Vitamin D supplementation and diabetic foot ulcers

NewsBot · Jan 8, 2024

Vitamin D supplementation improves foot ulcers among diabetic patients: Pooled analysis of randomized controlled trials
Muhammad IA. Putra et al
Source

Serum vitamin D level is associated with the development of diabetic foot ulcer (DFU), and it is intriguing to determine if the vitamin supplementation could reverse the diabetic complication. The aim of this study was to investigate the efficacy of vitamin D supplementation in DFU management through qualitative and quantitative systematic review. A systematic search was conducted to screen the records identified in PubMed, Scopus, Embase, Scillit, Sci-Finder, LILACS, EuropePMC, medRxiv, bioRvix, Google Scholar, Semantic Scholar, and Garuda databases as of 10 March 2023. Studies investigating the efficacy of a single dose supplementation of vitamin D in DFU management were included. Quality of the included studies was appraised by Cochrane ‘Risk of Bias’ 2.0. Random-effects-based pooled analysis using Cohen’s d was performed on the wound healing progress as the primary outcome. A sensitivity test with leave-one-out method and meta-regression were also conducted to analyze the effect of heterogenous data. Five studies with a total of 245 patients (123 versus 122 for experimental and control groups, respectively) were finally included in the qualitative and quantitative analysis. The pooled estimate suggested that administering vitamin D to DFU patients could reduce the wound area or depth significantly as compared to control group (p<0.001; Cohen’s d: 2.72; 95% CI: 1.02 to 4.42). The value remained positive throughout the leave-one-out analysis. Vitamin D supplementation significantly contributed to the increased level of serum vitamin D (p=0.026, Cohen’s d: -0.719; 95% CI: -1.35 to -0.09). Elevation of high-density lipoprotein was observed in pooled estimate with p=0.016 and Cohen’d: 1.34 (95% CI: 0.25 to 2.44). Qualitatively, significant reduction of HbA1C, total cholesterol, and C-reactive protein were reported in at least two trials. Significantly improved quantitative insulin sensitivity check index (QUICKI) and decreased malondialdehyde, fructosamine, and fasting blood glucose were reported in at least one trial each. There were conflicting results on the change of low-density lipoprotein level. This study highlights that vitamin D supplementation promotes wound healing process among DFU patients; however, it is too premature to draw solid conclusions as the efficacy could be affected by multiple factors. Therefore, clinical trials from various demographics and ethnicities by using a high- versus low-dose model are needed.
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NewsBot · Jan 8, 2024

Role of polymorphism in vitamin D receptor gene on diabetic foot ulcer: A systematic review and meta-analysis
Saminan Saminan et al
Journal of Pharmacy & Pharmacognosy Research, 12 (2), 348-362, 2024

Context: Once vitamin D is converted to its active form, the molecule binds to its receptor (VDR) and performs its function as a transcription factor in modulating immune response, inflammation cascade, and insulin signaling. Among diabetic individuals, these activities are thought to be correlated with foot ulceration. Gene polymorphisms could change the function of VDR, thereby affecting the development of foot ulceration among individuals with diabetes. Aims: To construct evidence on the role of VDR gene variants or single nucleotide polymorphisms (SNPs) on diabetic foot ulcers. Methods: Records reporting the distribution of genotypes and/or alleles among diabetic foot ulcer (DFU) patients and published until 10 March 2023 were retrieved from 12 major databases using predetermined keywords. The original research articles included in the study were assessed for reporting quality using the Newcastle Ottawa Scale. The quality of genotypic and allelic data was appraised by Hardy-Weinberg equilibrium (HWE). A quantitative analysisbased fixed-effects model was performed to estimate the proportion of genotype and allele frequencies among DFU patients. Results: Three studies were included in the systematic review reporting the FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232) SNPs. Based on pooled estimates, among DFU patients CC, CT, and TT genotypes of VDR FokI SNPs had a prevalence of 45%, 43%, and 12%, respectively, without significant heterogeneity found in the reported data (p-Het<0.001; I2>0%). ApaI and FokI were associated with DFU, while no association in all genotypic and allelic models was found between TaqI or BsmI and DFU. CC genotype of BsmI and T allele of FokI was associated with oxidative stress (one of the underlying factors in DFU). Conclusions: Certain genotypes and alleles of FokI and ApaI SNPs could act as the risk factor for foot ulceration among diabetic individuals. More high-quality studies are still needed to draw solid conclusions on the role of VDR SNPs among DFU patients.
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NewsBot · Jan 17, 2024

Analysis of the association between serum levels of 25(OH)D, retinol binding protein, and Cyclooxygenase-2 and the disease severity in patients with diabetic foot ulcers
Xuehui Chen, Yun Xu, Xiangyu Meng, Ruina Geng, Xu Wang, Guanying Zhang, Liwei Bai
16 November 2023

Diabetic foot ulcers (DFUs) pose significant clinical challenges, representing severe complications in diabetes mellitus patients and contributing to non-traumatic amputations. Identifying reliable biomarkers can optimize early diagnosis and improve therapeutic outcomes. This study focused on evaluating the association between serum levels of 25-hydroxyvitamin D [25-(OH)D], Serum Retinol Binding Protein (RBP), and Cyclooxygenase-2 (COX-2) in elderly DFU patients. A retrospective study involving 240 participants, from March 2020 to March 2023. The participants were segmented into three cohorts: 80 with DFUs, 80 diabetic patients without DFUs, and 80 healthy controls. Serum concentrations of the three biomarkers were assayed using methods like enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and an automated biochemistry analyser. Comparisons were made both between groups and within the DFU group based on disease severity. Statistical analysis revealed significant differences in biomarker levels across the groups (p < 0.05). COX-2 and RBP concentrations were highest in the DFU group, followed by the non-DFU diabetic group, and lowest in the control group. Conversely, 25(OH)D levels were highest in the control group, followed by the non-DFU diabetic group, and lowest in the DFU group. Within the DFU group, RBP and COX-2 levels increased with disease severity, while 25(OH)D levels decreased. These variations were especially pronounced in patients with the most severe Wagner grading. A significant positive correlation was observed between disease severity and levels of RBP (r = 0.651, p < 0.05) and COX-2 (r = 0.356, p < 0.05). Conversely, a significant negative correlation was identified between disease severity and 25(OH)D levels (r = −0.658, p < 0.05). Assessing 25(OH)D, RBP, and COX-2 serum levels offers a promising tool for evaluating the severity and progression of DFUs. Monitoring these biomarkers can enrich our understanding of the metabolic and inflammatory pathways of the disease and potentially refine therapeutic strategies.
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NewsBot · Feb 29, 2024

Literature Review: Role of Vitamin D in Diabetic Foot Ulcer Wound Healing.
Dahlan, K. ., Irfanuddin, Murti, K. ., & Muradi, A. . (2023).
Jurnal Penelitian Pendidikan IPA, 9(10), 854–867.

DFU is a common consequence of DM. Vitamin D has multiple positive effects on DFU. Search data from; Google Scholar, Science Direct, Elsevier, EBSCO, Medline and PubMed. Publication at least ten years (2013 until 2022). Inclusion criteria; full paper in English, Study about vitamin D and DFU in human, exclusion criteria; animal model and invitro study. Results; 27 journals; Seven Randomized Controlled Trial. Vitamin D phase on DFU which one substantially smaller. Severe vitamin D insufficiency known with significance linked for an elevated risk of DFU. Vitamin D supplementation can prevent or improve diabetic foot complications
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NewsBot · Jun 12, 2024

Correlation between initial serum 25-hydroxyvitamin D and granulation growth in diabetic foot ulcers
Em Yunir et al
J Wound Care. 2024 Jun 1;33(Sup6a):clii-clix.

Objective: To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment.

Method: This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment.

Results: The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86).

Conclusion: The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.
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NewsBot · Jun 29, 2024

Prospective evaluation of vitamin C, vitamin D and zinc deficiencies in patients with active foot ulceration
Ms. Nada Bechara, Dr. Peta Ellen Tehan, and Prof. Jenny Gunton
Source

Objective This prospective cohort study aimed to determine the relationship between serum vitamin C, D and zinc on foot wound healing and compare time to healing in individuals who are deficient versus those who have adequate levels. Approach One hundred adults with foot wounds were recruited from Blacktown high risk foot service with a follow up period of 12 months. Serum vitamin C, D and zinc as well as routine baseline blood testing was undertaken. Wounds were measured using a three-dimensional wound camera and classified using the WIfI system at regular intervals. Results Vitamin C deficiency was present in 75% of participants, 50% had vitamin D deficiency and 38% had zinc deficiency. Diabetes was present in 91% of participants, and 50% had history of a previous amputation. Wound chronicity (p=.03) and toe pressures (p=.04) were predictive of wound healing. Serum vitamin C, D and zinc were not associated with significant differences in wound healing, or time to wound healing. Innovation Deficiencies in vitamin C, D and zinc were highly prevalent in patients participants with active foot ulceration. Wound chronicity was predictive of healing outcomes, highlighting the importance of rapid access to best practice care. Conclusion This cohort had high deficiency rates of vitamin C, D and zinc consistent with previous literature, however there was not a relationship between these deficiencies and wound healing, or time to heal. Large randomised controlled trials are required to comprehensively determine if adequate levels of these nutrients improve wound healing outcomes.
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NewsBot · Aug 21, 2024

Association of vitamin D status and vitamin D receptor polymorphism in diabetic foot ulcer patients: A prospective observational study in a South-Indian tertiary healthcare facility
Shilia Jacob Kurian et al
Int Wound J. 2024 Aug;21(8):e70027.

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case-control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non-DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real-time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs
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NewsBot · Sep 29, 2024

Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis
Xiaokun Wu, Jinchan Zeng, Xuemei Ye, Mengmiao Peng, Yutao Lan, Shuyao Zhang, Haiyan Li
Postgraduate Medical Journal 31 August 2024

Purpose
To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing.

Methods
The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software.

Results
A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P = 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = −3.29, 95%CI −4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = −0.44, 95%CI -0.62 to −0.26, P < 0.01), fasting insulin (MD = −3.75, 95%CI −5.83 to −1.67, P < 0.01), HOMA - β (MD = −5.14, 95%CI −8.74 to −1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = −0.83, 95%CI −1.06 to −0.59, P < 0.01), erythrocyte sedimentation rate (MD = −15.74, 95%CI −21.78 to −9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P = 0.04), and malondialdehyde (MD = −0.43, 95%CI -0.61 to −0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05).

Conclusion
The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress.
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Key messages
What is already known on this topic

Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization.

Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response.

Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear.

What this study adds

This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress.

How this study might affect research, practice or policy

This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.
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NewsBot · Sep 29, 2024

The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: a comprehensive systematic review and meta‐analysis
Weiwei Tang, Dawei Chen, Lihong Chen, Guanjian Liu, Shiyi Sun, Chun Wang, Yun Gao & Xingwu Ran
Scientific Reports volume 14, Article number: 21932 (2024)

The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta‐analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random‐effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001).
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NewsBot · Oct 25, 2024

The role of vitamin D in diabetic foot ulcer; an umbrella review of meta-analyses
Lu LiuLu Liu et al
Sec. Clinical Nutrition

Background: Complications related to diabetic foot ulcers (DFU) due to diabetes are increasing. One of the factors influencing the management and treatment of complications related to DFU is the vitamin D serum levels of patients. Therefore, we sought to comprehensively review meta-analyses from randomized controlled trials and observational studies examining the link between serum vitamin D levels and DFU outcomes in diabetic patients.

Methods: We searched PubMed, Scopus, and ISI Web of Science until September 2024 and extracted the required data from related articles according to Inclusion criteria. The certainty of the evidence and the quality of conduct of the published meta-analyses were rated using the ASMTAR 2 tools, respectively.

Result: A total of 8 meta-analyses studies that met inclusion criteria were included. Based on the obtained results, it has been noted that individuals with DFU exhibit serum vitamin D levels significantly lower, ranging from −7.14 (5.44, 8.83) to −0.93 (95% CI: 0.17, 1.68) ng/ml, compared to those with diabetes but without DFU. Furthermore, individuals exhibiting severe vitamin D deficiency are found to be at least 1.82 times more susceptible to developing DFU. Conversely, administering varying doses of vitamin D supplementation has been shown to positively affect the size and number of ulcers in DFU patients.

Conclusion: This study suggests a potential link between lower levels of vitamin D in the blood and the risk of DFU, hinting at the benefits of vitamin D supplementation in improving outcomes associated with DFU. However, caution is warranted due to the potential bias present in the included studies.
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NewsBot · Nov 15, 2024

RISK OF INSUFFICIENT HYDROXYVITAMIN D LEVELS IN DIABETIC FOOT ULCERS IN RIVERS STATE NIGERIA
U D Batubo et al
West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S51-S52.

Background: The global increase in diabetes, especially in developing nations, has escalated complications like diabetic foot ulcers. Hypovitaminosis D is considerably prevalent among individuals with Type 2 Diabetes Mellitus (T2DM), especially among those with chronic vascular complications.
Objectives: To determine the association between vitamin D levels and foot ulcers among patients with T2DM.

Methods: The study population comprised of 176 individuals (88 individuals with diabetic foot ulcers (DFUs) and 88 individuals with T2DM without DFU). Vitamin D levels were assessed using blood samples according to standard methods.

Results: The majority of participants in the DFU group presented with Grade 2 and Grade 3 ulcers. There was a significant difference in serum vitamin D levels, indicating lower levels among cases (mean of 19.6 ng/ml ± 13.6) compared to controls (mean of 36.2 ng/ml ± 11.4) with a p-value of 0.014. Data shows 84.1% of persons with foot ulcers had deficient/insufficient vitamin D, while only 29.5% of persons without DFU had deficient/insufficient vitamin D levels. Regression analysis shows that persons with DFU were 12.6 (6.0 - 26.2) times likely to have deficient/insufficient vitamin D levels. Chi-square analysis shows that the distribution of the DFU severity was significantly higher among persons with deficient Vitamin D levels, compared to persons with sufficient Vitamin D levels (p = 0.0001).

Conclusion: Lower serum vitamin D levels are significantly associated with diabetic foot ulcers (DFUs), potentially hindering healing and immune function. Screening for and correcting vitamin D deficiency may potentially improve the outcome in patients with diabetic foot ulcers.
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NewsBot · Jun 13, 2025

Nonlinear Association Between Serum 25-Hydroxyvitamin D and Cardiac Autonomic Dysfunction in Diabetic Foot: A Threshold Effect on Heart Rate Variability
Mingxin Bai et al
J Diabetes. 2025 Jun;17(6):e70109

Background: Previous studies have shown that vitamin D deficiency was associated with both cardiac autonomic dysfunction and the development of diabetic foot (DF). However, the impact of vitamin D levels on heart rate variability (HRV) in individuals with DF, a high-risk group, remains unclear. We explored the association between vitamin D status and HRV in individuals with DF.

Methods: A total of 458 individuals with DF were assessed for vitamin D levels by 25-hydroxyvitamin D (25(OH)D) and evaluated for cardiovascular autonomic function using both time and frequency domains of the HRV measures. Multivariate regression analysis and restricted cubic spline regression were employed to examine the associations.

Results: Vitamin D levels were positively associated with HRV indices in people with DF, including standard deviation of the normal sinus interval (SDNN), standard deviation of the 5-min average RR intervals (SDANN), low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio (all p < 0.05). The associations between serum 25(OH)D and cardiac autonomic dysfunction were nonlinear. When 25(OH)D levels were < 50 nmol/L, the odds ratio (OR) for predicted cardiac autonomic dysfunction per SD increase in 25(OH)D was 0.56 (95% CI, 0.44-0.72). However, no significant effect was observed when 25(OH)D levels exceeded 50 nmol/L.

Conclusions: This study demonstrates that lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.
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NewsBot · Jun 22, 2025

Serum Calcium, Vitamin D and C-Reactive Protein as Early Predictors for Diabetic Foot Ulcer
Nasir Abdelrafie Hamad et al
Source

Background: Diabetic foot ulcer (DFU) has emerged as a leading cause of morbidity and mortality among diabetic patients, with the numbers of amputation and death are significantly increasing. DFU has a complex multifactorial etiology with several pathophysiological mechanisms and risk factors implicated. Finding reliable indicators to predict the prognosis of diabetic foot has become an urgent and critical need. The current study aimed to investigate the association between levels of serum calcium, vitamin D and C-reactive protein and the development of DF. Methods: One hundred and twenty diabetic patients with a confirmed diagnosis of DFU were included in the study. The ratio of cases and control subjects was 1:1. We measured serum calcium, vitamin D, CRP, HbA1C, blood urea nitrogen (BUN), creatinine, total cholesterol, low-density lipoproteins (LDL) and triglycerides in both cases and control subjects. Results: The study found significantly low levels of serum calcium and vitamin D as well as high levels of HbA1C, CRP, serum creatinine, LDL, and TAG among cases. Conclusion: Serum calcium, vitamin D and CRP were significantly associated with DFU. As the treatment of DFU is challenging, these parameters might predict the development of DFU in diabetic patient and might therefore help reduce the morbidity and mortality associated with DFU.
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NewsBot · Jun 26, 2025

The Multi-Dimensional Role of Vitamin D in the Pathophysiology and Treatment of Diabetic Foot Ulcers: From Molecular Mechanisms to Clinical Translation
Weiwei Tang et al
Int J Mol Sci. 2025 Jun 14;26(12):5719.

Diabetic foot ulcers (DFUs) constitute a severe and debilitating complication of diabetes, imposing a substantial global health burden due to their intricate pathophysiology and impaired wound healing processes. Vitamin D deficiency is highly prevalent among diabetic populations, and accumulating evidence indicates its potential involvement in the pathogenesis and prognosis of DFUs. This review comprehensively explores the diverse roles of vitamin D in DFUs, encompassing its molecular mechanisms such as immunomodulation, promotion of angiogenesis, neuroprotection, and induction of antimicrobial peptides, as well as the metabolic characteristics associated with various vitamin D forms and compromised vitamin D receptor (VDR) signaling pathways. Although robust observational studies have established an association between vitamin D deficiency and adverse outcomes in DFUs, the clinical validation of supplementation efficacy through randomized controlled trials (RCTs) remains constrained by limitations such as small sample sizes, heterogeneity in study protocols, and insufficient long-term follow-up. This highlights the critical need for large-scale, high-quality studies to ascertain optimal treatment regimens and to cater to individualized patient requirements, particularly for individuals with obesity or those with renal impairments. Innovative strategies, such as the topical administration of vitamin D through intelligent delivery systems leveraging advanced biomaterials like nanofibers and hydrogels, exhibit substantial preclinical potential in enhancing stability, achieving targeted controlled release, and augmenting local biological effects, including the induction of antimicrobial peptides. Nevertheless, significant challenges persist in conclusively establishing clinical efficacy, comprehensively elucidating the underlying mechanisms, ensuring the safe translation of novel delivery systems, and developing personalized therapeutic strategies. The future success of these interventions hinges on meticulous research and interdisciplinary collaboration to seamlessly integrate validated vitamin D-based interventions into a comprehensive multidisciplinary management framework for DFUs, thereby holding promise for improving the clinical outcomes of this debilitating condition.
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NewsBot · Jun 29, 2025

Plasma vitamin D status and its association with biochemical, clinical and humanistic outcomes in diabetic foot infection patients: a prospective observational study in a tertiary healthcare facility
Shilia Jacob Kurian et al
Expert Rev Endocrinol Metab. 2025 May;20(3):233-239.

Background: The study aimed to determine the association of vitamin D3 status with biochemical, clinical, and quality of life (QoL) in diabetic foot infection (DFI) patients.

Research design and methods: A longitudinal study was conducted in a tertiary care hospital. Baseline biochemical (glycemic, renal, plasma vitamin D3), clinical, and QoL data of the DFI patients were collected. Patients were followed up with over the telephone for four months to assess clinical outcomes (healed/not healed). A subgroup analysis was performed to investigate the effect of vitamin D3 supplementation.

Results: Eighty-nine DFI patients were enrolled, with a median age of 55 years and a male predominance (89.9%). A significant association between vitamin D3 levels and clinical outcome was not observed (p = 0.66). A moderate correlation was observed with the neutrophil-lymphocyte ratio (r = 0.24, p = 0.02). Regarding QoL, emotions (domain) were significantly associated with vitamin D3 levels (p < 0.01). The subgroup analysis showed that vitamin D3 supplements did not affect the clinical outcome.

Conclusion: The plasma vitamin D3 levels and vitamin D3 supplements do not significantly affect the biochemical, clinical, and humanistic outcomes, indicating vitamin D3 did not have a positive effect on DFI patients.
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NewsBot · Jul 18, 2025

Vitamin D levels in diabetic foot ulcer patients: a meta-analysis and systematic review
Remya Reveendran, Sara Jones, Rajesh Chandramohanadas, Sreelathakumari Krishnan Thankam & Suchithra Tharamel Vasu
International Journal of Diabetes in Developing Countries

Background

Vitamin D deficiency has been identified as a contributing factor for diabetes mellitus (DM) through its potential role in compromising innate immunity. Diabetic foot ulcer (DFU) patients are at a higher risk of infections and delayed wound healing.
Objective

This systematic review aims to evaluate whether there is a significant link between vitamin D status and the occurrence of diabetic foot ulcers.
Methods

A comprehensive literature search was conducted in PubMed, Embase, Google Scholar, and the Cochrane Library databases up to May 30, 2023. Sixteen studies that met the inclusion criteria were included in the analysis. The quality of the studies was assessed using the Newcastle–Ottawa Scale. A total of 8341 patients were analyzed, including 2019 DFU patients and 6322 diabetic patients without foot ulcers. Meta-analysis was performed using the R software environment (version 4.2.2).
Results

The meta-analysis demonstrated a significant association between 25(OH)D levels and the occurrence of DFU. The weighted mean difference (WMD) in the random effects model was −4.13 ng/mL (95% CI −5.04 to −3.22, I² = 64%, p < 0.01).
Conclusion

There is a significant association between vitamin D deficiency and the presence of DFU in diabetic patients. Further studies are required to determine the efficacy of vitamin D supplementation in improving clinical outcomes for DFU patients.
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NewsBot · Jul 25, 2025

Vitamin D status and its association with diabetic complications in type 2 diabetes mellitus: A case-control study
Ashna Chackochan et al
Nutr Health. 2025 Jul 24:2601060251359708.

Background: Vitamin D deficiency remains as a significant public health challenge, even in sun-rich countries like India. Emerging evidence indicates that vitamin D plays a critical role in the pathophysiology of various chronic conditions, including type 2 diabetes mellitus (T2DM). Aim: Our study aims to examine the association between vitamin D deficiency and diabetic complications. Methods: This case-control study was conducted at a south Indian tertiary care facility between August 2023 and August 2024. The medical records of patients with T2DM admitted to the Department of Medicine between 2017 and 2022, with recorded vitamin D levels, were included. Patients with diabetic complications were enrolled as cases (n = 873), and those without any complications (n = 566) served as controls. The association between vitamin D deficiency and diabetic complications was determined using multivariate logistic regression, expressed as odds ratios (OR) with 95% confidence intervals (CI) using R version 4.4.1. Results: Multivariate logistic regression indicated that vitamin D deficiency was significantly associated with the development of diabetic complications, specifically neuropathy (adjusted OR (AOR) = 4.09, 95% CI 2.34-7.63, p < 0.001), nephropathy (AOR = 5.23, 95% CI 2.72-10.85, p < 0.001), retinopathy (AOR = 2.52 95% CI 1.44-4.69, p < 0.001), ischaemic heart disease (IHD) (AOR = 2.19, 95% CI 1.33-3.76, p = 0.003) and diabetic foot disease (DFD) (AOR = 2.66, 95% CI 1.34-5.91, p = 0.008). Vitamin D levels were significantly associated with factors affecting sun exposure, such as gender (p = 0.005), place of residence (p < 0.001) and type of occupation (p = 0.006). Conclusion: Vitamin D deficiency was found to be independently associated with neuropathy, nephropathy, retinopathy, IHD and DFD, indicating its possible involvement in the pathophysiology of these diabetic complications.
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NewsBot · Jul 27, 2025

Plasma vitamin D status and its association with biochemical, clinical and humanistic outcomes in diabetic foot infection patients: a prospective observational study in a tertiary healthcare facility
Shilia Jacob Kurian et al
Expert Review of Endocrinology & Metabolism

The study aimed to determine the association of vitamin D3 status with biochemical, clinical, and quality of life (QoL) in diabetic foot infection (DFI) patients.

Research design and methods
A longitudinal study was conducted in a tertiary care hospital. Baseline biochemical (glycemic, renal, plasma vitamin D3), clinical, and QoL data of the DFI patients were collected. Patients were followed up with over the telephone for four months to assess clinical outcomes (healed/not healed). A subgroup analysis was performed to investigate the effect of vitamin D3 supplementation.

Results
Eighty-nine DFI patients were enrolled, with a median age of 55 years and a male predominance (89.9%). A significant association between vitamin D3 levels and clinical outcome was not observed (p = 0.66). A moderate correlation was observed with the neutrophil-lymphocyte ratio (r = 0.24, p = 0.02). Regarding QoL, emotions (domain) were significantly associated with vitamin D3 levels (p < 0.01). The subgroup analysis showed that vitamin D3 supplements did not affect the clinical outcome.

Conclusion
The plasma vitamin D3 levels and vitamin D3 supplements do not significantly affect the biochemical, clinical, and humanistic outcomes, indicating vitamin D3 did not have a positive effect on DFI patients.
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NewsBot · Aug 24, 2025

Risk of Insufficient Hydroxyvitamin D Levels in Diabetic Foot Ulcers in Rivers State Nigeria
U D Batubo et al
West Afr J Med. 2025 Mar 31;42(3):225-230.

Background: The global increase in diabetes, especially in developing nations, has escalated complications like diabetic foot ulcers. Hypovitaminosis D is considerably prevalent among individuals with Type 2 Diabetes Mellitus (T2DM) and chronic vascular complications. The aim of this study was to determine the association between vitamin D levels and foot ulcers among patients with T2DM.

Methods: This study population comprised 88 individuals with diabetic foot ulcers (DFUs) and 88 individuals with T2DM without DFUs. Vitamin D levels were assayed using blood samples according to standard methods. An independent t-test was done to analyze the difference between serum vitamin D levels in both groups. Pearson's correlation coefficient and linear regression analysis were also performed.

Results: Majority of participants in the DFU group presented with Grade 2 and Grade 3 ulcers (Wagner's classification). There was a significant difference in serum vitamin D levels, indicating lower levels among cases (mean of 19.6 ng/ml ± 13.6) compared to controls (mean of 36.2 ng/ml ± 11.4) with a p-value of 0.014. Data shows 84.1% of persons with foot ulcers had deficient/insufficient serum vitamin D levels, while only 29.5% persons without DFU had deficient/insufficient vitamin D levels. Regression analysis shows that persons with DFU were 12.6 (6.0 - 26.2) times likely to have deficient/insufficient vitamin D levels. Chi-square analysis shows that the distribution of the DFU severity was significantly higher among persons with deficient serum Vitamin D levels (p = 0.0001).

Conclusion: Lower serum vitamin D levels are significantly associated with diabetic foot ulcers (DFUs). Screening for and correcting vitamin D deficiency may potentially improve the outcome in patients with diabetic foot ulcers
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NewsBot · Aug 24, 2025

Vitamin D supplementation reduces infection rate and promotes wound healing in patients with diabetic foot ulcers
Yue-Qiao Gao et al
World J Diabetes. 2025 Aug 15;16(8):108166

BACKGROUND

Diabetic foot ulcers (DFUs) represent a common and serious complication of diabetes, characterized by impaired wound healing and an increased risk of infection. These infections severely impact patient health, necessitating extensive medical intervention, and increasing the risk of amputation. Vitamin D (VD) plays a critical role in immune regulation and tissue repair.
AIM

To investigate the effects of VD supplementation on infection rates, wound healing, and immune function in patients with DFUs.
METHODS

A randomized controlled trial was conducted involving 120 patients with DFUs. Participants were randomly assigned to either a control group (n = 60), which received standard care without VD supplementation, or an intervention group (n = 60), which received 2000 IU of oral VD3 (cholecalciferol) daily for 12 weeks. The primary outcomes included the incidence and severity of infections, whereas the secondary outcomes included wound healing rate, serum 25-hydroxyvitamin D level, levels of immune markers (cathelicidin, interleukin-6 and tumor necrosis factor-α), and adverse events, such as hypercalcemia.
RESULTS

The incidence of infection was significantly lower in the VD supplementation group (25%) compared with the control group (45%) (P = 0.01). Severe infections requiring systemic antibiotics or hospitalization were also less frequent in the VD supplementation group. Wound healing was notably enhanced in the VD supplementation group, with a 60% reduction in ulcer size compared with a 35% reduction in the control group (P < 0.01). Serum 25(OH)D level significantly increased in the VD supplementation group (from 16.5 ng/mL to 35.2 ng/mL), confirming the efficacy of VD supplementation. Immune function improved, as demonstrated by a 30% rise in cathelicidin level and a 20% decline in levels of pro-inflammatory cytokines. No adverse effects, including hypercalcemia, were reported.
CONCLUSION

The VD supplementation effectively reduced infection rate, promoted wound healing, and strengthened immune responses in patients with DFUs. These findings support the incorporation of VD as a safe and effective adjunctive therapy in the clinical management of DFUs.
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NewsBot · Oct 30, 2025

Effects of Oral Cholecalciferol on Chronic Wound Healing in Patients with Vitamin D Insufficiency or Deficiency
Hui Zhao et al
J Multidiscip Healthc. 2025 Oct 24:18:6887-6900.

Background: Chronic wounds significantly impact patients' physical and mental health. Several individuals with chronic wounds have low vitamin D levels. Most previous studies have concentrated primarily on diabetic foot ulcers. Few investigations have explored the effects of vitamin D supplementation on different types of chronic wounds.

Purpose: This study aimed to evaluate the impact of increasing serum 25-hydroxyvitamin D (25(OH)D) concentration on participants with chronic wounds and vitamin D insufficiency or deficiency following cholecalciferol (vitamin D3) supplementation. Additionally, it explored the combined effects of wound care and vitamin D supplementation on wound healing outcomes.

Patients and methods: A total of 46 participants with chronic wounds who were admitted to a wound ostomy care clinic between February and December 2023 were enrolled and randomly assigned to intervention (n=23) and control (n=23) groups. Both groups received local wound treatment based on the tissue, infection, moisture, and edge (TIME) principles and were advised on dietary changes and sunlight exposure. The intervention group received 6000 international units (IUs) of oral cholecalciferol daily until week 5, after which doses were adjusted based on serum concentration.

Results: Of the 46 participants, 40 completed the study with 57 chronic wounds. Per-protocol analysis revealed a statistically significant difference in serum 25(OH)D concentration between the two groups at week 5 (mean ± standard deviation (SD): 36.75±7.23 vs 29.58±5.29 ng/mL, P<0.01). The intervention group had a shorter average wound healing time than the control group (mean ± SD: 15.59±6.27 vs 26.16±12.70 days, P<0.01). Additionally, wound area reduction rate, wound depth reduction rate, and pressure ulcer scale for healing (PUSH) scores were significantly higher in the intervention group (P<0.05).

Conclusion: These findings suggest that oral cholecalciferol supplementation increases 25(OH)D concentrations and promotes chronic wound healing.
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NewsBot · Jan 4, 2026

Association of Serum Vitamin D Status with Multidimensional Health Parameters in Patients with Diabetic Foot Infections: A Cross-Sectional Analysis in a Tertiary Healthcare Facility
Ruby Benson, et al
Source

Aims/Introduction
Vitamin D deficiency is prevalent among individuals with diabetic foot infections (DFIs) and can influence a range of patient-related parameters. Hence, we aimed to find the association of serum vitamin D levels with various clinical, biochemical, and inflammatory parameters, as well as the microbial environment in the wounds of DFI patients.
Materials and Methods
From September 2022 to March 2024, 169 DFI patients participated in cross-sectional research at the hospital. Utilising an electrochemiluminescence immunoassay, vitamin D levels were determined. Vitamin D receptor (VDR) and Cathelicidin (LL-37) were estimated using ELISA Kits. The tissue culture plate technique was used to analyze biofilm formation. Patient-related parameters were obtained from medical records.
Results
The vitamin D status of DFI patients indicated that 70.4% were deficient, 19.5% were insufficient, and 10.1% were sufficient. The median vitamin D, VDR protein, and LL-37 values were 15.3 ng/mL, 0.832 ng/mL, and 1.54 ng/mL, respectively. Biofilm formation was seen in 84.36% of bacteria from vitamin D-deficient DFI patients (P < .001). Vitamin D levels were negatively correlated with ulcer duration, hospital stay, white blood cell count, neutrophil-lymphocyte ratio, C-reactive protein, and systemic inflammation index (r = −0.787, −0.849, −0.6, −0.475, −0.402, and −0.521, respectively; P < .001). However, vitamin D levels were positively correlated with VDR and LL-37 levels (r = 0.988 and 0.944, respectively; P < .001).
Conclusions
The majority of DFI patients exhibited vitamin D deficiency, which was significantly associated with most of the clinical, biochemical, and inflammatory parameters, in addition to the microbial environment within the wound.
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NewsBot · Mar 8, 2026

The Relationship Between Vitamin D Levels and the Presence of Ulcers, Balance, and Mobility in Patients with Diabetic Foot Disease
Elif Can Özdemir et al
Source

Objective
The objective of this study was to ascertain the relationships between Vitamin D levels and ulcers, balance, and mobility in patients with diabetic foot disease.
Material and Methods
This study is a cross-sectional study based on the prospective examination of diabetic foot patients referred from the diabetic foot outpatient clinic of Gülhane Training and Research Hospital to the Physical Medicine and Rehabilitation Clinic. The present study was conducted with a total of 120 diabetic patients, including 60 with diabetic foot ulcers (DFU group) and 60 with non-DFU group comprises of diabetic peripheral neuropathy. The Functional Ambulation Scale (FAS) and the 10-Meter Walk Test were utilized to assess mobility. The evaluation of balance was conducted using the Tinetti balance test.
Results
The study found no significant differences in vitamin D levels between the groups; however, calcium levels were found to be significant in DFU group. Patients with DFU group exhibited lower scores on the Tinetti balance test and the Functional Ambulation Scale (P < .05).
Conclusion
The findings of this study suggest that diabetic foot ulcers are associated with the risk of falling and mobility limitations. Conversely, no substantial discrepancy in vitamin D levels was observed between the two groups, with and without ulcers. This finding indicates that the balance and mobility impairments observed in the DFU group may have developed independently of vitamin D levels.
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NewsBot · Mar 16, 2026

Vitamin D status in relation to lower extremity arterial plaque and diabetic foot ulcers in type 2 diabetes
Yuqing Liu et al
J Int Med Res. 2026 Mar;54(3):3000605251367675

ObjectivesLimited evidence exists regarding the association of vitamin D status with lower extremity arterial plaque progression and diabetic foot ulcer outcomes. This study investigated the relationship between vitamin D status and the risk of lower extremity arterial plaque progression and diabetic foot ulcer development.MethodsIn this cross-sectional analysis of 7476 consecutively hospitalized type 2 diabetes patients (2018-2024), serum 25-hydroxyvitamin D level was measured using the electrochemiluminescence method. Vitamin D deficiency (<20 ng/mL) and insufficiency (20-30 ng/mL) were defined per the Endocrine Society guidelines. Lower extremity arterial plaque was identified using arterial Doppler ultrasonography, and diabetic foot ulcer was diagnosed using the International Working Group on the Diabetic Foot 2019 criteria. Multivariate logistic regression and receiver operating characteristic analyses were used to evaluate associations between parameters.ResultsDecreased 25-hydroxyvitamin D levels were correlated with adverse lipid profiles (high-density lipoprotein cholesterol: r = 0.152, P < 0.001) and elevated inflammatory markers (high-sensitivity C-reactive protein: r = -0.086, P < 0.001). Lower extremity arterial plaque patients (n = 4622) exhibited longer diabetes duration, higher glycosylated hemoglobin levels, and reduced 25-hydroxyvitamin D levels compared with those without lower extremity arterial plaque (19.98 vs. 23.41 ng/mL, P < 0.001). The prevalence of diabetic foot ulcer in lower extremity arterial plaque patients was 2.8%, and the levels of 25-hydroxyvitamin D were significantly lower in diabetic foot ulcer patients than in nondiabetic foot ulcer patients (14.77 vs. 19.98 ng/mL, P < 0.001). Adjusted models revealed that 25-hydroxyvitamin D level was an independent protective factor against lower extremity arterial plaque (odds ratio = 0.938, 95% confidence interval: 0.914-0.963) and diabetic foot ulcer (odds ratio = 0.938, 95% confidence interval: 0.932-0.944). Receiver operating characteristic curve analysis demonstrated that a 25-hydroxyvitamin D level ≤18.94 ng/mL predicted lower extremity arterial plaque, with an area under the curve value of 0.651, which improved to 0.703 when combined with the duration of diabetes and white blood cell count. For diabetic foot ulcer prediction, a 25-hydroxyvitamin D level ≤17.11 ng/mL achieved an area under the curve value of 0.674, which increased to 0.764 after adjusting for covariates.ConclusionVitamin D insufficiency is independently associated with lower extremity arterial plaque severity and incident diabetic foot ulcer in type 2 diabetes. Therapeutic implications of vitamin D supplementation warrant prospective investigation.
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Vitamin D supplementation and diabetic foot ulcers

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Vitamin D supplementation and diabetic foot ulcers

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Growing pains and vitamin D supplementation

Vitamin D deficiency and fatigue in children

Calcaneal spur and vitamin D, lipid profile and calcitonin

Vitamin C to prevent CRPS after foot surgery

Vitamin D and verrucae

Westmead study shows vitamin C prevents ulcer-related amputations

Vitamin B12 Deficiency and Foot Ulcers in Type 2 Diabetes Mellitus

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