DOI: 10.3138/cim-2025-0211 ISSN: 1488-2353

Serum vitamin D levels and chronic refractory wounds: Unveiling of association and exploration of potential molecular mechanisms

Guowei Zhou, Jia Fu, Qirui Xiong, Bing'e Ma, Chaoqun Ma

Abstract

Background:

This study aimed to explore the link between serum vitamin D levels and chronic refractory wounds (CRWs) using National Health and Nutrition Examination Survey (NHANES) data, as the exact relationship and molecular mechanisms have not been fully understood.

Methods:

This study included a cohort of 5,415 adult participants with complete data on serum vitamin D, CRW prevalence, and other pertinent covariates. To evaluate the associations between serum vitamin D levels and CRW prevalence, weighted logistic regression analysis, restricted cubic spline (RCS) models, and subgroup analyses were applied. Network pharmacology and molecular dynamics simulation (MDS) analyses were then performed to elucidate the potential pathways and key targets involved in vitamin D–mediated wound healing.

Results:

After controlling for all confounding variables, a significant inverse relationship was identified between serum vitamin D levels and CRW prevalence. When stratifying serum vitamin D levels into quartiles, individuals in the highest quartile exhibited an approximately 37% reduced risk of CRW ( P = 0.04) compared to those in the lowest quartile. RCS analysis indicated a linear dose–response relationship across serum vitamin D levels ( P for nonlinearity = 0.328). This inverse association was consistently observed across various population subgroups. Furthermore, network pharmacology analysis suggested that vitamin D may influence wound healing through various targets and pathways, notably the AGE-RAGE, IL-17, and PI3K-Akt signalling pathways.

Conclusion:

Our findings underscore a significant correlation between lower serum vitamin D levels and an increased risk of developing CRW. Vitamin D intake may constitute a modifiable lifestyle factor associated with CRW.

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