, el tipo de ejercicio realizado y el nivel de entrenamiento de los sujetos (11). ...
... En relación a los estudios consultados, e independientemente de la dosis suministrada (desde 8,0 hasta 12,0 g·d -1 ), la evidencia muestra un efecto positivo de la suplementación de corta duración con CM sobre el rendimiento deportivo (17,20,47,48,52). La disminución de la RPE y del dolor muscular después del esfuerzo emerge como principal beneficio de este compuesto (17,20). ...
... En relación a los estudios consultados, e independientemente de la dosis suministrada (desde 8,0 hasta 12,0 g·d -1 ), la evidencia muestra un efecto positivo de la suplementación de corta duración con CM sobre el rendimiento deportivo (17,20,47,48,52). La disminución de la RPE y del dolor muscular después del esfuerzo emerge como principal beneficio de este compuesto (17,20). En este sentido, Pérez-Guisado et al. (20) reportaron una menor percepción del dolor muscular a las 24 y 48 horas después del esfuerzo al comparar el tratamiento de CM con placebo, y también una menor percepción del dolor muscular a las 24 y 48 horas post-esfuerzo. ...
Article
Full-text available
Introducción: los aminoácidos L-arginina (L-arg) y L-citrulina (L-citr) se han utilizado dentro de la nutrición deportiva y se cree que ejercen un efecto sobre el rendimiento físico. Sin embargo, la información existente es variada y poco concluyente. Objetivo: revisar y analizar la evidencia científica existente dentro de los últimos diez años que relacionó los efectos de la suplementación con L-arg y L-citr sobre el rendimiento físico. Material y método: el estudio corresponde a una revisión sistemática de estudios previamente publicados, siguiendo el modelo PRISMA. Se evaluaron artículos publicados entre los años 2008 y 2018 que relacionaron la suplementación de L-arg y L-citr sobre el rendimiento físico. La búsqueda electrónica se realizó a través de Web of Science, Scopus, Sport Discus, PubMed, Medline. Se incluyeron todos los artículos que utilizaron un protocolo de suplementación de estos aminoácidos por separado o en conjunto. Resultados: se encontraron 38 artículos, los que se estratificaron según el protocolo utilizado: a) suplementación con L-arg (n = 19); b) suplementación con L-arg y L-citr (n = 1); y c) suplementación con L-citr (n = 18), tanto de corta duración como prolongada. Conclusión: existe evidencia de que la L-citr puede funcionar mejor como ayuda ergogénica que la L-arg sobre el rendimiento físico, ya que la L-citr mostró un efecto positivo sobre la percepción subjetiva del esfuerzo y el dolor muscular, además de una disminución en las concentraciones de lactato y una disminución del tiempo en pruebas máximas. Sin embargo, aún falta evidencia para establecer la dosis de L-citr beneficiosa para el rendimiento físico.
... L-citrulline studies have found similar results to those administering intravenous L-arginine for increasing vasodilation leading many pre-workout supplements to now include a compound form that is commonly referred to as citrulline malate (CM). Recent research suggests that exercisers may experience added ergogenic benefits when compared to L-citrulline alone [10][11][12][13][14]. Comparable to supplementing with L-citrulline, clinical doses of CM produce the same level of NO during exercise [15]. ...
... Recent research suggests that exercisers may experience added ergogenic benefits when compared to L-citrulline alone [10][11][12][13][14]. Comparable to supplementing with L-citrulline, clinical doses of CM produce the same level of NO during exercise [15]. Studies examining potential exercise benefits have found CM increases total work capacity during high intensity resistance exercise [11,13,14,16], but ergogenic benefits are not only limited to anaerobic exercise. The malate component of CM may provide additional benefits to aerobic metabolism via an increase in the efficiency of oxidative adenosine triphosphate production, because of its intermediate role in the tricarboxylic acid cycle [10]. ...
... The purpose of this study was to determine whether acute Nitrosigine or CM supplementation effected the NO producing capacity of endothelium dependent vasodilation as measured by change in FMD. Limited studies exist examining the effect of CM on endothelium dependent vasodilation [15] and results have been inconclusive compared to the observed ergogenic effects on high intensity exercise [11,13,14,16]. Meanwhile, the present study, to our knowledge, is the first to examine the acute effects of Nitrosigine supplementation on endothelium dependent vasodilation as measured by FMD. ...
Article
Full-text available
Background: Athletes are increasingly exploring ways to enhance their physical performance. Increasing blood flow to the working tissues through endothelium-dependent vasodilation is one factor athletes use to realize these results. Sports supplements such as pre-workouts tout this benefit; however, many have not been tested under laboratory conditions to examine the effects of commonly used supplements on vasodilation. Two popular supplements are Nitrosigine® and citrulline malate (CM). Thus, the purpose of this experiment was to determine the effective of Nitrosigine and CM on vasodilation using ultrasound and flow mediated dilation (FMD). Methods: Healthy, normotensive, and physically active male (n = 16) and female (n = 8) young adults participated in the present investigation. We utilized a randomized, double-blind, within-subjects design where participants reported for three trials, each preceded by a 7-day washout period. Baseline FMD measurement was obtained for each visit, followed by consumption of one clinical dose CM (8 g), Nitrosigine (1.5 g), or dextrose placebo (8 g). Following a 60-min digestion period, FMD was repeated. Supplementation order was randomized controlling for potential order effects. Results: Repeated measures ANOVA yielded a significant supplement (3) x time (2) effect (p < .001), such that Nitrosigine and CM yielded a greater improvement in FMD response than placebo. After supplementation, Nitrosigine and CM increased FMD by 31 and 34%, respectively, compared to a decrease of 2% during the placebo trial. After allometric scaling of the FMD values, supplement x time effect remained significant (p = .001) and changes were similar to non-scaled results. Nitrosigine (23%) and CM (25%) generated significantly greater allometric scaled FMD values when compared to the placebo trail (0.60%). Discussion: Both Nitrisigine and CM increased endothelial-dependent vasodilation as measured by a change in FMD. Increased vasodilation leads to an increase in skeletal muscle blood flow resulting in potential improvements in exercise performance.
... Ammonia plays an important role in fatigue because its intracellular accumulation favors glycolysis while inhibiting the aerobic utiliaztion of pyruvate. 11,16 This modified energy metabolism results in the formation of lactate, which may contribute to fatigue. 17,18 During high-intensity exercise, the rate of glycolysis is increased, and anaerobic glycolysis also leads to accumulation of blood lactate. ...
... 2À6,13,14 Therefore, malate may not provide additional benefit in lowering blood lactate levels, even though it is thought to bypass the ammonia-induced inhibition of the oxidative pathway and redirect lactic acid toward pyruvate production for aerobic utilization or gluconeogenesis. 11,47 Interestingly, in 2 studies that were excluded from our analysis due to longer periods of supplementation (2 weeks 48 and 4 weeks 49 ), supplementation with CM attenuated lactate response after high-intensity exercise. Therefore, even though acute supplementation with CM may not be effective, CM supplementation for 2 weeks may lower blood lactate levels after high-intensity exercise. ...
... Among the 13 studies, 8 reported the incidence of side effects. Although 6 studies stated that the participants did not experience any side effects, 1 study showed that 15% of the participants reported stomach discomfort after acute ingestion of 8 g CM. 11 One participant in another study reported gastrointestinal discomfort. 7 However, it occurred after both CM and placebo trials. ...
Article
Full-text available
Background: Citrulline is one of the non-essential amino acids that is thought to improve exercise performance and reduce post-exercise muscle soreness. We conducted a systematic review and meta-analysis to determine the effect of citrulline supplements on the post-exercise rating of perceived exertion (RPE), muscle soreness, and blood lactate levels. Methods: A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, muscle soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before exercise. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and muscle soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies. Results: The analysis included 13 eligible articles including a total of 206 participants. The most frequent dosage used in the studies was 8 g of citrulline malate. Citrulline supplementation significantly reduced RPE (n = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; n = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce muscle soreness 72-h post-exercise (n = 4, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17). Conclusion: Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting blood lactate levels.
... 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] . ...
Article
Full-text available
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.
... The potential ergogenic effects of CIT have been attributed to three main mechanisms: First, L-citrulline supplementation seems to increase L-arginine plasma levels [4][5][6] under rest and physical exercise conditions. Considering that L-arginine is the main substrate for nitric oxide synthesis (ON), an important blood flow modulator 7 , it has been suggested that CIT supplementation can indirectly increase ON synthesis 8 and thus increase blood flow to the active muscles. As a result, CIT supplementation could increase the release of nutrients and/or the removal of metabolic residues 9,10 (e.g. ...
... Considering that urea is the main vehicle for eliminating ammonia -a promoter of muscle fatigue through anaerobic glycolysis and resulting lactic acid production 13 -it has been suggested that supplementation with CIT can improve ammonia homeostasis 14 and, consequently, muscle function. Finally, malate is an intermediate of the Krebs cycle and its greater availability after supplementation with CIT seems to increase ATP production through anaplastic Krebs cycle reactions 2 , resulting in decreased muscle fatigue and increased muscle performance 2,8,15 . ...
... The objective of this study was to investigate the CIT supplementation effects on aerobic and muscular resistance in young adult individuals. Based on the physiological properties and supposed ergogenic effects of CIT 8,15,20 , the hypothesis was tested that CIT supplementation could increase the time until exhaustion and the number of maximum repetitions, as well as reduce the heart rate (HR) and the effort subjective perception (PSE) in the respective tests. ...
Article
Full-text available
The aim of this study was to evaluate the effects of citrulline malate (CIT) supplementation on aerobic and muscular endurance in young adult males. Eighteen young adult men (age: 21.5 ± 2.7 years) were randomized into two groups (Citrulline malate - CIT and Placebo - PLA; N = 9/group ) and received the respective supplements for 7 days. The CIT group was supplemented with 6 g CIT + 6 g dextrose (total: 12 g), while the PLA group received the same amount (12 g) of dextrose. At the pre- and post-supplementation, the following variables were analyzed: aerobic (maximal treadmill test, Tmax) and muscle (repetitions maximum test, Rmax) endurance tests, as well as mean and maximum heart rate (HR) in Tmax and ratings of perceived exertion (PSE) in Rmax. No significant (P > 0.05) differences were found between CIT and PLA groups in time until exhaustion in Tmax, total repetitions in Rmax, maximal HR and PSE from pre- to post-supplementation. The mean HR was statistically lower (P < 0.05) in the CIT group compared to the PLA in the Tmax. In conclusion, supplementation of CIT (6 g / day) does not improve aerobic and muscular endurance, as well as maximal HR or PSE in healthy young adults, despite reducing the mean HR during the maximal incremental test. Keywords: Endurance Training. Dietary Supplements. Physical Functional Performance. Citrulline. Nitric Oxide. ResumoO objetivo deste estudo foi avaliar os efeitos da suplementação de citrulina malato (CIT) sobre a resistência aeróbica e muscular em homens adultos jovens. Em um desenho experimental randomizado, duplo-cego e controlado com placebo, dezoito homens adultos jovens (idade: 21,5 ± 2,7 anos) foram randomizados em dois grupos (Citrulina malato – CIT e Placebo – PLA; N = 9/grupo) e receberam os respectivos suplementos por um período de 7 dias. O grupo CIT foi suplementado com 6 g de CIT + 6 g de dextrose (total: 12 g), enquanto o grupo PLA recebeu a mesma quantidade (12 g) de dextrose. Nos momentos pré e pós suplementação as seguintes variáveis foram analisadas: resistência aeróbia (teste incremental máximo em esteira rolante, Tmáx) e muscular (teste de repetições máximas, Rmáx), bem como a frequência cardíaca (FC) média e máxima no Tmáx e a análise da percepção subjetiva de esforço (PSE) no Rmáx. Nenhuma diferença significante (P > 0,05) foi encontrada entre os grupos CIT e PLA no tempo até a exaustão no Tmáx, total de repetições no Rmáx, FC máxima e PSE do momento pré para o pós suplementação. A FC média foi estatisticamente (P < 0,05) menor no grupo CIT comparado ao PLA no Tmáx. Em conclusão, a suplementação de CIT (6 g/dia) não melhora a resistência aeróbica e muscular, bem como a FC máxima ou PSE em adultos jovens saudáveis, apesar de reduzir a FC média durante o teste incremental máximo. Palavras-chave: Treino Aeróbico. Suplementos Nutricionais. Desempenho Físico Funcional. Citrulina. Óxido Nítrico.
... Nevertheless, several studies have investigated the ergogenic potential of CitMal supplementation on both aerobic and anaerobic exercise performance (Gonzalez & Trexler, 2020). Due to its potential to delay fatigue during highintensity exercise, studies have specifically investigated the acute effects of CitMal supplementation on strength, power, and resistance training performance (Chappell et al., 2018a(Chappell et al., , 2018bCunniffe et al., 2016;Cutrufello et al., 2015;da Silva et al., 2017;Farney et al., 2017;Glenn et al., 2015Glenn et al., , 2016Gonzalez et al., 2017;Martínez-Sánchez et al., 2017;Pérez-Guisado & Jakeman, 2010;Trexler et al., 2019a;Wax et al., 2015aWax et al., , 2015b. Although these studies have offered mixed findings, some have shown that acute CitMal supplementation may increase performance during highintensity strength and power tasks. ...
... The majority of the research pertaining to strength training has investigated the acute effect of CitMal supplementation on repetitions to failure during single-joint and/or multijoint exercise protocols. Here, several of the studies have demonstrated that subjects who consume a single dose of CitMal (6-8 g) experience less fatigue to the working muscles compared with a placebo groupallowing them to perform more repetitions to failure (Pérez-Guisado & Jakeman, 2010;Wax et al., 2015aWax et al., , 2015b. However, not all studies have shown such favorable results (Chappell et al., 2018a(Chappell et al., , 2018bda Silva et al., 2017;Gonzalez et al., 2017). ...
... Participants performed 3-10 (5 ± 3) sets to voluntary failure, on average, which resulted in 51 ± 23 total repetitions for each exercise. The dosage of CitMal supplementation ranged from 6 g (da Silva et al., 2017) to 8 g (Chappell et al., 2018a(Chappell et al., , 2018bGlenn et al., 2015;Gonzalez et al., 2017;Pérez-Guisado & Jakeman, 2010;Wax et al., 2015aWax et al., , 2015b and was ingested 40 min (Gonzalez et al., 2017) or 60 min preexercise (Chappell et al., 2018a(Chappell et al., , 2018bda Silva et al., 2017;Glenn et al., 2015;Pérez-Guisado & Jakeman, 2010;Wax et al., 2015aWax et al., , 2015b. To control for diet, all studies instructed participants to duplicate the nutritional intake prior to each experimental trial. ...
Article
Full-text available
Citrulline malate (CitMal) is a dietary supplement that is suggested to enhance strength training performance. However, there is conflicting evidence on this matter. Thus, the purpose of this meta-analysis was to determine whether supplementing with CitMal prior to strength training could increase the total number of repetitions performed before reaching voluntary muscular failure. A systematic search was conducted wherein the inclusion criteria were double-blind, placebo-controlled studies in healthy participants that examined the effect of CitMal on repetitions to failure during upper body and lower body resistance exercises. The Hedges’s g standardized mean differences (SMD) between the placebo and CitMal trials were calculated and used in a random effect model. Two separate subanalyses were performed for upper body and lower body exercises. Eight studies, including 137 participants who consisted of strength-trained men ( n = 101) and women ( n = 26) in addition to untrained men ( n = 9), fulfilled the inclusion criteria. Across the studies, 14 single-joint and multijoint exercises were performed with an average of 51 ± 23 total repetitions during 5 ± 3 sets per exercise at ∼70% of one-repetition maximum. Supplementing with 6–8 g of CitMal 40–60 min before exercise increased repetitions by 3 ± 5 (6.4 ± 7.9%) compared with placebo ( p = .022) with a small SMD (0.196). The subanalysis for the lower body resulted in a tendency for an effect of the supplement (8.1 ± 8.4%, SMD: 0.27, p = .051) with no significant effect for the upper body (5.7 ± 8.4%, SMD: 0.16, p = .131). The current analysis observed a small ergogenic effect of CitMal compared with placebo. Acute CitMal supplementation may, therefore, delay fatigue and enhance muscle endurance during high-intensity strength training.
... CM is a pharmaceutical compound (Stimol ® Biocodex, Gentilly, France), authorized for treating asthenia, with the recommended dose being 1 g thrice daily [72]. Higher rates of ATP production during CM supplementation have been demonstrated in active human skeletal muscle using magnetic resonance spectroscopy [73], this result is thought to be driven by malate's role in mitochondrial oxidative metabolism [74]. ...
... Accordingly, oral administration of CM in healthy rats, 1 g/kg thrice daily for 48 h, led to an improved muscular efficiency, enhancing specific muscle force production by 23%, associated with a significant fall in phosphocreatine (PCr) (28%) as well as in oxidative (32%) costs of contraction [78]. Additionally, Perez-Guisado and Jakeman [72] showed a fall of 40% in muscle soreness 24 and 48 h after a pectoral training session and a higher percentage response, over 90%, was reached using just one 8 g dose of supplementary CM. Moreover, other authors described less fatigue in working muscles, enabling them to carry out a larger number of repetitions on exercise performance during lower-body dynamic resistance exercise under CM supplementation (8 g) [79]. ...
Article
Full-text available
L-Arginine (Arg) has been widely used due to its functional properties as a substrate for nitric oxide (NO) generation. However, L-citrulline (CIT), whose main natural source is watermelon, is a non-essential amino acid but which has important health potential. This review provides a comprehensive approach to different studies of the endogenous synthesis of CIT, metabolism, pharmacokinetics, and pharmacodynamics as well as its ergogenic effect in exercise performance. The novel aspect of this paper focuses on the different effects of CIT, citrulline malate and CIT from natural sources such as watermelon on several topics, including cardiovascular diseases, diabetes, erectile dysfunction, cancer, and exercise performance. CIT from watermelon could be a natural food-sourced substitute for pharmacological products and therefore the consumption of this fruit is promoted.
... 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. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... [8,9,41] Furthermore, the addition of malate to dietary L-citrulline was chosen in this study, since previous studies observed higher levels of NO metabolites with the addition of malate. [11,42] Dosages of 8 g Lcitrulline malate and 3 g L-arginine hydrochloride were used in this study, because previous studies consider these dosages to be safe for healthy individuals and without adverse events. [31,33,34] It was observed in literature, that single doses of >15 g of Larginine cause gastrointestinal side effects (i.e., diarrhea and vomiting). ...
Article
Full-text available
Introduction: The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters," which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation.The aim of this study was to investigate 3 of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). Methods: This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6 and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30-male athletes between 18 and 40 years and will be compared with a placebo. On each of the 3 appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the 3 supplements once after a wash-out period of at least 1 week. Perfusion will be quantified via VueBox quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. Discussion: The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. Trial registration: German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.
... Kelelahan otot adalah penurunan performa otot akibat aktivitas fisik. Hal ini menyebabkan kapasitas kekuatan maksimal otot berkurang (Perez & Jakeman, 2010). Selain mengurangi kapasitas kekuatan maksimal, akumulasi dari sisa metabolit akibat dari aktivitas fisik menyebabkan sensasi terbakar dan nyeri pada otot yang akan semakin bertambah seiring waktu dan mencapai puncaknya pada 1-2 hari setelah latihan (Sirait et al., 2015). ...
Article
Full-text available
Tujuan dalam penelitian ini adalah: (1) Untuk mengetahui apakah ada perbedaan efektivitas active isolated stretching dan passive activity dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi; (2) Untuk mengetahui apakah ada perbedaan efektivitas antara VO2Max tinggi dan VO2Max rendah dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi; (3) Untuk mengetahui apakah ada interaksi antara active isolated stretching dan passive activity dengan VO2Max dalam mencegah terjadinya delayed onset muscle soreness setelah olahraga intensitas tinggi. Metode yang digunakan dalam penelitian ini adalah eksperimen. Bentuk penelitian menggunakan rancangan faktorial 2x2. Teknik pengambilan sampel yang digunakan dalam penelitian ini menggunakan menggunakan rumus dari Issac & Michael, sehingga didapat sampel sebanyak 40 orang. Berdasarkan hasil penelitian dan pembahasan yang penulis lakukan pada penelitian ini, dapat disimpulkan bahwa: (1) tidak ada perbedaan efektivitas Active Isolated Stretching dan passive activity dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. (2) Tidak ada perbedaan efektivitas antara VO2Max tinggi dan VO2Max rendah dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. (3) Tidak ada interaksi antara Active Isolated Stretching, Passive Activity dengan VO2Max dalam mencegah terjadinya Delayed Onset Muscle Soreness setelah olahraga intensitas tinggi. Effectiveness stretching, passive activity and VO2max prevent the delayed onset muscle soreness. Abstract The objectives of this study are: (1) To determine whether there are differences in the effectiveness of active isolated stretching and passive activity in preventing delayed onset of muscle soreness after high-intensity exercise; (2) To find out whether there is a difference in effectiveness between high VO2Max and low VO2Max in preventing delayed onset of muscle soreness after high-intensity exercise; (3) To determine whether there is an interaction between active isolated stretching and passive activity with VO2Max in preventing delayed onset of muscle soreness after high-intensity exercise. The method used in this research is an experiment. The analysis uses a 2x2 factorial design. Based on the results of research and discussion that the authors do in this study, it can be concluded that:(1) there is no difference in the effectiveness of Active Isolated Stretching and passive activity in preventing Delayed Onset Muscle Soreness after high-intensity exercise. (2) There is no difference in efficacy between high VO2Max and low VO2Max in preventing Delayed Onset Muscle Soreness after high-intensity exercise. (3) There is no interaction between Active Isolated Stretching, Passive Activity with VO2Max in preventing Delayed Onset Muscle Soreness after high-intensity exercise.
... Regarding performance outcomes, a recent systematic review and metaanalysis by Trexler et al. (126) found a significant, yet small, favorable effect of citrulline-based supplements on acute performance of high-intensity strength and power tasks in comparison with a placebo. Specific to resistance training, several studies have reported that acute ingestion of CitMal allows individuals to complete more repetitions-to-failure over a series of sets of single-joint and/ or multijoint exercises (48, 97,131,132). For example, resistance-trained males were able to complete a significantly greater number of repetitions during 5 sets of leg press, hack squat, and leg extension to failure at 60% one repetition maximum (1RM) (132). ...
Article
Full-text available
Several dietary supplements have been proposed as a means of improving muscle strength and hypertrophy when combined with resistance training. However, few have received sufficient attention from sports scientists to produce robust evidence for being well recommended. A growing body of literature has emerged for several dietary ingredients with the potential to promote muscular adaptations. Therefore, the aim of this review is to provide an evidence-based review of the efficacy of emerging nutritional supplements to allow athletes, coaches, and practitioners to make an informed decision when considering their use as a means of improving muscle strength and hypertrophy.
... In this study a combination of orally administered L-citrulline and L-arginine were selected due to the fact, that some studies described a more effective and rapid increase of plasma L-arginine and augmented NO-dependent response (8,9,41). Furthermore, the addition of malate to dietary L-citrulline was chosen in this study, since previous studies observed higher levels of NO metabolites than malate (11,42). Dosages of 8 g L-citrulline malate and 3 g L-arginine were used in this study, because previous studies consider these dosages to be safe for healthy individuals and without adverse events (31,33,34 ...
Preprint
Full-text available
Background The market for dietary supplements in the sports sector has been growing rapidly for several years, though there is still lacking evidence regarding their claimed benefits. One group is that of nitric oxide increasing supplements, so-called "NO-boosters", which are claimed to improve the supply of oxygen and nutrients to the muscle by enhancing vasodilation. The aim of this study was to investigate three of these supplements in healthy male athletes for their muscle perfusion-enhancing potential using contrast-enhanced ultrasound (CEUS). Methods This placebo-controlled, double-blind, randomized cross-over trial will be carried out at the Center for Orthopedics, Trauma Surgery and Spinal Cord Injury of the University Hospital Heidelberg. Three commercial NO enhancing products including 300 mg of the specific green tea extract VASO6™ and a combination of 8 g L-citrulline malate and 3 g L-arginine hydrochloride will be examined for their potential to increase muscular perfusion in 30 male athletes between 18 and 40 years and will be compared with a placebo. On each of the three appointments CEUS of the dominant biceps muscle will be performed at rest and after a standardized resistance training. Every athlete receives each of the three supplements once after a wash-out period of at least one week. Perfusion will be quantified via VueBox® quantification software. The results of CEUS perfusion measurements will be compared intra- and interindividually and correlated with clinical parameters. Discussion The results of this study may help to establish CEUS as a suitable imaging modality for the evaluation of potentially vasodilatory drugs in the field of sports. Other supplements could also be evaluated in this way to verify the content of their advertising claims. Trial registration German Clinical Trials Register (DRKS), ID: DRKS00016972, registered on 25.03.2019.
... In contrast, citrulline has substantially greater bioavailability, and oral citrulline supplementation efficiently increases blood arginine levels ( Schwedhelm et al., 2008). Perez-Guisado and Jakeman (2010) found citrulline enhanced repetitions to fatigue during resistance exercise. A recent meta-analysis ) reported a small, but significant effect of citrulline-based supplements for such outcomes. ...
Article
Full-text available
The popularity of physique sports is increasing, yet there are currently few comprehensive nutritional guidelines for these athletes. Physique sport now encompasses more than just a short phase before competition and offseason guidelines have recently been published. Therefore, the goal of this review is to provide an extensive guide for male and female physique athletes in the contest preparation and recovery period. As optimal protein intake is largely related to one’s skeletal muscle mass, current evidence supports a range of 1.8-2.7 g/kg. Furthermore, as a benefit from having adequate carbohydrate to fuel performance and activity, low-end fat intake during contest preparation of 10-25% of calories allows for what calories remain in the “energy budget” to come from carbohydrate to mitigate the negative impact of energy restriction and weight loss on training performance. For nutrient timing, we recommend consuming four or five protein boluses per day with one consumed near training and one prior to sleep. During competition periods, slower rates of weight loss (≤0.5% of body mass per week) are preferable for attenuating the loss of fat-free mass with the use of intermittent energy restriction strategies, such as diet breaks and refeeds, being possibly beneficial. Additionally, physiological and psychological factors are covered, and potential best-practice guidelines are provided for disordered eating and body image concerns since physique athletes present with higher incidences of these issues, which may be potentially exacerbated by certain traditional physique practices. We also review common peaking practices, and the critical transition to the post-competition period.
... Numerous studies have reported ergogenic effects on exercise tasks, including time to exhaustion, time-trial performance, and repetitions to fatigue from NO precursor supplements such as CitMal and BEET (Bailey et al. 2009;Perez-Guisado and Jakeman 2010;Bond et al. 2012;Cermak et al. 2012;Wax et al. 2015;Mosher et al. 2016;Wax et al. 2016). Ergogenic effects are thought to be mediated by NO, which is purported to enhance blood flow and energy efficiency during exercise. ...
Article
The ergogenic effects of citrulline malate (CitMal) and beetroot juice (BEET) have been widely studied, but their effects on physiological outcomes related to resistance exercise are not fully understood. The purpose of this randomized, double-blind, crossover study was to investigate the effects of CitMal (8 g) and BEET (400 mg nitrate) on blood pressure (BP), blood flow, and energy efficiency during submaximal leg extension. Recreationally active males (n = 27; age: 22 ± 4 yrs) completed familiarization, followed by three testing visits. Supine and standing BP were measured upon arrival, followed by supplement ingestion, a 2-h rest period, postsupplement BP measurement, and a bout of repeated submaximal isotonic leg extensions at 25% of maximal voluntary contraction torque. Diameter (aDIAM) and blood flow (aBF) of the superficial femoral artery, and cross-sectional area (CSA) and echo intensity (EI) of the vastus lateralis, were measured before and after exercise via ultrasonography. Muscle blood flow (mBF) and oxygen consumption (mVO2), along with whole-body energy expenditure (EE) and respiratory exchange ratio (RER), were measured before and during exercise via indirect calorimetry and near-infrared spectroscopy. Baseline RER values differed among treatments (p = 0.01); BEET was higher than CitMal (p = 0.01) but not PLA (p = 0.58); CitMal and PLA were not significantly different (p = 0.12). No other measurements were significantly affected by treatment (all p > 0.05). Results suggest that neither CitMal nor BEET significantly influence resting BP, blood flow, or metabolic efficiency during submaximal leg extension in recreationally active males.
... • Sekundäre Pflanzenstoffe (S. 28) o Theobromin (S. 28) o Catuaba Extrakt (S. 29) o Maca Extrakt (S. 31) o Grüntee Extrakt, entkoffeiniert (S. 32) o Ingwer Extrakt (S. 33) o Magnolia Extrakt (S. 35) o Piperin (S. 37) • Sonstiges/Beschreibung (S. 38) -Produkt 2: Proteinriegel (S. 39) • Inhaltsstoffe (S. 40) o Süßkartoffel-Pulver (S. 40) • Die wichtigsten Nährstoffe im Überblick (S. 41) o Eiklar-Pulver (S. 47) o Allulose (S. 48) o Datteln (S. 48) o Honig (S. 49) o Propolis (S. 51) o Gelee Royal (S. 52) o Flohsamenschalen (S. 53) o Bromelain (S. 54) o Curcuminoide (S. 54) o Piperin (S. 56) o Stevia E960 (S. 56) -Zusammenfassung (S. 58 10,11 Ein häufig behaupteter Zusammenhang zwischen tierischen Produkten (insbesondere Fleisch) und Zivilisationskrankheiten ist, in gesundem Maß, wissenschaftlich nicht haltbar. 12,13,14 Veganer und Vegetarier sollten sich hingegen um ihre Gesundheit bemühen, da eine Mangelsituation häufiger vorkommt als vermutet. ...
Article
Full-text available
Die hier vorgestellten Produkte mit Schwerpunkt Nachhaltigkeit und Evidenz-basierten Inhaltsstoffen (Energy-Drink & Protein-Riegel) erhalten im Verbrauchermarkt aufsteigendes Interesse. Dies liegt unter anderem daran, dass Nahrungsmittel mit gesundheits- und leistungsfördernden Eigenschaften benötigt werden, um der steigenden Anzahl an Krankheiten präventiv entgegenzuwirken. Besonders wichtig ist die adäquate Zufuhr von Proteinen und sekundären Pflanzenstoffe, um langfristig gesund zu bleiben. Im Gegensatz zu anderen bereits bestehenden Unternehmen liegt der Fokus dieses Konzepts auf der wissenschaftlichen Bestätigung zur Wirksamkeit der einzelnen Inhaltsstoffe. Damit soll dem Käufer ein optimales Preis-Leistungsverhältnis, auch in Bezug auf den Geschmack, geboten werden. Zusätzlich steht der Ressourcen-schonende Umgang mit Rohstoffen und Verpackungsmaterialien im Vordergrund, sodass zukunftsfähiges Handeln ermöglicht wird. Gerade in einer Zeit von hohen menschengemachten Umweltbelastungen, wie beispielsweise durch Plastikaufkommen in den Meeren, ist eine moralische Firmenpolitik notwendiger denn je.
... 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]. ...
Article
Full-text available
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.
... 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]. ...
Article
Full-text available
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]. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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.
... 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. ...
Article
Full-text available
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]. ...
Article
Full-text available
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]. ...
... L-citrulline supplementation acts as a source of energy during exercise and is involved in removal of excess metabolites from the body (2). Pérez-Guisado and Jakeman (3) reported that supplementation of 8 g of citrulline malate can reduce muscle soreness at 24 and 48 h following anaerobic exercise. An in vivo study by Meneguello et al. (4) investigated supplementation of mice with a single dose of supplement containing 0.26 g/kg body weight L-citrulline, 0.4 g/kg body weight L-arginine, and 0.2 g/kg body weight L-ornithine lowered blood ammonia accumulation after exercise and prolonged the time until exhaustion in swimming exercises. ...
Article
Full-text available
Nutritional intervention of fruit juice supplementation is able to maximize exercise performance. Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] contains high L-citrulline content and consumption of watermelon juice may promote ergogenic effects. The aim of the present study was to investigate the role of 100% flesh watermelon juice and 100% rind watermelon juice supplementation for 14 days on swimming performance in rats. Twenty four male Sprague-Dawley rats were randomly divided into four groups: Cx group of rats supplemented with filtered tap water (negative control), L-cit group of rats supplemented with L-citrulline (positive control), FR group of rats supplemented with 100% flesh watermelon juice, and RR group of rats supplemented with 100% rind watermelon juice. Each group was supplemented for 14 days ad libitum prior to swimming exercise protocol. The rats were performed swimming exercise for 3 days and swimming time until exhaustion was measured. Plasma samples were collected to measure lactate concentration, ammonia concentration, and nitric oxide production. Rats supplemented with 100% flesh watermelon juice demonstrated significantly prolonged of swimming time until exhaustion, reduction of lactate and ammonia concentrations, and increased of nitric oxide production compared to Cx and L-cit groups (P<0.05). These findings postulate that supplementation with 100% flesh watermelon juice improves endurance in swimming performance.
Article
Full-text available
Citrulline-malate (CM) purportedly increases exercise performance through increased nitric oxide production. The effects of CM on muscular strength performance are well-documented; however, the benefits of CM on aerobic and anaerobic biking performance are not well researched. Therefore, the present investigation examined the acute CM supplementation effects on aerobic and anaerobic cycling performance in recreationally active males. Methods: 28 recreationally active males (20.9 ± 2.8 years) completed randomized, double-blind, crossover trials consuming CM (12g dextrose + 8g CM) or a placebo (12g dextrose). Participants performed an aerobic cycling protocol (time-to-exhaustion [TTE]), followed by a subsequent 30-second Wingate cycling test, 60-minutes after supplement consumption. Results: Dependent t-tests showed no significant differences (p > 0.05) for TTE (PLA: 315.4 s ± 137.7 s; CM: 314.1 s ± 107.1 s) and Total Work Completed (TWC) (PLA: 74.7 ± 34.1 kilojoules (kJ); CM: 74.1 ± 26.4 kJ) during the aerobic cycling protocol. Dependent t-tests also showed no significant differences (p > 0.05) for mean watts (PLA: 586.1 ± 87.7 Watts (W); CM: 588.0 ± 93.0 W), peak watts (PLA: 773.0 ± 136.7 W; CM: 786.7 ± 133.0 W), and fatigue index (PLA: 12.9 ± 6.4 FI; CM: 14.3 ± 7.2 FI) during the Wingate protocol. Repeated-measures ANOVA results indicated a significant effect between each 5 s interval (p < 0.001), but no differences were observed between trials (p > 0.05). Conclusion: Acute CM supplementation in recreationally active males provides no ergogenic benefit in aerobic cycling performance followed by an anaerobic cycling test.
Article
Full-text available
Fernández-Hernández, A.; Casals-Vázquez, C. (2019). L-Citrulina y su efecto en deportes de resistencia, una revisión sistemática. 11(3):227-240.
Article
The objective of this study was to determine the effects of a single pre-exercise dose of watermelon juice on submaximal post-exercise heart rate (HR) recovery, blood lactate (BL), blood pressure (BP), blood glucose (BG), and muscle soreness in healthy adults. In a randomised crossover design, 27 healthy non-athletic participants (13 males/14 females) consumed 355 mL of watermelon juice, Gatorade, sugar water, or water. HR and BL were significantly higher post-exercise, and both watermelon juice and sugar water increased postprandial BG. However, there were no significant differences among the supplements in HR recovery, BL, or post-exercise muscle soreness. Watermelon juice prevented increased post-exercise systolic and diastolic BP in females, but not in males. More research is warranted to examine the effect of sex on the efficacy of watermelon consumption for controlling BP.
Article
Full-text available
The aim of this study was to investigate the effect of six weeks of High intensity interval training (HIIT) program and citrulline malate (CM) supplement on nitric oxide levels and exercise performance in elite wrestlers. In a randomized, placebo-controlled design, 28 elite males’ wrestlers (age, 21.9±2.4 y; height 174.5±3.8 cm) were randomly assigned to CM+training, placebo+training and training, while also all groups participating in 6 weeks of HIIT based on wrestling techniques. Participants completed testing sessions for body composition and aerobic and anaerobic tests before and after 6 weeks of HIIT program. Venous blood samples were obtained before and after 6 weeks. Nitric Oxide level after six weeks of HIIT and CM supplementation showed significant increase comparing to placebo+training (P=0.001) and training (P=0.035) groups. There is no significant difference between other groups for NO (P> 0.05). There was a significant difference between upper body anaerobic power (peak power, Mean power and fatigue index) of CM group and placebo group (P=0.22), and there was no significant difference between the other groups (P>0.05). Among all body composition data after six week HIIT just FFM of CM+training group showed significant increase comparing placebo and training group (P<0.05). Daily CM supplementation during six weeks of HIIT training increases serum NO levels and upper body anaerobic power in elite male wrestlers comparing HIIT alone.
Article
Gonzalez, AM and Trexler, ET. Effects of citrulline supplementation on exercise performance in humans: A review of the current literature. J Strength Cond Res XX(X): 000-000, 2020-L-citrulline, a nonessential amino acid found primarily in watermelon, has recently garnered much attention for its potential to augment L-arginine bioavailability, nitric oxide production, and exercise performance. Over the past decade, L-citrulline has received considerable scientific attention examining potentially ergogenic properties for both aerobic and anaerobic exercise performance. Thus, the purpose of this article is to summarize the theoretical rationale behind L-citrulline supplementation and to comprehensively review the available scientific evidence assessing the potential ergogenic value of L-citrulline supplementation on vascular function and exercise performance in humans. In addition, research that has investigated the potential synergistic effects of L-citrulline with other dietary ingredients (e.g., arginine, antioxidants, nitrates, and branched-chain amino acids) is reviewed. Oral L-citrulline and citrulline malate supplementation have shown to increase plasma citrulline and arginine concentrations, along with total nitrate and nitrite concentrations. Although blood flow enhancement is a proposed mechanism for the ergogenic potential of L-citrulline, evidence supporting acute improvements in vasodilation and skeletal muscle tissue perfusion after supplementation is scarce and inconsistent. Nevertheless, several studies have reported that L-citrulline supplementation can enhance exercise performance and recovery. Given the positive effects observed from some investigations, future studies should continue to investigate the effects of both acute and chronic supplementation with L-citrulline and citrulline malate on markers of blood flow and exercise performance and should seek to elucidate the mechanism underlying such effects.
Article
L-citrulline is an organic α-amino acid that has been shown to produce a number of salutary actions on whole-body physiology, which includes reducing muscle wasting and augmenting exercise/muscle performance. The latter has been suggested to arise from elevations in mitochondrial function. Because enhancing mitochondrial function has been proposed as a novel strategy to mitigate insulin resistance, our goal was to determine whether supplementation with L-citrulline could also improve glycemia in an experimental mouse model of obesity. We hypothesized that L-citrulline treatment would improve glycemia in obese mice, and this would be associated with elevations in skeletal muscle mitochondrial function. 10-week old C57BL/6J mice were fed either a low-fat (10% kcal from lard) or high-fat (60% kcal from lard) diet, while receiving drinking water supplemented with either vehicle or L-citrulline (0.6 g/L) for 15-weeks. Glucose homeostasis was assessed via glucose/insulin tolerance testing, while in vivo metabolism was assessed via indirect calorimetry, and forced exercise treadmill testing was utilized to assess endurance. As expected, obese mice supplemented with L-citrulline exhibited an increase in exercise capacity, which was associated with an improvement in glucose tolerance. Consistent with augmented mitochondrial function, we observed an increase in whole body oxygen consumption rates in obese mice supplemented with L-citrulline. Surprisingly, L-citrulline supplementation worsened insulin tolerance and reduced insulin signaling in obese mice. Taken together, although L-citrulline supplementation improves both glucose tolerance and exercise capacity in obese mice, caution must be applied with its broad use as a nutraceutical due to a potential deterioration of insulin sensitivity. NEW FINDINGS: What is the central question of the study? L-citrulline has been shown to augment performance in animals and athletes, possibly via increasing mitochondrial function. We were curious whether L-citrulline's potential mitochondrial actions would translate to obese animals, and whether this would improve glycemia. What is the main finding and its importance? Chronic supplementation with L-citrulline improves not only exercise capacity, but also glycemia in obese mice, which would be beneficial as obese individuals are at increased risk for type 2 diabetes. However, L-citrulline supplementation also caused a mild impairment in insulin signaling and insulin tolerance in obese mice. This article is protected by copyright. All rights reserved.
Chapter
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.
Article
Full-text available
PurposeThis review provides an overview of the current knowledge of the nutritional strategies to treat the signs and symptoms related to EIMD. These strategies have been organized into the following sections based upon the quality and quantity of the scientific support available: (1) interventions with a good level of evidence; (2) interventions with some evidence and require more research; and (3) potential nutritional interventions with little to-no-evidence to support efficacy.Method Pubmed, EMBASE, Scopus and Web of Science were used. The search terms ‘EIMD’ and ‘exercise-induced muscle damage’ were individually concatenated with ‘supplementation’, ‘athletes’, ‘recovery’, ‘adaptation’, ‘nutritional strategies’, hormesis’.ResultSupplementation with tart cherries, beetroot, pomegranate, creatine monohydrate and vitamin D appear to provide a prophylactic effect in reducing EIMD. β-hydroxy β-methylbutyrate, and the ingestion of protein, BCAA and milk could represent promising strategies to manage EIMD. Other nutritional interventions were identified but offered limited effect in the treatment of EIMD; however, inconsistencies in the dose and frequency of interventions might account for the lack of consensus regarding their efficacy.Conclusion There are clearly varying levels of evidence and practitioners should be mindful to refer to this evidence-base when prescribing to clients and athletes. One concern is the potential for these interventions to interfere with the exercise-recovery-adaptation continuum. Whilst there is no evidence that these interventions will blunt adaptation, it seems pragmatic to use a periodised approach to administering these strategies until data are in place to provide and evidence base on any interference effect on adaptation.
Article
Purpose of review: Primary mitochondrial disease is a highly heterogeneous but collectively common inherited metabolic disorder, affecting at least one in 4300 individuals. Therapeutic management of mitochondrial disease typically involves empiric prescription of enzymatic cofactors, antioxidants, and amino acid and other nutrient supplements, based on biochemical reasoning, historical experience, and consensus expert opinion. As the field continues to rapidly advance, we review here the preclinical and clinical evidence, and specific dosing guidelines, for common mitochondrial medicine therapies to guide practitioners in their prescribing practices. Recent findings: Since publication of Mitochondrial Medicine Society guidelines for mitochondrial medicine therapies management in 2009, data has emerged to support consideration for using additional therapeutic agents and discontinuation of several previously used agents. Preclinical animal modeling data have indicated a lack of efficacy for vitamin C as an antioxidant for primary mitochondrial disease, but provided strong evidence for vitamin E and N-acetylcysteine. Clinical data have suggested L-carnitine may accelerate atherosclerotic disease. Long-term follow up on L-arginine use as prophylaxis against or acute treatment for metabolic strokes has provided more data supporting its clinical use in individuals with mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome and Leigh syndrome. Further, several precision therapies have been developed for specific molecular causes and/or shared clinical phenotypes of primary mitochondrial disease. Summary: We provide a comprehensive update on mitochondrial medicine therapies based on current evidence and our single-center clinical experience to support or refute their use, and provide detailed dosing guidelines, for the clinical management of mitochondrial disease. The overarching goal of empiric mitochondrial medicines is to utilize therapies with favorable benefit-to-risk profiles that may stabilize and enhance residual metabolic function to improve cellular resiliency and slow clinical disease progression and/or prevent acute decompensation.
Article
Full-text available
Introduction Improving physical performance and delaying fatigue by using nutritional supplements always has been interesting in athletes. The aim of this study was to evaluate the effect of six weeks’ watermelon juice on nitric oxide and exercise performance in elite female taekwondo. Materials and Methods Twenty-five elite female taekwondo players (age 21.84±2.26 yrs; BMI 20.87±1.37 Kg/m2 ; VO2max 38.86±1.97 ml/min/kg) who had a training experience of more than five years were randomly and voluntary divided into two groups of watermelon juice supplement (n=15) and placebo (n=10). Subjects received 500 ml of watermelon juice or placebo 45 minutes before the taekwondo training sessions for six weeks. Blood samples were taken in the brachial vein in two steps; before and after 6 weeks of supplementation. Data were analyzed using dependent and independent t-test (p≤0.05). Results The results of this study showed levels of nitric oxide (P=0.016) and VO2max (P=0/001) significantly greater compared to the placebo group. Also, there was a significant decrease in muscle soreness 24 and 48 hours after exercise in the supplement group compared to the placebo group (p≤0.05). Conclusion According to the results, watermelon juice will help faster recovery and reduce muscle soreness after 24 and 48 hours follow exercise. Keywords Nitric Oxide, Watermelon juice, Muscle Soreness, Female Taekwondo
Article
Full-text available
Background. Judo is a combat sport that involves grappling and throwing techniques, and multiple high-intensity efforts. Citrul-line Malate (CM) is a nutritional supplement used to enhance physical performance, albeit not all studies have corroborated its ergogenic properties during high-intensity exercise. Problem and aim. To the best of our knowledge, the effects of CM on judo performance has not been investigated. To fill this gap the aim of the current study was to investigate the effects of acute CM ingestion on performance in judo athletes. Methods. Using a randomized crossover and double-blinded design, 10 judo athletes ingested 8g of CM (2:1 proportion) or placebo 60 minutes prior to the execution of three bouts of the Special Judo Fitness Test (SJFT). The number of throws, the SJFT index, blood lactate concentration before and after each bout and rating of perceived exertion (RPE) after each bout were assessed. Results. Acute CM ingestion did not result in an increase of throws during three sets of the SJFT, nor in the SJFT index and RPE. The blood lactate concentration was higher in the CM condition only after the second SJFT bout, with no differences at any other time points. Conclusions. Acute CM ingestion by judo athletes did not improve performance in the SJFT.
Article
Full-text available
Citrulline malate (CM) is an increasingly common dietary supplement that is thought to enhance exercise performance by increasing nitric oxide production. The aim of this study was to investigate the effect of short term use of CM supplement on NO, blood lactate, sport performance, LDH and CK in 8 healthy trained men. In a semi-experimental study, a group of 8 people randomly selected and after attending in the first session to measure anthropometry characteristics and basic performance factors, participated in three sessions of placebo (8g dexterose) and then three sessions of supplement (8g CM). Placebo or supplement was taken 60 minute before intervention sessions. Blood samples were taken in three phase, before the 4th session and after 2nd and 3rd sessions. Then blood factors were measured by laboratory kits. Exercise performance factors were measured by pushup, cooper and rast tests. At the end, data were analyzed by repeated measure test as well as the follow-up Bonfroni test, at a significance level of 0/05. Results showed that acute CM supplementation compared to placebo, significantly reduced CK response to exercise (ϼ=0/041), increased NO response to exercise (ϼ=0/006), increased average anaerobic power (ϼ=0/037) and increased muscular endurance (ϼ=0/005). Nevertheless, acute CM supplementation compared to placebo, didn't have a significant effect on LDH and lactate response to exercise (ϼ=1), maximal anaerobic power (ϼ=0/13) and aerobic endurance (ϼ=0/08). Acute CM supplementation may improve anaerobic performance, muscle performance, vasodilation and decrease muscle damage.
Chapter
L-citrulline and L-arginine are naturally occurring amino acids that are conditionally essential in periods of stress (sepsis, intestinal pathology). Previously considered to be only intermediates in the urea acid cycle, they are now found to be effective precursors of nitric oxide that are exploited in therapeutics. Its their supplementation is likely to be used in conditions like such as erectile dysfunction, male infertility, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hyperoxic lung damage, uric acid cycle disorders, and intrauterine growth restriction. Other emerging uses are include immunonutrition, immunomodulation, cystic fibrosis, Alzheimer’s disease, multiinfarct dementia, T-cell dysfunction, as an antioxidant in conditions like sepsis, and for athletic training. Overall, citrulline (Cit) is a more effective precursor of arginine than arginine itself. Its role as a biomarker in intestinal pathology and diagnosis of early rheumatoid arthritis is of considerable interest. These nutraceuticals should be further explored in large-scale clinical trials in these areas. Another area of interest regarding Cit is the detection of an antibody to citrullinated peptides that serve as predictors for diseases, thus serving as biomarkers in various diseases. Cit has been used as a biomarker for diseases such as rheumatoid arthritis, intestinal pathology, and short bowel syndrome short bowel syndrome as biomarkers. It will either be proved or disproved as a biomarker in the future for other conditions such as parenteral nutrition in HIV patients, congenital anomalies, acute rejections in transplantations, intrauterine growth restriction, critically ill patients, acute kidney failure, and nitrosative stress (NO/NOS) and reactive nitrogen species (RNS) in conditions such as anticholinesterase poisoning and, kainic acid-induced neurotoxicity because oxidative stress increases RNS and reactive oxygen species reactive oxygen species (when the rate of adenosine triphosphate demand exceeds production), causing lipid peroxidation and DNA damage. Further studies are required in this regards.
Article
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.
Article
Full-text available
Tujuan penelitian untuk menganalisa efek akut asam amino sitrulin alami terhadap kekuatan otot. Metode penelitian dengan desain -post test controlled group design. Sampel penelitian adalah mahasiwa IKOR FIK dibagi secara acak menjadi 2 kelompok yaitu kelompok kontrol dan kelompok sitrulin. Perlakuan pada kelompok sitrulin berupa pemberian jus semangka 428 ml (600-700 g daging buah semangka) kandungan sitrulin sebesar 1 mg. sedang pada kelompok control diberikan placebo yaitu air sirup. Jus semangka ataupun air sirup diberikan 60 menit sebelum dilakukan tes kekuatan otot yaitu kekuatan otot tungkai, punggung, bahu dan genggam tangan dengan menggunakan Dynamometer. Data dianalisis diuji T-test dengan SPSS. Hasil penelitian: rerata kekuatan otot total diperoleh dari hasil penjumalahan kekuatan otot punggung, tungkai, bahu, genggam tangan. Retata kekuatan otot total kelompok kontrol 362,98±87,26 kg, kelompok perlakuan critrulline alami (semangka) 378,46±128,23, p=0,782. Tidak terdapat perbedaan efek akut asam amino sitrulin alami terhadap kekuatan otot
Article
Approximately half of the United States adult population consumes some form of dietary supplementation, with that proportion rising in physically active adults and athletes (23). One of the most commonly consumed supplements is a “pre-workout”. Pre-workouts can be categorized as any supplement ingested prior to an exercise session or sporting event with the intent of increasing mental focus, endurance, blood flow, strength, power, aerobic and anaerobic capacity, or overall perceived increase in energy level. Pre-workouts come in a variety of forms ranging from single- (e.g., caffeine) to multi-ingredients (MIPS); stimulant versus stimulant-free; and powdered, pill, or liquid form (e.g., energy drinks). While countless formulas exist, Table 1 highlights and breaks down the individual ingredients most often found in these products and how each has been demonstrated to affect the body. Despite conflicting evidence of effectiveness, pre-workouts continue to gain popularity in both recreational and athletic populations due to the anecdotal claims of increased performance, reduced recovery time, and increased perceived energy. However, along with the increased usage of these products, there is an ever-growing cause for concern pertaining to not only their effectiveness, but also safety. Therefore, this article will discuss the most common individual ingredients typically found within pre-workouts and describe “the good, the bad, and the ugly” associated with its usage.
Article
Although the ergogenic mechanisms of supplementation with citrulline malate are well known, unclear findings regarding variables of muscle strength have been recorded. Such misleading findings in the literature illustrate the need for well-conducted meta-analysis research to elucidate the possible ergogenic impact, which could have major practical consequences for athletes and recreational practitioners seeking to optimize gains in muscle strength. The objective of this systematic review was to summarize the existing literature that evaluated the effects of citrulline malate supplementation on muscle strength outcomes from resistance exercise in resistance-trained individuals. A systematic electronic search in Medline and Scientific Electronic Library Online (SciELO) was completed in August 2020 identifying randomized controlled trials investigating the effect of citrulline malate supplementation on muscle strength in resistance-trained adults. A subsequent meta-analysis was performed. The meta-analysis involved four studies and 138 assessments (69 in citrulline-malate and 69 in placebo groups). We did not observe an overall effect favoring citrulline-malate supplementation (SMD95% = 0.13 [−0.21; 0.46]). Considering the lower (SMD95% = 0.06 [−0.47; 0.60]) and upper (SMD95% = 0.17 [−0.26; 0.60]) limbs, a non-significant overall effect was identified. The mean effects were similar for “limbs” (upper vs lower) [p = 0.763]. Accordingly, our findings suggest that citrulline malate supplementation does not improve muscle strength in healthy and resistance-trained individuals (PROSPERO registration number: CRD42020159338).
Chapter
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.
Article
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.
Article
Full-text available
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
Article
Full-text available
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.
Article
Full-text available
Introduction: The consumption of sports supplements and their effects on the performance of athletes needs to be evaluated. The purpose of this study was to determine the effects of L-citrulline supplementation on nitric oxide (NO) and blood lactate in young women after a maximal exercise session. Methods & Materials: The research method was quasi-experimental with double blind design. After filling out the health questionnaire, 24 voluntary inactive young women with body mass index less than 25 kg/m2 were randomly divided into two groups (n=12) and placebo (n=12). Subjects visited the laboratory twice; in the first session, the first blood samples were taken immediately after the exercise protocol. After 5 minutes of warm-up, the subjects were performed the Bruce treadmill test protocol to time to exhaustion. Then the supplement group consumed 6 grams daily L-citrulline powder and placebo (starch powder) for one week. The second session was performed one week later in the same conditions as the first session. Immediately after the test, time to exhaustion was recorded, blood samples collected and lactate and NO plasma levels measured. Analysis of variance with repeated measures with significant level P<0.05 was used for analyzing data. Findings: The results showed that there was no significant difference between time to exhaustion, plasma levels of lactate and NO of two groups (placebo and supplement) in two sessions. Discussion & Conclusions: It seems that acute supplementation of L-citrulline has no effect on nitric NO and blood lactate in young women after a maximal exercise session.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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.
Article
Full-text available
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
Article
Full-text available
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.
Article
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.
Article
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.
Article
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.
Article
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
Carbasse, M. Essai randomisé en double aveugle contre placebo du malate de citrulline en gériatrie. Rev Gériatrie 10: 286-288, 1985.
Evaluation clinique des antiasthéniques
  • R Dahan
  • C Caulin
Dahan, R, and Caulin, C. Evaluation clinique des antiasthéniques. Thérapie 39: 547-652, 1984.
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 ammonium in fatigue. Gazette Medicale 7: 62-72, 1986.