A critical review of citrulline malate supplementation and exercise performance

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 the most common approach, 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.

Effect of one-week supplementation of Citrulline-malate, L-arginine and their combination on CK, LDH and CRP levels in male wrestlers following simulated wrestling test

Background: The aim of this research was to evaluate the effect of one-week supplementation of citrulline-malate, L-arginine and their combination on aerobic and anaerobic powers, CK, LDH and CRP levels in male wrestlers. Methods: In this experimental study, 40 male wrestlers (aged 19-25 years; weight 60-90 kg; body fat percent 12-20%) in a randomized and double-blind design were divided in four equal citrulline-malate (Cit; 4g/days), L-arginine (Arg; 4g/days), their combination (2g/days Arg + 2g/days Cit) and placebo (dextrose; P) group. Before and after supplementation one week period, all subjects were participated in a competition like wrestling. Each test consisted of two 3 min periods of arm-cranking at maximal executable cadence against resistance of 0.1 kg ∙ kg−1 body mass interspersed with 30-s recovery periods between consecutive tests. Blood samples were obtained in the 4 phases: one hour before and 5 min after two competitions like wrestling protocols. Creatine kinase (CK), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were analyzed. Change any of the parameters (mean and standard deviation) of four stages repeated ANOVA and post hoc tests. The significance level was set at p<0.05. Results: Based on the present results, the Cit and Arg + Cit supplementation attenuated the exercise-induced increase in response of CK (p<0.05). However, the Arg supplementation had not any significant effect on the exercise-induced increase response of serum CK. Also, the Arg, Cit and Arg + Cit supplementation had not any significant effect on the exercise-induced increase response of total serum LDH and CRP. Conclusion: Based on the present results, it can be concluded that the one week citrulline-malate with L-arginine supplementation is more effective than the citrulline-malate or L-arginine supplementation to overcome the exercise-induced adverse responses in some muscle injury parameters. Therefore, combination of citrulline-malate and L-arginine supplementation is recommended to reduce exercise-induced adverse consequences.

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

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.

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

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

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.

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

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.

Acute Citrulline-Malate Oral Supplementation does not Improve Post-Aerobic-Exercise Autonomic Response in Normotensive and Hypertensive Subjects: a Pilot Randomized Controlled Study

The present study was designed to investigate whether citrulline malate (CM) supplementation might influence post-aerobic-exercise autonomic response in normotensive and hypertensive subjects. Forty individuals (20 normotensives and 20 hypertensives) were randomly assigned to one of the four experimental groups (normotensive-placebo [NP], normotensive-CM [NC], hypertensive-placebo [HP], and hypertensive-CM [HC]). The participants ingested CM (6 g) or placebo dissolved in water (100 ml) 120 min before the exercise session. The exercise session was conducted on a treadmill and consisted of 40 min of running/walking at 60-70% HRreserve. The heart rate variability (HRV) was recorded continuously for 60 min post-exercise. In normotensive subjects at “post-30”, LF increased and HF decreased after the CM supplementation (16% [P=0.041] and -32% [P=0.037], respectively). No significant differences were found in “pre”, “post-30” and “post-60” considering the pooled (NP, NC, HP, and HC) z-scores for time and frequency HRV domains. These results suggest that a single dose of CM supplementation does not promote significant effects on post-exercise autonomic modulation in normotensive and hypertensive subjects. Keywords: Autonomic Nervous System. Citrulline Malate. Hypertension. Exercise. ResumoO presente estudo foi desenvolvido para investigar se a suplementação de citrulina malato (CM) pode influenciar a resposta autonômica após exercício aeróbico em indivíduos normotensos e hipertensos. Quarenta indivíduos (20 normotensos e 20 hipertensos) foram aleatoriamente designados para um dos quatro grupos experimentais (normotenso-placebo [NP], normotenso-CM [NC], hipertenso-placebo [HP] e hipertenso-placebo [HP] e hipertenso-CM [HC]). Os participantes ingeriram CM (6 g) ou placebo dissolvido em água (100 ml) 120 minutos antes da sessão de exercícios. A sessão de exercícios foi realizada em esteira e consistiu em 40 minutos de corrida/caminhada a 60-70% da FCres. A variabilidade da frequência cardíaca (VFC) foi registrada continuamente por 60 minutos após o exercício. Nos normotensos “pós-30”, houve aumento para LF e redução para HF após a suplementação de CM (16% [P=0,041] e -32% [P=0,037], respectivamente). Não foram encontradas diferenças significativas nos momentos "pré", "pós-30" e "pós-60", considerando os escores-z combinados (NP, NC, HP e HC), tanto para os indicadores de domínio do tempo, quando para os de domínio da frequência. Estes resultados sugerem que uma dose única de suplementação de CM não promove efeitos significativos na modulação autonômica após exercício em indivíduos normotensos e hipertensos. Palavras-chave: Sistema Nervoso Autônomo. Citrulina Malato. Hipertensão, Exercício.