Processed meat intake and incident gout: Integrated evidence from epidemiology, plasma proteomics, and machine learning

Introduction Gout is a common metabolic inflammatory disorder whose incidence parallels modern dietary shifts. Although processed meat intake is linked to metabolic dysregulation, its independent association with incident gout and related biological signatures remains unclear. Objectives To investigate the association between processed meat intake and incident gout and to characterize related biological signatures using integrated epidemiological, machine-learning, and plasma proteomic approaches. Methods This prospective cohort study included 395,356 UK Biobank participants free of gout at baseline. Associations between processed meat intake and incident gout were assessed using Cox proportional hazards models and time-varying Cox proportional hazards models. Socioeconomic and lifestyle factors were incorporated into the analyses. Supervised machine learning models were applied to evaluate the relative importance of behavioral determinants. In a proteomic subcohort, circulating proteins jointly associated with processed meat intake and gout were identified, followed by pathway enrichment analyses. Results During a mean follow-up of 15.7 years, 8,215 participants developed gout. Higher processed meat intake was independently associated with increased gout risk, with hazard ratios of 1.12 (95% CI: 1.06–1.18, P < 0.001) and 1.19 (95% CI: 1.07–1.31, P < 0.001) for middle and high intake, respectively, compared with low intake. In time-varying Cox proportional hazards models, the corresponding risk estimates increased to 1.52 (95% CI: 1.19–1.95, P < 0.001) and 1.84 (95% CI: 1.14–2.98, P = 0.012). Lower socioeconomic status and unfavorable lifestyle profiles were also associated with higher gout risk. Proteomic analyses identified 40 plasma proteins jointly associated with processed meat intake and gout status, suggesting potential involvement of biological processes related to metabolic dysregulation, inflammation, and neuroendocrine signaling. Conclusions Processed meat intake was independently associated with a higher risk of incident gout. These findings support a consideration of processed meat intake within broader dietary, socioeconomic, and lifestyle contexts, and provide exploratory proteomic evidence for biological processes potentially related to this association.