Nitric oxide precursor interventions for post-exercise delayed onset muscle soreness: a systematic review and network meta-analysis of randomized placebo-controlled trials
- 1Department of Physical Education, Dankook University , , ,
- 2School of Sports Science and Engineering, Hunan Institute of Engineering , , ,
- 3Department of Physical Education, Xiangtan University , , ,
Abstract
Background
Delayed onset muscle soreness (DOMS) commonly follows high-intensity or unaccustomed exercise. Nitric oxide (NO) precursors may reduce DOMS, but their effects remain uncertain. We conducted a systematic review and network meta-analysis to evaluate NO precursor interventions across recovery time points.Methods
PubMed, Embase, Web of Science, and CENTRAL were searched to February 2026 for randomized controlled trials in healthy adults. Interventions were classified into four nodes: beetroot-derived nitrate, watermelon-derived citrulline, synthetic or isolated amino acid precursors (L-arginine and citrulline malate), and watermelon plus added citrulline. Random-effects network meta-analyses were conducted separately at 24, 48, and 72 h. Effects were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs); SUCRA rankings were exploratory. Risk of bias and evidence certainty were assessed using RoB 2 and CINeMA, with subgroup and sensitivity analyses examining robustness.Results
Nineteen trials involving 356 participants were included. At 24 h, watermelon plus added citrulline (SMD = -0.97, 95% CI -1.64 to -0.31) and beetroot-derived nitrate (SMD = -0.67, 95% CI -1.14 to -0.20) significantly reduced DOMS vs. placebo. At 48 h, beetroot-derived nitrate was the only intervention with a significant benefit (SMD = -1.18, 95% CI -1.91 to -0.45). No active intervention differed significantly from placebo at 72 h, while evidence for differences between active interventions was limited, with only watermelon plus added citrulline showing a significant advantage over synthetic or isolated amino acid precursors at 24 h. Beetroot-derived nitrate significantly reduced DOMS vs. placebo in the trained subgroup but not in the untrained subgroup. Sensitivity analyses generally supported the findings, although the beetroot-derived nitrate estimate was sensitive to some restrictions related to the exercise-induced muscle damage model.Conclusion
NO precursor supplementation may reduce post-exercise DOMS at specific recovery time points, particularly with beetroot-derived nitrate and watermelon plus added citrulline. However, evidence for differences between active interventions remains limited, and the sparse network, substantial heterogeneity, and low certainty of evidence preclude firm clinical conclusions.Systematic review registration
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261373938, identifier: CRD420261373938.
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BibTeX
@article{xu2026nitric,
title = {{Nitric oxide precursor interventions for post-exercise delayed onset muscle soreness: a systematic review and network meta-analysis of randomized placebo-controlled trials}},
author = {Kai-Xuan Xu and Shuai Guo and Zhen-Fan Xie and Yu-Wei Xiao},
journal = {Frontiers in nutrition},
year = {2026},
month = oct,
doi = {10.3389/fnut.2026.1868555},
url = {https://europepmc.org/article/PMC/PMC13718329},
note = {CC BY},
}
RIS
TY - JOUR
TI - Nitric oxide precursor interventions for post-exercise delayed onset muscle soreness: a systematic review and network meta-analysis of randomized placebo-controlled trials
AU - Kai-Xuan Xu
AU - Shuai Guo
AU - Zhen-Fan Xie
AU - Yu-Wei Xiao
PY - 2026
DA - 2026/10/15
JO - Frontiers in nutrition
DO - 10.3389/fnut.2026.1868555
UR - https://europepmc.org/article/PMC/PMC13718329
AB - Background Delayed onset muscle soreness (DOMS) commonly follows high-intensity or unaccustomed exercise. Nitric oxide (NO) precursors may reduce DOMS, but their effects remain uncertain. We conducted a systematic review and network meta-analysis to evaluate NO precursor interventions across recovery time points.Methods PubMed, Embase, Web of Science, and CENTRAL were searched to February 2026 for randomized controlled trials in healthy adults. Interventions were classified into four nodes: beetroot-derived nitrate, watermelon-derived citrulline, synthetic or isolated amino acid precursors (L-arginine and citrulline malate), and watermelon plus added citrulline. Random-effects network meta-analyses were conducted separately at 24, 48, and 72 h. Effects were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs); SUCRA rankings were exploratory. Risk of bias and evidence certainty were assessed using RoB 2 and CINeMA, with subgroup and sensitivity analyses examining robustness.Results Nineteen trials involving 356 participants were included. At 24 h, watermelon plus added citrulline (SMD = -0.97, 95% CI -1.64 to -0.31) and beetroot-derived nitrate (SMD = -0.67, 95% CI -1.14 to -0.20) significantly reduced DOMS vs. placebo. At 48 h, beetroot-derived nitrate was the only intervention with a significant benefit (SMD = -1.18, 95% CI -1.91 to -0.45). No active intervention differed significantly from placebo at 72 h, while evidence for differences between active interventions was limited, with only watermelon plus added citrulline showing a significant advantage over synthetic or isolated amino acid precursors at 24 h. Beetroot-derived nitrate significantly reduced DOMS vs. placebo in the trained subgroup but not in the untrained subgroup. Sensitivity analyses generally supported the findings, although the beetroot-derived nitrate estimate was sensitive to some restrictions related to the exercise-induced muscle damage model.Conclusion NO precursor supplementation may reduce post-exercise DOMS at specific recovery time points, particularly with beetroot-derived nitrate and watermelon plus added citrulline. However, evidence for differences between active interventions remains limited, and the sparse network, substantial heterogeneity, and low certainty of evidence preclude firm clinical conclusions.Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420261373938, identifier: CRD420261373938.
SN - 2296-861X
ER -