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Peer-reviewedCC BYFrontiers in nutrition

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

  • Yue Bi1
  • Jiaxing Yi2
  • Qiao Wang3
  • Hehe Chen4
  • Jishan Zheng5
  • Shanshan Wang5
  • Wenyuan Liu4
5 affiliations
  1. 1Laboratory of Medicine, Ningbo Zhenhai People's Hospital Group , , ,
  2. 2School of Medicine, Ningbo University , , ,
  3. 3Laboratory of Medicine, Qiu'ga Central Health Clinic , , ,
  4. 4Ningbo Key Laboratory for the Prevention and Treatment of Embryo Original Diseases, The Affiliated Women and Children’s Hospital of Ningbo University , , ,
  5. 5Department of Infectious Diseases, The Affiliated Women and Children's Hospital of Ningbo University , , ,
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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.

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Cite

BibTeXRIS
BibTeX
@article{bi2026association,
  title = {{Association between serum 25-hydroxyvitamin D₃ and retinol in Chinese children (2019–2023): an isoform-specific cross-sectional analysis}},
  author = {Yue Bi and Jiaxing Yi and Qiao Wang and Hehe Chen and Jishan Zheng and Shanshan Wang and Wenyuan Liu},
  journal = {Frontiers in nutrition},
  year = {2026},
  month = oct,
  doi = {10.3389/fnut.2026.1985336},
  url = {https://europepmc.org/article/PMC/PMC13718326},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Association between serum 25-hydroxyvitamin D₃ and retinol in Chinese children (2019–2023): an isoform-specific cross-sectional analysis
AU  - Yue Bi
AU  - Jiaxing Yi
AU  - Qiao Wang
AU  - Hehe Chen
AU  - Jishan Zheng
AU  - Shanshan Wang
AU  - Wenyuan Liu
PY  - 2026
DA  - 2026/10/15
JO  - Frontiers in nutrition
DO  - 10.3389/fnut.2026.1985336
UR  - https://europepmc.org/article/PMC/PMC13718326
AB  - 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.
SN  - 2296-861X
ER  -