Nutritional Supplementation Concurrent with Nutrition Education Accelerates the Wound Healing Process in Patients with Diabetic Foot Ulcers

Raedeh Basiri, Maria T Spicer, Cathy W Levenson, Michael J Ormsbee, Thomas Ledermann, Bahram H Arjmandi, Raedeh Basiri, Maria T Spicer, Cathy W Levenson, Michael J Ormsbee, Thomas Ledermann, Bahram H Arjmandi

Abstract

Trials on nutritional supplements for the treatment of diabetic foot ulcer (DFU) have only evaluated the effects of supplementation with specific nutrients. Additionally, nutrition education has not been a systematic part of these studies. The aim of this study was to evaluate the effects of a nutrient-dense formula combined with nutrition education on wound healing in DFU patients. Twenty-nine patients were randomly assigned to the treatment group (n = 15) receiving two servings of supplements daily plus nutrition education or control group (n = 14) that received the standard of care but no additional nutritional or educational intervention. Both groups were followed for a maximum of 12 weeks. Wound healing, as measured by planimetry, was examined at baseline and every four weeks until complete wound closure or up to 12 weeks. There were no significant differences between groups for BMI, age, duration of diabetes, wound age estimation, or wound area at baseline. The treatment group experienced a faster wound healing rate (6.43 mm2/week more reduction in the wound area) than the control group. The mean reduction in the wound area during the first four weeks of the study was almost 13-fold greater in the treatment group compared to the control group (18.0 mm2/week vs. 1.4 mm2/week, respectively). Our findings showed that nutrition supplementation plus nutrition education significantly accelerated wound healing in DFU patients compared to those who just received a standard-of-care regimen.

Keywords: antioxidants; diabetes; diabetic foot ulcers; malnutrition; nutrition education; nutrition supplementation; wound healing.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Mean percent nutrient intake in DFU patients. Numbers show the percentage intake compared to Dietary Recommended Intake at baseline.
Figure 3
Figure 3
(A–E). Intake of zinc (A), copper (B), vitamin A (C), C (D), and E (E) during the 12 weeks of follow up. The numbers for the control group show intake from diet and for treatment group show a combination of intakes from two servings of supplements and diet. The difference between the mean zinc intake of the two groups was statistically significant in weeks four and eight and twelfth of the study (p = 0.02). The interaction between group and time was statistically significant for copper, vitamin A, C, and E (p < 0.001, p = 0.001, p < 0.001, p < 0.001, respectively). Bars represent the means ± SEM. * Denotes a significant time by group interaction (p ≤ 0.05).
Figure 4
Figure 4
Comparison of the healing rate during the 12 weeks of the study period. Bars represent the means ± SEM. * Denotes a significant time by group interaction (p ≤ 0.05).

References

    1. Zhang P., Lu J., Jing Y., Tang S., Zhu D., Bi Y. Global epidemiology of diabetic foot ulceration: A systematic review and meta-analysis. Ann. Med. 2017;49:106–116. doi: 10.1080/07853890.2016.1231932.
    1. CDC CDC Press Releases. [(accessed on 7 March 2019)];2016 Available online: .
    1. Raghav A., Khan Z.A., Labala R.K., Ahmad J., Noor S., Mishra B.K. Financial burden of diabetic foot ulcers to world: A progressive topic to discuss always. Ther. Adv. Endocrinol. Metab. 2018;9:29–31. doi: 10.1177/2042018817744513.
    1. Maier H.M., Ilich-Ernst J., Arjmandi B., Kim J.-S., Spicer M. Deficiencies in Nutritional Intake in Patients with Diabetic Foot Ulcers. J. Nutr. Ther. 2016;5:85–92. doi: 10.6000/1929-5634.2016.05.04.1.
    1. Sajid N., Miyan Z., Zaidi S.I.H., Jaffri S.S.A., AbdeAli M. Protein requirement and its intake in subjects with diabetic foot ulcers at a tertiary care hospital. Pak. J. Med. Sci. 2018;34:886–890. doi: 10.12669/pjms.344.15399.
    1. Zhang S.-S., Tang Z.-Y., Fang P., Qian H.-J., Xu L., Ning G. Nutritional status deteriorates as the severity of diabetic foot ulcers increases and independently associates with prognosis. Exp. Ther. Med. 2013;5:215–222. doi: 10.3892/etm.2012.780.
    1. Gau B.-R., Chen H.-Y., Hung S.-Y., Yang H.M., Yeh J.T., Huang C.H., Sun J.H., Huang Y.Y. The impact of nutritional status on treatment outcomes of patients with limb-threatening diabetic foot ulcers. J. Diabetes Complicat. 2016;30:138–142. doi: 10.1016/j.jdiacomp.2015.09.011.
    1. Tatti P., Barber A.E. The Use of a Specialized Nutritional Supplement for Diabetic Foot Ulcers Reduces the Use of Antibiotics. J. Endocrinol. Metab. 2012;2:26–31. doi: 10.4021/jem64w.
    1. Sipahi S., Gungor O., Gunduz M., Cilci M., Demirci M.C., Tamer A. The effect of oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine and glutamine on wound healing: A retrospective analysis of diabetic haemodialysis patients. BMC Nephrol. 2013;14:8. doi: 10.1186/1471-2369-14-8.
    1. Afzali H., Jafari Kashi A.H., Momen-Heravi M., Razzaghi R., Amirani E., Bahmani F., Gilasi H.R., Asemi Z. The effects of magnesium and vitamin E co-supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial. Wound Repair Regen. 2019;27:277–284. doi: 10.1111/wrr.12701.
    1. Oyibo S.O., Jude E.B., Tarawneh I., Nguyen H.C., Harkless L.B., Boulton A.J.M. A Comparison of Two Diabetic Foot Ulcer Classification Systems: The Wagner and the University of Texas wound classification systems. Diabetes Care. 2001;24:84–88. doi: 10.2337/diacare.24.1.84.
    1. Arrendale J.R., Cherian S.E., Zineh I., Chirico M.J., Taylor J.R. Assessment of Glycated Hemoglobin Using A1CNow+TM Point-of-Care Device as Compared to Central Laboratory Testing. J. Diabetes Sci. Technol. 2008;2:822–827. doi: 10.1177/193229680800200512.
    1. Thompson C., Fuhrman M.P. Nutrients and Wound Healing: Still Searching for the Magic Bullet. Nutr. Clin. Pract. 2005;20:331–347. doi: 10.1177/0115426505020003331.
    1. Stechmiller J.K. Understanding the role of nutrition and wound healing. Nutr. Clin. Pract. 2010;25:61–68. doi: 10.1177/0884533609358997.
    1. Haesler E., editor. Prevention and Treatment of Pressure Ulcers: Quick Reference Guide. Cambridge Media; Osborne Park, Australia: 2014. National Pressure Ulcer Advisory Panel, European Pressure Ulcer Advisory Panel and Pan Pacific Pressure Injury Alliance.
    1. Razzaghi R., Pidar F., Momen-Heravi M., Bahmani F., Akbari H., Asemi Z. Magnesium Supplementation and the Effects on Wound Healing and Metabolic Status in Patients with Diabetic Foot Ulcer: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol. Trace Elem. Res. 2018;181:207–215. doi: 10.1007/s12011-017-1056-5.
    1. Cereda E., Klersy C., Serioli M., Crespi A., D’Andrea F. OligoElement Sore Trial Study Group. A nutritional formula enriched with arginine, zinc, and antioxidants for the healing of pressure ulcers: A randomized trial. Ann. Intern. Med. 2015;162:167–174. doi: 10.7326/M14-0696.
    1. Cereda E., Gini A., Pedrolli C., Vanotti A. Disease-Specific, Versus Standard, Nutritional Support for the Treatment of Pressure Ulcers in Institutionalized Older Adults: A Randomized Controlled Trial. J. Am. Geriatr. Soc. 2009;57:1395–1402. doi: 10.1111/j.1532-5415.2009.02351.x.
    1. Calder P.C., Albers R., Antoine J.-M., Blum S., Bourdet-Sicard R., Ferns G.A., Folkerts G., Friedmann P.S., Frost G.S., Guarner F. Inflammatory Disease Processes and Interactions with Nutrition. Br. J. Nutr. 2009;101:1–45. doi: 10.1017/S0007114509377867.
    1. Guo S., DiPietro L.A. Factors Affecting Wound Healing. J. Dent. Res. 2010;89:219–229. doi: 10.1177/0022034509359125.
    1. Langemo D., Anderson J., Hanson D., Hunter S., Thompson P., Posthauer M.E. Nutritional considerations in wound care. Adv. Skin Wound Care. 2006;19:297–303. doi: 10.1097/00129334-200607000-00007.
    1. Nutrient Recommendations: Dietary Reference Intakes (DRI) [(accessed on 18 September 2019)]; Available online: .
    1. Gould L., Abadir P., Brem H., Carter M., Conner-Kerr T., Davidson J., DiPietro L., Falanga V., Fife C., Gardner S. Chronic Wound Repair and Healing in Older Adults: Current Status and Future Research. J. Am. Geriatr. Soc. 2015;63:427–438. doi: 10.1111/jgs.13332.
    1. Jeffcoate W.J., Vileikyte L., Boyko E.J., Armstrong D.G., Boulton A.J.M. Current Challenges and Opportunities in the Prevention and Management of Diabetic Foot Ulcers. Diabetes Care. 2018;41:645–652. doi: 10.2337/dc17-1836.
    1. Niedert K.C. American Dietetic Association. Position of the American Dietetic Association: Liberalization of the diet prescription improves quality of life for older adults in long-term care. J. Am. Diet. Assoc. 2005;105:1955–1965. doi: 10.1016/j.jada.2005.10.004.
    1. Salgado R.M., Cruz-Castañeda O., Elizondo-Vázquez F., Pat L., De la Garza A., Cano-Colín S., Baena-Ocampo L., Krötzsch E. Maltodextrin/ascorbic acid stimulates wound closure by increasing collagen turnover and TGF-β1 expression in vitro and changing the stage of inflammation from chronic to acute in vivo. J. Tissue Viability. 2017;26:131–137. doi: 10.1016/j.jtv.2017.01.004.
    1. Musalmah M., Fairuz A.H., Gapor M.T., Wan Ngah W.Z. Effect of vitamin E on plasma malondialdehyde, antioxidant enzyme levels and the rates of wound closures during wound healing in normal and diabetic rats. Asia Pac. J. Clin. Nutr. 2002;11:S448–S451. doi: 10.1046/j.1440-6047.11.s.7.6.x.
    1. Aschner J.L., Aschner M. Nutritional aspects of manganese homeostasis. Mol. Aspects Med. 2005;26:353–362. doi: 10.1016/j.mam.2005.07.003.
    1. Das A., Chen G.-F., Kim H.W., Youn S.W., Varadarajan S., McKinney R.D., Finney L., Ushio-Fukai M., Fukai T. Abstract 16637: Antioxidant-1, a Novel Cu-Dependent Transcription Factor for NADPH Oxidase p47phox, Promotes Wound Healing by Regulating Inflammation and Angiogenesis. Circulation. 2014;130:A16637
    1. Martin F., Linden T., Katschinski D.M., Oehme F., Flamme I., Mukhopadhyay C.K., Eckhardt K. Copper-dependent activation of hypoxia-inducible factor (HIF)-1: Implications for ceruloplasmin regulation. Blood. 2005;105:4613–4619. doi: 10.1182/blood-2004-10-3980.
    1. Mirastschijski U., Haaksma C.J., Tomasek J.J., Agren M.S. Matrix metalloproteinase inhibitor GM 6001 attenuates keratinocyte migration, contraction and myofibroblast formation in skin wounds. Exp. Cell Res. 2004;299:465–475. doi: 10.1016/j.yexcr.2004.06.007.
    1. Armstrong D.G., Hanft J.R., Driver V.R., Smith A.P., Lazaro-Martinez J.L., Reyzelman A.M., Furst G.J., Vayser D.J., Cervantes H.L., Snyder R.J. Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: A prospective randomized controlled trial. Diabet Med. 2014;31:1069–1077. doi: 10.1111/dme.12509.
    1. Rice J.B., Desai U., Cummings A.K.G., Birnbaum H.G., Skornicki M., Parsons N.B. Burden of diabetic foot ulcers for medicare and private insurers. Diabetes Care. 2014;37:651–658. doi: 10.2337/dc13-2176.
    1. Lantis J.C., Boone D., Gendics C., Todd G. Analysis of patient cost for recombinant human platelet-derived growth factor therapy as the first-line treatment of the insured patient with a diabetic foot ulcer. Adv. Skin Wound Care. 2009;22:167–171. doi: 10.1097/01.ASW.0000305466.25177.a8.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel