Serum 25-hydroxyvitamin D and metabolic syndrome: a large cross-section study with dose response analysis in a health screening population

Background The association between serum 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome (MetS) remains controversial, particularly in large-scale health-screening populations where early metabolic abnormalities can be detected. This study aimed to investigate the independent and potential non-linear association between serum 25(OH)D levels and MetS in adults undergoing routine health examinations. Methods This cross-sectional study included 29,214 adults who underwent routine health examinations at a tertiary hospital between January 2024 and November 2025. MetS was defined according to the 2023 Chinese expert consensus criteria. Multivariable logistic regression models with sequential adjustment were used to estimate odds ratios (OR) and 95% confidence intervals (CI) across quartiles of serum 25(OH)D. Restricted cubic spline (RCS) analysis was performed to explore potential non-linear dose–response relationships. Sensitivity analyses included exclusion of outliers, additional adjustment for hepatic and renal function indicators, and E -value estimation to assess robustness to unmeasured confounding. Results Among 29,214 participants, 6,002 (20.5%) were diagnosed with MetS. After multivariable adjustment, higher serum 25(OH)D levels were independently associated with lower odds of MetS. Compared with the lowest quartile (Q1, <14.9 ng/mL), participants in the highest quartile (Q4, >25.2 ng/mL) had a 36% lower likelihood of MetS (OR = 0.64, 95% CI: 0.57–0.71). RCS analysis demonstrated an inverse dose–response relationship, with the strongest risk reduction observed above approximately 20 ng/mL. Conclusion In this large health screening–based population of 29,214 adults, higher serum 25(OH)D concentrations were independently associated with lower odds of metabolic syndrome after comprehensive adjustment for potential confounders. Although the findings support a robust inverse association, causal inference cannot be established, and residual confounding may remain. Prospective cohort studies and well-designed randomized trials are warranted to clarify whether vitamin D plays a causal role in the development of metabolic syndrome or primarily reflects underlying metabolic health status.