Plasma Metabolomic Signatures Linked to Healthy Lifestyle and Risk of Benign Prostatic Hyperplasia

The aim of this study was to identify and validate a plasma metabolomic signature associated with healthy lifestyle and to examine their relationship with the risk of incident benign prostatic hyperplasia (BPH).

From the UK Biobank, 89,388 male participants without baseline BPH were analyzed. Healthy lifestyle scores were calculated based on smoking status, alcohol consumption, physical activity, and sleep duration. Nuclear magnetic resonance-based metabolomics profiling was conducted on ethylenediaminetetraacetic plasma samples, measuring 251 metabolic biomarkers. An elastic net regression developed a metabolic signature representing a healthy lifestyle. Cox proportional hazard models assessed the associations between lifestyle, metabolic signature, and BPH risk, adjusting for confounders. Mediation analysis explored the metabolic signature's role in the lifestyle-BPH risk relationship.

Results showed that higher healthy lifestyle scores correlated with reduced BPH risk, with a hazard ratio (HR) of 0.94 per one-point increase (95% confidence interval [CI]: 0.92 to 0.96). A metabolic signature of 83 metabolites was identified, significantly linked to healthier lifestyles and independently associated with lower BPH risk (HR=0.78, 95% CI: 0.72 to 0.83). Mediation analysis indicated that 19.7% (95% CI: 13.7% to 29.6%) of the lifestyle-BPH risk association was mediated by this signature, mainly through lipoprotein particles, cholesteryl esters in high-density lipoprotein, and phosphatidylcholines.

In conclusion, healthy-lifestyle related metabolites were associated with a reduced risk of BPH. The findings highlight the potential of using metabolic signatures as biomarkers for personalized health strategies to reduce BPH incidence. Future research should aim to validate these results across diverse populations and investigate the long-term dynamics of lifestyle-induced metabolic changes.