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Nitric oxide precursor interventions for post-exercise delayed onset muscle soreness: a systematic review and network meta-analysis of randomized placebo-controlled trials

Year: 2026
Type: review
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.
DOI: 10.3389/fnut.2026.1868555
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7222051124
FWCI:
Cites: 65
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Related to: 10