SLR - May 2018 - Gavin Lee

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

Reference: Razzaghi R, Poubagheri H, Momen-Heravi M, Bahmani F, Shadi J, Soleimani Z, Asemi Z. 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.

Scientific Literature Review

Reviewed By: Gavin Lee, DPM
Residency Program: Kaiser Permanente North Bay Consortium, Vallejo, CA

Podiatric Relevance: While surgery is not the primary treatment option for diabetic foot ulcers (DFU), it becomes a necessary tool at times. In some cases, performing surgery with an active ulceration is unavoidable; however, it is always advisable to perform surgery after the ulceration has healed. DFUs are often multifactorial in etiology and can prove difficult to heal. Similar to the surgical perspective of adequate nutritional status for surgical healing, nutritional status also proves to be of the utmost importance when it comes to ulcer healing. One new consideration for DFU healing is vitamin D supplementation. This article set out to investigate how vitamin D would ultimately influence wound healing and metabolic status in patients with DFUs.

Methods: This prospective randomized double-blind placebo-controlled clinical trial included 60 patients ranging between 40 and 85 years old with grade 3 DFU using the Wagner-Meggitt’s classification system between 2015 and 2016.

Primary outcomes were designated as wound healing and markers of insulin resistance while secondary outcomes were designated as lipid profiles, biomarkers of inflammation and oxidative stress.

The interventional group received 50,000 IU vitamin D supplements every two weeks for 12 weeks versus placebo. Both groups received similar treatment protocol based on the Infectious Diseases Society of America recommendations with follow-up every two weeks for intermediate evaluation and ulcer debridement. Food and physical activity records in metabolic equivalents (METs) were recorded every three weeks.

Primary outcomes:

  • Ulcer size: significant reduction in ulcer length, width and depth
  • Markers of insulin resistance:
    • Significant reduction in homeostasis model of assessment-insulin resistance (HOMA-IR), homeostasis model of assessment-B cell function (HOMA-B) and HbA1c
    • Significant increase in quantitative insulin sensitivity check index (QUICKI)
    • No significant difference in fasting plasma glucose

  • Secondary outcomes:
    • Lipid profiles: significant reduction in serum total-, LDL-, total-/HDL-cholesterol ratio. No significant differences in triglyceride or VLDL.
    • Biomarkers of inflammation and oxidative stress: significant reduction in hs-CRP, ESR and plasma malondialdehyde (MDA) concentrations. No significant differences in plasma nitric oxide, plasma total antioxidant capacity or total glutathione.
  • Other: significant increase in serum 25-hydroxyvitamin D levels
Conclusions: Limitations: the main limitations of this study are a small sample size and individual differences that are difficult to control for like changes in insulin regimens, which would play a role in glucose management. 

This study’s results suggest that vitamin D supplementation of 50,000 IU for 12 weeks has a positive effect on ulcer healing in all dimensions in addition to improvement in markers of insulin resistance. However, it is difficult to discern whether the decrease in ulcer size is a direct effect of vitamin D or an indirect effect from glycemic control as hyperglycemia inherently impedes wound healing.

From a surgical perspective, vitamin D has also been a topic of interest when it comes to nutritional status and bone healing potential. Extrapolation of current data would suggest that vitamin D supplementation could assist in both bone and wound or soft-tissue healing, especially when it comes to high-risk patients with diabetes.

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