Absence of Effects of L-Arginine and L-Citrulline on Inflammatory Biomarkers and Oxidative Stress in Response to Physical Exercise: A Systematic Review with Meta-Analysis.

Andrey A Porto, Luana A Gonzaga, Cicero Jonas R Benjamim, Vitor E Valenti

Journal: Nutrients 2023;15(8):0

PMID: 37111214

Plain Language Summary

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L-citrulline is a non-essential amino acid that acts as a precursor to L-arginine. L-arginine is a semi-essential amino acid used for nitric oxide production which is crucial for maintaining physiological function and immune regulation. Previous research has shown that L-citrulline and L-arginine supplementation may offer antioxidant and anti-inflammatory benefits in reducing exercise-related oxidative stress and inflammation. This systematic review and meta-analysis included seven randomised controlled trials to investigate the effect of L-citrulline and L-arginine on antioxidants, oxidative stress, and inflammatory and anti-inflammatory markers. This systematic review and meta-analysis showed no significant improvements in oxidative stress and inflammation followed by the supplementation of L-citrulline and L-arginine before exercise. However, further robust studies that include different dosages and exercise intensities are required to assess the beneficial effects of L-citrulline and L-arginine supplements to support physical exercise-induced oxidative stress and inflammation due to the heterogeneity of the included studies. Healthcare professionals can use the results of this study to understand the potential benefits of L-citrulline and L-arginine supplementation in people prone to producing proinflammatory cytokines.

Abstract

The repercussions on oxidative and inflammatory stress markers under the effects of arginine and citrulline in response to exercise are not fully reached. We completed a systematic review to investigate the effects of L-Citrulline or L-Arginine on oxidative stress and inflammatory biomarkers following exercise. EMBASE, MEDLINE (PubMed), Cochrane Library, CINAHL, LILACS, and Web of Science databases were used to record the trials. This study includes randomized controlled trials (RCTs) and non-RCTs with subjects over 18 years old. Those under the intervention protocol consumed L-Citrulline or L-Arginine, and the controls ingested placebo. We recognized 1080 studies, but only 7 were included (7 studies in meta-analysis). We observed no difference between pre- vs. post-exercise for oxidative stress (subtotal = -0.21 [CI: -0.56, 0.14], = 0.24, and heterogeneity = 0%. In the sub-group "L-Arginine" we found a subtotal = -0.29 [-0.71, 0.12], = 0.16, and heterogeneity = 0%. For the "L-Citrulline" subgroup we observed a subtotal = 0.00 [-0.67, 0.67], = 1.00, and heterogeneity was not applicable. No differences were observed between groups ( = 0.47), and I² = 0%) or in antioxidant activity (subtotal = -0.28 [-1.65, 1.08], = 0.68, and heterogeneity = 0%). In the "L-Arginine" sub-group, we found a subtotal = -3.90 [-14.18, 6.38], = 0.46, and heterogeneity was not applicable. For the "L-Citrulline" subgroup, we reported a subtotal = -0.22 [-1.60, 1.16], = 0.75, and heterogeneity was not applicable. No differences were observed between groups ( = 0.49), and I² = 0%), inflammatory markers (subtotal = 8.38 [-0.02, 16.78], = 0.05, and heterogeneity = 93%. Tests for subgroup differences were not applicable, and anti-inflammatory markers (subtotal = -0.38 [-1.15, 0.39], = 0.34 and heterogeneity = 15%; testing for subgroup differences was not applicable). In conclusion, our systematic review and meta-analysis found that L-Citrulline and L-Arginine did not influence inflammatory biomarkers and oxidative stress after exercise.

Address: São Paulo State University (UNESP), Presidente Prudente 19060-080, SP, Brazil.; Autonomic Nervous System Center, São Paulo State University (UNESP), Marília 17525-900, SP, Brazil.; Department of Internal Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, SP, Brazil.
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