Goals. Chronic Wounds. Nutrition, the Often Forgotten Part of the Equation for Wound Healing. Nutritional Risk Factors for Impaired Wound Healing

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1 Goals Nutrition, the Often Forgotten Part of the Equation for Wound Healing Principles in wounds healing Critical Nutrients Marlene Grenon, MD Associate Professor of Surgery University of California San Francisco UCSF Vascular Surgery Symposium 2016 Role of omega-3 fatty acids Chronic Wounds Chronic Wounds: Wounds taking >4-6 weeks to heal Types Pressure ulcers Post-op wounds Ulcers (venous, arterial) Burns Stomas Amputation wounds Nutritional Risk Factors for Impaired Wound Healing Significant weight loss Inadequate protein intake Inadequate nutrient intake Extreme Body Mass index (low or high) with limited mobility Hypoalbuminemia Dehydration Dorner et al, Adv Skin Wound Care 2009 Dorner et al, Adv Skin Wound Care

2 Malnutrition (albumin < 3.5mg/dl) Renal impairment (egfr <60 ml/min) Wound Healing 27% 31% HR= % HR=2.72 HR=6.7 9% HR= % 18% HR=5.65 HR= % Hazard Ratios for Death -wound exudation -fibrin clot -neutrophils -macrophages -epithelialization -angiogenesis -fibroblast proliferation -collagen cross-linking -wound contraction -collagen maturation -tensile strength HR=4.54 Owens CD et al J Vasc Surg 2012 Inflammation (hscrp> 5mg/L) Wound Healing American Dietetic Association s Nutrition Care Process Protein Vitamin A Glucosamine Vitamin C ZInc Protein Medical Nutrition Therapy: Nutrition assessment Nutrition diagnosis Nutrition intervention Nutrition monitoring and evaluation Recommended assessments: Anthropometric measurements Biochemical data (anemias) Hydration status Nutrition-focused clinical examination Diet history American Dietetic Association

3 Water Critical Nutrients Aid in hydration of wound sites and oxygen perfusion Epithelial cells require moisture to migrate from the wound edge to close the wound Act as a solvent for minerals, vitamins, amino acids, glucose Transporting vital materials to cells and removing waste products Energy -Sources: carbohydrates and fat -Wound energy demand: collagen synthesis -Requirements kcal/kg but need to be individualized Fats Good source of energy (9cal/g) and spares protein for wound healing Carries Vitamins A, D, E, K Aids in absorption of Vit A Provides padding under body prominence and insulation of the skin Overall: Underweight: gain weight Overweight: weight maintenance Sources: meat, full-fat dairy, oils Carbohydrates Stimulate insulin production + release Prevent gluconeogenesis Inadequate supplies Poor wound healing Caution with diabetes required Sources: wholegrain cereals, breads, potatoes, rice, pasta, biscuits Williams JZ, Surg Clin N Am 2003; Ord H. Br J Nurs 2007; Edmonds J. Br J Community Nurs 2007 Maintenance and repair of body tissue Collagen synthesis Fibroblast proliferation Tissue remodeling Wound contraction Maintain oncotic pressure Skin structure Role of Proteins Daily intake of 1-1.5g/kg/day Up to 3g/kg/day in severe wounds Protein deficiency impairs all stages of wound healing Red and white meats, fish, eggs, liver, dairy products (milk, cheese yogurt), soy beans, legumes, seeds, nuts and grains Hurd TA, Wound Care 2004; Ord H Br J Nurs

4 Amino Acids- L-Arginine Albumin Essential structural protein synthesis and protein metabolism Decrease muscle loss Nitric oxide pathway Collagen deposition in wound healing Enhance immune function Improve secretion of growth hormone and insulin Average dietary intake provides 4g/day 9 g/day promotes wound healing for pressure ulcers * Source: proteins Side-effects: diarrhea. Albumin and prealbumin are a strong prognostic indicator and level of morbidity in many populations Albumin half-life almost 21 days Pre-albumin 3 days Normal range: g/dl Although reflective of malnutrition, affected by other conditions hydration status metabolism infection stress liver disease renal disease inflammation Supplementation: Arginine 9g, Vit C (500 mg), zinc (30 mg) *Desneves KJ, Clin Nutr 2005 Vitamin A Vitamin C Increases the inflammatory response in wounds Stimulates collagen synthesis and crosslinking Restore wound healing impaired by long-term steroid therapy or diabetes Mechanisms unclear If deficient, recommended dose: 10,000-25,000 IU x 7-10 days Sources: milk, cheese, eggs, fish dark green vegetables, oranges, red fruits, vegetables. Important in collagen synthesis + crosslinking Angiogenesis Immune system Increases absorption of iron Deficiency increases the risk of wound infection If deficient, recommended dose: mg daily Sources: fruit and vegetables (oranges, grapefruit, tomatoes, leafy vegetables) Side effects: diarrhea, scurvy Langemo D. Adv Skin Wound Care 2006; Ord H. Br J Nurs

5 Zinc and Iron Nutrition and Wound healing in PAD Zinc Protein and collagen synthesis, tissue growth and healing Recommended intake for non-healing pressure ulcers, 15-50mg/day (no more than 14 days as it can also interfere with wound healing) Sources: red meat, fish and shellfish, milk, poultry, eggs. Side-effects: GI complaints Iron Required in collagen production and wound strength Recommended intake in the general population: 8mg/day (18mg/day for menstruating females) Sources: red meat, fish, eggs, wholemeal bread, dark green leafy vegetables, dried fruits, nuts. Side-effects: nausea and constipation -double-blinded fashion -270 subjects -arginine, glutamine and b-hydroxy-b-methylbutyrate or a control drink -16 weeks ->wound closure and time to complete healing FIGURE 3 M edian wound area (cm 2 ) by week; arginine, glutamine and b-hydroxy-b-methylbutyrate supplementation (& ) (n = 129) and Control (s ) (n = 141). 5

6 Nutrient recommendations CVD Low albumin subgroup PAD subgroup FIGURE 4 Cumulative probability of wound closure vs. albumin at entry by patient subgroups. Each point (x, y) represents the proportion, y, of subjects with total wound closure in the subgroup of subjects with baseline albumin x. Specifically, for the subgroup of subjects (N = 127) with albumin 40 g/l, proportion healed is higher in the arginine, glutamine and b-hydroxy-b-methylbutyrate supplementation group (& ) (n = 61) vs. the control (s ) (n = 66) (P = ) Cochran M antel Haenszel test stratified by site. FIGURE 5 Cumulative probability of wound closure vs. ankle brachial index at entry by patient. Each point (x, y) represents the proportion, y, of subjects with total wound closure in the subgroup of subjects with baseline ankle brachial index x. Specifically, for the subgroup of subjects (N = 119) with ankle brachial index < 1.0, proportion healed is higher in the arginine, glutamine and b-hydroxyb-methylbutyrate supplementation group (& ) (n = 58) vs. the control group (s ) (n = 61) (P = ) CM H test stratified by site. Nosova, JVS 2015 OMEGA Studies + SPMs Studies To start recruitment Crosssectional Total: >200 patients Inflammation and Resolution SPM PAD I OMEGA STUDIES Completed (n=80) To start recruitment OMEGA EVAR PAD II Failure of resolution contributing to chronic inflammation Recruiting (8/30) PVI Recruiting (20/70) Serhan CN, Chiang N. Curr Op Pharm

7 Specialized Pro-Resolving Lipid Mediators ω-6 fatty acid ω-3 fatty acid Arachidonic acid AA Eicosapentaenoic acid EPA Docosahexaenoic acid DHA COX-1 COX-2 5-LOX 15-LOX 18-HEPE 15-LOX 12-LOX or 15-LOX typei TXA 2 PGE 2 Thromboxane Prostaglandins LTB 4 Leukotrienes LXA 4 LXB 4 Lipoxins RvE1 5-LOX RvE2 E-series Resolvins 17(S)-HDHA RvD1-RvD4 D-series Resolvins 17-HpDHA (N)PD1 Protectins 14-HpDHA 14-HDHA MaR1 Maresins RvD1 RvD2 PAD I Trial: 4.4g fish oil/day in PAD Grenon et al, JAHA

8 Summary Assessment, diagnosis, intervention and evaluation Perform nutritional assessment (weight, pre-albumin level and serum albumin level) Encourage dietary intake or supplementation Give vitamin and mineral supplements if deficiencies are confirmed or suspected Dietary consultation Await further trials and evidence Promising compounds 8