Dermatologists commonly manage a variety of wounds in the outpatient setting. Wound healing requires a multifaceted approach that often includes topical and oral therapies, adjustment of mechanical factors, and behavioral and lifestyle modifications. Physiologically, wound healing requires an inflammatory phase, a proliferative phase, and a remodeling phase. Chronic wounds undergo a prolonged inflammatory response hindered by decreased growth factors and increased wound bioburden.1 Malnutrition has been routinely associated with wound chronicity and serves as a modifiable risk factor that may improve wound healing outcomes.2
Although the causes of wounds encountered in dermatology vary extensively, the importance of nutrition underlies all wound healing. Caloric needs in wound healing have been estimated at 30 to 40 kcal/kg dependent on baseline body weight, age, medical comorbidities, activity level, stage of wound healing, wound size, and number of wounds.1,3,4 Nutritional supplementation is patient dependent, but this article serves to review the existing literature on macronutrient and micronutrient supplementation to clarify the potentially complementary role for nutritional support in chronic wounds. All patients should be screened with a thorough history, review of systems, and physical examination for existing nutrient deficiencies. Patients with age-related or chronic diseases are at increased risk for nutritional deficiency, and focused laboratory testing may be warranted. Supplementation for specific deficiencies with help from a registered dietician is recommended.
Macronutrients for Wound Healing
Protein—Protein is the most widely known macronutrient required for wound healing. The primary function of dietary protein is to provide amino acids to perform physiologic functions.5 Not only does cutaneous injury increase the metabolic needs of the wounded area, but large amounts of protein can be continually lost through wound exudates. Protein is necessary for the immune response required to transition from inflammatory to proliferative phases of wound healing.6 Protein energy deficiency has been reported to reduce fibroblast activity, delay angiogenesis, and decrease collagen formation.7 Additionally, protein is required for the formation of inflammatory cells and maintenance of oncotic pressure, specifically in venous insufficiency wounds.1
The current recommended dietary allowance for protein in healthy adults is 0.8 g/kg daily of body weight. In patients with pressure ulcerations, a goal recommended dietary allowance of 1.25 to 2.0 g/kg daily of body weight, dependent on ulceration size, has been recommended by the National Pressure Ulcer Advisory Panel and European Pressure Ulcer Advisory Panel.8 This recommendation was based on a series of studies that reported enhanced healing rates in patients with pressure ulcers receiving higher-protein diets.9 The largest study to date was double-blinded and included 89 residents of long-term care facilities with stage II to stage IV pressure ulcers.10 Participants were randomized to receive commercial protein supplementation vs placebo. At the end of 8 weeks, a statistically significant difference was seen in mean (SD) pressure ulcer scale for healing scores (3.55 [4.66] vs 3.22 [4.11]; P<.05).10 A 2014 Cochrane review failed to identify benefit associated with nutritional interventions for either the prevention and/or treatment of pressure ulcers.11 Specific recommendations on protein intake for other types of chronic wounds have not been proposed. Protein supplementation generally is provided orally, if tolerated. Liquid supplements such as Boost (Nestlé), Carnation Breakfast Essentials (Nestlé), NuBasics (SupremeMed), Resource (Nestlé Health Science), and Ensure (Abbott Laboratories) are frequently used to supplement both protein and caloric intake. Protein oversupplementation has not been associated with improved outcomes and may cause or exacerbate other medical comorbidities.
Fatty Acids for Wound Healing
Wound healing is an anabolic process that requires adequate intake of substrates such as glucose and fat. Carbohydrates serve as the major energy source required for wound healing, while fats are thought to play roles in cell membrane development and modulation of cellular signaling.1 Fats utilize a unique pathway for energy production through beta-oxidation and the production of adenosine triphosphate, allowing available protein to be harnessed for wound healing.1 Omega-3 and omega-6 fatty acids serve as precursors to prostaglandins, leukotrienes, and thromboxane—all key mediators of the inflammatory phase of wound healing.3 Omega-3 fatty acids are thought to downregulate genes involved in proinflammatory pathways,12 as well as to diminish lymphocyte proliferation and levels of IL-1β, tumor necrosis factor α, and IL-6 in vitro.13 In vivo studies assessing the impact of omega-3 fatty acid supplementation on wound healing are minimal, and the role of dietary supplementation for this indication remains unknown. Fish oil contains the omega-3 fatty acid–rich eicosapentaenoic acid and docosahexaenoic acid, which has been compared to mineral oil supplementation for wound healing in healthy adults. When fish oil was supplemented for 4 weeks, no significant differences were identified in time to complete wound healing between groups. Interestingly, significantly higher levels of the proinflammatory cytokine IL-1β were identified in blister fluid at 24 hours after blistering vs the placebo group (t=2.52, df=25, P<.05).14 Prior studies evaluating wound healing in animal models similarly identified longer times to re-epithelialization after omega-3 polyunsaturated fatty acid supplementation orally and topically.15,16 The fatty acid quality and composition consumed also may impact wound healing, as high-fat diets that are not rich in omega-3 fatty acids have been shown to promote inflammation and impair wound healing in rats, but this has not been thoroughly explored in human trials.17 Although adequate intake of these macronutrients is important, excessive intake may be harmful. Larger prospective trials are needed to shed light on the dose and composition of fatty acid supplementation that may optimize wound healing.
Vitamins and Micronutrients Required for Wound Healing
Vitamin A—Many vitamins serve as cofactors for the enzymatic processes required in wound healing. Vitamin A is an essential fat-soluble vitamin that serves a variety of dermatologic functions and promotes wound healing through stimulation of fibroblasts and ground substance, and it facilitates epithelial cell differentiation when applied topically.3,18 Vitamin A works through the activation of retinoid receptors on endothelial cells, fibroblasts, keratinocytes, melanocytes, and sebocytes, and has purported anti-inflammatory effects that aid the healing of open wounds.3 Additionally, vitamin A is thought to enhance cytokine release in the inflammatory phase of wound healing.19 Supplemental vitamin A has been associated with positive effects on acute wound healing, burns, and radiation injuries.3 The utility of vitamin A supplementation in chronic wounds remains unknown; however, it has been shown to be beneficial in patients with inflammatory disease, such as rheumatoid arthritis, on corticosteroid therapy. Vitamin A supplementation in this population has been shown to counteract the negative effects of corticosteroids on wound healing via downregulation of transforming growth factor β and insulinlike growth factor 1.20 Vitamin A deficiency has been associated with impaired progression through inflammatory and remodeling phases of healing due to altered B-cell and T-cell function and antibody production.1 Some experts recommend short courses of oral vitamin A supplementation to enhance wound healing at doses between 10,000 and 25,000 IU daily.2,3 Large, population-based studies are needed, and the safety supporting this recommendation in all patients remains unknown.
Vitamin C—Vitamin C is widely known for its role in collagen formation, immunomodulation, and antioxidant capacity.1 Although vitamin C deficiency is associated with decreased collagen synthesis and impaired wound healing,21 the utility of long-term supplementation in patients who are not deficient remains unexplored. A systematic review evaluating interventional studies utilizing vitamin C supplementation on pressure ulcerations and surgical wound healing concluded that convincing evidence exists only for supplementation with at least 500 mg of vitamin C. The authors noted, “There is little evidence for improved healing of surgical wounds by high-dose single vitamin C supplementation (1–3 g/day).”22 In a prospective, randomized, controlled trial, 20 patients with pressure ulcerations were supplemented with vitamin C vs placebo with a mean reduction in pressure-sore area of 84% after 1 month in the vitamin C–supplemented group compared to 42.7% in the placebo group (P<.005). A limitation of this study is the small population.23 One current recommendation for vitamin C supplementation in chronic wounds is for 500 mg daily in uncomplicated wounds to 2 g daily in severe wounds.3 Additional studies have suggested that the benefits of vitamin C supplementation are maximized when given in combination with zinc and arginine.22 At this time, evaluation for vitamin C deficiency and appropriate supplementation in patients with chronic wounds is needed.