Metabolomic Signatures of Recovery: A Secondary Analysis of Public Longitudinal LC–MS Datasets Shows Polyphenol-Rich Interventions Attenuate Purine Degradation and Oxidative Stress Following Exhaustive Exercise

Background: Post-exercise recovery involves coordinated metabolic restoration and redox rebalancing. Although dietary polyphenols have been proposed to facilitate recovery, the metabolic mechanisms underlying their effects—particularly during the recovery phase—remain insufficiently characterized. This study aimed to investigate how polyphenol supplementation modulates post-exercise metabolic recovery using an integrative metabolomics approach. Methods: We conducted a secondary analysis of publicly available longitudinal human LC–MS metabolomics datasets from exercise intervention studies with polyphenol supplementation. Datasets were obtained from the NIH Metabolomics Workbench and MetaboLights repositories; study-level metadata were used as provided by the original investigators. Global metabolic trajectories were assessed using principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Targeted analyses focused on purine degradation intermediates and redox-related metabolites. Correlation-based network and pathway enrichment analyses were applied to characterize recovery-phase metabolic reorganization. Results: Exercise induced a pronounced global metabolic perturbation in both placebo and polyphenol groups. During recovery, polyphenol supplementation was associated with a partial reversion of the metabolome toward the pre-exercise state, whereas placebo samples remained metabolically displaced. Discriminant metabolite analyses identified purine degradation intermediates and oxidative stress-related lipid species as key contributors to group separation during recovery. Polyphenol supplementation attenuated recovery-phase accumulation of hypoxanthine, xanthine, and uric acid and was associated with a sustained suppression of the uric acid-to-hypoxanthine ratio. Network analyses revealed weakened correlations between purine metabolites and oxidative stress markers, along with reduced network centrality of stress-responsive metabolic hubs. Conclusions: These findings indicate that polyphenol supplementation is associated with accelerated metabolic normalization during post-exercise recovery, potentially through modulation of purine-associated oxidative pathways and system-level metabolic network reorganization.