Work

Association between serum 25-hydroxyvitamin D₃ and retinol in Chinese children (2019–2023): an isoform-specific cross-sectional analysis

Year: 2026

Type: article

Abstract: Background China’s national pediatric supplementation program exclusively uses vitamin D₃ (cholecalciferol). Yet, the association between circulating 25-hydroxyvitamin D₃ [25(OH)D₃] and retinol in Chinese children has not been fully characterized with isoform-specific assays in a large, temporally expanded cohort. This study aimed to characterize the non-linear dose–response relationship between serum 25(OH)D₃ and retinol and to examine how this association varies across demographic and seasonal strata. Methods We retrospectively analyzed 6,774 children aged 0–10 years who underwent routine health surveillance across 22 community centers in Ningbo, China (2019–2023). Serum 25(OH)D₃ was resolved separately from D₂ by liquid chromatography–tandem mass spectrometry. Restricted cubic splines (RCS), multivariable linear regression, and bootstrap-validated ( n = 1,000) non-linear modeling were used to characterize the D₃–retinol association. Subgroup analyses by sex, age, season, and D₃ stratum were visualized using forest plots. Results Mean serum 25(OH)D₃ was 30.9 ± 11.1 ng/mL and mean retinol was 272.5 ± 80.6 ng/mL. A significant non-linear, saturable relationship was evident ( p -overall < 0.001; p -non-linearity <0.001). In the lower repletion range, each 1 ng/mL increment in D₃ corresponded to a 3.16 ng/mL rise in retinol (95% CI: 2.66–3.65; p < 0.001); as D₃ increased, the slope progressively attenuated to 1.80 (95% CI: 1.46–2.15; p < 0.001) but remained positive. Bootstrap resampling confirmed a stable transition zone centered at 28.7 ng/mL (95% CI: 26.4–31.2). The association was strongest in winter ( β = 2.70; 95% CI: 2.23–3.17), with significant seasonal heterogeneity ( p for interaction = 0.002); the point estimate was largest in children aged 6–10 years ( β = 4.10; 95% CI: 2.10–6.11), although the age-by-D₃ interaction was not significant ( p = 0.358), and this subgroup comprised only 93 children (1.4%). Conclusion Serum 25(OH)D₃ exhibits a non-linear, isoform-specific association with retinol, with the steepest relationship observed in the insufficient-to-sufficient transition range. Maintaining D₃ within optimal repletion—particularly during winter—may support retinol status for bone development and mucosal immunity.

Source: Frontiers in Nutrition

DOI: 10.3389/fnut.2026.1985336