Improved Healing of Diabetic Foot Ulcers After High-dose Vitamin D: A Randomized Double-blinded Clinical Trial

Abstract

Background. Chronic foot ulcers are a major cause of morbidity in people with diabetes with a lifetime risk of 25%. Treatment is challenging and the recurrence rates of foot ulcers are >50% after 3 years. Vitamin D deficiency is more common in people with diabetes with chronic foot ulcers, compared to both people without diabetes as well as people with diabetes but without foot ulcers. Purpose/aim of study. To assess the efficacy of high-dose compared to low-dose Cholecalciferol vitamin D3 on healing of chronic diabetic foot ulcers. Materials and methods. We included people with diabetes with one or more foot ulcers lasting for more than 6 weeks. Patients were randomly allocated to either a daily oral intake of high-dose (170 μg) or low-dose (20 μg) vitamin D3 (Cholecalciferol). We saw patients in the outpatient clinic after 4, 12, 24, 36, and 48 weeks. At each visit, we measured the ulcer with a specialized camera, and associated software and the area (cm²) was calculated. Patients and assessors were blinded to treatment allocation. We followed all patients for 48 weeks or until wound healing or surgical treatment. Findings/results. We included 48 patients in the analysis (24 in each group), with a total of 64 ulcers. Among them 41 ulcers were followed until healing or 48-week follow-up and 20 ulcers were surgically treated during the study period. Three patients were lost for follow-up. The intention-to-treat analysis showed a significantly higher rate of ulcer healing in the high-dose group with 21 of 30 (70%) healed ulcers compared to 12 of 34 (35%) in the low-dose group (P = .012). Median ulcer reduction at final follow-up was 100% (interquartile range [IQR]: 72-100) in the high-dose group and 57% (IQR: −28 to 100) in the low-dose group. Furthermore, we found a significant effect of high-dose vitamin D on ulcer reduction in the repeated measures analysis of variance. Conclusions. We found high-dose vitamin D3 to be efficient, compared to low-dose vitamin D3, in promoting healing in chronic diabetic foot ulcers.