DOI: 10.5061/dryad.2rbnzs7pd
title: Effectiveness of acute L-arginine supplementation on physical performance in strength training: a systematic review and meta-analysis

description: The oral administration of L-arginine has been related to improved
 physical performance due to a likely reduction in muscle fatigue,
 resulting from the vasodilator effect of nitric oxide on skeletal muscle.
 However, there is no precise and quantitative analysis of the information
 in the literature. Objective: The main objective was to assess the
 effectiveness of L-arginine supplementation on physical performance in
 strength training with a systematic review and meta-analysis. Methods:
 Systematic review and meta-analysis, the PRISMA® (Preferred Reporting
 Items for Systematic Reviews and Meta-Analysis), PICOS statement and
 methodology guidelines, the quality of evidence by Classification of
 Assessment, Development and Assessment Recommendations (GRADE), Multiple
 Systematic Review Tool Assessment (AMSTAR2), and to assess the risk of
 bias of randomized clinical trials, the RoB 2.0 tool (Risk of Bias -
 Cochrane risk of bias tool revised for randomized trials). The inclusion
 process established articles with well-designed human experiments that
 included only L-arginine supplementation testing the effects of L-arginine
 supplementation on sports performance related to strength training;
 identical experimental conditions in placebo or control group; and
 publications in the last ten years (until December 31, 2020). Three
 studies were included that compared L-arginine supplementation with
 placebo in anaerobic performance tests. Results: There was no significant
 heterogeneity (p&gt;0.05) in the analysis of the three selected
 articles and the effects of L-arginine supplementation in muscular
 endurance; performance had a mean of 0.26 (95% CI = -0.129; 0.649; p =
 0.190), peak torque with a mean of -0.002 (95% CI = -0.531; 0.527; p = 0.
 99) of the third series of exercises and, furthermore, when comparing the
 integrated effect (resistance rate with the peak torque) there was no
 difference with a mean of 0.168 (95% CI = -0.145; 0.481; p = 0.292).
 Conclusions: Acute L-arginine supplementation provides no ergogenic effect
 on strength training performance.
description: This systematic review and meta-analysis were performed according
 to PRISMA® (<i>Preferred Reporting Items for Systematic Reviews and
 Meta-Analysis</i>) PICOS declaration guidelines and methodology,
 which defines the “Population,” “Intervention,” “Comparisons,” “Results,”
 and “Study Design.” The review research was carried out considering the
 following phases: Population: Adults
 who practice physical activity (male and female); Intervention: Impact
 of L-arginine supplementation by strength training
 practitioners; Comparisons: Changes or alterations
 in the results in the same sample of participants, when there is a
 comparison of variables related to the use of L-arginine compared to
 placebo in strength training; Outcomes: Any measures of physical
 performance and variables that relate to improvement in strength training
 (ex, peak strength, fatigue, number of repetitions, muscle performance);
 Study
 design: Clinical trial. The identification of the article
 selection process in the first phase was carried out in January 2021 in
 the Cochrane, PubMed, MEDLINE, LILACS, and SciELO databases. For the
 selection of keywords, the descriptors in Health
 Sciences-<i>DeCS</i> were used, obtained through advanced
 searches in the union of search terms, including the “Mesh.” The
 descriptors used were: “L-arginine”; “resistance exercises” and “strength
 training,” a cognitive logical operator “AND,” and “NOT,” were used for
 the effective tracking of publications. The inclusion process established
 that articles with the following characteristics would be used: (1)
 well-planned experiments that included L-arginine supplementation only
 (without any additional compounds); (2) studies with English and Spanish
 languages[BN1] ; (3) identical experimental conditions in the placebo or
 control group; (4) test the effects of L-arginine supplementation on
 sports performance related to strength training; (5) clinical trial; (6)
 publications in the last ten years (until December 31, 2020); (7)
 investigations carried out on humans; (8) results related to the use of
 L-arginine; (09) clear information about funding sources; and (10) absence
 of conflict of interest. Texts with the following
 characteristics were excluded: (1) L-arginine supplementation with some
 other compound; (2) investigations in which the topic was not essentially
 the use of L-arginine; (3) different samples of the effects of using the
 L-arginine not mentioning its effects (articles that do not show
 L-arginine results, in particular); (4) data from studies without
 <i>Qualis</i> status and surveys that did not show results;
 (5) other types of outcomes exclusively from reviews, pneumatic,
 contagious, cancerous and transmissible diseases.
 Two authors independently screened
 and agreed with the selected studies for eligibility (CP, ROG, and TRL).
 Likewise, after the inclusion/exclusion criteria are applied to each
 study, the source study data (including authors and year of publication),
 sample size, participant characteristics (level, race, and gender),
 supplement administration (dose and time), and final results of
 interventions were extracted independently (CP and ROG) using an Excel
 spreadsheet (Microsoft Inc, Seattle). Then, possible disagreements were
 resolved through discussion until a consensus was reached, or by
 third-party judgment (MJK). In this sense, the Kappa coefficient, which
 indicates the reliability between raters, among the authors was above 90
 with a level of agreement "almost
 perfect". The Assessment of Multiple
 Systematic Reviews (AMSTAR2) tool was applied in the systematic review to
 assess the methodological quality of the studies. The reviewers searched
 the studies for data that answered each question, and each reviewer's
 final ratings were placed on a spreadsheet to discuss agreements and
 disagreements, with a score assigned to each assessed study. To assess the
 quality of the evidence and the strength of the recommendations, the
 Grading of Recommendations Assessment, Development, and Evaluation (GRADE)
 system was used, in which the research question was structured considering
 the domains of the acronym PICOS. According to the Cochrane
 Collaboration Guidelines, to assess the risk of bias of randomized
 clinical trials, the RoB 2.0 tool (Risk of Bias - Cochrane risk of bias
 tool revised for randomized trials) was used and evaluated by two authors
 independently, and disagreements were resolved by discussion and/or a
 third author. The list was separated into six different domains: selection
 bias (random sequence generation, allocation concealment); performance
 bias (blinding of participants and researchers); detection bias (masking
 the outcome assessment); friction bias (incomplete result data); reporting
 bias (selective reporting); and other sources of
 bias. Domains were considered as
 'low' if the criteria met a low risk of bias (probable bias that
 would not seriously alter the results) or 'high' if the criteria
 presented a high risk of bias (probable bias that seriously weakens
 confidence in the results), or it was considered "not clear" (a
 plausible bias that raises some doubts about the results), whether the
 risk of bias was unknown. Full details of each article and
 domain. The
 Clinical Trials database was queried using the terms
 "descriptor" and "descriptors" to locate potential
 studies with L-arginine. Phase 2, 3, and 4 clinical studies enrolled in
 the aforementioned database were considered. For this review, approval by
 the ethics committee was not required due to the use of secondary
 data. <i>Statistical
 analyses</i> The meta-analysis was performed
 using the Comprehensive Meta-Analysis (CMA) software, version 3.3.070,
 including the three selected articles, one for each exercise series
 (first, second and third). The effect size was calculated based on the
 difference in performance between groups L-arginine and control group. We
 calculated the effect standardized by the standard deviation (SMD), since
 the variables ​​were not presented in the same unit in all studies, for
 example, total work of the series and total work presented in Joule, peak
 torque in Nanometer, number of maximum repetitions and rate of
 resistance). Some
 studies presented performance measures for more than one muscle group,
 each subgroup of these studies was included in the analysis as if it were
 a different study. To test the effect of L-arginine with no sample
 overlap, combined analyzes with all subgroups from each study were also
 presented and included in the analysis as a single effect per study.
 Sensitivity analyzes were also performed for strength endurance
 measurements (total set work and total work, peak torque, maximum
 repetition number, and endurance rate) and peak torque (Nanometer). In the
 case of peak torque, as all studies presented data in the same measurement
 unit (Nanometer), we present the data in gross mean difference.
 The inconsistency statistic
 (I<sup>2</sup>) was calculated as an indicator of the
 percentage of the total variation observed within the studies due to real
 heterogeneity rather than chance, to avoid errors when using the Q
 statistic in the evaluation of heterogeneity [14].
 I<sup>2</sup> values ​​were included from 0 to 100%,
 representing a small amount of inconsistency between 25% and 50%, the
 average amount of heterogeneity between 50% and 75%, and a large amount of
 heterogeneity when the I<sup>2</sup> value was greater than 75
 % [15] In this sense, low, moderate and high adjectives would be accepted
 referring to I2 values ​​of 25%, 50%, and 75%, respectively, although a
 restrictive categorization was not appropriate in all
 circumstances. Publication bias was analyzed
 using the Egger test and a p-value ≤0.05 was considered significant. Data
 were presented as standardized mean difference and 95% confidence
 interval, and we considered significant p ≤ 0.05.