Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: a Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Reza Razzaghi
Zatollah Asemi
Fereshteh Bahmani
Mansooreh Momen-Heravi
Farangis Pidar
Hossein Akbari
Journal: Biological trace element research (2018)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Diabetic foot; Magnesium supplementation; Metabolic status; Wound healing.
Affiliations: Department of Infectious Disease, School of Medicine, Kashan University of Medical Sciences, Kashan, IR, Iran., Social Determinants of Health Research Center, Kashan University of Medical Sciences, Kashan, IR, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, IR, Iran., Department of Biostatistics, Kashan University of Medical Sciences, Kashan, IR, Iran., Research Center for Biochemistry and Nutrition in Metabolic Diseases, Kashan University of Medical Sciences, Kashan, IR, Iran. .

Abstract:  Hypomagnesemia is associated with the development of neuropathy and abnormal platelet activity, both of which are risk factors for diabetic foot ulcer (DFU). This study was carried out to evaluate the effects of magnesium administration on wound healing and metabolic status in subjects with DFU. This randomized, double-blind, placebo-controlled trial was performed among 70 subjects with grade 3 DFU. Subjects were randomly divided into two groups (35 subjects each group) to receive either 250 mg magnesium oxide supplements or placebo daily for 12 weeks. Pre- and post-intervention wound depth and appearance were scored in accordance with the "Wagner-Meggitt's" wound assessment tool. Fasting blood samples were taken at baseline and after the 12-week intervention to assess related markers. After the 12-week treatment, compared with the placebo, magnesium supplementation resulted in a significant increase in serum magnesium (+0.3 ± 0.3 vs. -0.1 ± 0.2 mg/dL, P &lt; 0.001) and significant reductions in ulcer length (-1.8 ± 2.0 vs. -0.9 ± 1.1 cm, P = 0.01), width (-1.6 ± 2.0 vs. -0.8 ± 0.9 cm, P = 0.02), and depth (-0.8 ± 0.8 vs. -0.3 ± 0.5 cm, P = 0.003). In addition, significant reductions in fasting plasma glucose (-45.4 ± 82.6 vs. -10.6 ± 53.7 mg/dL, P = 0.04), serum insulin values (-2.4 ± 5.6 vs. +1.5 ± 9.6 μIU/mL, P = 0.04), and HbA1c (-0.7 ± 1.5 vs. -0.1 ± 0.4%, P = 0.03) and a significant rise in the quantitative insulin sensitivity check index (+0.01 ± 0.01 vs. -0.004 ± 0.02, P = 0.01) were seen following supplementation of magnesium compared with the placebo. Additionally, compared with the placebo, taking magnesium resulted in significant decrease in serum high-sensitivity C-reactive protein (hs-CRP) (-19.6 ± 32.5 vs. -4.8 ± 11.2 mg/L, P = 0.01) and significant increase in plasma total antioxidant capacity (TAC) concentrations (+6.4 ± 65.2 vs. -129.9 ± 208.3 mmol/L, P &lt; 0.001). Overall, magnesium supplementation for 12 weeks among subjects with DFU had beneficial effects on parameters of ulcer size, glucose metabolism, serum hs-CRP, and plasma TAC levels. Clinical trial registration number: http://www.irct.ir : IRCT201612225623N96. 

Retracted: No

PubPeer comments:
 There are many concerns about the integrity of 172 publications by this research group, including this one. Some of the concerns are published 1. Anaesthesia 2020;75:1683u201392, see Supplementary data. This paper is A162 2. Account Res 2020;28:149-61. 3. J Clin Epidemiol 2021;131:22-29. Journals and publishers were notified of these concerns in July 2019. 18 publications have an expression of concern, and 6 have been retracted. To our knowledge there has been no public response about any of the concerns. We think these publications are unreliable , 
 Could you check the citation to Anaesthesia, please? I looked for it but while the year and issue exist and span those page numbers, the paper is not there. , 
 I think, in particular, Dr. Grey is trying to draw attention to  Empirically generated reference proportions for baseline p values from rounded summary statistics in Anaesthesia 2020;75:1685-1687; I believe the supplementary information is available in the web edition of said publication under  Supporting information , 
 Thanks. Yes, please see Supporting Information at: https: associationofanaesthetists-publications.onlinelibrary.wiley.com doi full 10.1111 anae.15165 ,