Association between serum 25-hydroxyvitamin D concentrations and overactive bladder in female: a mediation analysis of inflammatory biomarkers

Background Overactive bladder (OAB) is a prevalent condition that substantially impairs quality of life. Although 25-hydroxyvitamin D [25(OH)D] plays an important role in immune modulation, its association with OAB and the potential contribution of inflammation remain incompletely understood. Methods We analyzed 25,096 participants from National Health and Nutrition Examination Survey (NHANES) 2007–2018 and 2,442 participants from a hospital-based replication cohort (FAH-DMU-DB) using multivariable logistic regression and restricted cubic spline models. Inflammatory biomarkers were incorporated to evaluate their influence on the association between 25(OH)D and OAB. A two-sample Mendelian randomization (MR) analysis was additionally performed to assess potential relationship. Results In the NHANES cohort, higher serum 25(OH)D levels were inversely associated with the risk of OAB among females but not males. Female in the highest quartile of 25(OH)D exhibited a significantly lower risk of OAB compared with those in the lowest quartile (OR = 0.733, 95% CI: 0.589–0.912, p = 0.005). Consistent findings were observed in the FAH-DMU-DB cohort, where serum 25(OH)D levels were significantly associated with decreased risk of OAB (OR = 0.490, 95% CI: 0.245–0.978, p = 0.043). Inflammatory biomarkers, particularly the systemic immune-inflammation index and neutrophil count, attenuated the protective association between 25(OH)D and OAB. MR analysis provided additional support for the observed association, showing that genetically predicted higher vitamin D levels were associated with a reduced risk of urinary incontinence/bladder problem (inverse variance weighted: both p < 0.05). Conclusion Higher serum 25(OH)D levels are associated with a lower prevalence of OAB in females. Concordant observational and genetic evidence suggests a potential protective role of vitamin D, with systemic inflammation potentially modulating this association.