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.
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.
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.
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
size: significant reduction in ulcer length, width and depth
of insulin resistance:
reduction in homeostasis model of assessment-insulin resistance (HOMA-IR), homeostasis
model of assessment-B cell function (HOMA-B) and HbA1c
increase in quantitative insulin sensitivity check index (QUICKI)
- No significant
difference in fasting plasma glucose
profiles: significant reduction in serum total-, LDL-, total-/HDL-cholesterol
ratio. No significant differences in triglyceride or VLDL.
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.
significant increase in serum 25-hydroxyvitamin D levels
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.
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.