Expression of Concern: The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double‐blind, placebo‐controlled trial

Abstract

This study was performed to determine the effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer. The current randomized, double-blind, placebo-controlled trial was conducted among 60 patients (aged 40-85 years old) with grade 3 diabetic foot ulcer. Participants were randomly divided into two groups (30 participants in each group) to take either 220 mg zinc sulfate supplements containing 50 mg elemental zinc or placebo daily for 12 weeks. After the 12-week intervention, compared with the placebo, zinc supplementation was associated with significant reductions in ulcer length (-1.5 ± 0.7 vs. -0.9 ± 1.2 cm, p = 0.02) and width (-1.4 ± 0.8 vs. -0.8 ± 1.0 cm, p = 0.02). In addition, changes in fasting plasma glucose (-40.5 ± 71.0 vs. -3.9 ± 48.5 mg/dl, p = 0.02), serum insulin concentration (-8.0 ± 15.4 vs. +1.1 ± 10.3 µIU/ml, p = 0.009), homeostasis model of assessment-estimated insulin resistance (-3.9 ± 7.1 vs. +0.8 ± 5.9, p = 0.007), the quantitative insulin sensitivity check index (+0.01 ± 0.03 vs. -0.002 ± 0.02, p = 0.04) and HbA1c (-0.5 ± 0.8 vs. -0.1 ± 0.5%, p = 0.01) in the supplemented group were significantly different from the changes in these indicators in the placebo group. Additionally, significant increases in serum HDL-cholesterol (+4.1 ± 4.3 vs. +1.1 ± 5.1 mg/dl, p = 0.01), plasma total antioxidant capacity (+91.7 ± 213.9 vs. -111.9 ± 188.7 mmol/L, p < 0.01) and total glutathione (+68.1 ± 140.8 vs. -35.0 ± 136.1 µmol/L, p = 0.006), and significant decreases in high sensitivity C-reactive protein (-20.4 ± 24.6 vs. -6.8 ± 21.3 µg/ml, p = 0.02) and plasma malondialdehyde concentrations (-0.6 ± 0.9 vs. -0.2 ± 0.7 µmol/L, p = 0.03) were seen following supplementation with zinc compared with the placebo. Zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles.

Update on management of diabetic foot ulcers

“…96,97 There has been growing interest in various vitamins and supplements and their impact on wound healing. In 2017, several RCTs evaluated the use of magnesium, omega-3 fatty acids, zinc sulfate, and vitamin D. [98][99][100][101] All of the aforementioned studies showed significant benefits in reduction in wound size when compared with placebo. More studies will need to be performed to validate these findings.…”

Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update)

“…It is recognized that in individuals with DFUs, infection, antimicrobial agent use, and reduced mobility coupled with possible suboptimal glycaemic control may drive a catabolic state leading to protein energy malnutrition as well as inherent inability to optimize macro and micronutrient usage. 109 We found one study on zinc supplementation, 110 one study on magnesium replacement, 111 one on omega-3 supplementation 112 another on the effect of vitamin D replacement on diabetic foot ulceration, 113 and one on the use of probiotics. 114 All observed an apparent benefit from supplementation, on ulcer length, width, and depth as secondary outcome measures.…”

Preventing Diabetes and Diabetic Cardiovascular Diseases with Dietary Zinc

“…This was further confirmed by subsequent systemic review, showed that zinc supplementation in T2D patients has improved glycemic control, since the %HbA1c significantly reduced in these individuals [16]. In addition, a recent randomized, doubleblind, placebo-controlled trial confirmed that zinc supplementation for 12 weeks among diabetic foot ulcer patients had beneficial effects on parameters of ulcer size and metabolic profiles [17].…”