Does the Production of Lactate and H+ Result in Doms Peer Review
J Sport Health Sci. 2020 Dec; 9(6): 553–561.
Effect of citrulline on post-exercise rating of perceived exertion, muscle soreness, and claret lactate levels: A systematic review and meta-analysis
Hye Chang Rhim
aHigher of Medicine, Korea University, Seoul 02842, South korea
Sung Jong Kim
aCollege of Medicine, Korea University, Seoul 02842, Democracy of Korea
Precious stone Park
aCollege of Medicine, Korea University, Seoul 02842, South korea
Ki-Mo Jang
aCollege of Medicine, Korea Academy, Seoul 02842, Republic of Korea
bDepartment of Orthopaedic Surgery, Anam Hospital, Korea University Higher of Medicine, Seoul 02841, Republic of Korea
Received 2019 Jun 11; Revised 2019 Aug 4; Accustomed 2019 Dec 30.
Abstract
Background
Citrulline is one of the non-essential amino acids that is idea to better exercise performance and reduce post-exercise musculus soreness. We conducted a systematic review and meta-analysis to decide the effect of citrulline supplements on the mail service-exercise rating of perceived exertion (RPE), musculus soreness, and claret lactate levels.
Methods
A random effects model was used to calculate the effect sizes due to the high variability in the study design and study populations of the articles included. A systematic search of PubMed, Spider web of Science, and ClinicalTrials.gov was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving healthy individuals and that investigated the acute effect of citrulline supplements on RPE, musculus soreness, and blood lactate levels. The supplementation time frame was limited to 2 h before practice. The types and number of participants, types of exercise tests performed, supplementation protocols for L-citrulline or citrulline malate, and primary (RPE and musculus soreness) and secondary (blood lactate level) study outcomes were extracted from the identified studies.
Results
The analysis included 13 eligible articles including a full of 206 participants. The nigh frequent dosage used in the studies was 8 grand of citrulline malate. Citrulline supplementation significantly reduced RPE (northward = 7, p = 0.03) and muscle soreness 24-h and 48-h after post-exercise (n = 7, p = 0.04; due north = 6, p = 0.25, respectively). However, citrulline supplementation did not significantly reduce musculus soreness 72-h post-do (n = iv, p = 0.62) or lower blood lactate levels (n = 8, p = 0.17).
Conclusion
Citrulline supplements significantly reduced post-exercise RPE and muscle soreness without affecting claret lactate levels.
Keywords: Amino acids, Dietary supplements, Ergogenic aid, Nitric oxide, Watermelon juice
Graphical abstract

i. Introduction
L-citrulline is one of the non-essential amino acids mainly found in watermelon (Citrullus vulgaris).1 Supplements containing L-citrulline have been manufactured in different forms, including pure 50-citrulline, watermelon juice, and citrulline malate (CM), and their effects have been studied under clinical and applied exercise settings.2, iii, 4, v, 6, seven, 8, ix, 10, xi, 12, 13, 14 Recently, Trexler et al.15 published a meta-analysis evaluating the acute effect of citrulline supplementation on high-intensity strength and power functioning. Co-ordinate to the meta-assay, citrulline supplementation significantly enhanced the performance of high-intensity and power exercises.15 Other contempo studies accept investigated the consequence of citrulline supplements on the rating of perceived exertion (RPE) and muscle soreness, as well as exercise performance.2, three, iv, v, 6, 7, viii, 9, x, eleven, 12, thirteen, 14
The potential use of citrulline supplements to salvage fatigue or muscle soreness is based on 2 hypothetical mechanisms. Offset, Fifty-citrulline, 1 of the amino acids involved in the ureagenesis cycle, may facilitate the clearance of ammonia. Ammonia plays an important role in fatigue considering its intracellular aggregating favors glycolysis while inhibiting the aerobic utiliaztion of pyruvate.11,16 This modified energy metabolism results in the formation of lactate, which may contribute to fatigue.17,xviii During high-intensity practise, the rate of glycolysis is increased, and anaerobic glycolysis also leads to accumulation of blood lactate.xviii The synthesis of lactate may exist diminished via L-citrulline supplementation because information technology buffers ammonia through the urea cycle, thereby enhancing the aerobic utilization of pyruvate.19 Second, L-citrulline in the kidney tin be converted to L-arginine,20 which is a substrate for nitric oxide synthase (NOS).21 Different L-arginine, L-citrulline bypasses the intestinal or hepatic emptying.22 Oral 50-citrulline supplementation tin can increase plasma L-arginine concentrations and amplify NO-dependent signaling in a dose-dependent manner.23 Indeed, previous studies have shown that citrulline supplementation increased claret NO levels24 and plasma arginine availability25 for NO synthesis. NO is non only a powerful vasodilator, but also a regulator of multiple physiological functions of skeletal muscles, such as glucose uptake and oxidation, mitochondriogenesis, contractile functions, and muscle repair, via satellite jail cell activation and the release of myotrophic factors.26, 27, 28 Considering NO is involved in musculus contractile function and repair, enhanced NO production through citrulline supplementation may decrease muscle soreness.
Although additional studies are required to elucidate the mechanisms of action underlying the efficacy of citrulline supplementation, citrulline supplements have attracted researchers and sports coaches who are constantly looking for effective ways to decrease fatigue and muscle soreness after exercise. Therefore, the chief aim of this meta-analysis and systematic review was to evaluate the effect of citrulline supplements on the post-practice RPE and musculus soreness. Since lactate accumulation has been associated with muscle fatigue and soreness, the secondary outcome was to assess the effect of citrulline supplements on claret lactate levels subsequently do.
two. Methods
2.1. Search strategy and quality assessment
A systematic literature search was performed using PubMed and Web of Scientific discipline databases to identify manufactures published up to April 2019 that evaluated the furnishings of Fifty-citrulline or CM on the mail-exercise RPE, muscle soreness, and blood lactate levels. The literature search process followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.29 Various combinations of keywords such as "citrulline", "exercise", "strength", "ability", "operation", "athlete", "muscle", "fatigue", "recovery", "exertion", "soreness", "lactate", and "lactic acrid" were used with "AND" or "OR" commands. A transmission search was also performed using reference lists of identified relevant manufactures to ensure that all appropriate studies were included in the analysis. Afterwards deleting indistinguishable articles, ii researchers (HCR and SJK) individually assessed each study based on predefined inclusion and exclusion criteria, every bit described in Section 2.2, to select the eligible articles. The quality of each article was assessed based on the Cochrane risk of bias tool for randomized controlled trials.30 Unpublished clinical trials were besides searched using the term "citrulline" on ClinicalTrials.gov to identify any unpublished trials.
ii.2. Study selection criteria
The study inclusion criteria were: (1) randomized controlled trials of healthy individuals; (2) studies that investigated the result of 50-citrulline or CM; (3) placebo-controlled and blinded trials; (4) studies published in English language and accessible online through PubMed and Web of Scientific discipline search engines or unpublished studies with results reported at ClinicalTrials.gov; (5) reports of changes in RPE, muscle soreness, or blood lactate level equally an outcome, regardless of the nature of the exercise; and (6) L-citrulline or CM ingestion within 2 h of the exercise program. The supplementation ingestion fourth dimension frame was limited to 2 h earlier exercise because information technology is known that plasma L-arginine peaks after an oral dose of Fifty-citrulline within 1 h to 2 h later on ingestion.31 Hence, studies involving supplementation >2 h before practise likely missed the effect of acute supplementation of citrulline on muscle fatigue or soreness and thus were excluded from our analysis.
2.3. Data extraction and outcome measures
The characteristics of the studies, such as types and number of participants, types of practice tests performed, supplementation protocols for L-citrulline or CM, and primary (RPE and muscle soreness) or secondary (claret lactate level) outcomes were extracted manually for each article. The means and SD of the RPE, muscle soreness, and claret lactate levels for the citrulline supplementation group and the placebo grouping were determined from the original data included in the article. If the data were presented only graphically, they were read via WebPlotDigitizer.32,33 WebPlotDigitizer is a web-based program that allows conversion of graphical information to numerical information through manual plotting.33 Although WebPlotDigitizer relies on transmission plotting, the intercoder reliability is high. WebPlotDigitizer has been used in previous systematic reviews and meta-analyses, including those pertaining to nutritional supplements.33, 34, 35
2.4. Statistical analysis
The standardized mean difference was used as a measure of effect size. The standardized hateful deviation was calculated by diving the divergence between the mean outcome of the citrulline supplementation group and that of the placebo grouping past the pooled SD, reflecting the size of the effect of the citrulline intervention relative to the variability observed in each study. Due to the high variability in study designs and study populations beyond articles included in the assay, a random effects meta-analysis was carried out using the calculated effect sizes. Cochrane Q and I 2 statistics were calculated to assess the heterogeneity among the manufactures. Outliers were identified through Melt's distance, and sensitivity analysis was carried out to examine the impact of outliers on the meta-analysis. Publication bias was assessed using the Begg's rank correlation test and the Egger'southward regression disproportion test. All analyses were carried out using R-3.5.three software (R Foundation for Statistical Computing, Vienna, Austria).
three. Results
3.1. Eligible studies and characteristics of included studies
The initial search of published articles yielded a total of 172 manufactures. Later on deleting the duplicate articles, 85 articles remained. Of these 85 articles, 60 irrelevant articles were excluded based on their titles. Based on the study choice criteria, 11 studies identified in the search qualified for the meta-analysis. A full of 2 additional articles were identified through the review of reference lists of manufactures. No unpublished clinical trials were identified on ClinicalTrials.gov. Thus, 13 studies were included in our meta-analysis (Fig. one). A total of 7 studies examined RPE immediately post-exercise. A total of 4 studies measured subjective muscle soreness 24 h, 48 h, and 72 h post-practise, and 3 studies analyzed subjective muscle soreness 24 h and 48 h post-exercise. A full of eight studies measured blood lactate levels before and immediately after practice.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram of study option process and results. RCT = randomized controlled trial.
A total of xiii studies comprising 206 participants met the inclusion criteria.2, three, 4, 5, 6, 7, 8, 9, x, xi, 12, xiii, fourteen The sample size of the studies ranged from seven to 41, with an boilerplate of 16 participants. All participants were young and salubrious and were recreationally active or resistance trained. In terms of age, the majority of the participants were in their 20 due south. The dosage of CM used in the studies ranged from 6 g to 12 g; for L-citrulline, the dosage ranged from iii grand to 6 chiliad. The most often used dosage was 8 yard of CM. The exercise protocols included resistance exercises,ii,3,5, 6, seven, 8,ten,11,13,fourteen cycling,4,12 and running.9 The characteristics of each study, including the supplementation protocols, types of exercise, and reported side effects are summarized in Tabular array one.
Table 1
Characteristics of studies included in the assay.
Study (first author, published year) | Design | Participants (n, historic period (mean ± SD)) | Supplement protocol | Exercise examination | Master and secondary outcomes | Side effects |
---|---|---|---|---|---|---|
ane. Chappel et al. (2020)ii | RDB | Resistance-trained males and females (19, 25.7 ± 7.7 years) | eight g CM 1 h before exercise | Ten sets of 10 repetitions of barbell curls at fourscore% of the participant'south 1RM until failure with 60 southward balance between sets | Muscle soreness, lactate level | No |
2. Chappel et al. (2018)3 | RDB | Moderately trained males and females (15, 23.vii ± two.4 years) | viii g CM 1 h before exercise | Ten sets of 10 repetitions of unmarried-leg extensor exercises at 70% of the subject area's 1RM until failure with 60 s rest between sets | Musculus soreness, lactate level | No |
3. Cunniffe et al. (2016)four | RDB | Salubrious trained males (10, 23.five ± 3.7 years) | 12 k CM ane h before practice | Ten sets of 15 s maximal sprints on wheel ergometer with 30 due south active recovery betwixt sets | RPE, lactate level | No |
4. da Silva et al. (2017)5 | RDB | Untrained males (9, 24.0 ± 3.3 years) | 6 chiliad CM 1 h before exercise | 3 sets of 8−12 repetitions of leg printing and hack squats at 90% of x RM with ii min residue between sets and exercises | RPE, muscle soreness, lactate level | No |
5. Farney et al. (2019)half dozen | RSB | Recreationally trained males and females (12, 24.1 ± 3.ix years) | 8 g CM 1 h before exercise | Isokinetic leg extension test (15 maximal leg extensions) and 3 high-intensity exercise sessions (20 s each of squats, lunge jumps, squat jumps, and lateral jumps, with 30 due south residue between exercises) with 1 min rest between rounds | Lactate level | Northward/A |
half-dozen. Glenn et al. (2017)7 | RDB | Resistance-trained females (15, 23.0 ± 3.0 years) | 8 thou CM 1 h before practise | Six sets of bench press and leg press each at lxxx% of 1RM until failure with threescore south rest betwixt sets and 120 s interval between exercises | RPE | No |
seven. Gonzalez et al. (2018)8 | RDB | Resistance-trained males (12, 21.4 ± 1.six years) | eight thousand CM xl min before exercise | 5 sets of 15 repetitions of bench printing at 75% of 1RM until failure with ii min rest between sets | RPE | Northward/A |
8. Martínez-Sánchez et al. (2017)9 | RDB | Good for you amateur male runners (21, 35.3 ± xi.4 years) | iii.45 m C in WMJ 2 h before exercise | Squat jump and countermovement bound heights before and after two one-half-marathons | RPE, muscle soreness, lactate level | Due north/A |
9. Martínez-Sánchez et al. (2017)10 | RDB | Resistance-trained males (19, 23.9 ± 3.7 years) | iii.3 thousand C in WMJ i h before exercise | 8 sets of viii repetitions of half squats with 2 min rest betwixt sets | RPE, muscle soreness | Due north/A |
10. Pérez-Guisado et al. (2010)11 | RDB | Healthy trained males (41, 29.80 ± vii.64 years) | 8 g CM ane h earlier do | Four sets each of flat bench press (80% 1RM), incline bench printing (lxxx% 1RM for apartment demote printing), incline fly (lx% 1RM for flat bench press), and flat bench press (fourscore% 1RM) to failure with 1 min rest between sets and 2 min rest between exercises | Musculus soreness | Stomach discomfort later on astute ingestion (northward = half-dozen) |
11. Tarazona-Díaz et al. (2013)12 | RSB | Healthy males (vii, 22.7 ± 0.eight years) | half dozen one thousand C in WMJ or one.17 g C in WMJ ane h earlier exercise | 8 repetitions of 30 s cycling with 4.v−5.0 kg resistance and 1 min rest between repetitions | RPE, muscle soreness | N/A |
12. Wax et al. (2015)13 | RDB | Resistance-trained males (12, 22.1 ± 1.4 years) | 8 g CM ane h before do | Five sets each of leg printing, hack squats, and leg extension at lx% of 1RM with 3 min rest between sets | Lactate level | No |
13. Wax et al. (2016)14 | RDB | Resistance-trained males (14, 23.three ± 1.5 years) | 8 g CM 1 h before do | Three sets each of chin-ups, contrary chin-ups, and push-ups until failure with 3 min rest between sets | Lactate level | N/A |
three.two. Study quality and risk of bias assessment
Most studies were judged to have a low chance of bias for each component in the Cochrane risk of bias tool.xxx All studies were randomized, and 2 studies specifically used random number generators.2,three A total of seven studies specifically stated that persons unrelated to the report performed concealment.ii, 3, 4, five,7,8,xi Merely 2 studies were not double blinded.6,12 In the study by Farney et al.,6 no drinks were given to the control group, and only the participants were blinded. Blinding was incomplete in another written report in which the authors compared natural watermelon juice, watermelon juice enriched with L-citrulline, and a placebo drinkable composed of various fruit flavors without whatever citrulline content.12 The participants in the report would take been able to differentiate the watermelon juice from the placebo drink. However, this study was withal included in this meta-analysis because the comparing was made between the results of watermelon juice and watermelon juice enriched with L-citrulline and the participants would not have been able to differentiate between those 2 drinks.12 Also, because watermelon juice that was not enriched with Fifty-citrulline contained just 1.17 g of L-citrulline, the authors justified its apply by stating that this watermelon juice could serve equally better placebo than another drink that could be differentiated. Other studies had a low run a risk for performance bias in that they masked placebo treatments by appearance and taste; in particular, 4 studies controlled for taste and olfactory property by having participants habiliment a olfactory organ prune when consuming the supplement.7,8,13,xiv
The studies by and large provided instructions for participants to avoid factors before the exercise sessions that might affect the results of the written report, such every bit vigorous exercise, dietary supplements, booze, and caffeine. Only 2 studies2,iii instructed the participants to continue, instead of avoiding, their usual supplements, and 1 study6 did not provide whatever instructions regarding supplements. The studies generally had a depression take a chance for attrition bias because there was no missing outcome information, and but ii studies reported minimal attrition due to factors unrelated to the study.v,13 Other time commitments was given equally the reason for attrition in i study,iii and i written report did not study a reason for attrition.2 Although none of the studies had prespecified protocols, there were no other evidence of reporting bias.
3.3. Meta-analysis of effect measures
A meta-analysis of 7 studies investigating post-exercise RPE suggested that supplementation with 50-citrulline or CM significantly reduced RPE, with an event size of 0.81 (p = 0.03) (Fig. 2). A pregnant heterogeneity among the studies supported the option of the random effects model (I ii = 81.9, Q = 28.9, p < 0.001). Sensitivity assay demonstrated that 1 report might have been highly influential, with a Cook'due south distance of 0.83, suggesting that this result may be an outlier.7 Withal, even subsequently the exclusion of this report, citrulline supplementation resulted in a significant reduction in RPE (p = 0.05).

The effect of citrulline supplementation on rating of perceived exertion.
A meta-analysis of seven studies investigating subjective feelings of muscle soreness 24-h mail-exercise suggested that supplementation of L-citrulline or CM significantly reduced the feelings of muscle soreness, with an effect size of 0.99 (p = 0.04) (Fig. 3A). There was pregnant heterogeneity among the studies (I 2 = 92.i, Q = 62.1, p < 0.001), merely no single report was constitute to be highly influential according to the sensitivity analysis.

The outcome of citrulline supplementation on subjective rating of muscle soreness. (A) At 24 h subsequently exercise; (B) At 48 h after exercise; (C) At 72 h afterward exercise.
No significant clan (p = 0.25) was detected between citrulline ingestion and muscle soreness 48-h postal service-exercise (Fig. 3B). The event from 1 written report was not included in the analysis due to identical values of muscle soreness in all subjects at 48 h after exercise in both citrulline supplementation and the placebo groups, and the standard difference values of both groups were 0, making it impossible to summate the issue size.12 Still, the bulk of the studies suggested that citrulline supplements reduced muscle soreness at 48 h after exercise. Only one of the 6 studies suggested that there was a significant positive association betwixt citrulline supplements and muscle soreness.3 A sensitivity analysis suggested that this written report might have been highly influential, with a Melt's altitude of 0.53, which may justify the exclusion of this study. After exclusion, a statistically meaning association between citrulline supplements and muscle soreness 48-h postal service-exercise was observed (p = 0.03). There was significant heterogeneity among the studies (I 2 = 93.4, Q = 73.7, p < 0.001), which remained significant even after exclusion of this study3 (I 2 = 88.6, Q = 35.iv, p < 0.001). No meaning association between citrulline ingestion and muscle soreness was observed at 72 h after exercise (p = 0.62) (Fig. 3C).
In a meta-assay of 8 studies, citrulline supplements did not significantly reduce blood lactate levels later on practise (p = 0.17) (Fig. 4). No prove of heterogeneity was observed (I 2 = 0.0, Q = vi.6, p = 0.47).

The issue of citrulline supplementation on lactate levels later on exercise.
No significant asymmetries were observed in the funnel plots, and no testify of publication bias was detected co-ordinate to the Begg's rank correlation exam and the Egger'due south regression test, in whatever of the analyses conducted.
4. Discussion
To the best of our knowledge, this systematic review and meta-assay is the start to determine the result of citrulline supplements on RPE, musculus soreness, and blood lactate levels. Our master finding was that citrulline supplements were effective in reducing both RPE and muscle soreness. The effect of citrulline on reducing muscle soreness was about pregnant at 24 h after exercise, and the effect appeared to diminish close to 72 h after do. This result may imply that the effect of citrulline occurred inside 24 h of completing the practise and declined subsequently. Nevertheless, citrulline supplements did non significantly lower post-practise claret lactate levels.
four.ane. RPE and muscle soreness
All of the studies included in this analysis used either the Borg scale4,9,10,12 or OMNI (omnibus)-RPE scale,5,viii which are the 2 most widely used RPE tools.36 The Borg scale ranges from six (no exertion at all) to 20 (maximal exertion),36 and the OMNI-RPE ranges from 0 to 10 with mode-specific pictures.37 These two scales accept demonstrated reliability and validity in a healthy, clinical, and able-bodied adult population,38 which is similar to the population included in this analysis. RPE tin can exist used in both aerobic and anaerobic exercises to subjectively quantify private perception of physical demands, exercise tolerance, and impending fatigue associated with activeness.36,39 Additional recovery may exist required for loftier RPE during or afterwards practise. In the absence of adequate recovery, a temporary reduction in muscle strength and increased feelings of soreness may occur,40 which tin can last several days and touch the capacity to train at the desired intensity in the post-obit sessions. The results of this meta-analysis propose that either ingestion of CM or even L-citrulline lonely may convalesce RPE and muscle soreness. Specifically, the effect size of citrulline supplements for RPE reduction was 0.81 and for reduction of muscle soreness at 24 h was 0.99, which may suggest a large difference between the citrulline supplementation group and the control grouping.41 However, due to the large heterogeneity in exercise protocols and the written report population included in the assay, it may not be appropriate to hash out the magnitude of the issue size in this written report.
four.2. Claret lactate levels
Simply a few studies in animals and humans have suggested that citrulline supplementation may repress elevations of exercise-induced blood lactate levels. Using a swimming exercise protocol with mice, Takeda et al.42 demonstrated that L-citrulline supplementation inhibited the elevations in exercise-induced blood ammonia and lactate. Similar results were found in humans, showing that blood lactate levels were lower in a citrulline-supplemented group subsequently running a half marathon.nine In that study, the authors also observed that L-citrulline ingestion increased the plasma concentration of lactate dehydrogenase (LDH), an enzyme known to reversibly catechumen pyruvate to lactate, with concomitant interconversion of nicotinamide adenine dinucleotide and its reduced class, nicotinamide adenine dinucleotide hydrogen. The study9 hypothesized that elevated plasma LDH might enhance the aerobic pathway fifty-fifty further past converting lactate to pyruvate.43, 44, 45 In mice, increased LDH gene expression exhibited enhanced oxygen consumption and mitochondrial enzyme activity,46 simply whether elevated plasma LDH tin can really enhance the aerobic pathway still needs experimental prove. In addition, none of the other studies included in our analysis plant that citrulline supplementation adulterate blood lactate levels after practice.two, 3, four, 5, 6,13,xiv This departure in lactate response may be attributed to differences in exercise or supplementation protocols. The studies that did not show a decrease in blood lactate levels involved anaerobic exercises, such as cycling sprint and time to exhaustion,iv and resistance exercises.2,iii,five,6,13,fourteen Past contrast, the study reporting attenuation used aerobic exercise (half marathon).9 Moreover, L-citrulline was supplemented in half marathon runners, whereas a CM supplement was given to subjects who performed anaerobic exercises.ii, iii, 4, 5, six,xiii,14 Therefore, malate may not provide additional benefit in lowering blood lactate levels, even though it is thought to bypass the ammonia-induced inhibition of the oxidative pathway and redirect lactic acid toward pyruvate production for aerobic utilization or gluconeogenesis.eleven,47 Interestingly, in 2 studies that were excluded from our assay due to longer periods of supplementation (2 weeks48 and 4 weeks49), supplementation with CM attenuated lactate response after high-intensity exercise. Therefore, even though astute supplementation with CM may not be effective, CM supplementation for ≥2 weeks may lower blood lactate levels afterwards high-intensity exercise.
The role of the blood lactate level has been challenged for its suitability every bit an indicator of musculus fatigue or soreness, since lactate accumulates in non-active muscles during exercise likewise.50 Rather than lowering blood lactate levels after exercise, citrulline supplements may human activity via other mechanisms to reduce the rating of fatigue and muscle soreness. One of the possible mechanisms may be based on energy production efficiency associated with the intake of citrulline supplements. Bendahan et al.51 showed that CM increased the rate of oxidative ATP production during do past 34% and the rate of phosphocreatine recovery afterward exercise by 20%. In add-on, Giannesini et al.52 constitute that curt-term CM supplementation decreased the oxidative and phosphocreatine toll of skeletal musculus force generated in rat gastrocnemius muscles, indicating that CM supplementation may improve the efficiency of muscle contraction in rats. Bailey et al.53 corroborated these results by demonstrating that citrulline supplementation enhanced oxygen uptake kinetics and improved tolerance during high-intensity practise. Thus, efficient energy production during exercise and faster energy recovery after practice may play a role in alleviating the sensations of fatigue and soreness.
four.iii. Recommended dosage, timing, and safety
In studies reporting reduced RPE following citrulline supplementation, 8 g CM7 or watermelon juice containing 3.3 g10 and six g12 of L-citrulline were used. Considering that the purported ratio of 2:1 L-citrulline to malate in CM may be every bit depression as 1.one:1,2 at least 3−four g of 50-citrulline lone or in CM may be necessary to alleviate fatigue. All the same, citrulline supplements were not effective in lowering RPE in other studies using 6 grand CM,5 8 g CM,viii 12 g CM,4 and 3.45 g Fifty-citrulline in watermelon juice.9 This lack of response may be related to the timing of ingestion. In 5 studies,4,5,7,x,12 citrulline supplements were ingested i h earlier practice to obtain the peak Fifty-arginine levels after an acute oral dose of L-citrulline.31 In 2 studies reporting that citrulline supplements were non effective in reducing RPE, a supplement of 8 thousand CM was administered 40 min earlier exercise in 1 study,8 and iii.45 g 50-citrulline in watermelon juice was provided two h before exercise in the other study.9 Thus, despite subtle differences, the timing of ingestion of citrulline supplements may be optimized by administering ane h before exercise.
In terms of musculus soreness, in that location was no articulate design or trend in which dosage and timing were effective. A total of five studies that demonstrated that citrulline supplements may reduce post-practice muscle soreness used 8 g CM or iii−6 g L-citrulline.2,9, ten, 11, 12 Also, supplementation of iii.45 yard L-citrulline 2 h before a half marathon did non lower RPE only reduced post-exercise muscle soreness.9 Therefore, ingestion of citrulline supplements containing more than 3 g Fifty-citrulline ane h to 2 h before practise may alleviate post-exercise musculus soreness.
Among the thirteen studies, 8 reported the incidence of side effects. Although 6 studies stated that the participants did not experience any side effects, 1 study showed that 15% of the participants reported tummy discomfort afterward acute ingestion of 8 thou CM.11 One participant in another study reported gastrointestinal discomfort.vii However, it occurred after both CM and placebo trials. Thus, CM was unlikely to be the crusade of self-reported discomfort.7 Supplementation with 12 k CM was well-tolerated by all ten participants in 1 study.four Therefore, CM ingested 1 h earlier practice for the purpose of alleviating fatigue and muscle soreness is probable to be safe.
4.4. Limitations
Our report has some limitations. Although nigh studies used 8 g of CM containing 4−5 g of Fifty-citrulline, the supplement dosages differed slightly among the studies. Second, the practice types varied amongst the studies (Tabular array ane). A total of 9 studies implemented anaerobic exercises, with significant variation in the types of exercises, for case, bench press, leg printing, and chin-ups. Also, only 1 study assessed the event of 50-citrulline in aerobic exercise. Such variations in the types of exercise might have contributed to the study heterogeneity, and the effect of our analysis should be interpreted with caution when applied to aerobic do. In addition, the number of included studies was small because nosotros limited studies to those that provided citrulline supplements ane h or 2 h before exercise. Thus, studies in which supplements were given >2 h earlier exercise were excluded from this analysis. Considering in that location were a express number of studies evaluating the effect of long-term supplementation compared with acute supplementation, further research should investigate the effect of long-term supplementation on RPE and muscle soreness. Additional studies are required to elucidate the mechanisms by which citrulline supplements lower the perceived sensations of fatigue and musculus soreness.
5. Decision
The results of our systematic review and meta-analysis support the effectiveness of citrulline supplements in lowering RPE and musculus soreness. Athletes may benefit from ingesting either L-citrulline alone or CM i h before exercise to resist fatigue or relieve muscle soreness. Citrulline supplements are especially recommended for ability and strength athletes for them to adequately recover and later on railroad train at their desired intensity level. Farther evidence is needed to confirm the efficacy of citrulline supplementation among endurance athletes.
Acknowledgments
This study was supported by the Technology Innovation Program (or Industrial Strategic Engineering science Development Program) (20003688, Development of cosmeceutical and medical device platform using biodegradable metal patch delivering microcurrent) funded past the Ministry building of Trade, Manufacture & Energy (MOTIE, Korea).
Authors' contributions
HCR conceived the written report, designed information technology, and drafted the showtime version of manuscript; SJK performed the statistical analysis and drafted the showtime version of manuscript; JP drafted the first version of manuscript; and KMJ reviewed the report and drafted the last manuscript. All authors accept read and approved the final version of the manuscript, and agree with the gild of the presentation of the authors.
Competing interests
The authors declare that they have no competing interests.
Footnotes
Peer review nether responsibility of Shanghai University of Sport.
Supplementary materials
Supplementary material associated with this commodity can exist constitute in the online version at doi:10.1016/j.jshs.2020.02.003.
Appendix. Supplementary materials
References
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Articles from Journal of Sport and Wellness Science are provided here courtesy of Shanghai University of Sport
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749242/
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