The Role of Nutrition in Chronic Wound Care Management

THE DIABETIC FOOT

What patients eat affects how they heal.

By Leland Jaffe, DPM and Stephanie Wu, DPM, MSc

he multi-faceted approach tients who are malnourished may plying the body with glucose. During to the management of lack the necessary fundamental this stress response with increased chronic wounds can be a building blocks to promote tissue re- cortisol production, elevated levels daunting challenge. Treat- generation, leading to wound chro- of inflammatory cytokines, including 77 ment strategies for chronic nicity.1 Patients may be malnourished interleukin 1 (IL-1), interleukin 6 (IL- Twounds of the lower extremity often for a number of reasons, including 6), and tumor necrosis factor alpha entail a multidisciplinary approach limited financial resources, lack of will be elevated, contributing to a focusing on therapies, including off- family support, dietary constraints, delay in wound healing.4 loading modalities, serial wound anxiety, depression, and diminished This systemic inflammation will debridements, assessment of arte- appetite. Malnourishment ensues if a also cause a decrease in negative rial vascular inflow, and managing patient’s nutritional intake does not acute phase reactants including al- bacterial bioburden. While these do meet the body’s metabolic demands. bumin and pre-albumin.4 With con- represent the major pillars of chronic wound management, evaluation and optimization of nutritional status should be included as part of Evaluation and optimization of nutritional status the comprehensive treatment of the should be included as part of the comprehensive chronic wound patient. Hippocrates in 5th century B.C. treatment of the chronic wound patient. recognized the value of nutrition and the potential of certain foods for good health and said “Let food be thy Malnutrition tinual lack of nutritional intake, the medicine and medicine be thy food.” Malnutrition is defined as loss body will begin metabolizing fat for Wound healing requires the body to of body tissue and diminished body energy, sparing the sustained break- be in an anabolic state that necessi- functions caused by inadequate nutri- down of muscle tissue for protein.3 tates specific macro- and micronutri- tional intake.2 Firstly, during a period This transition from primarily pro- ents as well as proper hydration to of malnourishment the patient will tein to fat metabolism will minimize fuel the physiologic process. Since deplete the liver’s glycogen stores to muscle and overall weight loss. A dietary depletion may contribute to ensure glucose is continually sup- consequence of adipose tissue de- wound chronicity,1 proper assess- plied to vital body cellular functions. pletion, however, may contribute to ment of nutritional status is para- However, glycogen stores are often increased pressure on osseous prom- mount to predict healing potential. depleted within the first 24 hours inences leading to pressure ulcer for- The complex wound healing cas- following starvation. The continued mation. cade progresses from hemostasis, stress of starvation will increase the Following the depletion of fat inflammation, proliferation, and ul- metabolic rate and result in the re- stores, the body will again rely pri- timately tissue remodeling. Among lease of cortisol from the adrenal marily on skeletal muscle for energy other factors, this process relies on glands.3 This will improve the body’s demands, resulting in rapid weight adequate levels of macro-and mi- ability to mobilize amino acids from loss and overall cachexia. Clinically, cro-nutrients to ensure a timely pro- protein sources to support hepatic a malnourished status will contrib- gression through these stages. Pa- gluconeogenesis and continually sup- Continued on page 78 www.podiatrym.com NOVEMBER/DECEMBER 2017 | PODIATRY MANAGEMENT The Diabetic FOoT

Nutrition (from page 77) and localized/generalized edema.11 inflammatory phase of healing are The prevalence of obesity, defined primarily protein-driven and include ute to impaired immunity,5 decreased as a body mass index (BMI) > 30, is macrophages, phagocytes, leukocytes, muscle mass leading to weakness on the rise in the United States and and lymphocytes.18 With a blunted and immobility,6 and an overall de- involves 36.5% of the adult popula- immune response and a diminished crease in wound healing potential.7 tion.12 Obesity should not rule out the inflammatory phase of wound healing possibility of a malnourished status, due to protein deficiency, clearing of Assessment of Nutritional Status as excess adipose tissue may conceal cellular and bacterial debris will be Nutritional status associated with underlying skeletal muscle atrophy.13 compromised. This could prolong the an increased risk for the develop- Moreover, adipose tissue is con- inflammatory phase of wound healing ment of ulcers include reduced body sidered poorly vascularized, causing a and limit the ability to progress to- mass index (BMI), low body weight, further delay in wound healing due to wards tissue proliferation. A decrease altered ability to dine independent- decreased oxygenated blood flow to a in protein availability will also de- ly, reduced food intake, low dietary wound bed. Anthropometric measure- crease fibroblastic activity and colla- protein intake, low serum albumin concentration (<3.5 mg/dL), and decreased total lymphocyte count (< A thorough nutritional screening mechanism 1.8 x 109/L). While no cause-effect re- lationship can be established between is important to identify patients malnutrition and ulcer formation, a thorough nutritional screening mech- at risk of a potential nutritional deficit. anism is important to identify patients at risk of a potential nutritional deficit. 78 ments include patient’s BMI, recent gen production during the prolifera- The Mini Nutritional Assessment weight loss, and head circumference tive stage of healing.19 (MNA) (in children). Unintentional weight loss Protein malnutrition can pres- The Mini Nutritional Assessment of <5% in 6 months is defined as mild ent in a patient with decreased pro- (MNA) is a frequently referenced tool loss, 5-10% as moderate-severe loss, tein intake, absorption, or metabo- to assist in identifying malnutrition, and >10% as severe loss of weight.14 lism, contributing to insufficiencies particularly in the elderly popula- in LBM. Protein deficiency may also tion.8 The MNA screening tool eval- Macronutrients in Wound Healing stem from a deficiency in certain uates multiple parameters, including Wound healing is an anabolic amino acids such as arginine and food intake and decline, weight loss, event that requires adequate intake glutamine. Arginine is a condition- mobility, neuropsychological prob- of macronutrients, including carbo- ally essential amino acid, especially lems, BMI, and calf circumference hydrates, fats, protein, and water. during times of stress. It is acquired to define nutritional risk. Patients Fats provide about 9 kcal per gram, from diet and derived endogenous- frequently recognized as high risk carbohydrates about 4 kcal per gram, ly from citrulline in a reaction cat- for nutritional deficit include the el- and protein about 4 kcal per gram. alyzed by arginine synthetase. Ar- derly, patients with food intolerance Protein is a macronutrient that is ginine functions as a precursor to (chemotherapy), limited income, de- critically important during the entire collagen formation and production pression, lack of teeth/dentures, and cascade of the wound healing pro- of nitric oxide, thus promoting tis- inability to self-feed. cess. Protein stores within the body sue formation and oxygenation of the Patients with diabetes and ulcer- may be diminished due to overall wound.20,21 ations have also been recognized as decreased intake, or excessive daily Glutamine is another amino acid a cohort at risk of malnutrition, re- protein loss via wound exudate.15 The that has been suggested to serve sulting in a poor prognosis of heal- daily recommended protein intake a function during the cascade of ing.9 Zhang and colleagues identified for a healthy individual is 0.8 grams wound healing.16 As with arginine, that as the severity of the Wagner of protein per 24 hours. This number glutamine is conditionally essential diabetic foot ulceration classification may vary based upon activity level, during injury or disease as demand increased, the patient’s nutritional total caloric intake, and gender. outstrips supply. It is involved in status declined.9 Patients with open wounds, how- protein synthesis as a precursor for Assessment of nutritional status ever, may require an additional 1.25 nucleotides and glutathione and is es- also includes anthropomorphic data to 1.5 grams of protein per kilogram sential for immune system function. and an overall clinical assessment of of body weight to support the anabolic Glutamine serves as a fuel source for the patient. The physical examina- process of wound healing.16 The body fibroblasts, epithelial cells, lympho- tion includes findings such as coarse increases protein demand about 250% cytes, and macrophages, and indi- hair and reduced skin turgor.10 Other and caloric demand 50% to support rectly assists in the process of inflam- clinical findings suggestive of nutri- synthesis of new tissue and maintain mation and phagocytosis. Therefore, tional depletion include muscle at- lean body mass (LMB) stores.17 supplementation of glutamine has rophy, reduced subcutaneous tissue, Numerous factors involved in the Continued on page 80

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Nutrition (from page 78) in cases of diarrhea, fever, diuresis, damaged matrix and bacterial con- and copious wound exudate. Proper tents, the quantity of inflammatory often been suggested in cases of nu- hydration also facilitates the trans- cytokines and MMPs decrease, and tritional depletion.16 portation of macro-and micro-nutri- the wound progresses to the prolif- Carbohydrates and fats compose ents to the site of tissue injury to erative and inflammatory phases of the other two macronutrients that are augment healing. Adequate hydration healing.27 This anabolic process relies important during the stages of wound status can be assessed through the on a multitude of vitamins and min- healing. Carbohydrates are metabo- evaluation of serum sodium, blood erals, including but not limited to vi- lized to form glucose, providing 4 kcal urea nitrogen measurement (normal tamin A, vitamin C, copper, iron, and of energy per gram of carbohydrate in- 7-23 mg/dl), or urine-specific gravity. zinc. Vitamin A has been beneficial gested. Glucose is the body’s main en- to support collagen deposition in the ergy source, providing the fuel needed Micronutrients in Wound Healing wound and can also antagonize the for collagen production during the pro- Micronutrient intake should be negative effects of corticosteroids on liferative phase of healing.22 However, evaluated and optimized in patients wound healing.28 hyperglycemia can have detrimental with open wounds. This includes the effects on tissue repair, including de- consumption of essential vitamins, Vitamin C creased fibroblastic activity,23 reduced amino acids, and minerals that sup- Vitamin C is a water-soluble vita- growth factor production and effective- port wound healing through hemo- min that is critical in the proliferative ness,23 and a compromise in cell-medi- stasis, inflammation, proliferation phase of healing, as fibroblasts rely ated immunity.24,25 on this vitamin for the Adequate fat in- production of collagen. take is also important, providing 9 calories Table 1 Copper and Iron 80 per gram of fat. Di- Finally, the minerals etary fat is not only Nutrient Food Sources copper and iron sup- an essential source of port the formation of calorie dense energy, Vitamin E Almond, Spinach, Avocado, Olive oil collagen. Copper fur- but is needed for the Vitamin C Red pepper, Orange, Grapefruit , Strawberry ther assists with the absorption of fat-solu- Vitamin A Carrot, Sweet Potato, Spinach, Kale, Broccoli cross-linking of colla- ble micronutrients, in- Selenium Chia seeds, Salmon, Tuna, Eggs gen, strengthening the cluding vitamins A, D, repair process. Supple- E, K, and the omega-3 mentation of these vital (alpha-linolenic acid) and omega-6 and remodeling. Following an initial minerals should be based on each fatty acids (linoleic acid). insult to the skin, the body responds patient’s serum depletion. A proper ratio of omega-3 to by creating hemostasis. Vitamin K is There are 50 known essential nu- omega-6 essential fatty acids is im- the necessary nutrient that supports trients for sustaining human life. Nu- portant for optimal health, as too blood coagulation and this can be merous published clinical trials have much omega-6 fat can lead to elevat- found in leafy green vegetables, kale, attempted to determine the macro-or ed arachidonic acid, prolonging sys- broccoli, cucumber, or asparagus. micro-nutrient supplementation that temic inflammation within the body. Following hemostasis, platelets in- will positively impact wound healing. Moreover, adequate daily intake of volved with hemostasis degranulate An article recently published in the carbohydrates and fats prevents the and release growth factors into the Journal of Diabetes and Its Compli- body from utilizing dietary or tissue wound that assist in the recruitment cations attempted to determine the proteins as a source of energy. of macrophages and neutrophils. effect of vitamin D supplementation Fluid intake should also be con- The macrophages and neutro- on wound healing in patients with di- sidered in the nutritional assessment phils, in turn, secrete inflammatory abetic foot ulcers. In this prospective, and recommendations for wound cytokines including interleukin-1 (IL- randomized double-blinded, place- treatment.26 Adequate hydration is 1), interleukin-6 (IL-6), tumor necro- bo-controlled trial, 50,000IU vitamin necessary not only to maintain nor- sis factor-alpha, and matrix metal- D supplements every two weeks for mal skin turgor but to also assist with loproteinases (MMPs) that assist in 12 weeks appeared to play a role in vascular inflow and oxygenation of the removal of bacteria and cellular improved glycemic index, which in- tissues. The recommended daily fluid debris. This process results in the directly improved wound healing.29 intake for wound care patients is 1 formation of free radicals and reac- mL of fluid per 1 kcal ingested,19 or tive oxidative species (ROS) that can Zinc 30-35 mL per kg of body weight.22 damage healthy tissue.22 Zinc is an essential trace mineral Special considerations should be Nutrients rich in antioxidants, for over 300 enzymes. It plays an given to patients with underlying including vitamins E, C, A and sele- important role in the metabolism of medical conditions that result in ei- nium, can neutralize the free radicals proteins, carbohydrates, and nucle- ther excessive fluid retention such as and augment wound healing (Table ic acids. Zinc also maintains struc- renal or cardiac disease, or fluid loss 1). Following the removal of cellular Continued on page 82

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Nutrition (from page 80) critical to evaluate and screen for pa- doi: 10.3892/etm.2012.780 [doi]. tients with chronic wounds who may 10 Seidel HM et al, editors: Mosby’s ture and integrity of cell membranes, be nutritionally depleted, thus poten- guide to physical assessment, philadelphia, and deficiency of zinc can result in tially compromising the process of 2008, mosby. 11 an increased susceptibility to oxi- wound healing. The nutritional goal White JV, Guenter P, Jensen G, et al. Consensus statement of the academy dative damage. Deficiency of zinc is for the patient to consume nutrient of nutrition and dietetics/american society is more common in vegetarians as dense foods and have proper hydra- for parenteral and enteral nutrition: Char- acteristics recommended for the identifi- cation and documentation of adult mal- The nutritional goal is for the patient to consume nutrition (undernutrition). J Acad Nutr Diet. 2012;112(5):730-738. doi: 10.1016/j. nutrient dense foods and have proper hydration that jand.2012.03.012 [doi]. 12 Https://Www.cdc.gov/obesity/data/ supports the anabolic process of wound healing. adult.html. 13 Gallagher S, Gates JL. Obesity, pan- niculitis, panniculectomy, and wound care: Understanding the challenges. J Wound Os- the bio-availability of zinc from a tion that supports the anabolic pro- tomy Continence Nurs. 2003;30(6):334-341. vegetarian diet is lower than from a cess of wound healing. While some doi: 10.1016/S1071 [doi]. non-vegetarian diet. studies are inconclusive regarding 14 Evans E. Nutritional assessment in Vegetarians consume high levels the recommendations of specific vita- chronic wound care. J Wound Ostomy of legumes and whole grains that min and mineral supplementation, it Continence Nurs. 2005;32(5):317-320. doi: contain phytates which bind zinc and does appear evident that meeting the 00152192-200509000-00009 [pii]. 15 inhibit its absorption.30 Long-term al- balanced macro- and micro-nutrient Pompeo M. Misconceptions about 82 cohol consumption impairs zinc ab- needs of the patient will help to sup- protein requirements for wound healing: Re- sorption and increases its urinary ex- port the wound healing process. PM sults of a prospective study. Ostomy Wound Manage. 2007;53(8):30-2, 34, 36-38 passim. cretion.31 Digestive disorders such as 16 Demling RH. Nutrition, anabolism, ulcerative colitis and Crohn’s disease, References and the wound healing process: An over- as well as certain medications, can 1 Thompson C, Fuhrman MP. Nutri- view. Eplasty. 2009;9:e9. also impair zinc absorption. 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A.S.P.E.N. adult nutrition mined that the supplementation of tritional assessment. in fauci AS et al, edi- support core curriculum. 2nd ed. silver 220 mg zinc sulfate, containing 50 tors: Harrison’s principles of internal medi- spring, MD: American society for parenteral mg elemental zinc, for 12 weeks in cine, ed 17, new york, 2008, McGraw-hill. and enteral nutrition; 2012:348-363. diabetic patients with foot ulcerations 4 Rote NS. innate immunity: Inflamma- 20 Schaffer MR, Tantry U, Thornton FJ, resulted in a reduction in ulceration tion and wound healing. in: Huether SE, Mc- Barbul A. Inhibition of nitric oxide synthe- length and width, and improvement Cance KL. understanding pathophysiology. sis in wounds: Pharmacology and effect in metabolic profiles as compared to 5th ed. st. lous, MO: Elsevier; 2012:118-141. on accumulation of collagen in wounds in 5 Chandra RK. Nutrition and immunity. the placebo group.33 Razzaghi and col- mice. 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Food and wounds: Nu- daily supplement of 250 mg magne- Enteral Nutr. 1986;10(6):550-554. doi: tritional factors in wound formation and sium oxide for 12 weeks resulted in 10.1177/0148607186010006550 [doi]. healing. Br J Community Nurs. 2002:43-4, 8 significant reductions in ulcer length, Norman K, Pichard C, Lochs H, Pirlich 46, 48 passim. M. Prognostic impact of disease-related mal- 23 width, and depth, with an overall im- Lerman OZ, Galiano RD, Armour M, nutrition. Clin Nutr. 2008;27(1):5-15. doi: Levine JP, Gurtner GC. Cellular dysfunction provement in metabolic control.34 S0261-5614(07)00168-9 [pii]. in the diabetic fibroblast: Impairment in mi- Several other studies have been 9 Zhang SS, Tang ZY, Fang P, Qian HJ, gration, vascular endothelial growth factor performed to help practitioners provide Xu L, Ning G. Nutritional status deteriorates production, and response to hypoxia. Am evidence-based recommendations to as the severity of diabetic foot ulcers increas- J Pathol. 2003;162(1):303-312. doi: S0002- the patient to augment wound healing. es and independently associates with prog- 9440(10)63821-7 [pii]. Proper nutritional assessment is nosis. Exp Ther Med. 2013;5(1):215-222. Continued on page 84

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Dr. Leland Jaffe is an Assistant Professor in the Department of Medicine and Radiology at Scholl College of Podiatric Medicine. In addition to teaching, Dr. Jaffe serves on two wound care panels and is involved in research with the Center for Lower Extremity Ambula- tory Research (CLEAR) at Scholl College. Dr. Wu is Associate Dean of Research and Professor of Surgery; Professor, Stem Cell and Regenerative Med- icine. She is Director at the Center for Lower Extremity Ambulatory Research (CLEAR) of the Dr. William M. Scholl College of Podiatric Medicine at Rosalind Franklin University of Medicine and Science.

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