SLR - January 2024 - Talisse
Title: Improved Healing of Diabetic Foot Ulcers After High-dose Vitamin D: A Randomized Double-blinded Clinical TrialReference: Halschou-Jensen PM, Sauer J, Bouchelouche P, Fabrin J, Brorson S, Ohrt-Nissen S. Improved Healing of Diabetic Foot Ulcers After High-dose Vitamin D: A Randomized Double-blinded Clinical Trial. Int J Low Extrem Wounds. 2023;22(3):466-474.
Level of Evidence: Level II
Scientific Literature Review
Reviewed By: Peter Talisse, DPM
Residency Program: Emory University School of Medicine
Podiatric Relevance: Chronic foot ulcers are among the most common complications of patients with diabetes mellitus. The morbidity and cost burden surrounding diabetic foot ulcers result in a severe reduction in quality of life for patients. Vitamin D deficiency has been shown to be common in adults aged 30 to 60 and targeting patients with chronic illnesses. Clinical studies report vitamin D supplementation to have an inhibitory effect on the development of osteoporosis, insulin resistance, biomarkers of inflammation, and oxidative stress. With this knowledge, this study examines diabetic foot ulcer healing rates with high dose oral vitamin D through a randomized controlled trail.
Methods: Forty-eight patients with sixty-four ulcers with diabetes mellitus were included in this randomized, parallel, double-blinded, and controlled clinical trial. Patients with one or more ulcers of the lower extremity without healing for more than six weeks were included. Exclusion criteria included critical ischemia, sepsis or ulcers that required surgical debridement upon initial visit. Also, patients with hypercalcemia, renal impairment, or patients already on vitamin D supplements were excluded. Patients were allocated to either a daily oral intake of high-dose (170 μg) or low-dose (20 μg) vitamin D3. A specialized camera was used to measure the ulcer area throughout each scheduled follow up visit until complete healing, surgical treatment, or a total time of forty-eight weeks. Vaseline vitamin D levels were tested to explore the importance of vitamin D deficiency. Blood levels of hemoglobin A1c were also measured throughout the trial noting its effects on healing capacity.
Results: Forty-one ulcers were followed until complete healing or the forty-eight-week follow-up. Twenty ulcers were surgically treated during this period which excluded them from the final measurement. A significantly higher rate of ulcer healing was found in the high-dose group with 21 of 30 (70%) compared to 12 of 34 (35%) in the low-dose group (P=.012). The median ulcer reduction at final follow-up was 100% in the high-does group compared to 57% in the low-does group. The baseline vitamin D levels revealed deficiency in twenty-three patients (48%).
Conclusions: The authors found a substantial effect of high-dose compared to low-dose vitamin D in promoting healing in chronic diabetic foot ulcers. Vitamin D promotes healing by regulation of cellular proliferation, differentiation, and angiogenesis. This study provides clinical and statistical significance of vitamin D’s effects in wound healing. Whether the patient at baseline was deficient or not, oral intake of vitamin D showed a positive effect. Dosing for each patient may differ to reach a target serum 25(OH)D concentration. Moving forward, I will start by utilizing a moderate to higher daily dose with patients with chronic foot ulcers. In the study, there was no evidence of adverse effects with the high-dose group as subjects were monitored with ionized calcium, PTH, and 25(OH)D serum levels. This information allows me to feel comfortable prescribing oral vitamin D intake for patients with diabetic foot ulcers.