The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial

J Diabetes Complications. 2017 Apr;31(4):766-772. doi: 10.1016/j.jdiacomp.2016.06.017. Epub 2016 Jun 23.


Objective: This study was conducted to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer (DFU).

Methods: This randomized, double-blind, placebo-controlled trial was performed among 60 patients with grade 3 DFU according to "Wagner-Meggitt's" criteria. Participants were randomly divided into two groups (each 30 participants) and received either 50,000IU vitamin D supplements every 2weeks for 12weeks (group A) or placebo (group B). Fasting blood samples were taken at study baseline and after 12-week intervention to determine related markers.

Results: After 12weeks of intervention, compared with the placebo, vitamin D supplementation resulted in a significant reduction in ulcer length (-2.1±1.1 vs. -1.1±1.1cm, P=0.001), width (-2.0±1.2 vs. -1.1±1.0cm, P=0.02) and depth (-1.0±0.5 vs. -0.5±0.5cm, P<0.001), and erythema rate (100% vs. 80%, P=0.01). In addition, in supplemented patients changes in serum insulin concentration (-3.4±9.2 vs. +2.8±9.3 μIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-1.5±4.1 vs. +1.7±5.1, P=0.01), the quantitative insulin sensitivity check index (+0.006±0.02 vs. -0.006±0.02, P=0.03) and HbA1c (-0.6±0.6 vs. -0.1±0.5%, P=0.004) were significantly different from those of patients in the placebo group. Additionally, following supplementation with vitamin D, significant reductions in serum total- (-15.8±18.9 vs. +5.3±31.8mg/dL, P=0.003), LDL- (-17.2±19.8 vs. +2.2±28.6mg/dL, P=0.003), total-/HDL-cholesterol ratio (-1.1±0.8 vs. -0.2±1.1, P=0.001), high sensitivity C-reactive protein (hs-CRP) (-0.4±2.5 vs. +1.9±4.2μg/mL, P=0.01), erythrocyte sedimentation rate (ESR) (-34.7±32.4 vs. -18.0±26.6mm/h, P=0.03) and plasma malondialdehyde (MDA) concentrations (-0.7±0.9 vs. -0.2±0.5μmol/L, P=0.008) were seen compared with the placebo.

Conclusions: Overall, vitamin D supplementation for 12weeks among patients with DFU had beneficial effects on glucose homeostasis, total-, LDL-, total-/HDL-cholesterol, ESR, hs-CRP and MDA levels. In addition, vitamin D may have played an indirect role in wound healing due to its effect on improved glycemic control.

Keywords: Diabetic foot; Inflammation; Insulin resistance; Vitamin D supplementation; Wound healing.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / therapeutic use
  • Biomarkers / blood
  • Combined Modality Therapy
  • Diabetic Foot / complications*
  • Diabetic Foot / metabolism
  • Diabetic Foot / physiopathology
  • Diabetic Foot / therapy
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin Resistance*
  • Iran
  • Male
  • Middle Aged
  • Oxidative Stress
  • Severity of Illness Index
  • Vitamin D / therapeutic use*
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / diet therapy*
  • Wound Healing


  • Anti-Inflammatory Agents
  • Biomarkers
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Vitamin D