Crucial Considerations In Diabetic Foot Ulceration And Nutrition
Podiatrists treat many lower extremity wounds due to anatomic and physiological reasons such as pressure, diabetes, neuropathy, ischemia, and trauma. Additionally, when it comes to lower extremity wounds, a podiatrist is usually the first physician to recognize the presence of an ulceration.1 Specifically, diabetic foot ulcers (DFUs) develop in around 10 to 15 percent of patients with diabetes.2 Recognition is imperative because DFU precedes 85 percent of lower extremity amputations in the diabetic population.1 These patients also experience higher risk for wound complications such as dehiscence and delayed healing.3 Wounds require multidisciplinary treatment including debridement, dressing changes, and offloading, along with addressing socioeconomic factors such as a patient difficulties with obtaining proper nutrition.
Although wounds develop for many reasons, they all require proper nutrition to heal.4 Wound healing treatment plans commonly ignore this fact, and proper nutrition may be inaccessible to the patient.5 Interestingly, throughout the four years of podiatric medical school, there is no strong emphasis on nutrition in the curriculum.6 Due to these circumstances, there may be no discussion of nutrition’s impact, and the patient may be unaware of the effect their diet has on wound healing. Furthermore, a patient can become acutely malnourished even when meeting everyday nutritional needs, because metabolic demands increase in the presence of an injury such as a wound.5
There are two major categories in nutrition, macronutrients and micronutrients, differing by the amount the body requires. Macronutrients are those required in high amounts by the body, while only minute amounts of micronutrients are needed. Three primary macronutrients are protein, carbohydrates, and fat, all of which have essential roles in the phases of wound healing. The USDA’s Dietary Guidelines for Americans 2020-2025 recommends that individuals receive roughly 50 percent of their calories from carbohydrates, 25 percent from protein, and 25 percent from fat. Daily values vary from person to person, which is why percentages can be a more helpful guide.7 Additionally, increased energy requirements during wound healing may increase recommended values (especially protein) for some patients.3,8
A Closer Look At Protein’s Role In Wound Healing
Amino acids are protein building blocks which play a vital role in all stages of wound healing. Protein deficiency is a common finding in patients with highly exudative wounds,5 affecting all stages of wound healing due to its involvement in the formation of collagen, leukocytes, and other immune cells. Therefore, the body cannot create the cells required for a proper immune response without proteins, and wound healing cannot progress past the inflammatory stage.5
Additionally, certain amino acids such as arginine and glutamine, along with the leucine metabolite, B-hydroxy-B-methyl butyrate (HMB), play an essential role in wound healing. Glutamine and arginine supplementation shortened time to wound healing in trauma patients.9,10 Glutamine is also a precursor to the antioxidant glutathione, an antioxidant cofactor needed for specific enzymatic reactions that play a role in counteracting reactive oxygen species.11 In addition, glutamine influences the body’s nitrogen levels, lymphocyte, fibroblast, and macrophage metabolism, and the body’s catabolic response.3,11-13 Ziegler and colleagues found that patients tolerated oral (0.285 and 0.570 g/kg/daily) and intravenous (IV) (0.0125 and 0.025 g/kg/ hr) supplementation of glutamine.14 Additionally, five-day supplementation with a balanced nutritional solution containing the maximum safe dose of supplemental glutamine (0.570 g/kg/day), showed enhancement of nitrogen retention.4,14 Da Costa and team reported that glutamine supplementation (1.5g/kg/day) increased collagen maturation in mammalian studies involving rats and colonic anastomoses.15
For trauma patients, supplemental L-arginine is also important for nitrogen balance, as it is a precursor of nitric oxide, ultimately aiding in its increase.3,4,11 Nitric oxide plays an important role in wound healing by stimulating vasodilation. Arginine supplementation also amplifies the body’s immune response by increasing collagen production. This can prove beneficial for DFU treatment, as diabetes causes a delayed immune response.3,4 A normal diet requires 5.4 grams of arginine daily. However, research shows that instituting 14-day supplementation of 17 or 24.8 grams of arginine increased wound collagen accumulation, which can help increase wound tensile strength.4,10,11,16,17
Similar to arginine and glutamine, HMB also has a positive influence on nitrogen balance. HMB positively affects wound healing by increasing protein production and decreasing proteolysis.10,18,19 Interestingly, HMB can also aid in preserving muscle mass, especially in patients on bed rest.18 This is important because one form of treatment for DFU is immobilization, which can negatively impact muscle mass. Additionally, a study by Kuhls and colleagues showed that 3g HMB calcium salt supplementation alone, or 3g HMB with 14g arginine and 14g glutamine, can improve nitrogen balance in critically ill patients.18 Another study by Ellis and team showed that supplementation of all three had positive outcomes on endothelial function by promoting vasodilation.11 Diabetes can negatively impact the inflammatory phase by inhibiting endothelial cell and fibroblast activity; therefore, nutritional supplementation that improves endothelial function should positively impact DFU healing.3 Sufficient protein intake is vital; therefore, every meal should include a high-protein source.8 Specifically, a patient with wounds should consume roughly 1.2-1.5g of protein per kg body weight daily. If there is a wound is highly exudative, daily protein requirement can potentially increase by 250 percent.4,5,8
What Do We Know About Other Macronutrients For DFUs?
In addition to protein, the other two macronutrients, carbohydrates and fats, supply the energy needed for healing to progress through the proliferation phase. The body uses energy provided by carbohydrates for cellular proliferation, fibroblast migration, and promotion of leukocyte activity.20 As for the role of fats in wound healing, fatty acids are primarily involved in the formation of prostaglandins. The body requires two primary essential Omega-6 fatty acids to make prostaglandins: linoleic and arachidonic acid. Since these are essential fatty acids, they cannot be synthesized by the human body and, therefore, must be obtained from the diet. A dietary deficiency in these two fatty acids negatively affects prostaglandin synthesis, impacting the body’s immune response.3,4
Understanding The Contribution Of Micronutrients
Along with macronutrients, it is important meet nutritional requirements for micronutrients. Micronutrients such as zinc and vitamins A, C, D, and E, also play a vital role in wound healing. It is not uncommon for patients with DFUs to exhibit micronutrient deficiency, especially for vitamins.21,22 Although zinc is a trace element, its involvement in protein synthesis, catalytic activity for metalloproteinases, and collagen metabolism (as a cofactor for the enzyme lysyl oxidase) makes it essential for wound healing. Correlating this importance, one study showed that patients with type 2 diabetes and DFU had decreased zinc levels.23 Literature reviews also show that a nutritional zinc deficiency negatively affects the immune system and can even increase wound complications such as infection. Given that a zinc deficiency can cause delayed wound healing, one may increase zinc supplementation from the Food and Drug Administration (FDA) daily value of 11 mg to up to 40 mg.5,22,24
Vitamin A promotes epithelial growth, as well as amplifies monocyte and macrophage activity in a wound, providing an anti-inflammatory effect.5,22 Currently, FDA daily value for vitamin A is about 3,000 IU. Kulprachakarn and team recommends 25,000 IU daily to help enhance the immune system, while Stetchmiller suggests oral supplementation of 10,000 to 15,000 IU daily.3,22 Overall, both studies suggest increasing the daily vitamin A in the presence of a wound.
Another vitamin beneficial to wound healing is vitamin E, which has antioxidant effects.22 Specifically, Jain and Jain concluded that 800 IU of vitamin E daily may decrease the onset of diabetic complications such as a DFU.25 Moreover, vitamin C (ascorbic acid) has a variety of positive influences on wound healing because it stimulates collagen synthesis/ maturation, has antioxidant effects, and can promote fibroblast/neutrophil migration.22 Brooke and colleagues mention that patients with DFU that ultimately required amputation had lower vitamin C levels.21 The FDA states that a healthy person requires 90 mg/day of vitamin C, and Stetchmiller and coworkers suggest 100 to 200 mg/day supplementation for patients with wounds.3 In cases of severe wounds, oral supplementation of 1,000 to 2,000 mg/day may promote healing.3,24
It seems that even with trace requirements, micronutrients can have a significant positive impact on wound healing. Another vitamin involved in the inflammatory process is Vitamin D. This particular vitamin positively influences glycemic control.21,26 Additionally, deficiency in Vitamin D (25 (OH) D less than 25 nmol/L) can cause an increase in the likelihood of diabetic foot complications.26
Key Considerations In Nutritional Supplementation And Hydration
Since macronutrients and micronutrients can positively impact wound healing, enteral nutritional supplements exist to promote this process. Moore and Williams and their respective teams showed that the benefits of nutritional supplementation, such as significantly increasing collagen accumulation in wounds of elderly patients, typically arise within two weeks.10,27 Given the established positive effects of macronutrients and micronutrients on wound healing and general tolerability of nutritional supplementation among patients, it may prove beneficial to add this practice to a DFU care plan. As seen in the table above, many food sources overlap and can fulfill daily requirements for different macro and micronutrients.
Moreover, a discussion about nutrition is incomplete without including hydration. Since hydration is beneficial to nutrient absorption, it is important for patients with a DFU. Moisture is necessary for migration of epithelial cells on the wound’s edge, and it may support tissue oxygenation. Further, water is a solvent for protein, carbohydrate, vitamin, and mineral transport in and out of cells via diffusion. It also functions to remove waste from the cell as tissue heals.28 Goals for fluid intake in wound patients are 1ml per kcal per day.4 The Dietary Guidelines for Americans 2020-2025 recommends that healthy beverages are low calorie and nutrient-dense, such as water, fat-free milk, and unsweetened beverages.7 The table above also shows foods that are high in water content which can contribute to preventing dehydration while fulfilling the daily recommended percentage of macronutrients.
Final Thoughts
Nutrition is something every provider should discuss with patients with diabetes. American Diabetes Association recommends the “diabetes plate” method to ensure adequate nutritional intake.29 Recognizing possible nutritional deficiencies,
along with educating patients, or even referring to a nutritionist/dietician, could help in DFU prevention or healing, and potentially improve overall health.
Ms. Curreri is a fourth-year podiatry student at Temple University School of Podiatric Medicine in Philadelphia.
Mrs. Johnson is a nutritionist and graduate student in the registered dietician program at Keiser University in Brunswick, Md.
Dr. Khan is a Clinical Associate Professor in the Department of Podiatric Medicine at Temple University School of Podiatric Medicine in Philadelphia.
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7. US Department of Agriculture and US Department of Health and Human Services. Dietary guidelines for Americans, 2020- 2025. 9th Edition. Available at: https:// www.dietaryguidelines.gov/sites/default/ files/2020-12/Dietary_Guidelines_for_Americans_2020-2025.pdf . Published December 2020. Accessed August 5, 2021.
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34. National Institutes of Health Office of Dietary Supplements. Vitamin D. Available at: https://ods.od.nih.gov/factsheets/VitaminD-Consumer/ . Updated March 22, 2021. Accessed August 5, 2021.
