Article

Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness

April 2010
The Journal of Strength and Conditioning Research 24(5):1215-22

Source
PubMed

Authors:

University of Limerick

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.

The use and dosage of pre-workout supplements amongst recreational athletes

Article

Full-text available

Feb 2019

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.

Acute Citrulline-Malate Supplementation Increases Total Work in Short Lower-Body Isokinetic Tasks for Recreationally Active Females During Menstruation

Article

Full-text available

Jul 2021

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.

Acute Effect of Citrulline Malate on Repetition Performance During Strength Training: A Systematic Review and Meta-Analysis

Article

Full-text available

May 2021

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.

Effects of Citrulline Malate Supplementation on Aerobic and Muscular Endurance in Young Adults Men

Article

Full-text available

Mar 2021

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.

Acute Effect of L-Citrulline Supplementation on Resistance Exercise Performance and Muscle Oxygenation in Recreationally Resistance Trained Men and Women

Article

Full-text available

Jun 2023

L-citrulline serves as a nitric oxide precursor with the potential to increase blood flow and improve resistance exercise performance, yet more research is needed to examine its ergogenic potential. To examine the effect of L-citrulline supplementation on resistance exercise performance, muscle oxygenation, and the subjective perception of effort, energy, focus, fatigue, and muscle pump, eighteen resistance-trained men (n = 11) and women (n = 7) (21.4 ± 1.8 years; 172.3 ± 7.5 cm; 76.9 ± 10.8 kg) were randomly assigned for supplementation with 8 g of L-citrulline (CIT) or a placebo (PL) in a cross-over fashion one hour prior to testing. Participants completed an isometric mid-thigh pull test (IMTP), a ballistic bench press protocol [two sets of two repetitions at 75% 1-repetition maximum (1 RM) with maximum ballistic intent], and a strength-endurance bench press protocol [five repetition-maximum sets at 75% 1RM]. Barbell velocity and power were measured via a linear position transducer during the ballistic protocol, while the repetitions completed, volume load and muscle oxygenation were quantified during the strength-endurance protocol. Subjective measures were assessed at the baseline and immediately pre- and post-exercise. Repeated measures of the analysis of variance and Bayesian equivalents revealed no significant interactions, providing evidence favoring the null hypothesis (BF10 < 1) for IMTP (PL 497.5 ± 133.6 vs. CIT 492.5 ± 129.4 N), barbell velocity, and power, and repetitions completed (PL 36.7 ± 7.2 vs. CIT 36.9 ± 8.1 repetitions). There were also no significant interactions for muscle oxygenation parameters or subjective measures except perceived fatigue. Women reported greater fatigue across all time points compared to men (~1.88 au, p = 0.045, BF10 = 0.2). The results indicate that a single 8 g dose of L-citrulline did not enhance isometric force production, muscle endurance, or muscle oxygenation parameters during the protocol implemented in this study.

A Randomized, Single-Blind, Crossover Study to Evaluate the Efficacy of a Novel Dietary Supplement Blend with L-Citrulline on Biomarkers of Hydration, Muscle Size, Affect, Inflammation, and Muscular Endurance: Original Research

Article

Full-text available

May 2023

Introduction: Citrulline is a non-essential amino acid that has previously been shown to improve athletic performance, reduce fatigue, and increase blood flow. The purpose of this study was to examine the efficacy of a novel dietary supplement blend (3D PUMP BREAKTHROUGH®, 3DPump) vs. citrulline alone on changes in muscle volume, fluid shifts, markers of hydration, inflammation, recovery, affect, and muscular endurance. Methods: Twenty-eight recreationally active subjects (6 women, 22 men) participated in a randomized, positive-controlled, single-blind, crossover study which involved 4 testing visits (2 workout visits each with a 24-hr follow-up visit). Participants ingested 3DPump (containing 3g L-citrulline, 1.2g glycerol, 165mg Amla fruit extract) or 8g of L-citrulline alone 45min before an aerobic and resistance training workout. Assessments of body fluid shifts (via BIA), markers of hydration (urine and serum osmolality, USG, hemoglobin), and appendicular girth were taken before and after exercise while markers of damage and inflammation (neutrophils, CK, ESR, MCP-1, CRP) were taken before and 24 hours after exercise, muscular endurance (reps to failure) was assessed during resistance exercises, and subjective measures of affect and recovery were taken before, after and 24 hours after exercise. Mixed factorial ANOVAs with dependent t-tests were used to compare treatments. Results: A significant interaction occurred for right thigh circumference; however post hoc testing indicated both groups increased similarly in post workout girth (p<0.05). A significant interaction occurred for ECF/TBW indicating post workout was greater than pre workout in 3DPump only (p=0.002). An interaction trend (p≤0.010) occurred for SBP and DBP indicating that 3DPump was uniquely able to significantly lower blood pressure (SBP and DBP) post workout compared to baseline and 24 hours after exercise (p<0.001). Conclusions: 3DPump, which contains 3g L-citrulline was able to provide similar effects in muscular endurance, muscle pump and other subjective feelings of affect, hydration, damage and inflammation markers, and body fluid shifts as an 8g dose of L-citrulline alone. 3DPump may have unique benefits on improving post exercise vascular tone and ECF/TBW.

Dietary Arginine and Citrulline Supplements for Cardiovascular Health and Athletic Performance: A Narrative Review

Article

Full-text available

Mar 2023

The global market for nutritional supplements (NS) is growing rapidly, and the use of L-arginine (Arg), L-citrulline (Cit), and citrulline malate (CitMal) supplements has been shown to enhance cardiovascular health and athletic performance. Over the past decade, Arg, Cit, and CitMal supplements have received considerable attention from researchers in the field of exercise nutrition, who have investigated their potential effects on hemodynamic function, endothelial function, aerobic and anaerobic capacity, strength, power, and endurance. Previous studies were reviewed to determine the potential impact of Arg, Cit, and CitMal supplements on cardiovascular health and exercise performance. By synthesizing the existing literature, the study aimed to provide insight into the possible uses and limitations of these supplements for these purposes. The results showed that both recreational and trained athletes did not see improved physical performance or increased nitric oxide (NO) synthesis with 0.075 g or 6 g doses of Arg supplement per body weight. However, 2.4 to 6 g of Cit per day for 7 to 16 days of various NSs had a positive impact, increasing NO synthesis, enhancing athletic performance indicators, and reducing feelings of exertion. The effects of an 8 g acute dose of CitMal supplement were inconsistent, and more research is needed to determine its impact on muscle endurance performance. Based on the positive effects reported in previous studies, further testing is warranted in various populations that may benefit from nutritional supplements, including aerobic and anaerobic athletes, resistance-trained individuals, elderly people, and clinical populations, to determine the impact of different doses, timing of ingestion, and long-term and acute effects of Arg, Cit, and CitMal supplements on cardiovascular health and athletic performance.

L-Citrulline Supplementation and Exercise in the Management of Sarcopenia

Article

Full-text available

Sep 2021

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.

A critical review of citrulline malate supplementation and exercise performance

Article

Full-text available

Dec 2021
EUR J APPL PHYSIOL

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.

L-Citrulline: A Non-Essential Amino Acid with Important Roles in Human Health

Article

Full-text available

Apr 2021

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.

Effect of isolated and combined ingestion of caffeine and citrulline malate on resistance exercise and jumping performance: a randomized double-blind placebo-controlled crossover study

Article

Full-text available

Jul 2023
EUR J NUTR

Purpose The aim of this study was to explore the isolated and combined effects of caffeine and citrulline malate (CitMal) on jumping performance, muscular strength, muscular endurance, and pain perception in resistance-trained participants. Methods Using a randomized and double-blind study design, 35 resistance-trained males (n = 18) and females (n = 17) completed four testing sessions following the ingestion of isolated caffeine (5 mg/kg), isolated CitMal (12 g), combined doses of caffeine and CitMal, and placebo. Supplements were ingested 60 min before performing a countermovement jump (CMJ) test (outcomes included jump height, rate of force development, peak force, and peak power), one-repetition maximum (1RM) squat and bench press, and repetitions to muscular failure in the squat and bench press with 60% of 1RM. Pain perception was evaluated following the repetitions to failure tests. The study was registered at ISRCTN (registration number: ISRCTN11694009). Results Compared to the placebo condition, isolated caffeine ingestion and co-ingestion of caffeine and CitMal significantly enhanced strength in 1RM bench press (Cohen’s d: 0.05–0.06; 2.5–2.7%), muscular endurance in the squat (d: 0.46–0.58; 18.6–18.7%) and bench press (d: 0.48–0.64; 9.3–9.5%). However, there was no significant difference between isolated caffeine ingestion and caffeine co-ingested with CitMal, and isolated CitMal supplementation did not have an ergogenic effect in any outcome. No main effect of condition was found in the analysis for CMJ-derived variables, 1RM squat and pain perception. Conclusion Caffeine ingestion appears to be ergogenic for muscular strength and muscular endurance, while adding CitMal does not seem to further enhance these effects.

The Effect of Acute Pre-Workout Supplement Ingestion on Basketball-Specific Performance of Well-Trained Athletes

Article

Full-text available

May 2023

A pre-workout supplement’s (PWS; 200 mg caffeine, 3.3 g creatine monohydrate, 3.2 g β-alanine, 6 g citrulline malate and 5 g branched chained amino acid (BCAA) per dose) acute effects on the alactic (jumping, sprinting, agility), lactic (Running-Based Anaerobic Sprint Test, RAST) and aerobic performance (Yo-Yo Intermittent Recovery Test Level 1, Yo-Yo IRL1 VO2max) of well-trained basketball players was investigated in this double-blind placebo-controlled study. Thirty players (age 18–31 years, height 166–195 cm, weight 70.2–116.7 kg, body fat 10.6–26.4%) were allocated to pre-workout (PWS, n = 15) or placebo (PL, n = 15) groups. Half of the participants in each group performed the evaluations without PWS or PL, while the rest consumed PWS or PL 30 min before the assessments (1st trial) and vice versa (2nd trial). Significant improvements in counter-movement jump (CMJ) (PWS: 4.3 ± 2.1%; PL: 1.2 ± 1.0%), agility (PWS: −2.9 ± 1.8%; PL: 1.8 ± 1.7%), RAST average (PWS: 18.3 ± 9.1%; PL: −2.2 ± 2.0%), minimum power (PWS: 13.7 ± 8.9%; PL: −7.5 ± 5.9%), and fatigue index (PWS: −25.0 ± 0.9%; PL: −4.6 ± 0.6%) were observed in the PWS group vs. the PL group (p < 0.05). No differences were found regarding sprinting, aerobic performance, and blood lactate concentrations. Thus, although players’ alactic and lactic anaerobic performance could be improved, peak power, sprinting and aerobic performance are not.

Molecular Profiling of Athletes Performing High-Intensity Exercises in Extreme Environments

Article

Full-text available

Feb 2023

The aim of this study was to determine the influence of high-intensity training under extreme conditions (T = 40 °C) on the metabolism and immunological reactions of athletes. Male triathletes (n = 11) with a high level of sports training performed load testing to failure (17 ± 2.7 min) and maximum oxygen consumption (64.1 ± 6.4 mL/min/kg). Blood plasma samples were collected before and immediately after exercise. Mass spectrometric metabolomic analysis identified 30 metabolites and 6 hormones in the plasma, of which 21 and 4 changed after exercise, respectively. Changes in the intermediate products of tricarboxylic and amino acids were observed (FC > 1.5) after exercise. The obtained data can be associated with the effect of physical activity on metabolism in athletes. Therefore, constant monitoring of the biochemical parameters of athletes can help coaches identify individual shortcomings in a timely manner and track changes, especially as the volume of training increases. In addition, it was revealed that the immunological reaction (manifestation of a hyperactive reaction to food components) is personalized in nature. Therefore, it is important for coaches and sports doctors to analyze and control the eating behavior of athletes to identify food intolerances or food allergies in a timely manner and develop an individual elimination diet.

Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature

Article

Full-text available

Jan 2023

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

Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults

Article

Full-text available

Dec 2022
AMINO ACIDS

Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers, but the safe supplementation levels of these compounds are unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults ( n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2, and 12 g/day) or citrulline (6, 12, 18, and 24 g/day) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality, and mental self-assessment. In the ornithine hydrochloride supplementation group, minor increase in plasma aspartic acid and glutamic acid concentrations was observed at the highest intake dosages. In the citrulline supplementation group, minor changes in laboratory data for serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, arginine, and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4 weeks), respectively.

Dietary supplements for improving nitric-oxide synthesis

Article

Full-text available

Oct 2022

Aysha Kiani

Nitric oxide (NO) is an essential component of the human body, involved in blood vessel dilation, stimulation of hormone release, signaling and regulation of neurotransmission. Nitric oxide is synthesized by nitric-oxide-synthase-dependent and -independent pathways. Nitric oxide supplementation improves cardiac health, enhances performance during exercise, reduces high blood pressure during pregnancy, reduces erectile dysfunction and improves healing processes and respiratory response. Nitric-oxide-associated benefits are mostly apparent in untrained or moderately trained individuals. L-arginine and L-citrulline supplementation contributes to nitric oxide levels because L-arginine is directly involved in NO synthesis, whereas L-citrulline acts as an L-arginine precursor that is further converted to NO by a reaction catalyzed by NO synthase. L-arginine supplements increase respiratory response and enhance performance during exercise, while L-citrulline with malate and other molecules increase working capacity. Various studies involving beetroot juice have reported a significant increase in plasma nitrite levels, regarded as markers of NO, after intake of beetroot juice. Although NO supplementation may have mild to moderate side-effects, using smaller or divided doses could avoid some of these side-effects. Since nitric oxide supplementation may worsen certain health conditions and may interfere with certain medicines, it should only be taken under medical supervision.

Essential Amino Acid Ingestion Facilitates Leucine Retention and Attenuates Myofibrillar Protein Breakdown following Bodyweight Resistance Exercise in Young Adults in a Home-Based Setting

Article

Full-text available

Aug 2022

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.

The Effects of Consuming Amino Acids L-Arginine, L-Citrulline (and Their Combination) as a Beverage or Powder, on Athletic and Physical Performance: A Systematic Review

Article

Full-text available

Aug 2022

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.

Subchronic tolerance trials of graded oral supplementation with ornithine hydrochloride or citrulline in healthy adults

Preprint

Full-text available

Jun 2022

Ornithine and citrulline are amino acids used in dietary supplements and nutritional products consumed by healthy consumers; however, the safe intake level of ornithine or citrulline supplementation is unknown. The objective of this study was to conduct two 4-week clinical trials to evaluate the safety and tolerability of graded dosages of oral ornithine (as hydrochloride) and citrulline. Healthy male adults (n = 60, age 41.4 ± 1.5 years) completed graded dosages of either ornithine hydrochloride (3.2, 6, 9.2 and 12 g/d) or citrulline (6, 12, 18 and 24 g/d) supplement for 4 weeks with 2-week wash-out periods in between. Primary outcomes included vitals, a broad spectrum of circulating biochemical analytes, body weight, sleep quality and mental self-assessment. In the ornithine hydrochloride supplementation group, minor changes in plasma aspartic acid, glutamic acid concentrations and increased its plasma concentration at highest intake dosages were observed. In the citrulline supplementation group minor changes in laboratory data of serum lactate dehydrogenase and plasma amino acid concentration of lysine, methionine, threonine, aspartic acid, glutamic acid, glutamine and ornithine, as well as arginine and citrulline itself were measured. No other changes in measured parameters were observed, and study subjects tolerated 4-week-long oral supplementation of ornithine hydrochloride or citrulline without treatment-related adverse events. A clinical, no-observed-adverse-effect-level (NOAEL) of ornithine hydrochloride and citrulline supplementation in healthy adult males was determined to be 12 g/day and 24 g/day (4weeks), respectively.

The influence of caffeinated and non-caffeinated multi-ingredient pre-workout supplements on resistance exercise performance and subjective outcomes

Article

Full-text available

Apr 2022
Sports Nutr Rev J

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.

Güncel Verilerle Vücut Geliştirme Sporcularında Beslenme (Nutrition in Bodybuilding Athletes with Current Data)

Article

Full-text available

Apr 2022

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.

Long-Term Combined Effects of Citrulline and Nitrate-Rich Beetroot Extract Supplementation on Recovery Status in Trained Male Triathletes: A Randomized, Double-Blind, Placebo-Controlled Trial

Article

Full-text available

Jan 2022

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.

Long-Term Combined Effects of Citrulline and Nitrate-Rich Beetroot Extract Supplementation on Recovery Status in Trained Male Triathletes: A Randomized, Double-Blind, Placebo-Controlled Trial

Article

Full-text available

Jan 2022

"Increasing Exercise Work Capacity via Nutritional Intervention by Administration of Mitochondrial Augmentation Therapy (MAT) Associated Nutrients"

Article

Dec 2019

Frank Merante

Combined Effects of Citrulline Plus Nitrate-Rich Beetroot Extract Co-Supplementation on Maximal and Endurance-Strength and Aerobic Power in Trained Male Triathletes: A Randomized Double-Blind, Placebo-Controlled Trial

Article

Full-text available

Dec 2021

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.

Contrast-enhanced ultrasound for determining muscular perfusion after oral intake of L-citrulline, L-arginine, and galloylated epicatechines: A study protocol

Article

Full-text available

Oct 2020
MEDICINE

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.

Supplementation of 100% Flesh Watermelon [Citrullus lanatus (Thunb.) Matsum. and Nakai] Juice Improves Swimming Performance in Rats

Article

Full-text available

Mar 2019

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.

Konzept für nachhaltige evidenz-basierte Sportnahrungsprodukte (full-text)

Article

Full-text available

Jul 2020

Tristan Nolting

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.

Maximal Number of Repetitions at Percentages of the One Repetition Maximum: A Meta-Regression and Moderator Analysis of Sex, Age, Training Status, and Exercise

Article

Full-text available

Oct 2023
SPORTS MED

The maximal number of repetitions that can be completed at various percentages of the one repetition maximum (1RM) [REPS ~ %1RM relationship] is foundational knowledge in resistance exercise programming. The current REPS ~ %1RM relationship is based on few studies and has not incorporated uncertainty into estimations or accounted for between-individuals variation. Therefore, we conducted a meta-regression to estimate the mean and between-individuals standard deviation of the number of repetitions that can be completed at various percentages of 1RM. We also explored if the REPS ~ %1RM relationship is moderated by sex, age, training status, and/or exercise. A total of 952 repetitions-to-failure tests, completed by 7289 individuals in 452 groups from 269 studies, were identified. Study groups were predominantly male (66%), healthy (97%), < 59 years of age (92%), and resistance trained (60%). The bench press (42%) and leg press (14%) were the most commonly studied exercises. The REPS ~ %1RM relationship for mean repetitions and standard deviation of repetitions were best described using natural cubic splines and a linear model, respectively, with mean and standard deviation for repetitions decreasing with increasing %1RM. More repetitions were evident in the leg press than bench press across the loading spectrum , thus separate REPS ~ %1RM tables were developed for these two exercises. Analysis of moderators suggested little influences of sex, age, or training status on the REPS ~ %1RM relationship, thus the general main model REPS ~ %1RM table can be applied to all individuals and to all exercises other than the bench press and leg press. More data are needed to develop REPS ~ %1RM tables for other exercises.

Acute Citrulline Malate Supplementation Does Not Improve Anaerobic Capacity in Healthy Young Adults: A Pilot Study: Original Research

Article

Full-text available

Jun 2023

Introduction: The aim of this study was to investigate the potential ergogenic properties of citrulline malate (CM) during a 300-yard shuttle run. Methods: Thirty-two recreationally active subjects (M=24; F=8) participated in a randomized, placebo-controlled, double-blind study. Participants completed baseline testing which consisted of two 300-yard shuttle runs for time. Immediately post-exercise blood lactate was taken via a finger stick. An average of the two trials (time in seconds and blood lactate in mmols/L) were recorded and used for analysis. One week later, participants were randomly assigned to one of four groups (control, placebo, 4 grams CM, or 8 grams of CM) and repeated the same exercise protocol. Data were analyzed using a two-way repeated measures analysis of variance. Results: No main effect for shuttle-run time (F=0.149; p=0.702) or shuttle run time by group interaction was observed (F=0.672; p=0.576). There was a main effect for blood lactate (F=17.079; p<0.001) with lactate accumulation during the pre-test (11.64±2.83 mmol/L) being significantly greater compared to the post-treatment lactate levels (9.65±1.94 mmol/L). There was no blood lactate by group interaction (F=0.867; p=0.47). Conclusions: These results indicated that acute CM supplementation did not improve anaerobic performance in healthy, young adults.

Effects of branched chain amino acids, l-citrulline, and alpha-glycerylphosphorylcholine supplementation on exercise performance in trained cyclists: a randomized crossover trial

Article

May 2023
Sports Nutr Rev J

Renee Harrington

Background: Nutrition plays a key role in training and athletic performance and dietary supplements can make a small, but potentially valuable, contribution to achieving peak athletic performance. This study is the first to investigate the effects of supplementation from the combination of BCAAs, L-citrulline, and A-GPC on exercise performance. Methods: In this randomized, double-blind, crossover study 30 male trained cyclists (age: 43.7 ± 8.5 years) completed a 20 km cycling time trial (TT) test and a high intensity endurance cycling (HIEC) test following a 7-day supplementation period with either a supplement containing 8 g BCAAs, 6 g L-citrulline, and 300 mg A-GPC or a placebo (15 g maltodextrin). For each trial, mean values for time to completion, peak and average power output, OMNI rating of perceived exertion, and visual analogue scale (VAS) responses on perceived exertion were computed for the 20 km TT test. Mean values for time to fatigue and VAS responses on perceived exertion were computed for the HIEC test. Procedures for dietary intake and exercise patterns were implemented to achieve consistency throughout the study period. Results: There was a significant increase (p = .003) in peak power in the 20 km TT (354.27 ± 87.88 and 321.67 ± 63.65, for supplement and placebo trials, respectively) and a significant increase (p = .001) in time to fatigue in the HIEC test (0:19:49 ± 0:11:13 min and 0:14:33 ± 0:09:59 min, for supplement and placebo trials, respectively) with the test supplement compared to the placebo. With the test supplement, there was an average increase in TT peak power of 11% and an average increase in time to fatigue of 36.2% in the HIEC test compared to the placebo. There was no significant improvement in time to completion, average power, OMNI rating of perceived exertion, or VAS responses on perceived exertion in the TT test and no significant improvement in VAS measures of perceived exertion in the HIEC test. Conclusions: The combination of BCAAs, L-citrulline, and A-GPC used in this study improves cycling performance and may be useful for individuals seeking to improve athletic performance, particularly in disciplines requiring lower body muscular strength and endurance.

Effects of citrulline on endurance performance in young healthy adults: a systematic review and meta-analysis

Article

May 2023
Sports Nutr Rev J

Background Citrulline is a popular dietary supplement, primarily thought to exert ergogenic effects on exercise performance through the enhancement of nitric oxide (NO) synthesis and ammonia buffering. However, recent findings surrounding citrulline’s effect on endurance performance have been inconsistent. A systematic review and meta-analysis of the relevant literature have yet to be undertaken. Aim To determine if acute ingestion of citrulline has an ergogenic effect on endurance performance in young healthy adults. Methods A systematic search of three databases was undertaken to find peer-reviewed randomized controlled trials (RCTs) published in English investigating the effects of citrulline supplementation on endurance performance in young healthy adults. Two independent investigators completed a three-phased screening procedure against pre-determined eligibility criteria. Included studies evaluated loading or bolus dosage regimes of citrulline in participants aged 18 or over that were at least recreationally active. Outcome measures focused on time-to-completion (TTC) or time-to-exhaustion (TTE) in continuous submaximal intensity exercise. Cochrane’s Risk of Bias 2 (RoB 2) tool was used to assess the risk of bias in individual studies. Meta-analysis was conducted using a fixed-effects model to pool the weighted estimate of standardized mean differences (SMD) across studies. A chi-squared test assessed heterogeneity between studies. This review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results Nine studies (n = 158 participants) met the eligibility criteria; five reported TTE outcomes (I² = 0%, χ² = 0.37, df = 4, P = 0.99) and four reported TTC outcomes (I² = 0%, χ² = 0.46, df = 3, P = 0.93), both with a low between-study heterogeneity. The results of the meta-analyses showed no significant difference in the endurance performance measures, TTE (pooled SMD = 0.03 [−0.27, 0.33]) and TTC (pooled SMD = −0.07 [−0.50, 0.15]), after acute ingestion of citrulline supplementation or a control in young healthy adults. Discussion The current evidence suggests no significant benefit of citrulline supplementation for endurance performance. However, the small evidence base requires further research to fully evaluate this topic. Recommendations include a focus on female populations; higher continuous doses of citrulline over seven days; and TTC outcome measures over longer distances to simulate competition.

The Effects of Protein and Supplements on Sarcopenia in Human Clinical Studies: How Older Adults Should Consume Protein and Supplements

Article

Full-text available

Oct 2022

Young Jin Jang

Sarcopenia is a condition in which muscle mass, strength, and performance decrease with age. It is associated with chronic diseases such as diabetes, cardiovascular disease, and hypertension, and contributes to an increase in mortality. Because managing sarcopenia is critical for maintaining good health and quality of life for the elderly, the condition has sparked concern among many researchers. To counteract sarcopenia, intake of protein is an important factor, while a lack of either protein or vitamin D is a major cause of sarcopenia. In addition, essential amino acids, leucine, βhydroxy β-methylbutyrate (HMB), creatine, and citrulline are used as supplements for muscle health and are suggested as alternatives for controlling sarcopenia. There are many studies on such proteins and supplements, but it is necessary to actually organize the types, amounts, and methods by which proteins and supplements should be consumed to inhibit sarcopenia. In this study, the efficacy of proteins and supplements for controlling sarcopenia according to human clinical studies is summarized to provide suggestions about how the elderly may consume proteins, amino acids, and other supplements.

Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition: Implications for Malabsorption and Nutrition

Chapter

Oct 2022

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.

Effect of citrulline malate supplementation on muscle function and bioenergetics during short-term repeated bouts of fatiguing exercise

Article

Oct 2022
J SPORT SCI

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.

A comprehensive review on the watermelon phytochemical profile and their bioactive and therapeutic effects

Article

Full-text available

Aug 2022

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.

Citrulline as a Marker of Villous Abnormality and Implications for Diet and Nutrition: Implications for Malabsorption and Nutrition

Chapter

Jan 2022

Nutritional Integrative Approaches for the Management of Sarcopenia

Article

Full-text available

Jan 2022

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

Acute and Chronic Citrulline Malate Supplementation on Muscle Contractile Properties and Fatigue Rate of the Quadriceps

Article

Sep 2021

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.

Amino Acids and Their Metabolites for Improving Human Exercising Performance

Chapter

Jul 2021
ADV EXP MED BIOL

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.

Effects of Citrulline Malate Supplementation on Muscle Strength in Resistance-Trained Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Article

Jun 2021

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).

Pre-workout Supplementation: The Good, The Bad, and The Ugly

Article

Jun 2021

Ronald Snarr

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.

Efek Akut Pemberian Asam Amino Citrulin Alami Terhadap Kekuatan Otot

Article

Full-text available

Dec 2020

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

Effects of a L-citrulline supplementation on nitric oxide and blood lactate in young women after a maximum exercise session

Article

Full-text available

Nov 2020

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.

Arginine and citrulline as nutraceuticals: efficacy and safety in diseases

Chapter

Jan 2021

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.

‫Effects of acute citrulline malate supplementation on NO, lactate, sport performance and some markers of muscle damage in healthy trained men

Article

Full-text available

May 2020

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.

Acute citrulline-malate ingestion does not enhance performance in judo athletes

Article

Full-text available

Jan 2021

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.

The effect of six weeks’ watermelon juice on nitric oxide and exercise performance in elite female taekwondo

Article

Full-text available

Dec 2020

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

Mitochondrial medicine therapies: rationale, evidence, and dosing guidelines

Article

Oct 2020

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.

Nutritional interventions for reducing the signs and symptoms of exercise-induced muscle damage and accelerate recovery in athletes: current knowledge, practical application and future perspectives

Article

Full-text available

Sep 2020
EUR J APPL PHYSIOL

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.

Antioxidative defence alterations in skeletal muscle during prolonged acclimation to cold: Role of L-arginine/NO-producing pathway

Article

Full-text available

Feb 2008

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.

Use of a microbial model for the determination of drug effects on cell metabolism and energetics: Study of citrulline-malate

Article

Full-text available

Jan 1992

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.

Citrulline/malate promotes aerobic energy production in human exercising muscle

Article

Full-text available

Sep 2002

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.

Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection

Article

Full-text available

Dec 2004

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.

L-Citrulline and L-arginine supplementation retards the progression of high-cholesterol-diet-induced atherosclerosis in rabbits.

Article

Full-text available

Oct 2005

The objective of this study was to evaluate the influence of ingested l-arginine, l-citrulline, and antioxidants (vitamins C and E) on the progression of atherosclerosis in rabbits fed a high-cholesterol diet. The fatty diet caused a marked impairment of endothelium-dependent vasorelaxation in isolated thoracic aorta and blood flow in rabbit ear artery in vivo, the development of atheromatous lesions and increased superoxide anion production in thoracic aorta, and increased oxidation-sensitive gene expression [Elk-1 and phosphorylated cAMP response element-binding protein]. Rabbits were treated orally for 12 weeks with l-arginine, l-citrulline, and/or antioxidants. l-arginine plus l-citrulline, either alone or in combination with antioxidants, caused a marked improvement in endothelium-dependent vasorelaxation and blood flow, dramatic regression in atheromatous lesions, and decrease in superoxide production and oxidation-sensitive gene expression. These therapeutic effects were associated with concomitant increases in aortic endothelial NO synthase expression and plasma [Formula] and cGMP levels. These observations indicate that ingestion of certain NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can abrogate the state of oxidative stress and reverse the progression of atherosclerosis. This approach may have clinical utility in the treatment of atherosclerosis in humans. • antioxidant • nitric oxide • amino acids • endothelial nitric oxide synthase

Citrulline and the gut

Article

Full-text available

Sep 2007

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.

Muscular Exercise, Lactic Acid, and the Supply and Utilisation of Oxygen

Article

Jan 1924

Citrulline malate limits increase in muscle fatigue induced by bacterial endoto×ins

Article

Mar 1997
CAN J PHYSIOL PHARM

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.

Relationship between pyruvate carboxylation and citrulline synthesis in rat liver mitochondria: The effect of ammonia and energy

Article

Feb 1979
Int J Biochem

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.

Activity of citrulline malate on acid-base balance and blood ammonia and amino acid levels. Study in the animal and in man

Article

Jul 1991

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.

Ammonia production in muscle and other tissues: The purine nucleotide cycle

Article

May 1972

J.M. Lowenstein

Citrulline malate limits increase in muscle fatigue induced by bacterial endotoxins

Article

Apr 1997

Essai randomisé en double aveugle contre placebo du malate de citrulline en gériatrie

Jan 1985
286-288

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

Jan 1984
THERAPIE
547-652

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

Jan 1986
62-72

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.

Citrulline Malate Enhances Athletic Anaerobic Performance and Relieves Muscle Soreness

Abstract

No full-text available

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