Abstract
BACKGROUND: Benign prostatic hyperplasia (BPH) frequently affects men in middle and later life; however, the potential influence of ultra-processed food (UPF) consumption and the metabolic pathways involved has not been fully elucidated. This study investigated associations between the percentage of total food weight (% of total g/day) contributed by foods stratified by processing level and plant origin and the risk of BPH. METHODS: This prospective cohort study included 77,951 men aged ≥ 45 years from the UK Biobank, with a median follow-up of 10.5 years. Dietary intake was assessed using repeated 24-hour dietary recalls and expressed as the percentage of total food weight (% of total g/day) from all UPF, plant-sourced UPF, plant-sourced non-UPF, and all plant-sourced foods. Incident BPH (n = 7,387) was identified using ICD-10 codes. Associations were evaluated using Cox proportional hazards models, stratified analyses, restricted cubic splines, and sensitivity analyses. Mediation analysis assessed 251 metabolites as potential mediators of the association between the percentage of total food weight from all UPF and BPH. RESULTS: In the fully adjusted model (Model 3), each 10% increase in the percentage of total food weight from all UPF was associated with a 4% higher risk of BPH (hazard ratio [HR] 1.04; 95% confidence interval [CI] 1.01–1.06). A similar 10% increase in plant-sourced UPF was associated with a 3% higher BPH risk (HR 1.03; 95% CI 1.01–1.06). Conversely, each 10% increase in the percentage of total food weight from plant-sourced non-UPF and all plant-sourced foods was associated with a 5% and 9% lower risk of BPH, respectively. Restricted cubic spline analyses indicated a significant non-linear inverse association between the percentage of total food weight from plant-sourced non-UPF and BPH risk. Mediation analyses identified high-density lipoprotein (HDL)-related metabolites as key mediators linking the percentage of total food weight from all UPF to BPH development. CONCLUSION: A higher percentage of total food weight from UPF was associated with a higher risk of incident BPH among middle-aged and older men, with HDL-related metabolites partially mediating this association. These findings support the potential benefit of reducing UPF and increasing plant-sourced non-UPF, without implying causality. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12937-026-01310-0.