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.