Association of Vitamin D Supplementation with VDR and CAMP Expression and Ulcer Healing in Diabetic Foot Infection Involving Biofilm-Forming Bacteria: An Exploratory Prospective Cohort Study

Background/Objectives: Diabetic foot infections (DFIs) are a major cause of morbidity and lower-limb amputation. Vitamin D exerts immunomodulatory effects through vitamin D receptor (VDR), which regulates the cathelicidin antimicrobial peptide (CAMP) gene that encodes cathelicidin (LL-37). However, their association with DFIs remains poorly understood. This study investigated the association between vitamin D supplementation, the vitamin D–VDR–CAMP–LL-37 pathway, and ulcer healing in DFIs involving biofilm-forming bacteria. Methods: This study (September 2022–March 2026) included 16 DFI patients in the study group (SG), 16 in the reference group (RG), and 16 healthy controls (HCs). The SG received vitamin D supplementation (60,000 IU) in addition to standard care, whereas the RG received standard care alone. Participants were followed up for 4 months. Vitamin D assessment (electrochemiluminescence immunoassay), VDR and LL-37 quantification (ELISA), biofilm formation (tissue culture plate method), and VDR and CAMP gene expression (mRNA quantitation) were all considered. Results: At baseline, serum vitamin D, VDR protein, and LL-37 levels differed significantly among the groups (p ≤ 0.002), whereas VDR and CAMP gene expressions did not. Following supplementation, the SG showed significant increases in serum vitamin D, VDR protein and LL-37 (p ≤ 0.001). At the four-month follow-up, there was no significant difference in VDR and CAMP gene expression or in ulcer healing between the groups. Although a higher proportion of participants in the SG achieved ulcer healing, the difference was not statistically significant. Conclusions: Although changes in the circulating elements of the vitamin D-VDR-LL-37 pathway were noted with physician-prescribed vitamin D supplementation, no statistically significant association with ulcer healing was observed. This finding requires validation through a thorough investigation.