The mediation effect of vitamin A and vitamin D supplement in the association between serum vitamin K levels and musculoskeletal disorders in preschool children

Qiaoyue Ge; Lu Zhang; Zeyuan Sun; Jiarui Cai; Xia Jiang; Hong Wang; Xinxi Li; Chuan Yu; Chenghan Xiao; Zhenmi Liu

doi:10.3389/fnut.2023.1239954

The mediation effect of vitamin A and vitamin D supplement in the association between serum vitamin K levels and musculoskeletal disorders in preschool children

Front Nutr. 2023 Dec 22:10:1239954. doi: 10.3389/fnut.2023.1239954. eCollection 2023.

Authors

Qiaoyue Ge^#^{1

2}, Lu Zhang^#^{1

2}, Zeyuan Sun³, Jiarui Cai¹, Xia Jiang^{1

2}, Hong Wang⁴, Xinxi Li^{1

2}, Chuan Yu¹, Chenghan Xiao^{1

2}, Zhenmi Liu^{1

2}

Affiliations

¹ Department of Maternal and Child Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
² Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, China.
³ Department of Child and Adolescent Psychiatry, School of Academic Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁴ Department of Child Health Care of Sichuan Maternal and Child Health Hospital, Chengdu, Sichuan, China.

^# Contributed equally.

Abstract

Introduction: Vitamin K deficiency may elevate the incidence of musculoskeletal disorders (MSD), whereas it lacks validation for pediatric populations and has uncertain dose recommendations. In this context, we hypothesized that serum vitamin K levels are associated with MSD in preschool children, and the widely used vitamin A and vitamin D supplements may mediate these associations based on potential mechanisms, which expects to provide guidance for future practice.

Methods: A cross-sectional study was conducted in Sichuan province in southwestern China, from January 2021 to May 2022. Serum levels of vitamin K1/K2 and 25(OH)D were determined using the high-performance liquid chromatography method, and the diagnosis of MSD was executed by clinicians. Overall and stratified logistic regression analysis based on categorized 25(OH)D levels were conducted to assess association between serum vitamin K levels and MSD prevalence after adjusting for confounders. Mediation analysis was further performed and vitamin A and D supplementation was regressed as the mediator.

Results: A total of 6,368 children aged 0-6 years old were enrolled. MSD was identified in 1179 (18.51%) of the children, while 5,189 (81.49%) of them did not present such disorder. After adjusting confounders, a significant difference was found in serum vitamin K1 level between children in MSD and Non-MSD group (OR = 0.802, 95%CI 0.745-0.864). No significant difference was found in serum vitamin K2 level between the two groups (OR = 0.975, 95%CI 0.753-1.261). The association between vitamin K1 level and MSD prevalence was partly (36.8%) mediated by vitamin A and D supplementation.

Conclusions: A low serum vitamin K1 level is connected with an increased risk of MSD among children, highlighting that vitamin A and D supplementation is a helpful intervention to prevent MSD in children with vitamin K deficiency.

Keywords: a cross-sectional study; musculoskeletal disorders; preschool children; serum vitamin K levels; vitamin A and vitamin D supplement.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Natural Science Foundation of China (Project No. U20A20411 to ZL).