Hill s Evidence-Based Clinical Nutrition for Dermatology Specialists

Hill s Evidence-Based Clinical Nutrition for Dermatology Specialists

Discover the most complete and clinically proven line of dermatologic nutrition from Hill s Hill s Prescription Diet d/d Formulated to help manage inflammatory skin conditions such as atopy, flea allergy dermatitis and otitis externa, as well as adverse reactions to food, including food allergy and intolerance Increased omega-3 fatty acids, including EPA, to nourish the skin and help manage inflammation Added antioxidants to help support skin barrier function Available in a wide range of novel protein options: venison, duck, salmon, lamb, egg and rabbit Hill s Prescription Diet z/d Effective as the gold standard (home prepared foods) for diagnosing and managing adverse reactions to food including food allergies and intolerance Formulated with hydrolyzed animal proteins to eliminate the potential for an allergic response Added antioxidants to help support skin barrier function Hill s Science Diet Sensitive Skin Formulated to meet the nutrient and energy needs of adult pets with sensitive skin Increased levels of omega-6 and omega-3 fatty acids to nourish skin and coat Added antioxidants to help support skin barrier function

Discover the most complete and clinically proven line of dermatologic nutrition from Hill s

Hill s Prescription Diet d/d Canine Canned Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders d/d Duck Formula Canine: Cans of 13 oz (7003) in cases of 12 d/d Lamb Formula Canine: Cans of 13 oz (7002) in cases of 12 d/d Salmon Formula Canine: Cans of 13 oz (7004) in cases of 12 d/d Venison Formula Canine: Cans of 13 oz (7005) in cases of 12 2 Indications Inflammatory skin conditions such as atopy, flea allergy dermatitis and otitis externa. Adverse reactions to food (food allergy or intolerance). Not recommended for Growing puppies, pregnant or nursing dogs. Patients with hyperlipidemia, pancreatitis, history of pancreatitis or at risk of pancreatitis. Additional information Prescription Diet d/d Canine canned foods contain a single, novel animal protein source (duck, salmon, venison and lamb) which is not generally associated with adverse reactions to food in dogs. A limited number of digestible novel meat protein and carbohydrate ingredients help avoid common food allergies. Prescription Diet d/d Canine foods can help aid in the management of pruritic dermatitis, chronic gastroenteritis or colitis, inflammatory bowel disease (IBD), chronic otitis externa, flea allergy dermatitis, and contact dermatitis. Supplementation is unnecessary (including fatty acid supplements) and may decrease the effectiveness of the food. Other products to consider For use as an elimination diet (for maximum reliability in the identification of dietary sensitivity): Prescription Diet z/d ULTRA Allergen-Free Canine. To manage and eliminate adverse reactions to food: Prescription Diet z/d ULTRA Allergen-Free Canine or Prescription Diet z/d Low Allergen Canine. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Prescription Diet d/d Canine provides complete and balanced nutrition for the maintenance of adult dogs. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) Venison, Salmon & Duck FormulaS Can(s) (13 oz) 5 ½ - 2 /3 Lamb Formula Can(s) (13 oz) 1 /3 - ½ 10 ¾ - 1 2 /3 - ¾ 20 1 1 /3-1 ¾ 1-1 1 /3 40 2 ¼ - 3 1 2 /3-2 1 /3 60 3-4 ¼ 2 ¼ - 3 ¼ 80 3 ¾ - 5 ¼ 2 ¾ - 4 100 4 ½ - 6 ¼ 3 1 /3-4 2 /3 1 cup is equal to 1 can. 1 can is equal to 1 cup. These characteristics make Prescription Diet d/d Canine veterinary exclusive pet foods useful as a nutritional aid for dogs with adverse reactions to food or certain gastrointestinal disorders: KEY benefits Protein Single, novel animal source Highly digestible Reduced Helps avoid common food allergens. Limits the amount of undigested protein in the gastrointestinal tract able to provoke an allergic reaction. Number of Novel Protein Formulas Carbohydrate Antioxidants Four Potato or rice Added Duck, salmon, venison and lamb provide more choices related to a suspected allergy or patient preference. Allergies to potato or rice are uncommon. Help maintain a healthy immune system and the skin barrier function.

Ingredients Duck Formula: Water, Duck, Potato, Duck Liver, Potato Starch, Soybean Oil, Powdered Cellulose, Dicalcium Phosphate, Fish Oil, Calcium Carbonate, Iodized Salt, DL-Methionine, Taurine, Vitamin E Supplement, Potassium Chloride, Choline Chloride, L-Tryptophan, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Beta-Carotene, Thiamine Mononitrate, Niacin, Manganous Oxide, Copper Sulfate, Vitamin A Supplement, Calcium Pantothenate, Vitamin B12 Supplement, Biotin, Riboflavin, Vitamin D3 Supplement, Pyridoxine Hydrochloride, Cobalt Carbonate, Calcium Iodate, Folic Acid, Sodium Selenite, Menadione Dimethylpyrimidinol Bisulfite (source of vitamin K). CANNED Lamb Formula: Water, Rice, Lamb, Lamb Liver, Rice Flour, Powdered Cellulose, Soybean Oil, Fish Oil, Calcium Carbonate, Potassium Chloride, Sodium Tripolyphosphate, Iron Oxide, Dicalcium Phosphate, Choline Chloride, Vitamin E Supplement, Taurine, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Beta-Carotene, Thiamine Mononitrate, Manganous Oxide, Niacin, Calcium Pantothenate, Vitamin B12 Supplement, Pyridoxine Hydrochloride, Biotin, Vitamin D3 Supplement, Riboflavin, Calcium Iodate, Folic Acid, Sodium Selenite. Average Nutrient Contents duck LAMB As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 4.3 % 17.4 % 4.5 g 4.6 % 15.8 % 3.5 g Fat 4.1 % 16.6 % 4.3 g 7.8 % 26.8 % 5.9 g Carbohydrate (NFE) 14.4 % 58.3 % 15.0 g 14.2 % 48.8 % 10.7 g Crude Fiber 0.5 % 2.0 % 0.5 g 1.0 % 3.4 % 0.8 g Calcium 0.20 % 0.81 % 208 mg 0.17 % 0.58 % 128 mg Phosphorus 0.17 % 0.69 % 177 mg 0.09 % 0.31 % 68 mg Sodium 0.09 % 0.36 % 94 mg 0.10 % 0.34 % 75 mg Potassium 0.22 % 0.89 % 229 mg 0.21 % 0.72 % 158 mg Magnesium 0.016 % 0.065 % 17 mg 0.018 % 0.062 % 14 mg Total Omega-3 Fatty Acids 0.20 % 0.81 % 208 mg 0.33 % 1.13 % 248 mg Metabolizable Energy kcal/kg 961 3,891 1,330 4,570 kcal/can 356 492 % Calories From: Protein 15 Fat 35 Carbohydrates 50 Protein 12 Fat 50 Carbohydrates 38 3 Ingredients Salmon Formula: Water, Salmon, Potato, Potato Starch, Potato Protein, Soybean Oil, Fish Oil, Powdered Cellulose, Dicalcium Phosphate, Iodized Salt, Vitamin E Supplement, Choline Chloride, DL-Methionine, Taurine, Calcium Carbonate, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Niacin, Thiamine Mononitrate, Vitamin A Supplement, Beta-Carotene, Calcium Pantothenate, Biotin, Vitamin B12 Supplement, Pyridoxine Hydrochloride, Manganous Oxide, Copper Sulfate, Riboflavin, Folic Acid, Cobalt Carbonate, Calcium Iodate, Sodium Selenite. CANNED Venison Formula: Water, Venison, Potato, Potato Starch, Potato Protein, Soybean Oil, Powdered Cellulose, Fish Oil, Calcium Carbonate, Dicalcium Phosphate, Iodized Salt, Taurine, DL-Methionine, Choline Chloride, Vitamin E Supplement, L-Tryptophan, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Beta-Carotene, Thiamine Mononitrate, Niacin, Copper Sulfate, Manganous Oxide, Calcium Pantothenate, Vitamin B12 Supplement, Vitamin A Supplement, Pyridoxine Hydrochloride, Biotin, Riboflavin, Vitamin D3 Supplement, Calcium Iodate, Folic Acid, Sodium Selenite, Menadione Dimethylpyrimidinol Bisulfite (source of vitamin K). Average Nutrient Contents Salmon venison As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 4.6 % 18.9 % 4.7 g 4.6 % 18.9 % 4.2 g Fat 3.6 % 14.8 % 3.7 g 4.0 % 16.4 % 3.7 g Carbohydrate (NFE) 14.4 % 59.0 % 14.7 g 14.0 % 57.4 % 12.8 g Crude Fiber 0.5 % 2.0 % 0.5 g 0.5 % 2.0 % 0.5 g Calcium 0.19 % 0.78 % 194 mg 0.16 % 0.66 % 147 mg Phosphorus 0.17 % 0.70 % 174 mg 0.13 % 0.53 % 119 mg Sodium 0.08 % 0.33 % 82 mg 0.09 % 0.37 % 82 mg Potassium 0.19 % 0.78 % 194 mg 0.21 % 0.86 % 192 mg Magnesium 0.015 % 0.061 % 15 mg 0.015 % 0.061 % 14 mg Taurine 0.71 % 2.91 % 725 mg 0.20 % 0.82 % 183 mg Metabolizable Energy kcal/kg 979 4,012 1,091 4,471 kcal/can 362 404 % Calories From: Protein 17 Fat 32 Carbohydrates 51 Protein 16 Fat 34 Carbohydrates 50 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Prescription Diet d/d Canine Dry Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders Potato & Duck Potato & Venison d/d Rice & Egg Formula Canine: Bags of 8 lbs (5645) and 17.6 lbs (5646) d/d Potato & Duck Formula Canine: Bags of 8 lbs (5347) and 17.6 lbs (5343) d/d Potato & Venison Formula Canine: Bags of 8 lbs (5348) and 17.6 lbs (5342) d/d Potato & Salmon Formula Canine: Bags of 8 lbs (5346) and 17.6 lbs (5345) Potato & Salmon Rice & Egg 4 Indications Inflammatory skin conditions such as atopy, flea allergy dermatitis and otitis externa. Adverse reactions to food (food allergy or intolerance). Not recommended for Growing puppies, pregnant or nursing dogs. Patients with hyperlipidemia, pancreatitis, history of pancreatitis or at risk of pancreatitis. Additional information Prescription Diet d/d Canine foods contain a single, novel animal protein source (egg, duck, salmon and venison) which is not generally associated with adverse reactions to food in dogs. A limited number of digestible novel meat protein and carbohydrate ingredients help avoid common food allergies. Prescription Diet d/d Canine foods can help aid in the management of pruritic dermatitis, chronic gastroenteritis or colitis, inflammatory bowel disease (IBD), chronic otitis externa, flea allergy dermatitis, and contact dermatitis. Supplementation is unnecessary (including fatty acid supplements) and may decrease the effectiveness of the food. Other products to consider For use as an elimination diet (for maximum reliability in the identification of dietary sensitivity): Prescription Diet z/d ULTRA Allergen-Free Canine. To manage and eliminate adverse reactions to food: Prescription Diet z/d ULTRA Allergen-Free Canine or Prescription Diet z/d Low Allergen Canine. Animal feeding tests using AAFCO procedures substantiate that Prescription Diet d/d Canine provides complete and balanced nutrition for the maintenance of adult dogs. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) DAILY FEEDING AMOUNTS Rice & egg FormulaS Dry Cups potato & duck Formula Dry Cups potato & venison Formula and potato & salmon Formula Dry Cups 5 ½ - 5 /8 ½ - 2 /3 ½ - 2 /3 10 ¾ - 1 1 /8 ¾ - 1 1 /8 ¾ - 1 1 /8 20 1 1 /3-1 ¾ 1 1 /3-1 ¾ 1 1 /3-1 ¾ 40 2 ¼ - 3 2 ¼ - 3 2 ¼ - 3 60 3-4 3-4 ¼ 3-4 ¼ 80 3 2 /3-5 3 ¾ - 5 ¼ 3 ¾ - 5 ¼ 100 4 1 /3-6 4 ½ - 6 4 ½ - 6 ¼ 1 cup is equal to 1 can. 1 can is equal to 1 cup. These characteristics make Prescription Diet d/d Canine veterinary exclusive pet foods useful as a nutritional aid for dogs with adverse reactions to food or certain gastrointestinal disorders: KEY benefits Protein Single, novel animal source Highly digestible Reduced Helps avoid common food allergens. Limits the amount of undigested protein in the gastrointestinal tract able to provoke an allergic reaction. Number of Novel Protein Formulas Carbohydrate Antioxidants Four Potato or rice Added Duck, salmon, venison and egg provide more choices related to a suspected allergy or patient preference. Allergies to potato or rice are uncommon. Help maintain a healthy immune system and the skin barrier function.

Ingredients Rice and Egg Formula: Brewers Rice, Dried Egg Product, Pork Fat (preserved with mixed tocopherols and citric acid), Natural Flavor, Soybean Oil, Powdered Cellulose, Dicalcium Phosphate, Fish Oil, Potassium Chloride, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), Calcium Carbonate, Vitamin E Supplement, Choline Chloride, Iodized Salt, Taurine, preserved with Mixed Tocopherols, Citric Acid & Ethoxyquin, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 17.0 % 18.5 % 4.4 g Fat 15.2 % 16.5 % 3.9 g Carbohydrate (NFE) 54.9 % 59.7 % 14.1 g Crude Fiber 1.0 % 1.1 % 0.3 g Calcium 0.55 % 0.60 % 142 mg Phosphorus 0.46 % 0.50 % 118 mg Sodium 0.26 % 0.28 % 67 mg Potassium 0.64 % 0.70 % 165 mg Magnesium 0.062 % 0.067 % 16 mg Taurine 0.64 % 0.70 % 165 mg Metabolizable Energy kcal/kg 3,885 4,223 kcal/cup 383 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 16 Fat 34 Carbohydrates 50 Dry 5 Ingredients Potato and Duck Formula: Potato, Potato Starch, Duck, Potato Protein, Pork Fat (preserved with mixed tocopherols and citric acid), Soybean Oil, Natural Flavor, Dicalcium Phosphate, Potassium Chloride, Powdered Cellulose, Fish Oil, Iodized Salt, Calcium Carbonate, Duck By-Product Meal, Choline Chloride, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), DL-Methionine, Vitamin E Supplement, Taurine, Glycerol Monostearate, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), L-Tryptophan, preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 16.6 % 18.0 % 4.5 g Fat 15.6 % 17.0 % 4.2 g Carbohydrate (NFE) 52.2 % 56.7 % 14.0 g Crude Fiber 1.5 % 1.6 % 0.4 g Calcium 0.73 % 0.79 % 196 mg Phosphorus 0.53 % 0.58 % 143 mg Sodium 0.33 % 0.36 % 89 mg Potassium 0.72 % 0.78 % 194 mg Magnesium 0.066 % 0.072 % 18 mg Total Omega-3 Fatty Acids 0.72 % 0.78 % 194 mg Metabolizable Energy kcal/kg 3,719 4,042 kcal/cup 366 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 16 Fat 36 Carbohydrates 48 Dry 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Ingredients Potato and Venison Formula: Potato, Potato Starch, Venison, Potato Protein, Pork Fat (preserved with mixed tocopherols and citric acid), Soybean Oil, Natural Flavor, Dicalcium Phosphate, Potassium Chloride, Powdered Cellulose, Venison Meal, Fish Oil, Iodized Salt, Calcium Carbonate, Choline Chloride, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), DL-Methionine, Vitamin E Supplement, Taurine, Glycerol Monostearate, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), L-Tryptophan, preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, Beta-Carotene, Rosemary Extract. Dry 6 Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 16.6 % 18.0 % 4.5 g Fat 15.2 % 16.5 % 4.1 g Carbohydrate (NFE) 52.6 % 57.2 % 14.2 g Crude Fiber 1.5 % 1.6 % 0.4 g Calcium 0.73 % 0.79 % 197 mg Phosphorus 0.52 % 0.57 % 140 mg Sodium 0.33 % 0.36 % 89 mg Potassium 0.72 % 0.78 % 194 mg Magnesium 0.064 % 0.070 % 17 mg Taurine 0.71 % 0.77 % 191 mg Metabolizable Energy kcal/kg 3,711 4,034 kcal/cup 366 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 16 Fat 35 Carbohydrates 49 Ingredients Dry Potato and Salmon Formula: Potato, Potato Starch, Salmon, Potato Protein, Pork Fat (preserved with mixed tocopherols and citric acid), Soybean Oil, Natural Flavor, Dicalcium Phosphate, Fish Meal, Potassium Chloride, Powdered Cellulose, Fish Oil, Iodized Salt, Calcium Carbonate, Choline Chloride, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), Vitamin E Supplement, DL-Methionine, Taurine, Glycerol Monostearate, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, L-Tryptophan, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 16.6 % 18.0 % 4.5 g Fat 15.2 % 16.5 % 4.1 g Carbohydrate (NFE) 52.4 % 57.0 % 14.1 g Crude Fiber 1.6 % 1.7 % 0.4 g Calcium 0.74 % 0.80 % 199 mg Phosphorus 0.53 % 0.58 % 143 mg Sodium 0.34 % 0.37 % 92 mg Potassium 0.75 % 0.82 % 202 mg Magnesium 0.070 % 0.076 % 19 mg Total Omega-3 Fatty Acids 1.30 % 1.41 % 350 mg Metabolizable Energy kcal/kg 3,710 4,033 kcal/cup 366 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 16 Fat 35 Carbohydrates 49 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed.

1-800-548-VETS (8387). www.hillsvet.com 7

Hill s Prescription Diet z/d ULTRA Allergen-Free Canine Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders z/d ULTRA Allergen-Free Canine: Cans in 5.5 oz (5403) in cases of 24 and 13 oz (7018) in cases of 12 Bags of 8 lbs (7901) and 18 lbs (7902) 8 Indications Adverse reactions to food (food allergy or intolerance). Gastrointestinal disorders. Not recommended for Growing puppies, pregnant or nursing dogs. Additional information The hydrolyzed animal proteins in Prescription Diet z/d ULTRA Allergen-Free Canine have an average molecular weight less than 3,000 daltons. This allows them to escape detection by the immune system, which helps avoid adverse reactions. The hydrolyzed animal protein source and a single, highly digestible carbohydrate source (corn starch in canned formulas or starch in dry formulas) help avoid common food allergens. Pruritic dermatitis, chronic otitis externa: Adverse food reactions in dogs typically occur as non-seasonal pruritic dermatitis. Many dogs with adverse food reactions only have clinical signs of chronic otitis externa. Chronic gastroenteritis, chronic colitis: Adverse food reactions can result in chronic vomiting and/or diarrhea associated with gastrointestinal inflammation. Mildly affected dogs may only show an increase in the number of bowel movements or may have occasional vomiting. Inflammatory bowel disease (IBD): Adverse reactions to food may be associated with IBD. Prescription Diet z/d products may be helpful for dogs with inflammatory bowel disease. Other products to consider For dogs with adverse reactions to food: Prescription Diet d/d Canine. For dogs with colitis, gastroenteritis (acute or chronic), inflammatory bowel disease (IBD) or vomiting (acute or chronic): Prescription Diet i/d Canine. These characteristics make Prescription Diet z/d ULTRA Allergen-Free Canine veterinary exclusive pet food useful as a nutritional aid for dogs with adverse reactions to food or certain gastrointestinal disorders: KEY benefits Animal feeding tests using AAFCO procedures substantiate that Prescription Diet z/d ULTRA Allergen-Free Canine provides complete and balanced nutrition for the maintenance of adult dogs. The smooth, moist texture is perfect for mixing with z/d ULTRA Allergen-Free Canine or z/d Low Allergen Canine Dry. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Supplementation is unnecessary (including fatty acid supplements) and may decrease the effectiveness of the food. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) DAILY FEEDING AMOUNTS Can(s) (5.5 oz) 5 1 ¼ - 1 2 /3 ½ - 2 /3 Can(s) (13 oz) Dry Cups 2 /3-1 10 2-2 ¾ ¾ - 1 ¼ 1 ¼ - 1 5 /8 20 3 1 /3-4 2 /3 1 1 /3-2 2-2 ¾ 40 5 2 /3-7 ¾ 2 1 /3-3 ¼ 3 1 /3-4 2 /3 60 7 2 /3-10 ½ 3 ¼- 4 ½ 4 ½ - 6 1 /3 80 9 ½ - 13 4-5 ½ 5 2 /3-7 ¾ 100 11 ¼ - 15 ½ 4 ¾ - 6 ½ 6 2 /3-9 ¼ 1 cup is equal to 1 2 /3 cans (5.5 oz). 1 can (5.5 oz) is equal to 5 /8 cup. 1 cup is equal to 2 /3 can (13 oz). 1 can (13 oz) is equal to 1 3 /8 cups. Protein Carbohydrate Omega-3 Fatty Acids Omega-6 Fatty Acids Antioxidants Hydrolyzed Refined Increased Added Highly digestible animal protein source with an average molecular weight <3,000 daltons; no intact animal protein. A single, highly digestible carbohydrate source helps avoid common food allergens. Help manage associated inflammation and nourish the skin and coat. Help maintain a healthy immune system and the skin barrier function.

Ingredients canned Water, Hydrolyzed Chicken Liver, Corn Starch, Powdered Cellulose, Soybean Oil, Dicalcium Phosphate,Calcium Carbonate, Potassium Citrate, DL-Methionine, Choline Chloride, Iodized Salt, Vitamin E Supplement, Taurine, Ascorbic Acid (source of vitamin C), L-Threonine, Zinc Oxide, Ferrous Sulfate, L-Tryptophan, Beta-Carotene, Thiamine Mononitrate, Copper Sulfate, Manganous Oxide, Niacin, Calcium Pantothenate, Vitamin B12 Supplement, Pyridoxine Hydrochloride, Biotin, Calcium Iodate, Vitamin D3 Supplement, Riboflavin, Sodium Selenite, Folic Acid. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 4.8 % 19.6 % 4.9 g Fat 3.4 % 13.9 % 3.5 g Carbohydrate (NFE) 13.9 % 56.7 % 14.3 g Crude Fiber 1.1 % 4.5 % 1.1 g Calcium 0.18 % 0.73 % 185 mg Phosphorus 0.14 % 0.57 % 144 mg Sodium 0.05 % 0.20 % 51 mg Potassium 0.16 % 0.65 % 164 mg Magnesium 0.014 % 0.057 % 14 mg Total Omega-3 Fatty Acids 0.12 % 0.49 % 123 mg Total Omega-6 Fatty Acids 0.99 % 4.04 % 1,017 mg Metabolizable Energy kcal/kg 973 3,971 kcal/can small (5.5 oz): 152; large (13 oz): 360 % Calories From: Protein 18 Fat 31 Carbohydrates 51 9 Ingredients Starch, Hydrolyzed Chicken Liver, Soybean Oil (preserved with BHA, propyl gallate and citric acid), Hydrolyzed Chicken, Powdered Cellulose, Dicalcium Phosphate, Calcium Carbonate, Glyceryl Monostearate, Potassium Chloride, Iodized Salt, Choline Chloride, Vitamins (vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, l-ascorbyl-2-polyphosphate [source of vitamin C], calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), DL-Methionine, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), Taurine, Ethoxyquin (a preservative), Beta-Carotene. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 17.5 % 19.0 % 4.7 g Fat 12.8 % 13.9 % 3.4 g Carbohydrate (NFE) 54.6 % 59.3 % 14.7 g Crude Fiber 2.5 % 2.7 % 0.7 g Calcium 0.61 % 0.66 % 164 mg Phosphorus 0.47 % 0.51 % 126 mg Sodium 0.27 % 0.29 % 73 mg Potassium 0.61 % 0.66 % 164 mg Magnesium 0.050 % 0.054 % 13 mg Total Omega-3 Fatty Acids 0.50 % 0.54 % 134 mg Total Omega-6 Fatty Acids 3.86 % 4.20 % 1,037 mg Metabolizable Energy kcal/kg 3,724 4,048 kcal/cup 254 Weight oz/cup 2.4 Cups per lb 6.6 % Calories From: Protein 17 Fat 30 Carbohydrates 53 dry 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Prescription Diet z/d Low Allergen Canine Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders z/d ULTRA Low Allergen Canine: Bags of 8 lbs (7903) and 27.5 lbs (7904) 10 Indications Adverse reactions to food (food allergy or intolerance). Gastrointestinal disorders. Not recommended for Growing puppies, pregnant or nursing dogs. Additional information The hydrolyzed animal proteins in Prescription Diet z/d Low Allergen Canine have an average molecular weight less than 3,000 daltons. This allows them to escape detection by the immune system, which helps avoid adverse reactions. The hydrolyzed animal protein source and a single, highly digestible carbohydrate source (potato) help avoid common food allergens. Pruritic dermatitis, chronic otitis externa: Adverse food reactions in dogs typically occur as non-seasonal pruritic dermatitis. Many dogs with adverse food reactions only have clinical signs of chronic otitis externa. Chronic gastroenteritis, chronic colitis: Adverse food reactions can result in chronic vomiting and/or diarrhea associated with gastrointestinal inflammation. Mildly affected dogs may only show an increase in the number of bowel movements or may have occasional vomiting. Inflammatory bowel disease (IBD): Adverse reactions to food may be associated with IBD. Prescription Diet z/d products may be helpful for dogs with inflammatory bowel disease. Other products to consider For dogs with adverse reactions to food: Prescription Diet d/d Canine or Prescription Diet z/d ULTRA Allergen-Free Canine (canned). For dogs with colitis, gastroenteritis (acute or chronic), inflammatory bowel disease (IBD) or vomiting (acute or chronic): Prescription Diet i/d Canine. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Prescription Diet z/d Low Allergen Canine provides complete and balanced nutrition for the maintenance of adult dogs. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) Dry Cups 5 ½ - 2 /3 10 7 /8-1 1 /8 20 1 1 /3-2 40 2 1 /3-3 ¼ 60 3 ¼ - 4 1 /3 80 4-5 ½ 100 4 2 /3-6 ½ These characteristics make Prescription Diet z/d Low Allergen Canine veterinary exclusive pet food useful as a nutritional aid for dogs with adverse reactions to food or certain gastrointestinal disorders: KEY benefits Protein Carbohydrate Omega-3 Fatty Acids Omega-6 Fatty Acids Antioxidants Hydrolyzed Single source Increased Added Highly digestible animal protein source with an average molecular weight <3,000 daltons; no intact animal protein. A single, highly digestible carbohydrate source helps avoid common food allergens. Help manage associated inflammation and nourish the skin and coat. Help maintain a healthy immune system and the skin barrier function.

Ingredients Dried Potato Product, Hydrolyzed Chicken Liver, Potato Starch, Soybean Oil (preserved with BHA, propyl gallate and citric acid), Hydrolyzed Chicken, Powdered Cellulose, Calcium Sulfate, Dicalcium Phosphate, Glyceryl Monostearate, Iodized Salt, Choline Chloride, Vitamins (vitamin E supplement, l-ascorbyl-2-polyphosphate [source of vitamin C], niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), Calcium Carbonate, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), DL-Methionine, Taurine, Ethoxyquin (a preservative), Beta-Carotene. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 18.9 % 20.5 % 5.1 g Fat 12.0 % 13.0 % 3.3 g Carbohydrate (NFE) 51.3 % 55.8 % 13.9 g Crude Fiber 3.2 % 3.5 % 0.9 g Calcium 0.57 % 0.62 % 155 mg Phosphorus 0.49 % 0.53 % 133 mg Sodium 0.36 % 0.39 % 98 mg Potassium 1.20 % 1.30 % 326 mg Magnesium 0.089 % 0.097 % 24 mg Total Omega-3 Fatty Acids 0.38 % 0.41 % 103 mg Total Omega-6 Fatty Acids 2.95 % 3.21 % 802 mg Metabolizable Energy kcal/kg 3,679 3,999 kcal/cup 363 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 19 Fat 29 Carbohydrates 52 DRy 11 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Prescription Diet d/d Feline Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders Duck & Green Pea d/d Duck Formula Feline: Cans of 5.5 oz (5364) in cases of 24 d/d Venison Formula Feline: Cans of 5.5 oz (5365) in cases of 24 d/d Duck & Green Pea Formula Feline: Bags of 3.5 lbs (5351) and 8.5 lbs (5355) d/d Rabbit & Green Pea Formula Feline: Bags of 3.5 lbs (5352) and 8.5 lbs (5357) d/d Venison & Green Pea Formula Feline: Bags of 3.5 lbs (5350) and 8.5 lbs (5356) Venison & Green Pea Rabbit & Green Pea 12 Indications Inflammatory skin conditions such as atopy, flea allergy dermatitis and feline eosinophilic granuloma complex Adverse reactions to food (food allergy or intolerance). Not recommended for Growing kittens, pregnant or nursing cats. Patients with concurrent use of urinary acidifiers. Additional information Prescription Diet d/d Feline foods contain a single, novel animal protein source (duck, rabbit, or venison) which is not generally associated with adverse reactions to food in cats. Prescription Diet d/d Feline foods may help aid in the management of the following: Pruritic dermatitis: Adverse food reactions in cats typically occur as pruritic dermatitis, with or without concurrent gastrointestinal signs. Chronic gastroenteritis, chronic colitis: Adverse food reactions can result in chronic vomiting and/or diarrhea associated with gastrointestinal inflammation; mildly affected cats may only show an increase in the number of bowel movements or may have occasional vomiting. Inflammatory bowel disease (IBD): Adverse reactions to food may potentiate IBD. Atopic dermatitis, food allergy and flea allergy can occur in the same patient concurrently. Allergic dermatitis patients may have clinical signs of eosinophilic granuloma complex. Contact dermatitis. Supplementation beyond the analogous canned or dry formula (including fatty acid supplements) is unnecessary and may decrease the effectiveness of the food. Other products to consider For use as an elimination food, for patients with IBD, or to manage and eliminate adverse reactions to food: Prescription Diet z/d Ultra Allergen-Free Feline and Prescription Diet z/d Low Allergen Feline. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Prescription Diet d/d Feline provides complete and balanced nutrition for the maintenance of adult cats. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) all canned FormulaS Can(s) (5.5 oz) all dry Formulas Dry Cups 5 2 /3-1 ¼ - 3 /8 10 1 ¼ - 1 2 /3 ½ - 5 /8 15 1 ½ - 2 ¼ 5 /8-7 /8 1 cup is equal to 2 5 /8 cans. 1 can is equal to 3 /8 cup. 1 cup is equal to 2 ½ cans (venison formulas only). These characteristics make Prescription Diet d/d Feline veterinary exclusive pet foods useful as a nutritional aid for dogs with adverse reactions to food: KEY benefits Protein Single, novel animal source Highly digestible Helps avoid common food allergens. Limits the amount of undigested protein in the gastrointestinal tract able to provoke an allergic reaction. Number of Novel Protein Formulas Carbohydrate Antioxidants Three Green pea Added Duck, rabbit or venison provide more choices related to a suspected allergy or patient preference. Allergies to green pea are uncommon. Help maintain a healthy immune system and the skin barrier function.

Ingredients Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 10.1 % 38.1 % 8.4 g Fat 7.7 % 29.1 % 6.4 g Carbohydrate (NFE) 5.9 % 22.3 % 4.9 g Crude Fiber 1.2 % 4.5 % 1.0 g Calcium 0.21 % 0.79 % 174 mg Phosphorus 0.20 % 0.75 % 165 mg Sodium 0.08 % 0.30 % 66 mg Potassium 0.25 % 0.94 % 207 mg Magnesium 0.022 % 0.083 % 18 mg Taurine.015 % 0.57 % 124 mg Total Omega-3 Fatty Acids 0.31 % 1.17 % 256 mg Metabolizable Energy kcal/kg 1,209 4,562 kcal/can 189 canned Duck Formula: Water, Duck, Duck Liver, Ground Green Pea, Powdered Cellulose, Soybean Oil, Pea Protein Concentrate, Brewers Dried Yeast, Fish Oil, Glucose, Calcium Carbonate, DL-Methionine, Dicalcium Phosphate, Taurine, L-Cysteine, Choline Chloride, Iron Oxide, Glycine, Potassium Chloride, Iodized Salt, Vitamin E Supplement, Potassium Citrate, Thiamine Mononitrate, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Thiamine Hydrochloride, Niacin, Pyridoxine Hydrochloride, Beta-Carotene, Manganous Oxide, Calcium Pantothenate, Vitamin B12 Supplement, Riboflavin, Biotin, Vitamin D3 Supplement, Calcium Iodate, Folic Acid, Sodium Selenite. % Calories From: Protein 29 Fat 54 Carbohydrates 17 13 Ingredients canned Venison Formula: Venison, Water, Venison Liver, Ground Green Pea, Pea Protein Concentrate, Soybean Oil, Powdered Cellulose, Fish Oil, DL-Methionine, Choline Chloride, Calcium Carbonate, Iron Oxide, Calcium Sulfate, Iodized Salt, Potassium Chloride, Taurine, Dicalcium Phosphate, Vitamin E Supplement, Thiamine Mononitrate, Ascorbic Acid (source of vitamin C), Zinc Oxide, Ferrous Sulfate, Beta-Carotene, Niacin, Manganous Oxide, Copper Sulfate, Pyridoxine Hydrochloride, Calcium Pantothenate, Vitamin B12 Supplement, Riboflavin, Biotin, Vitamin D3 Supplement, Calcium Iodate, Folic Acid, Sodium Selenite. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 9.7 % 37.3 % 7.7 g Fat 7.9 % 30.4 % 6.3 g Carbohydrate (NFE) 5.5 % 21.2 % 4.4 g Crude Fiber 1.2 % 4.6 % 1.0 g Calcium 0.21 % 0.81 % 166 mg Phosphorus 0.19 % 0.73 % 150 mg Sodium 0.09 % 0.35 % 71 mg Potassium 0.24 % 0.92 % 190 mg Magnesium 0.023 % 0.088 % 18 mg Taurine 0.10 % 0.38 % 79 mg Total Omega-3 Fatty Acids 0.48 % 1.85 % 380 mg Metabolizable Energy kcal/kg 1,263 4,858 kcal/can 197 % Calories From: Protein 28 Fat 56 Carbohydrates 16 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

14 Ingredients Dry Duck & Green Pea Formula: Pea Protein Concentrate, Duck, Pea Bran Meal, Ground Green Peas, Pork Fat (preserved with mixed tocopherols and citric acid), Duck Meal, Soybean Oil, Calcium Sulfate, Natural Flavor, Fish Oil, Choline Chloride, DL-Methionine, Iodized Salt, L-Cysteine, Taurine, Dicalcium Phosphate, Vitamin E Supplement, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, riboflavin, biotin, vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement), Potassium Sulfate, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 30.1 % 32.0 % 7.8 g Fat 22.5 % 23.9 % 5.9 g Carbohydrate (NFE) 30.5 % 32.4 % 7.9 g Crude Fiber 4.7 % 5.0 % 1.2 g Calcium 0.68 % 0.72 % 177 mg Phosphorus 0.68 % 0.72 % 177 mg Sodium 0.38 % 0.40 % 99 mg Potassium 0.94 % 1.00 % 245 mg Magnesium 0.104 % 0.111 % 27 mg Taurine 0.35 % 0.37 % 91 mg Total Omega-3 Fatty Acids 0.70 % 0.74 % 182 mg Metabolizable Energy kcal/kg 3,842 4,087 kcal/can 466 Weight oz/cup 4.3 Cups per lb 3.7 % Calories From: Protein 26 Fat 47 Carbohydrates 27 Ingredients Rabbit & Green Pea Formula: Pea Protein Concentrate, Rabbit, Pea Bran Meal, Ground Green Peas, Pork Fat (preserved with mixed tocopherols and citric acid), Rabbit Meal, Soybean Oil, Calcium Sulfate, Natural Flavor, Fish Oil, DL-Methionine, Dicalcium Phosphate, Choline Chloride, L-Cystene, Iodized Salt, Taurine, Calcium Carbonate, Vitamin E Supplement, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, riboflavin, biotin, vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement), Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 30.1 % 32.0 % 7.9 g Fat 20.9 % 22.2 % 5.5 g Carbohydrate (NFE) 32.1 % 34.1 % 8.5 g Crude Fiber 4.7 % 5.0 % 1.2 g Calcium 0.69 % 0.73 % 182 mg Phosphorus 0.69 % 0.73 % 182 mg Sodium 0.32 % 0.34 % 84 mg Potassium 0.89 % 0.95 % 235 mg Magnesium 0.111 % 0.118 % 29 mg Taurine 0.34 % 0.36 % 90 mg Total Omega-3 Fatty Acids 0.67 % 0.71 % 177 mg Metabolizable Energy kcal/kg 3,794 4,036 kcal/can 460 Weight oz/cup 4.3 Cups per lb 3.7 % Calories From: Protein 27 Fat 45 Carbohydrates 28 dry

Ingredients Venison & Green Pea Formula: Pea Protein Concentrate, Venison, Pea Bran Meal, Ground Green Peas, Pork Fat (preserved with mixed tocopherols and citric acid), Venison Meal, Soybean Oil, Calcium Sulfate, Natural Flavor, Fish Oil, Choline Chloride, DL-Methionine, L-Cysteine, Iodized Salt, Taurine, Vitamin E Supplement, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, riboflavin, biotin, vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement), Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), preserved with Mixed Tocopherols, Citric Acid and Ethoxyquin, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 30.1 % 32.0 % 7.8 g Fat 21.4 % 22.8 % 5.5 g Carbohydrate (NFE) 31.7 % 33.7 % 8.2 g Crude Fiber 4.6 % 4.9 % 1.2 g Calcium 0.79 % 0.84 % 204 mg Phosphorus 0.70 % 0.74 % 181 mg Sodium 0.28 % 0.30 % 72 mg Potassium 0.90 % 0.96 % 232 mg Magnesium 0.109 % 0.116 % 28 mg Taurine 0.35 % 0.37 % 90 mg Total Omega-3 Fatty Acids 0.68 % 0.72 % 176 mg Metabolizable Energy kcal/kg 3,872 4,119 kcal/can 470 Weight oz/cup 4.3 Cups per lb 3.7 % Calories From: Protein 26 Fat 46 Carbohydrates 28 dry 15 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Prescription Diet z/d ULTRA Allergen-Free Feline Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders z/d ULTRA Allergen-Free Feline: Cans of 5.5 oz (5238) in cases of 24 16 Indications Adverse reactions to food (food allergy or intolerance). Gastrointestinal disorders. Not recommended for Growing kittens, pregnant or nursing cats. Patients with concurrent use of urinary acidifiers. Additional information The hydrolyzed animal proteins in z/d ULTRA Allergen-Free Feline have an average molecular weight less than 3,000 daltons. This allows them to escape detection by the immune system, which helps avoid adverse reactions. The hydrolyzed animal protein source and a refined, highly digestible carbohydrate source (corn starch) helps avoid common food allergens. Pruritic dermatitis, eosinophilic granuloma complex: Adverse food reactions in cats typically occur as non-seasonal pruritic dermatitis. Some cats with adverse food reactions have clinical signs of eosinophilic granuloma complex. Chronic gastroenteritis, chronic colitis: Adverse food reactions can result in chronic vomiting and/or diarrhea associated with gastrointestinal inflammation. Mildly affected cats may only show an increase in the number of bowel movements or may have only occasional vomiting. Inflammatory bowel disease (IBD): Adverse reactions to food may potentiate IBD. Prescription Diet z/d ULTRA Allergen-Free Feline may aid in the nutritional management of inflammatory bowel disease in cats. Supplementation beyond the Prescription Diet z/d ULTRA Allergen-Free Feline canned formula (including fatty acid supplements) is unnecessary and may decrease the effectiveness of the food. Other products to consider For cats with adverse reactions to food or inflammatory bowel disease: Prescription Diet d/d Feline. For cats with colitis, diarrhea (acute or chronic) gastroenteritis (acute or chronic), inflammatory bowel disease or vomiting (acute or chronic): Prescription Diet i/d Feline. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Prescription Diet z/d ULTRA Allergen-Free Feline provides complete and balanced nutrition for the maintenance of adult cats. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) all canned FormulaS Can(s) (5.5 oz) 5 3 /4-1 10 1 ¼ - 1 3 /4 15 1 3 /4-2 1 /3 1 cup is equal to 2 1 /3 cans. 1 can is equal to 3 /8 cup. These characteristics make Prescription Diet z/d ULTRA Allergen-Free Feline veterinary exclusive pet foods useful as a nutritional aid for cats with adverse reactions to food: KEY benefits Protein Carbohydrate Hydrolyzed Refined source Highly digestible animal protein source with an average molecular weight <3,000 daltons; no intact animal protein. Highly digestible carbohydrate source helps avoid common food allergens. Omega-3 Fatty Acids Omega-6 Fatty Acids Antioxidants High Increased Added Help manage associated inflammation and nourish the skin and coat. Help maintain a healthy immune system and the skin barrier function.

Ingredients As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 8.9 % 33.7 % 8.2 g Fat 4.8 % 18.2 % 4.4 g Carbohydrate (NFE) 10.7 % 40.5 % 9.9 g Crude Fiber 0.4 % 1.5 % 0.4 g Calcium 0.19 % 0.72 % 176 mg Phosphorus 0.17 % 0.64 % 157 mg Sodium 0.08 % 0.30 % 74 mg Potassium 0.21 % 0.80 % 194 mg Magnesium 0.017 % 0.064 % 16 mg Taurine 0.10 % 0.38 % 93 mg Total Omega-3 Fatty Acids 0.12 % 0.45 % 111 mg Total Omega-6 Fatty Acids 1.07 % 4.05 % 990 mg Metabolizable Energy kcal/kg 1,081 4,095 kcal/can 169 canned Hydrolyzed Chicken Liver, Water, Corn Starch, Soybean Oil, Powdered Cellulose, Calcium Carbonate, DL-Methionine, Potassium Chloride, Dicalcium Phosphate, Choline Chloride, Iodized Salt, Vitamin E Supplement, Taurine, Calcium Sulfate, Thiamine Mononitrate, Zinc Oxide, Ascorbic Acid (source of vitamin C), Ferrous Sulfate, Niacin, Beta-Carotene, Manganous Oxide, Copper Sulfate, Pyridoxine Hydrochloride, Calcium Pantothenate, Vitamin B12 Supplement, Riboflavin, Biotin, Vitamin D3 Supplement, Calcium Iodate, Folic Acid, Sodium Selenite. Average Nutrient Contents % Calories From: Protein 28 Fat 37 Carbohydrates 35 17 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Prescription Diet z/d Low Allergen Feline Disease Category: Adverse Reactions to Food & Inflammatory Skin Conditions Gastrointestinal Disorders z/d Low Allergen Feline: Bags of 4 lbs (7905) and 10 lbs (9623) 18 Indications Adverse reactions to food (food allergy or intolerance). Gastrointestinal disorders. Not recommended for Growing kittens, pregnant or nursing cats. Patients with concurrent use of urinary acidifiers. Additional information The hydrolyzed animal proteins in z/d Low Allergen Feline have an average molecular weight less than 3,000 daltons. This allows them to escape detection by the immune system, which helps avoid adverse reactions. The hydrolyzed animal protein source and a single, highly digestible carbohydrate source (rice) help avoid common food allergens. Pruritic dermatitis, eosinophilic granuloma complex: Adverse food reactions in cats typically occur as non-seasonal pruritic dermatitis. Some cats with adverse food reactions have clinical signs of eosinophilic granuloma complex. Chronic gastroenteritis, chronic colitis: Adverse food reactions can result in chronic vomiting and/or diarrhea associated with gastrointestinal inflammation. Mildly affected cats may only show an increase in the number of bowel movements or may have only occasional vomiting. Inflammatory bowel disease (IBD): Adverse reactions to food may potentiate IBD. Prescription Diet z/d Low Allergen Feline may aid in the nutritional management of inflammatory bowel disease in cats. Supplementation beyond the z/d Low Allergen Feline dry formula (including fatty acid supplements) is unnecessary and may decrease the effectiveness of the food. Other products to consider For cats with adverse reactions to food or inflammatory bowel disease: Prescription Diet d/d Feline. For cats with colitis, diarrhea (acute or chronic) gastroenteritis (acute or chronic), inflammatory bowel disease or vomiting (acute or chronic): Prescription Diet i/d Feline. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Prescription Diet z/d Low Allergen Feline provides complete and balanced nutrition for the maintenance of adult cats. The following ranges are a starting point only and should be adjusted as needed to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. Body Weight (lb) Dry Cups 5 1 /3 - ½ 10 ½ - 3 /4 15 3 /4-1 1 cup is equal to 2 1 /3 cans. 1 can is equal to 3 /8 cup. These characteristics make Prescription Diet z/d Low Allergen Feline veterinary exclusive pet foods useful as a nutritional aid for cats with adverse reactions to food: KEY benefits Protein Carbohydrate Hydrolyzed Single source Highly digestible animal protein source with an average molecular weight <3,000 daltons; no intact animal protein. Highly digestible carbohydrate source helps avoid common food allergens. Omega-3 Fatty Acids Omega-6 Fatty Acids Antioxidants High Increased Added Help manage associated inflammation and nourish the skin and coat. Help maintain a healthy immune system and the skin barrier function.

Ingredients Rice Protein Concentrate, Brewers Rice, Hydrolyzed Chicken Liver, Soybean Oil (preserved with BHA, propyl gallate and citric acid), Powdered Cellulose, Hydrolyzed Chicken, Calcium Carbonate, Potassium Chloride, Glyceryl Monostearate, Choline Chloride, Dicalcium Phosphate, Vitamins (vitamin E supplement, l-ascorbyl-2-polyphosphate [source of vitamin C], niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, riboflavin, biotin, vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement), Iodized Salt, Calcium Sulfate, Taurine, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), Ethoxyquin (a preservative), Beta-Carotene. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 37.0 % 40.0 % 9.7 g Fat 15.9 % 17.2 % 4.2 g Carbohydrate (NFE) 32.7 % 35.4 % 8.6 g Crude Fiber 1.7 % 1.8 % 0.4 g Calcium 0.65 % 0.71 % 172 mg Phosphorus 0.56 % 0.61 % 147 mg Sodium 0.33 % 0.36 % 88 mg Potassium 0.68 % 0.74 % 180 mg Magnesium 0.067 % 0.072 % 18 mg Taurine 0.21 % 0.23 % 55 mg Total Omega-3 Fatty Acids 0.61 % 0.66 % 161 mg Total Omega-6 Fatty Acids 5.30 % 5.73 % 1,396 mg Metabolizable Energy kcal/kg 3,797 4,105 kcal/cup 396 Weight oz/cup 3.7 Cups per lb 4.4 % Calories From: Protein 34 Fat 36 Carbohydrates 30 dry 19 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Science Diet Sensitive Skin Adult Canine Disease Category: Adult dogs with sensitive skin Sensitive Skin Adult Canine: Bags of 4.5 lbs (8533), 17.5 lbs (8534) and 35 lbs (8535) 20 Recommended for Adult dogs 1 6 years of age with dry, flaky, itchy and sensitive skin. Not recommended for Puppies, pregnant or nursing dogs. Additional information Formulated with high levels of skin-essential nutrients: vitamins E and C, omega-6 and omega-3 fatty acids. Supports skin and coat health to help avoid dry, flaky, itchy, sensitive skin, and dull unhealthy coat. 100% Guarantee pets will love the taste or consumers can return the unused portion for a full refund. Other products to consider For dogs with skin problems due to adverse reactions to food or inflammatory skin conditions: Prescription Diet z/d Canine or Prescription Diet d/d Canine. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Science Diet Sensitive Skin Adult Canine dry food provides complete and balanced nutrition for the maintenance of adult dogs. These ranges are a starting point only and should be adjusted to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. For maximum benefit, this product must be fed as the only food. Use of supplements or mixing with any other food is not recommended. Body Weight (lb) Dry Cups 5 ½ - 5 /8 10 3 /4-1 1 /8 20 1 1 /3-1 3 /4 40 2 ¼ - 3 60 3-4 80 3 2 /3-5 100 4 1 /3-6 KEY benefits for pet owners Unique Protein Combination for Skin Health High-quality protein, including egg protein and other essential amino acids provide key building blocks for healthy skin and a shiny coat. High Fatty Acid Levels High levels of omega-6 and omega-3 fatty acids to nourish skin and help replenish its natural oils. Superior Antioxidant Formula A higher level of vitamins E + C versus major competitive brands. A powerful combination of antioxidants helps keep the immune system healthy. Antioxidants are known to help slow cell damage. Vitamins E and C are known to support healthy skin and coat. Naturally Preserved Mixed tocopherols (a form of vitamin E) preserve freshness and great taste.

Ingredients Brewers Rice, Ground Whole Grain Corn, Corn Gluten Meal, Pork Meal, Dried Egg Product, Soybean Oil, Flaxseed, Animal Fat (preserved with mixed tocopherols and citric acid), Chicken Liver Flavor, Potassium Chloride, L-Lysine, Iodized Salt, DL-Methionine, Vitamins (l-ascorbyl-2- polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, biotin, vitamin B12 supplement, pyridoxine hydrochloride, riboflavin, folic acid, vitamin D3 supplement), Calcium Carbonate, Choline Chloride, Vitamin E Supplement, L-Tryptophan, preserved with Mixed Tocopherols and Citric Acid, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), Taurine, Beta-Carotene, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 25.3 % 27.5 % 6.7 g Fat 16.0 % 17.4 % 4.2 g Carbohydrate (NFE) 44.8 % 48.7 % 11.8 g Crude Fiber 1.3 % 1.4 % 0.3 g Calcium 0.74 % 0.80 % 195 mg Phosphorus 0.56 % 0.61 % 148 mg Sodium 0.32 % 0.35 % 84 mg Potassium 0.64 % 0.70 % 169 mg Magnesium 0.078 % 0.085 % 21 mg Total Omega-3 Fatty Acids 1.37 % 1.49 % 361 mg Total Omega-6 Fatty Acids 4.61 % 5.01 % 1,216 mg Vitamin C 305 mg/kg (ppm) 332 mg/kg (ppm) 8.05 mg Vitamin E 559 mg/kg (ppm) 608 mg/kg (ppm) 14.75 IU/100 kcal Metabolizable Energy kcal/kg 3,791 4,121 kcal/cup 374 Weight oz/cup 3.5 Cups per lb 4.6 % Calories From: Protein 23 Fat 36 Carbohydrates 41 dry 21 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Hill s Science Diet Sensitive Skin Adult Feline Disease Category: Adult cats with sensitive skin Sensitive Skin Adult Feline: Bags of 3.5 lbs (8526) and 8.5 lbs (8527) 22 Recommended for Adult cats 1 6 years of age with sensitive skin. Not recommended for Kittens, pregnant or nursing cats. Additional information Supports skin health to help avoid scratching and shedding associated with dry, flaky skin. Formulated with high levels of the skin-essential nutrients vitamin E, omega-6 and omega-3 fatty acids. 100% Guarantee pets will love the taste or consumers can return the unused portion for a full refund. Other products to consider For cats with skin problems due to adverse reactions to food or inflammatory skin conditions: Prescription Diet z/d Feline or Prescription Diet d/d Feline. DAILY FEEDING AMOUNTS Animal feeding tests using AAFCO procedures substantiate that Science Diet Sensitive Skin Adult Feline dry food provides complete and balanced nutrition for the maintenance of adult cats. These ranges are a starting point only and should be adjusted to maintain proper weight. Mix increasing amounts of the pet s new food with decreasing amounts of the old food over a 7-day period. For maximum benefit, this product must be fed as the only food. Use of supplements or mixing with any other food is not recommended. Body Weight (lb) Dry Cups 5 1 /3 - ½ 10 ½ - 3 /4 15 3 /4-1 KEY benefits for pet owners Unique Protein Combination for Skin Health Increased Fatty Acid Levels Superior Antioxidant Formula Naturally Preserved Target Urine ph 6.2 6.4 * High-quality protein, including egg protein enhanced with selected amino acids, provides key building blocks for healthy skin and a shiny coat. Increased levels of omega-6 and omega-3 fatty acids to nourish skin and coat. A higher level of vitamins E + C versus major competitive brands. A powerful combination of antioxidants helps keep the immune system healthy. Antioxidants are known to help slow cell damage. Vitamins E and C are known to support healthy skin and coat. Mixed tocopherols (a form of vitamin E) preserve freshness and great taste. Promotes a normal acid urine to support urinary tract health. * Urine ph of individual cats may vary due to complicating factors such as time of feeding before urine collection, type of urine collection, individual animal variation, and test methodology.

Ingredients Brewers Rice, Corn Gluten Meal, Chicken By-Product Meal, Ground Whole Grain Corn, Animal Fat (preserved with mixed tocopherols and citric acid), Dried Egg Product, Soybean Oil, Chicken Liver Flavor, Potassium Chloride, Calcium Carbonate, Choline Chloride, DL-Methionine, L-Lysine, Vitamins (l-ascorbyl-2-polyphosphate [source of vitamin C], vitamin E supplement, niacin, thiamine mononitrate, vitamin A supplement, calcium pantothenate, riboflavin, biotin, vitamin B12 supplement, pyridoxine hydrochloride, folic acid, vitamin D3 supplement), Vitamin E Supplement, Iodized Salt, Taurine, Fish Oil, Minerals (ferrous sulfate, zinc oxide, copper sulfate, manganous oxide, calcium iodate, sodium selenite), preserved with Mixed Tocopherols and Citric Acid, Beta-Carotene, L-Tryptophan, Rosemary Extract. Average Nutrient Contents As Fed 1 Dry Matter 2 As Fed, Caloric Basis 3 Protein 32.3 % 35.1 % 8.3 g Fat 20.4 % 22.2 % 5.2 g Carbohydrate (NFE) 33.6 % 36.5 % 8.6 g Crude Fiber 0.7 % 0.8 % 0.2 g Calcium 0.71 % 0.77 % 182 mg Phosphorus 0.68 % 0.74 % 174 mg Sodium 0.38 % 0.41 % 97 mg Potassium 0.62 % 0.67 % 159 mg Magnesium 0.056 % 0.061 % 14 mg Taurine 0.19 % 0.21 % 49 mg Total Omega-3 Fatty Acids 0.44 % 0.48 % 113 mg Total Omega-6 Fatty Acids 4.69 % 5.10 % 1,201 mg Vitamin C 240 mg/kg (ppm) 261 mg/kg (ppm) 6.15 mg Vitamin E 829 IU/kg 901 IU/kg 21.23 IU/100 kcal Metabolizable Energy kcal/kg 3,904 4,243 kcal/cup 400 Weight oz/cup 3.6 Cups per lb 4.4 % Calories From: Protein 28 Fat 43 Carbohydrates 29 dry 23 1. Differs from label guarantees which are either maximums or minimums. 2. The nutrient in the product after moisture is removed. It is used to make direct comparisons of nutrient profiles with differing moisture contents. 3. Nutrient intake for every 100 kilocalories consumed. 1-800-548-VETS (8387). www.hillsvet.com

Fatty Acid Supplementation: Does It Really Work? From Proceedings, ACVIM Forum, 2006 Philip Roudebush, DVM, DACVIM (Small Animal Internal Medicine) Hill s Scientific Affairs, Topeka, Kansas Basic fatty acid metabolism All mammals synthesize fatty acids de novo up to palmitic acid (16:0), which may be elongated to stearic acid (18:0) and converted into oleic acid (18:1). Plants, unlike mammals, can insert additional double bonds into oleic acid and produce the polyunsaturated fatty acids (PUFA) linoleic acid (LA, 18:2n-6) and alpha-linolenic acid (ALA, 18:3n-3). Both LA and ALA are considered essential fatty acids (EFA) because animals cannot synthesize them from other series of fatty acids; thus, they must be supplied by the diet. Dietary PUFA serve as substrates that may be metabolized to form important, biologically active compounds. To produce those metabolites, a number of cells contain a group of enzymes that desaturate (introducing a double bond between carbon atoms), elongate (increasing length of fatty acid chain) and oxygenate fatty acids. All PUFA are categorized based on the position of the first double bond in the structure from the terminal end. The two most important PUFA series are the omega-6 series (the first double bond is located at the sixth carbon atom) and the omega-3 series (the first double bond is located at the third carbon atom). In the omega-6 series, linoleic acid can be desaturated to yield gamma-linolenic acid (GLA, 18:3n-6), which is elongated to dihomogammalinolenic acid (DGLA, 20:3n-6) and ultimately desaturated again to produce arachidonic acid (AA, 20:4n-6) in the animal. Many marine plants, especially algae, elongate chains and add double bonds to ALA to yield omega-3 PUFA with 20 and 22 carbon atoms and five or six double bonds. Formation of these long-chain omega-3 PUFA by marine algae and their transfer through the food chain to fish account for the abundance of eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) in certain marine fish oils. AA and EPA act as precursors for the synthesis of eicosanoids, a significant group of immunoregulatory molecules that function as local hormones and mediators of inflammation. The amounts and types of eicosanoids synthesized are determined by the availability of the PUFA precursor and by the activities of the enzyme system to synthesize them. In most conditions the principal precursor for these compounds is AA, although EPA competes with AA for the same enzyme systems. The eicosanoids produced from AA appear to be more inflammatory than those formed from EPA. Ingestion of oils containing omega-3 PUFA results in a decrease in membrane AA levels, since omega-3 PUFA replace AA in the substrate pool, and also produces an accompanying decrease in the capacity to synthesize eicosanoids from AA. In contrast, eicosanoids derived from EPA promote less inflammatory activity and may alter vascular function. Inflammatory eicosanoids produced from AA may be depressed when animals consume foods with high levels of omega-3 fatty acids. Clinical use of fatty acids Use of fatty acid supplementation for patients with seborrhea Fats and fatty acids have been recommended for many years as supplements to improve the sheen and luster of hair. In the past, animal and vegetable sources of fat were recommended to improve coat quality. Investigators showed that dogs with seborrhea have abnormally low cutaneous levels of linoleic acid and increased cutaneous levels of oleic acid. These low cutaneous levels are found despite normal food and serum fatty acid concentrations. Following supplementation for 30 days with a vegetable oil high in linoleic acid (sunflower oil), the cutaneous fatty acid concentrations return to near normal and clinical signs of seborrhea improved. This suggests that clinical signs of seborrhea in dogs may be partly attributable to a localized deficiency of linoleic acid, elevated levels of arachidonic acid in the skin, or both. However, other investigators found no significant differences in the serum and skin fatty acid profiles of normal and a small number of seborrheic dogs. Seborrhea sicca is also associated with increased transepidermal water loss, which can be reversed with cutaneous administration of vegetable oils rich in linoleic acid. Transepidermal water loss can also be decreased by supplementing the food with alphalinolenic acid. Further studies will be needed to determine the effects of supplementation of food with other fatty acids and to determine the optimal dose of fatty acid supplements for patients with seborrhea. Use of fatty acid supplementation for patients with inflammatory skin diseases The use of fatty acids as antipruritic agents in dogs and cats has been the subject of numerous studies and considerable debate. The inflammation associated with allergic skin disease may be partially caused by abnormal essential fatty acid metabolism and inappropriate eicosanoid synthesis. A unique feature of skin is that it lacks -6- and -5-desaturase enzyme activity, and thus is incapable of making AA from LA or EPA from ALA. Skin can elongate GLA to DGLA and EPA to DHA. Normal dogs metabolize dietary sources of ALA to EPA and DHA elsewhere in the body. These fatty acids are then incorporated into the skin. DGLA, 24

25 EPA and DHA in cutaneous cellular membranes may decrease inflammation through competition with AA for metabolic enzymes or because of the anti-inflammatory nature of the eicosanoids produced. The rationale for specifically administering products high in GLA is that GLA can be incorporated into the skin, where it is rapidly elongated to DGLA. Because skin lacks desaturase enzymes, DGLA is not further metabolized to arachidonic acid. As a result, DGLA competes with AA for metabolic enzymes. Thus there is a decrease in AA-derived eicosanoids and an increase in the anti-inflammatory eicosanoids. ALA is an omega-3 PUFA that is metabolized to EPA and DHA and incorporated into the skin of normal dogs. Findings suggest that atopic dermatitis in human beings is associated with a deficiency of -6-desaturase activity, which prevents the rapid conversion of ALA to EPA and DHA in atopic individuals. Comparable studies using atopic dogs and cats have not been published. However, one study suggested that subsets of atopic dogs exist with different fatty acid metabolic capabilities. The use of fatty acids for treating atopic dermatitis and chronic pruritus has been extensively studied in dogs. Unfortunately, most of these studies have been uncontrolled, nonblinded clinical trials using low doses of fatty acids for short periods. Well-controlled clinical studies using placebos and high doses of fatty acids for six weeks or more showed decreased pruritus in 0 to more than 50% of the patients. Dogs who did not have decreased pruritus still showed improvement in other clinical signs, including less erythroderma and skin edema. The benefit of fatty acid supplementation is maximized in dogs if other contributing diseases such as adverse reactions to food, flea hypersensitivity, bacterial pyoderma, and Malassezia dermatitis are controlled. Overall, it is probably safe to inform clients that 50 to 65% of dogs with allergic dermatitis and otitis externa will improve with modification in fatty acid intake, if secondary bacterial and yeast infections are controlled. Synergistic effects have been documented between fatty acid supplementation and use of other antipruritic agents such as antihistamines and glucocorticoids. The use of fatty acids for management of allergic skin disease and papulocrustous (miliary) dermatitis in cats has been reported. More than 50% of allergic cats may improve, based on the results of uncontrolled, nonblinded clinical trials. Recommendation for use of fatty acids for inflammatory skin disease in dogs and cats: deliver 50 to 250 mg total omega-3 fatty acids/kg body weight/day, or 0.8 to 3.0% total omega-3 fatty acids in the food (dry matter basis) with omega-6 to omega-3 ratio of 2:1 to 5:1. Use of fatty acid supplementation for patients with arthritis Canine models have been widely used to study the biological and molecular mechanisms involved in cartilage matrix degradation as the pathogenesis of degenerative joint disease progresses. Mechanisms of cartilage metabolism in canine osteoarthritis (OA) and the potential role of omega-3 fatty acids to ameliorate the early events in the disease process have been investigated with these in vitro models. These studies use cartilage tissue explants exposed to a variety of different cytokines, growth factors and chemical mediators that activate degradative enzymes and metabolic factors that induce and propagate cartilage matrix degradation. Studies were conducted to investigate the potential for omega-3 fatty acids to modulate these degenerative processes in canine cartilage metabolism. Importantly, EPA was the only omega-3 fatty acid able to significantly decrease loss of aggrecan and potentially ameliorate cartilage degradation in the clinical setting. Based on the results of these in vitro studies, clinical studies were conducted with a therapeutic food designed to be useful as a nutrition aid for dogs with OA. Four clinical studies (randomized, double-masked, controlled studies) were completed in dogs with spontaneous OA fed either a control or a test food. The test food contained a 39-fold increase in the total omega-3 fatty acid concentration and a 39-fold increase in EPA concentration compared to the control food. Owners could feed either a dry food or a combination of a dry plus canned foods of the control or test formulas. Studies were conducted as six-month (one study) or three-month prospective studies (two studies) in veterinary hospitals in the United States. A fourth study was conducted as a three-month prospective study in two academic specialty practices in the United States. Investigators reported that the animals being fed the EPAsupplemented test formula improved in several parameters which were evaluated during scheduled physical examinations throughout the studies. Veterinarians reported a significant improvement in range of motion and ability to bear weight, along with a decrease in pain (upon palpation of the affected joint) and lameness as compared with the condition of these dogs prior to participating in the studies. In addition, pet owners observed improvements in multiple clinical signs associated with OA: rising from rest, running, walking, and playing. In the academic specialty practice study, variables were assessed at the beginning of the study and at 45 and 90 days after onset of feeding the control or test food. Additionally, gait analyses using a computerized biomechanical force plate were also conducted at the same time intervals. On clinical orthopedic examination, a significantly greater percentage of dogs consuming the test food were evaluated as improved vs. those consuming the control food. In addition, more dogs in the

test group had a reduction in pain at the end of the 90-day trial when the affected joint was palpated. Vertical peak force was the key parameter measured to determine weight bearing of affected limbs. There was no significant change in mean peak force over the duration of the 90-day feeding trial for the control group. The mean vertical peak force increased significantly for the test group over the same time interval. The percent mean change in vertical peak force was also significantly different between groups, indicating that the test group increased weight bearing on the affected limb over the course of the study. Additionally, only 31% of dogs in the control group had improved weight bearing after the 90- day feeding trial, whereas 82% of dogs in the test group increased weight bearing; this difference was also statistically significant. The objective of one clinical study was to determine if the test food altered the dose of a nonsteroidal anti-inflammatory drug (NSAID) required to manage clinical signs in dogs with OA. In this particular study, all dogs were administered the NSAID carprofen to help manage clinical signs. At each evaluation period (three, six, nine and 12 weeks), the veterinarian considered the results of the orthopedic examination and the pet owner s assessment to determine if lowering the dose of carprofen was feasible. For the group consuming the test food, the mean carprofen dose reduction was 25%. Significantly greater reductions in carprofen dose (mg/lb body weight) were possible in the dogs consuming the test food compared with the control food. These clinical studies indicate that nutrition management using a therapeutic food with high levels of total omega-3 fatty acids and EPA helps improve the clinical signs of OA in dogs as measured by pet owner evaluation, clinical orthopedic examination, and gait analysis of ground reaction forces. Furthermore, doses of NSAID can often be reduced in dogs with osteoarthritis consuming these types of foods. Recommendation for use of fatty acids for canine osteoarthritis: deliver 70 to 150 mg EPA/kg body weight/day, or 3.5 to 4.5% total omega-3 fatty acids and 0.45 to 1.1% EPA in the food (dry matter basis) with omega-6 to omega-3 ratio of around 0.7:1. Use of fatty acid supplementation for patients with chronic kidney disease Recent studies in several species have suggested a potential benefit from dietary polyunsaturated fatty acid supplementation in patients with chronic kidney disease (CKD), especially those with systemic hypertension and inflammatory glomerular lesions. Dietary supplementation with omega-3 fatty acids has been shown to be beneficial in dogs with induced chronic kidney disease. Compared with dogs fed foods high in saturated fats or omega-6 fatty acids, dogs consuming a food supplemented with omega-3 fatty acids had lower mortality, better renal function, fewer renal lesions, less proteinuria and lower cholesterol levels. In dogs fed the food with higher omega-3 fatty acid levels, renal function actually increased and remained above baseline over 20 months of study. Lesions of glomerulosclerosis, tubulointerstitial fibrosis, and interstitial inflammatory cell infiltrates were also diminished in dogs fed the food with higher levels of omega-3 fatty acids. Many therapeutic renal foods already contain sources of omega-3 fatty acids and additional supplementation may not be appropriate for animals already consuming these foods. There is strong evidence from randomized, controlled clinical trials to support a recommendation to feed therapeutic renal foods to dogs and cats with stages 2, 3 and 4 CKD. The benefits shown to accrue from this recommendation, including increased survival, reduced risk of uremia, and improved quality of life, are of great clinical consequence to owners and pets. Recommendation for use of fatty acids for pets with chronic kidney disease: deliver 200 to 250 mg total omega-3 fatty acids/ kg body weight/day or 1 to 2% total omega-3 fatty acids in the food (dry matter basis) with omega-6 to omega-3 ratio of 2:1 as part of a therapeutic renal food. Use of fatty acid supplementation for patients with cancer The use of high levels of omega-3 fatty acids (EPA and DHA) has been evaluated in both experimental rodent models of cancer and in naturally occurring cancer cases in dogs and people. Results of well-controlled clinical trials in dogs suggest that such dietary manipulation reverses metabolic abnormalities (hyperinsulinism, hyperlactatemia) recognized in canine patients with cancer, improves survival in dogs undergoing chemotherapy, and improves quality of life. In other clinical trials, high levels of dietary omega-3 fatty acids also appear to be protective against the negative effects of radiation therapy. Recommendation for use of fatty acids for dogs with cancer: deliver 800 mg total omega-3 fatty acids/kg body weight/day or 7.5% total omega-3 fatty acids in the food (dry matter basis) with omega-6 to omega-3 ratio of 0.3:1. Use of fatty acid supplementation for patients with heart disease One study characterized the nutritional and cytokine alterations in dogs with heart failure and tested the ability of fish oil to reduce cytokines and improve clinical outcome. Body composition, insulin-like growth factor-1, fatty acids, and cytokines were measured in 28 dogs with heart failure and in five healthy controls. Dogs with heart failure then were randomized to receive either fish oil or placebo for eight weeks. All parameters were measured again at the end of the study period. Baseline plasma AA, EPA and DHA concentrations were lower in dogs with heart failure than in controls. Fish oil supplementation decreased interleukin-1 beta (IL-1) concentrations and improved cachexia compared with the 26

27 placebo group. The mean caloric intake of the heart failure dogs as a group was below the maintenance energy requirement, but no difference was found in food intake between the fish oil and placebo groups. Insulin-like growth factor-1 concentrations and reductions in circulating IL-1 concentrations over the study period correlated with survival. These data demonstrate that canine heart failure is associated with cachexia, alterations in fatty acids, and reduced caloric intake. Fish oil supplementation decreased IL-1 concentrations and improved cachexia. Intravenous administration of omega-3 fatty acids has been shown to prevent fatal ventricular arrhythmias in a canine model of sudden cardiac death. Omega-3 fatty acids appear to electrically stabilize myocardial cells by modulating ion channels. Additional studies have shown that fish oil supplementation reduces cardiac arrhythmias (ventricular premature contractions) in dogs with cardiomyopathy. Recommendation for use of fatty acids for dogs with heart disease and/or cardiac dysrhythmias: deliver at least 65 to 100 mg total omega-3 fatty acids/kg body weight/day or 0.5 to 1% total omega-3 fatty acids in the food (dry matter basis) as part of a therapeutic cardiac food. How to use fatty acid supplementation In answer to the question posed in the title of this article, it is clear that dietary fatty acid levels well above those needed to avoid fatty acid deficiency benefit some animals with seborrhea, arthritis, allergic skin disease, chronic kidney disease, heart disease and cancer. Dietary omega-3 fatty acid concentrations can be increased by using a supplement (usually cold water marine oils) or changing to food(s) that contains flaxseed, fish meal and/ or fish oil as major ingredients. Dietary GLA concentrations can be increased by using a supplement with evening primrose, borage or black currant oil. Most commercial pet foods already exceed the omega-6 essential fatty acid requirement for linoleic acid by using vegetable oil and/or vegetable ingredients in their formulas. Many commercial pet foods also contain levels of omega-3 fatty acids higher than those found in popular fatty acid supplements (Tables 1 & 2). What is less clear are answers to the following questions: 1) which fatty acid or combination of fatty acids is most effective, 2) what ratio of omega-6 to omega-3 fatty acids is optimal, 3) what absolute amount of omega-6 and omega-3 fatty acids is appropriate in normal animals and what amount is effective in animals with clinical disease, 4) what levels of other nutrients (vitamins, trace minerals) are needed to allow fatty acid therapy to be effective and 5) what level of total dietary fat is needed to optimize fatty acid metabolism and clinical efficacy. Although definitive answers to these questions are lacking in many situations, laboratory and clinical studies in a number of species have established a daily dosage for total omega-3 fatty acids that seems to be a reasonable starting point in patients with inflammatory and other diseases. An initial dose of 50 to 250 mg of total omega-3 fatty acids (ALA, EPA and/or DHA) per kg body weight per day seemed to be effective in a large number of studies. This total dose can be supplied through a combination of appropriate foods and supplements. It is important to note that many therapeutic foods contain much higher levels of fatty acids than those found in typical fatty acid supplements. Use of fatty acids in management of a wide variety of conditions will be easier and more cost effective if an appropriate food is used vs. adding a fatty acid supplement to the regular diet. Very high levels of omega-3 fatty acids appear beneficial in canine patients with cancer and can only be provided effectively in a therapeutic food. The risks and side effects of high levels of dietary fatty acids are few. Soft feces, overt diarrhea, flatulence, vomiting and halitosis ( fishy breath ) are most commonly noted at typical levels of fatty acid supplementation. More serious potential side effects include hemorrhage due to reduced platelet function, decreased plasma vitamin E concentrations, and increased susceptibility to oxidative injury. Hemorrhagic problems have not been recognized in dogs consuming levels of omega-3 fatty acids found in pet foods and typical supplements; cats, however, appear to be more susceptible to hemorrhagic problems associated with fatty acid supplementation, and caution should be used with high omega-3 fatty acid intake in cats.

Table 1 Foods Food consumed (g) Total omega-6 consumed (mg) Total omega-3 consumed (mg) Hill s Prescription Diet d/d Lamb Formula Canine Canned 451 3,972 1,488 Hill s Prescription Diet d/d Potato & Duck Formula Canine Dry 161 4,854 1,164 Hill s Prescription Diet d/d Duck Formula Canine Canned 624 4,932 1,248 Hill s Prescription Diet d/d Potato & Salmon Formula Canine Dry 162 4,206 2,100 Hill s Prescription Diet d/d Salmon Formula Canine Canned 613 5,148 4,350 Hill s Prescription Diet d/d Potato & Venison Formula Canine Dry 161 4,932 1,146 Hill s Prescription Diet d/d Venison Formula Canine Canned 550 4,950 1,098 Hill s Prescription Diet d/d Rice & Egg Formula Canine Dry 154 4,692 990 Hill s Prescription Diet n/d Canine Canned 380 2,772 8,088 Hill s Prescription Diet z/d ULTRA Allergen-Free Canine Canned 617 6,102 738 Hill s Prescription Diet z/d Canine Low Allergen Dry 163 4,812 618 Hill s Prescription Diet z/d ULTRA Allergen-Free Canine Dry 161 6,222 804 Hill s Prescription Diet a/d Canine/Feline Canned 521 6,882 3,126 Hill s Prescription Diet b/d Canine Dry 165 4,884 1,548 Hill s Prescription Diet j/d Canine Canned 446 4,104 6,066 Hill s Prescription Diet j/d Canine Dry 176 4,032 5,688 Hill s Science Diet Adult Original Canine Dry 162 5,310 726 Hill s Science Diet Active Adult Canine Dry 130 5,976 678 Hill s Science Diet Lamb Meal & Rice Recipe Adult Canine Dry 162 4,815 1,002 Hill s Science Diet Advanced Protection Adult Canine Dry 158 4,554 1,410 Hill s Science Diet Senior 7+ Original Canine Dry 163 4,590 1,710 Hill s Science Diet Advanced Protection Senior 7+ Canine Dry 163 5,640 1,974 Hill s Science Diet Light Adult Canine Dry 200 5,988 618 Hill s Science Diet Sensitive Skin Canine Dry 158 7,392 2,166 Eukanuba Adult Maintenance Formula, dry 139 4,800 600 Eukanuba Reduced Fat Adult Formula, dry 155 3,600 600 Eukanuba Senior Maintenance Formula, dry 142 3,600 600 Eukanuba Veterinary Diets Senior Plus, dry 142 4,200 600 Eukanuba Veterinary Diets Response FP, dry 147 1,600 400 Eukanuba Veterinary Diets Response FP, moist 475 9,600 1,200 Royal Canin IVD Limited Ingredient Diets Potato & Duck Canine Formula, dry 175 2,940 1,020 Royal Canin IVD Limited Ingredient Diets Potato & Rabbit Canine Formula, dry 177 3,120 1,380 Royal Canin IVD Limited Ingredient Diets Whitefish Canine Formula, moist 522 6,600 3,300 Royal Canin IVD Limited Ingredient Diets Duck Canine Formula, moist 536 5,340 720 Royal Canin Veterinary Diet Skin Support SS21, dry 153 4,884 1,758 Royal Canin Veterinary Diet Hypoallergenic HP19, dry 143 7,158 1,158 Royal Canin Veterinary Diet Sensitivity RC21, dry 168 3,354 1,512 Nutro Ultra Adult, dry 166 7,998 1,290 Nutro Ultra Senior, dry 168 7,392 1,380 Purina Veterinary Diets LA Limited Antigen Canine Formula, dry 151 1,680 1,680 Supplements 3V Caps for Large & Giant Breeds 1 capsule 0 417 3V Caps for Medium & Large Breeds 1 capsule 0 300 3V Caps for Small & Medium Breeds 1 capsule 0 171 3V Caps Liquid 0.75 ml 0 187 3V Caps Liquid HR 1 ml 0 450 DermCaps 100 lb 1 capsule 402 252 DermCaps ES 1 capsule 368 123 DermCaps ES Liquid 1 ml 375 130 DermCaps Liquid 1 ml 621 65 28 (Table 1 continues on next page)

Table 1 (continued) Supplements Food consumed (g) Total omega-6 consumed (mg) Total omega-3 consumed (mg) DermCaps Regular 1 capsule 402 108 Nutrived O.F.A. Granules 1 scoop 539 129 EicosaDerm 1 pump 0 600 Welactin 1 pump 0 330-364 Nordic Naturals Omega-3 1 capsule 0 350 Nordic Naturals Arctic Cod Liver Oil 1 capsule 0 280 Nordic Naturals Ultimate Omega 1 capsule 0 700 Table 1. The total essential fatty acid intake for a 10-kg dog eating 600 kcal per day of selected commercial foods or being given one of the selected supplements. Table 2 29 Foods Food consumed (g) Total omega-6 consumed (mg) Total omega-3 consumed (mg) Hill s Prescription Diet d/d Duck & Green Pea Formula Feline Dry 68 2,254 473 Hill s Prescription Diet d/d Duck Formula Feline Canned 215 3,354 666 Hill s Prescription Diet d/d Rabbit & Green Pea Formula Feline Dry 69 2,304 460 Hill s Prescription Diet d/d Rabbit Formula Feline Canned 233 3,403 699 Hill s Prescription Diet d/d Venison & Green Pea Formula Feline Dry 67 2,142 458 Hill s Prescription Diet d/d Venison Formula Feline Canned 206 4,178 988 Hill s Prescription Diet z/d ULTRA Allergen-Free Feline Canned 241 2,574 289 Hill s Prescription Diet z/d Low Allergen Feline Dry 69 3,630 419 Hill s Prescription Diet a/d Canine/Feline Canned 226 3,344 1,422 Hill s Science Diet Adult Original Feline Dry 64 2,301 140 Hill s Science Diet Advanced Protection Adult Feline Dry 66 2,025 354 Hill s Science Diet Mature Adult 7+ Original Feline Dry 66 2,114 146 Hill s Science Diet Advanced Protection Senior 7+ Feline Dry 68 1,932 361 Hill s Science Diet Savory Salmon Entrée Adult Feline Canned 250 2,072 1,147 Hill s Science Diet Sensitive Skin Adult Feline Dry 67 3,123 294 Eukanuba Chicken & Rice Formula Cat Food, dry 55 2,158 302 Eukanuba Mature Care Formula for Cats, dry 61 2,049 411 Eukanuba Veterinary Diets Response LB/Feline, moist 199 2,600 520 Royal Canin IVD Limited Ingredient Diets Green Pea & Venison Feline Formula, dry 73 1,794 624 Royal Canin Veterinary Diet Feline Hypoallergenic HP 23, dry 63 3,003 486 Royal Canin Veterinary Diet Feline Sensitivity RD 30, dry 67 2,140 213 Royal Canin Skin Care 30 Cat Food, dry 63 2,951 499 Royal Canin Adult Fit 32 Cat Food, dry 68 2,462 322 Royal Canin Indoor 27 Cat Food, dry 70 2,395 408 Royal Canin Persian 30 Cat Food, dry 60 2,889 481 Supplements 3V Caps for Small & Medium Breeds 1 capsule 0 171 3V Caps Liquid HR 1 ml 0 450 DermCaps ES Liquid 1 ml 375 130 DermCaps Liquid 1 ml 621 65 DermCaps Regular 1 capsule 402 108 Nutrived O.F.A. Granules 1 scoop 539 129 EicosaDerm 1/2 pump 0 300 Welactin 1 pump 0 330-364 Nordic Naturals Omega-3 1 capsule 0 350 Table 2. The total essential fatty acid intake for a 4.5-kg cat eating 260 kcal per day of selected commercial foods or being given one of the selected supplements.

What s New in Fatty Acids: Resolvins, Protectins and Omega-3-Derived Mediators Philip Roudebush, DVM, DACVIM (SAIM) Hill s Scientific Affairs Beneficial actions of polyunsaturated fatty acids were noted many years ago, but the underlying mechanisms for these effects are poorly understood. It is clear that arachidonic acid is transformed into many potent bioactive compounds such as prostaglandins, leukotrienes and lipoxins. The departure of fatty acids from simply playing structural roles in cell membranes and/or as energy stores came largely from the recognition of the rapid transformation of arachidonic acid to these potent eicosanoids by both cyclooxygenase and lipoxygenase mechanisms. Many of the classic prostaglandins and leukotriene mediators are pro-inflammatory and play a decisive role in inflammation and/or in systems where prostaglandins are key physiologic regulators. Inflammation is a vital reaction, but it also plays a central role in many prevalent chronic diseases such as osteoarthritis, periodontal disease, inflammatory bowel disease, cancer, brain aging/dementia, allergic dermatitis and lower urinary tract disease. In sharp contrast, it has become clear in recent years that counterregulatory substances such as lipoxins are generated during the resolution of acute inflammation, and that these serve as agonists for endogenous anti-inflammatory mechanisms. This constitutes the first evidence that the resolution of inflammation, which was once thought to be a passive process, is actually an active process that involves up-regulating specific pro-resolution circuits. Thus, resolution of inflammation is an active endogenous process aimed at protecting the host from exacerbated inflammation. The omega-3 fatty acid connection The molecular mechanisms underlying the beneficial actions of polyunsaturated fatty acids remain an area of active research (Figure 1). Investigators have recently identified novel oxygenated products generated by enzymatic processes from the precursor omega-3 fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). These new compounds possess potent actions in the resolution of inflammation and may also have neuroprotective properties. The term resolvin (resolution phase interaction products) has been proposed for some of these compounds since they display both potent anti-inflammatory and immunoregulatory properties, reducing neutrophil traffic and the magnitude of the inflammatory response. The term protectin (or neuroprotectin) has been proposed, given the protective actions of some of these compounds in neural and retinal tissues. Resolvins are derived from both EPA (E series) and DHA (D series). Both the D and E classes of resolvins appear as biosynthetic products involving cell-to-cell interaction with vascular endothelial cells and are potent regulators of leukocyte infiltration. Specifically, resolvin E1 (RvE1) has been shown to dramatically reduce dermal inflammation, peritonitis, colitis, periodontitis, dendritic cell migration and interleukin (IL)-12 production in animal models. Resolvins of the D series block tumor necrosis factor (TNF)-a activity and act as potent regulators to limit leukocyte infiltration into inflamed brain, skin and peritoneum. Among the essential fatty acids, DHA is concentrated in the central nervous system, neurons and retina, where it is thought to regulate membrane fluidity and ion fluxes. The term docosanoids has been proposed to describe products generated from DHA. DHA-derived docosatrienes have neuroprotective action in retinal cells and can improve the sequelae associated with stroke and dementia. The terms protectin or neuroprotectin describe these compounds, which are rapidly generated from DHA and released locally into tissues. There is emerging evidence that resolvins and docosanoid compounds may also have immunoregulatory actions by influencing antigen-presenting cells and T-cell traffic. Conclusion and clinical implications Fatty acid supplementation has been used for many years to help manage patients with a variety of inflammatory diseases. The underlying mechanisms for the beneficial effects of fatty acid supplementation have been poorly understood. Recent research has identified novel oxygenated compounds termed resolvins and protectins, which are generated from the omega-3 fatty acids EPA and DHA. These endogenous lipid/chemical mediators are switched-on in the resolution phase of an inflammatory response, thus acting as braking-signals in inflammation and reducing leukocyte-mediated injury in several different tissues (Figure 1). The discovery of resolvins and protectins offers molecular mechanisms that could underlie some of the beneficial actions of dietary fatty acid supplementation observed in many patients. References Arita M, Clish CB, Serhan CN. The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids. Biochem Biophys Res Commun 2005;338:149-157. Bannenberg GL, Chiang N, Ariel A, et al. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol 2005;174:4345-4355. Schwab JM, Serhan CN. Lipoxins and new lipid mediators in the resolution of inflammation. Curr Opin Pharm 2006;6:414-420. Serhan CN. Novel eicosanoid and docosanoid mediators: resolvins, docosatrienes and neuroprotectins. Curr Opin Clin Nutr Metab Care 2005;8:115-121. 30

(a) Lipid mediator class switching orchestrates the sequence of resolution Onset Resolution -6-3 Prostaglandins leukotrienes Cell-cell interaction: lipoxins -3 PUFAderived: resolvins protectins Initiation Time Termination return to homeostasis (b) PMN phagocytosis Lipid mediator class switching 31 Venule LTB PGD 2 4 PGE 2- PGE 2 Vasodilation Vessel lumen PMN activation Blood flow Venule Vessel lumen Block recruitment/limiting leukocyte influx T Resolvins (E-series: D-series) Neuroprotectins LXA 4 Acute inflammatory phase: AA-derived lipid mediator LTB 4 drives extravasation and recruitment to the inflammation site Resolution phase: RVE1 and PD1 stop extravasation and recruitment to the inflammation site Current Opinion in Pharmacology Figure 1 (from Schwab JM, Serhan CN. Curr Opin Pharm 2006). Pro-inflammatory to pro-resolving: switch of lipid mediators over time during inflammation (ontogeny). (a) Hypothetical sequence of lipid-derived mediators moderating the ontogeny of self-limited, acute inflammation: from onset (initiation, acute phase of inflammation) toward resolution (termination, return to homeostasis). (b) Lipid mediators controlling influx into the inflammation site: switching from pro-inflammatory (PGE 2, PGI 2, LTB 4 ) to anti-inflammatory and pro-resolution (LXA 4 ). As exemplified by LTB 4, AA-derived mediators foster extravasation and homing of inflammatory cells at the inflammatory site. In contrast, cell-cell interactions, exemplified by platelet-leukocytes within the vasculature and/or PMN-mucosal interactions, enhance generation of LXs. With time, a class-shift occurs toward pro-resolving lipid-derived mediators (LXA 4, Rvs, PDs) that block ongoing leukocyte extravasation into the inflammation site as characteristic hallmarks of inflammatory resolution. The -3/ -6-derived lipid mediators LXA 4, ATL, Rv E/D series and PDs share anti-inflammatory properties but have distinct impacts within resolution, suggesting a characteristic role in the orchestrated resolution program 1,2. 1 Levy BD, Clish CB, Schmidt B, et al. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol. 2001;2:612 619. 2 Bannenberg N, Chiang A, Ariel M, et al. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol. 2005;174:4345 4355.

Review of literature on canine food allergy (1967-present) 278 Canine cases with ingredient causing problem clearly identified 278 canine cases (problem ingredient was clearly identified) 100 90 80 Beef - 95 Dairy - 55 Wheat - 42 Number of Cases 70 60 50 40 30 20 10 0 Total Allergic Reaction Chicken - 24 Egg - 18 Lamb - 13 Soy - 13 Corn - 7 Pork - 7 Fish - 6 Rice - 5 References Carlotti DN, Remy I, Prost C. Food allergy in dogs and cats. A review and report of 43 cases. Vet Dermatol 1990;1:55-62. Chesney CJ. Food sensitivity in the dog: a quantitative study. J Sm Anim Pract 2002;43:203-207. Elwood CM, Rutgers HC, Batt RM. Gastroscopic food sensitivity testing in 17 dogs. J Sm Anim Pract 1994;35:199-203. Harvey RG. Food allergy and dietary intolerance in dogs: a report of 25 cases. J Sm Anim Pract 1993;34:175-179. Ishida R, Masuda K, Sakaguchi M, et al. Antigen-specific histamine release in dogs with food hypersensitivity. J Vet Med Sci 2003;65:435-438. Ishida R, Masuda K, Kurata K, et al. Lymphocyte blastogenic responses to inciting food allergens in dogs with food hypersensitivity. J Vet Intern Med 2004;18:25-30. Jeffers JG, Shanley KJ, Meyer EK. Diagnostic testing of dogs for food hypersensitivity. J Am Vet Med Assoc 1991;189:245-250. Jeffers JG, Meyer EK, Sosis EJ. Responses of dogs with food allergies to single-ingredient dietary provocation. J Am Vet Med Assoc 1996;209:608-611. Kunkle G, Horner S. Validity of skin testing for diagnosis of food allergy in dogs. J Am Vet Med Assoc 1992;200:677-680. Mueller RS, Tsohalis J. Evaluation of serum allergen-specific IgE for the diagnosis of food adverse reactions in the dog. Vet Dermatol 1998;9:167-171. Mueller RS, Friend S, Shipstone MA, et al. Diagnosis of canine claw disease a prospective study of 24 dogs. Vet Dermatol 2000;11:133-141. Nichols PR, Morris DO, Beale KM. A retrospective study of canine and feline cutaneous vasculitis. Vet Dermatol 2001;12:255-264. Paterson S. Food hypersensitivity in 20 dogs with skin and gastrointestinal signs. J Sm Anim Pract 1995;36:529-534. Tapp T, Griffin C, Rosenkrantz W, et al. Comparison of a commercial limited-antigen diet versus home-prepared diets in the diagnosis of canine adverse food reactions. Vet Therapeutics 2002;3:244-251. Walton GS. Skin responses in the dog and cat to ingested allergens. Vet Rec 1967;81:709-713 32

Review of literature on feline food allergy 56 (1967-present) Feline cases with ingredient causing problem clearly identified 56 feline cases (problem ingredient was clearly identified) Number of Cases 20 15 10 5 Beef - 16 Dairy - 16 Fish - 13 Lamb - 4 Wheat - 3 Chicken - 4 Corn gluten/corn - 4 Egg - 2 0 Total Skin only Skin & GI GI only Allergic Reaction 33 References Carlotti DN, Remy I, Prost C. Food allergy in dogs and cats. A review and report of 43 cases. Vet Dermatol 1990;1:55-62. Guaguere E. Food intolerance in cats with cutaneous manifestations: a review of 17 cases. Eur J Companion Anim Pract 1995;5:27-35. Guilford WG, Jones BR, Harte JG, et al. Prevalence of food sensitivity in cats with chronic vomiting, diarrhea or pruritus (abstract). J Vet Intern Med 1996;10:156. Guilford WG, Jones BR, Markwell PJ, et al. Food sensitivity in cats with chronic idiopathic gastrointestinal problems. J Vet Intern Med 2001;15:7-13. Ishida R, Masuda K, Kurata K, et al. Lymphocyte blastogenic responses to food antigens in cats with food hypersensitivity. Unpublished data. University of Tokyo, 2002. Reedy RM. Food hypersensitivity to lamb in a cat. J Am Vet Med Assoc 1994;204:1039-1040. Stogdale L, Bomzon L, Bland van den Berg P. Food allergy in cats. J Am Anim Hosp Assoc 1982;18:188-194. Walton GS. Skin responses in the dog and cat to ingested allergens. Vet Rec 1967;81:709-713. Walton GS, Parish WE, Coombs RRA. Spontaneous allergic dermatitis and enteritis in a cat. Vet Rec 1968;83:35-41. White SD, Sequoia D. Food hypersensitivity in cats: 14 cases (1982-1987). J Am Vet Med Assoc 1989;194:692-695.

Synopses of clinical studies supporting use of Hill s Prescription Diet z/d and d/d and Hill s Science Diet Sensitive Skin formulas Campbell KL, Roudebush P. Effects of four diets on serum and cutaneous fatty acids, transepidermal water losses, skin surface lipids, hydration and condition of the skin and haircoat of dogs (abstract), in Proceedings. Annual Meeting of AAVD/ACVD, Santa Fe, New Mexico, 1995. Thirty-two clinically normal dogs were divided into four groups, each group receiving one of four different foods for two months: Eukanuba Adult, ProPlan Turkey & Barley, Nutro Max and a dry skin and coat food with flaxseed as a plant source of omega-3 fatty acids. The skin and coat were evaluated for parameters of shine, scale, ease of epilation of hairs, and skin surface character. Transepidermal water loss (TEWL), skin hydration and skin lipid concentration were also evaluated on days 0, 28 and 56. Dogs consuming the food containing flaxseed had increased serum and cutaneous concentrations of omega-3 fatty acids compared with the other three groups; these dogs also tended to have shinier hair coats and significantly lower TEWL. Flaxseed is a good source of dietary omega-3 fatty acids and increases omega-3 fatty acid concentrations in both serum and skin. These changes often lead to improved skin and hair coat. Cave NJ. The nutritional management of food hypersensitivity in dogs and cats: an assessment of a protein hydrolysate. Master s Thesis, Massey University, Palmerston North, New Zealand, 2001. A candidate chicken-protein hydrolysate was subjected to high performance size-exclusion chromatography to characterize its molecular weight profile. An inhibition ELISA assay was developed to assess the residual antigenicity, using canine serum IgG produced by dogs sensitized to the intact protein through electrophoresis and immunoblotting. The chicken hydrolysate had a suitable molecular weight profile with 96.9% reduced to less than 10kDa peptides. The inhibition ELISA demonstrated a residual antigenic mass of 1.5% compared with the intact protein. Immunoblotting demonstrated a strong immunoreactive band at 68 to 70kDa consistent with chicken serum albumin in the intact protein, which was absent in the hydrolysate. These results demonstrate the suitability of the chicken hydrolysate for use in a protein hydrolysate food. Cave NJ, Guilford WG, Roudebush P. In vivo assessment of antigenicity of a protein hydrolysate and characterisation of a major antigen in chicken (abstract), in Proceedings. Veterinary Medical Forum (ACVIM), Seattle, Washington, 2000. A chicken hydrolysate showed a 25-fold reduction in antigenicity over the intact protein. Western blots of the intact proteins using chicken-sensitized dog serum identified a strong immunogenic band at 70kDA that was absent in the hydrolysate. It is speculated that this major chicken protein antigen is chicken serum albumin. Cave NJ, Guilford WG. A method for in vitro evaluation of protein hydrolysates for potential inclusion in veterinary diets. Res Vet Sci 2004;77:231-238. A chicken-protein hydrolysate was subjected to high-performance size-exclusion chromatography to characterize its molecular weight profile. An inhibition ELISA assay was developed to assess the residual antigenicity, using canine serum IgG produced by dogs sensitized to the intact protein. Finally, the hydrolysate was compared to the intact protein through electrophoresis and immunoblotting. The chicken hydrolysate had a suitable molecular weight profile with 96.9% reduced to less than 10kDa peptides. The inhibition ELISA demonstrated a residual antigenic mass of 1.5% compared with the intact protein. Immunoblotting demonstrated a strong immunoreactive band at 68 to 70kDa consistent with chicken serum albumin in the intact protein, which was absent in the hydrolysate. Chicken hydrolysates are acceptable for use in foods designed for dogs with suspected adverse food reactions. Crass K. An underweight Gordon setter with brittle claws. Vet Med 2004;99:511-514. A 4-year-old female Gordon setter dog was examined because of brittle claws of one year s duration. Diagnostic evaluation eventually confirmed a diagnosis of inflammatory bowel disease contributing to systemic dermatologic signs. Treatment with a combination of antibiotics, corticosteroids and Hill s Prescription Diet z/d ULTRA Canine resulted in weight gain and improved hair coat. Prescription Diet z/d ULTRA Canine can be used successfully as part of the treatment regimen for dogs with inflammatory bowel disease and concurrent skin lesions. Ishida R, Masuda K, Kurata K, et al. Lymphocyte blastogenic responses to inciting food allergens in dogs with food hypersensitivity. J Vet Intern Med 2004;18:25-30. Lymphocyte blastogenic responses against food allergens in dogs with food hypersensitivity were evaluated in this study. Eleven dogs with food hypersensitivity, based on food elimination and oral food provocation tests and allergic responses to food allergens, were examined by various tests such as intradermal testing, antigen-specific IgE testing, and lymphocyte blastogenic responses. The number and kinds of food allergens identified as positive by these tests were compared with the offending foods that were found in an oral food provocation test. In nine (82%) of the 11 dogs with food hypersensitivity, there was close agreement for positive allergens between the results of lymphocyte blastogenic responses increased to 2.0-10.1 upon food provocation; however, there was little agreement for intradermal and IgE testing of the positive allergens with those of the oral food provocation test (11% and 31%, respectively). In the nine dogs, the stimulation indices of lymphocyte blastogenic responses may fluctuate because of exposure to offending food allergens in dogs with food hypersensitivity. 34

35 Jeffers JG, Shanley KJ, Meyer EK. Diagnostic testing of dogs for food hypersensitivity. J Am Vet Med Assoc 1991;198:245-250. Thirteen food-allergic dogs were studied to evaluate the efficacy of feeding a commercial dry rice and egg food (Hill s Prescription Diet d/d Rice & Egg Formula Canine) and intradermal skin testing and serologic testing by ELISA for diagnosing and/or characterizing food hypersensitivity. Eleven of 13 dogs (85%) tolerated the commercial dry rice and egg therapeutic food without manifesting clinical signs of food allergy. Skin testing and serologic testing by ELISA were not valuable in diagnosing suspected food allergy. Jergens AE, Miles KG. Endoscopy case of the month: chronic postprandial vomiting in a dog. Vet Med 1994;89:754-760. This case report describes a 4-year-old male golden retriever evaluated for chronic vomiting of two years duration. Endoscopy and biopsy diagnosed chronic gastritis with a secondary gastric motility disorder. The patient was successfully managed with Prescription Diet d/d Lamb Formula Canine therapeutic food, metronidazole and metoclopramide. The medications were discontinued after six weeks, but the moist lamb and rice food was continued. The dog had been free of clinical signs for over 18 months. Jewell DE, Yu S, Joshi DK. Effects of serum vitamin E levels on skin vitamin E levels in dogs and cats. Vet Therapeutics 2002;3:235-243. Because of its role as a barrier, the skin is uniquely challenged by oxidants (i.e., free radicals), and lipophilic antioxidants such as alpha-tocopherol (i.e., vitamin E) are expected to play a major role in scavenging reactive oxygen species in the skin. Vitamin E protects against UV-induced skin photodamage through a combination of antioxidant and UV-absorptive properties. The purpose of this study was to determine the effect of feeding foods with varying amounts of vitamin E on serum and skin concentrations of vitamin E in dogs and cats. Dogs and cats were fed a low vitamin E food for three weeks before onset of the study. Dogs and cats were then fed either a low or a high vitamin E food for eight weeks. All animals were fed to maintain current body weight and condition. Blood and skin samples for vitamin E analysis were obtained at days -3, 14, 28 and 56 of the study. There were no significant differences in serum vitamin E concentrations for either species at the beginning of the study. At each subsequent time point, serum concentrations of vitamin E in dogs and cats fed high vitamin E foods were significantly different from serum concentrations of dogs and cats fed low vitamin E foods. There were no significant differences in skin vitamin E concentrations between groups for either species at the beginning of the study. At the end of the study, vitamin E concentrations were significantly influenced by initial vitamin E concentration, body surface area and final serum vitamin E concentration. The results of this study revealed that increasing vitamin E amounts in food significantly increased vitamin E concentrations in serum and skin. Previous studies have shown that increased vitamin E levels decrease serum levels of some biomarkers associated with oxidative stress. This suggests that increases in dietary vitamin E concentrations are likely to be beneficial. However, the relationship between increases in serum and skin vitamin E concentrations and the prevention, development and treatment of specific skin diseases remains to be elucidated by intervention studies. Johnson LW. Food allergy in a dog: diagnosis by dietary management. Mod Vet Pract 1987 (April): 236-239. An adverse food reaction was diagnosed in a 22-month-old Australian shepherd dog that had a history of pruritus since 2 months of age. Use of a commercial moist lamb and rice food (Prescription Diet d/d Lamb Formula Canine) for three weeks resulted in dramatic improvement. Severe pruritus returned after two days exposure to the original food. The lamb and rice food was reintroduced and the pruritus stopped. Novel-protein moist foods can be used to successfully manage cutaneous manifestations of adverse food reactions in dogs. Knowles JO. Provocative exposure for the diagnosis and treatment of certain canine allergies. J Am Vet Med Assoc 1966;149:1303-1306. Four dogs with either chronic diarrhea, abdominal pain, objectionable flatulence, chronic dermatitis or severe pruritus were treated successfully by changing to a commercial moist lamb and rice food (Prescription Diet d/d Lamb Formula Canine). Loeffler A, Lloyd DH, Bond R, et al. Dietary trials with a commercial chicken hydrolysate diet in 63 pruritic dogs. Vet Rec 2004;154:519-522. This study reported a retrospective analysis of dietary elimination trials with a chicken hydrolysate food in dogs examined at an academic referral practice (Royal Veterinary College, United Kingdom). The owners of 63 dogs were instructed to feed Prescription Diet z/d ULTRA Canine Dry exclusively for at least six weeks as part of diagnostic evaluation for non-seasonal pruritus (59 dogs) or ear disease (four dogs). Ectoparasitism and microbial infections were eliminated during the dietary trial. Pruritus, skin lesions, gastrointestinal signs and defecation frequency were assessed before starting the dietary trial, at the end of feeding the elimination food for six weeks, and after challenge with the original food. Adverse food reaction was diagnosed if pruritus resolved during the food trial with recurrence after dietary challenge. Initial clinical signs involved the face, ventrum and paws in 29 dogs (46%); erythroderma was observed in seven dogs (11%); perineal skin (anal pruritus) was involved in three dogs (5%); and otitis externa was observed in 46 dogs (73%). Concurrent signs of gastrointestinal involvement such as soft feces, intermittent diarrhea, flatus or frequent defecation were noted in 29 dogs (46%). Seventeen of the 63 dogs were withdrawn from the study in the first two weeks, including eight for compliance failure (dogs were not fed the elimination food exclusively) and four dogs who would not eat the food. However, overall palatability was reported by owners to be good or excellent in 48 dogs (76%). Overall, 30 of

46 dogs (65%) completing the feeding trial had improvements in pruritus and clinical scores. Of these 30 dogs, 22 had improvement in pruritus that recurred after challenge with their original food, indicating that an adverse food reaction was involved in their clinical condition. Adverse food reaction alone was diagnosed in nine dogs (20%), atopic dermatitis was diagnosed in 17 dogs (37%), and atopic dermatitis with concurrent adverse food reaction was diagnosed in nine dogs (20%). Concurrent signs of gastrointestinal disease were reported in six dogs with adverse food reactions. These gastrointestinal signs resolved in all cases and recurred in five dogs when challenged with the original food. Average defecation frequency was higher in dogs with adverse food reactions (3.1 times per day) than in dogs without adverse food reactions (2.1 times per day). Overall, 19 of 21 dogs with concurrent signs of gastrointestinal disease had complete resolution of their clinical signs during the dietary trial. Prescription Diet z/d ULTRA Canine Dry is useful in the diagnosis of adverse food reactions in dogs with non-seasonal pruritus when fed exclusively at least six weeks. Loeffler A, Soares-Magalhaes R, Bond R, et al. A retrospective analysis of case series using home-prepared and chicken hydrolysate diets in the diagnosis of adverse food reactions in 181 pruritic dogs. Vet Dermatol 2006;17:273-279. The purpose of this retrospective study was to compare homeprepared and chicken hydrolysate foods in the diagnosis of canine adverse reactions to food (ARF). Seventy-two dogs were fed home-prepared foods and 109 were fed a hydrolysate-based food (Prescription Diet z/d ULTRA Canine Dry). Owners chose the type of food at presentation, and ingredients of home-prepared diets were selected depending on each dog s dietary history. Ectoparasitic infestations and microbial infections were treated during the trials. Cutaneous and gastrointestinal signs and pruritus scores were recorded before starting the diet, six weeks into the trials, and after provocation with the original foods. ARF was diagnosed if pruritus resolved during the trial and recurred on dietary provocation. The dropout rate was lower for homeprepared foods, although not statistically significant (18.1% home prepared; 24.7% hydrolysate, P = 0.377). ARF alone was diagnosed in 10 dogs (17%) using home-prepared diets and in 15 (18.3%) fed the hydrolysate. Gastrointestinal problems were more frequent in dogs with ARF than in dogs without ARF (P = 0.001). Another 11 dogs (18.6%) in the home-prepared food group and 20 (24.4%) in the hydrolysate diet group had ARF concurrent with other pruritic diseases, mainly atopy. The similar frequencies of ARF diagnosis in the two groups (P = 0.837 ARF; P = 0.416 concurrent ARF) indicate that Prescription Diet z/d ULTRA Canine may be a valuable alternative to home-prepared foods in the diagnosis of canine ARF. Madsen LM. A mysterious effusion. Vet Forum 2003;20:24-28. A 3-year-old male Norwich terrier was evaluated for respiratory distress and found to have pleural effusion associated with hypoproteinemia and hypoalbuminemia. Diagnostic evaluation showed evidence of protein-losing enteropathy due to inflammatory bowel disease. The dog was successfully managed with prednisone, metronidazole and Prescription Diet z/d ULTRA Canine therapeutic food. This food can be used as an aid in management of inflammatory bowel disease in dogs. Nelson RW, Stookey LJ, Kazacos E. Nutritional management of chronic colitis in the dog. J Vet Intern Med 1988;2:133-137. Idiopathic chronic colitis was diagnosed in 13 dogs. A lymphocytic, plasmacytic infiltration in the colonic lamina propria was found on colonic biopsy specimens. Clinical signs resolved in all 13 dogs after they were fed a homemade cottage cheese and rice food. Long term management was successful in four dogs with use of a commercial dry rice and egg food (Prescription Diet d/d Rice & Egg Formula Canine). Rosser EJ. Diagnosis of food allergy in dogs. J Am Vet Med Assoc 1993;203:259-262. The diagnosis of food allergy was confirmed in 51 dogs. The primary clinical sign of allergy detected and evaluated in all dogs was persistent and nonseasonal pruritic skin disease. Clinical signs of pruritus resolved in 25 of 29 dogs (86%) eating a commercial canned lamb and rice food (Prescription Diet d/d Lamb Formula Canine) and in six of nine dogs (67%) eating a commercial dry rice and egg food (Prescription Diet d/d Rice & Egg Formula Canine). It was also determined that elimination foods should be fed for at least 10 weeks before a food allergy can be ruled out. Roudebush P, Schick RO. Evaluation of a commercial canned lamb and rice diet for the management of adverse reactions to food in dogs. Vet Dermatol 1994;5:63-67. A commercial canned lamb and rice food (Prescription Diet d/d Lamb Formula Canine) was fed to 20 dogs with previously diagnosed dermatologic problems due to adverse reactions to food. Fifteen of the 20 dogs had concurrent atopic dermatitis and flea allergy, which were being treated with hyposensitization and aggressive flea control. Recurrence of previous dermatologic signs did not occur in 15 of 20 dogs (75%) while they were fed the moist lamb and rice food. A novel-protein moist therapeutic food can be used to successfully manage cutaneous manifestations of food allergy in dogs, including those dogs with concurrent atopic or flea allergic dermatitis. Roudebush P, Gross KG, Lowry SR. Protein characteristics of commercial canine and feline hypoallergenic diets. Vet Dermatol 1995;5:69-74. Eight feline, 13 moist canine and nine dry canine commercial pet foods were compared for protein sources, protein quantity and protein digestibility. Prescription Diet d/d Lamb Formula Canine Canned and Prescription Diet d/d Rice & Egg Formula Canine Dry had high or very high protein digestibility. Only commercial foods with high or very high protein digestibility should be routinely recommended for patients with adverse food reactions to minimize antigen exposure. 36

37 Waisglass SE, Landsberg GM, Yager JA, et al. Underlying medical conditions in cats with presumptive psychogenic alopecia. J Am Vet Med Assoc 2006;228:1705-1709. The objective of the study was to identify underlying medical conditions in cats with a presumptive diagnosis of psychogenic alopecia. The case series included 21 adult cats referred with a presumptive diagnosis of psychogenic alopecia. A detailed behavior and dermatologic questionnaire was completed by the primary caregiver, and complete behavioral and dermatologic examinations were performed. All cats included in the study and all other cats in participating households were exclusively fed Prescription Diet z/d Low Allergen Feline therapeutic food. A standard diagnostic testing protocol that included cytologic examination of skin scrapings, fungal culture of hairs, evaluation of responses to parasiticides and an exclusion diet, assessment for atopy and endocrinopathies, and histologic examination of skin biopsy specimens was used to establish a definitive diagnosis in all cats. Cats who did not respond to an elimination diet were treated with methylprednisolone acetate to determine whether pruritus was a factor. Medical causes of pruritus were identified in 16 cats (76%). Only two cats (10%) were found to have psychogenic alopecia alone, and an additional three cats (14%) had a combination of psychogenic alopecia and a medical cause of pruritus. An adverse food reaction was diagnosed in 12 cats (57%) and was suspected in an additional two cats. All cats with histologic evidence of inflammation in skin biopsy specimens were determined to have a medical condition, but of six cats without histologic abnormalities, four had an adverse food reaction, atopic dermatitis, or a combination; only two cats had psychogenic alopecia alone. White SD. Food hypersensitivity in 30 dogs. J Am Vet Med Assoc 1986;188:695-698. Food hypersensitivity was diagnosed in 30 dogs. Pruritus, erythema and papules were the most common clinical signs. Diagnosis was based on resolution of clinical signs when the dogs were fed an elimination diet and recurrence of signs when fed their original food or other foods. None of the owners could relate the onset of clinical signs with a recent change in diet. Eleven of the 30 dogs were managed long-term on either homemade or commercial moist lamb and rice foods. The other dogs were managed successfully with a variety of other homemade or commercial foods. Yu S, Wedekind KJ, Kirk CA, et al. Primary hair growth in dogs depends on dietary selenium concentrations. J Anim Physiol Anim Nutr (Berl) 2006;90:146-151. Selenium (Se) is an essential trace mineral and plays an important role in hair growth. Selenium also has a vital role in maintaining normal thyroid hormone and iodine metabolism, particularly through the control of deiodinase enzymes that regulate conversion of T 4 to T 3. The objective of this study was to determine safe lower and upper limits for dietary Se in adult dogs. Thirty-six adult beagle dogs (mean age = 2.2 years) were randomized to six treatment groups (six dogs per group). Dogs were fed a low Se food (0.04 mg Se/kg food) for three weeks and were then fed one of six dietary levels of selenomethionine for six months (0, 0.5, 0.10, 0.50, 1.0 and 5.0 mg Se/kg food, dry matter). Response variables measured included serum Se concentrations, Se-dependent glutathione peroxidase (GSHpx) activity in serum and RBC, complete thyroid hormone profile, complete blood count, serum biochemistry profile, and hair growth rate. No significant changes in body weight, complete blood count, serum biochemistry profiles or clinical appearance were observed. All thyroid hormone levels were within normal ranges. Breakpoints (lower limits) were similar for the various Se markers yielding a recommendation of 0.13 mg Se/kg food (serum Se = 0.11, serum GSHpx = 0.08 and RBC GSHpx = 0.13). Hair growth responded in a quadratic fashion (i.e., bellshaped curve) with significantly decreased hair growth at Se concentrations of five and below 0.1 mg Se/kg food. These results suggest a lower limit of 0.13 mg Se/kg food for adult dogs. Correcting for low bioavailability of Se in pet foods (30%), commercial adult dog foods should contain at least 0.43 mg Se/kg food. Five mg Se/kg food appears to be excessive. Optimal hair growth and antioxidant protection occur in adult dogs when dietary selenium levels are adequate but not excessive.

Frequently asked questions Q: What are the most common food ingredients or food allergens causing adverse reactions in dogs and cats? A: The most common foods or ingredients causing adverse reactions are beef, dairy products or wheat in dogs, and beef, dairy products or fish in cats. There have been few studies documenting specific allergens in food that cause adverse reactions in pets. Studies to date have identified bovine IgG (beef, cow s milk), ovine IgG (lamb), chicken serum albumin (chicken) and phosphoglucomutase (beef, lamb) as specific food allergens in dogs. No specific food allergens have been identified in cats. Q: What is known about allergic cross reactivity of ingredients in pet foods? A: Only a few studies have been completed on cross reactivity of food ingredients in pets with adverse food reactions. In these studies, dogs allergic to soy were not more likely to react to wheat, and dogs allergic to beef were not more likely to react to cow s milk. However, based on identification of specific allergens noted above, cross reactivity between beef and lamb may be common in dogs. In human beings, cross reactivity is common for fish, avian meat, milk, egg proteins and invertebrates (mites, insects). It is unknown if such cross reactivity occurs in pet animals as well. In vitro cross reactivity with venison has been reported in beefallergic human beings, but it is not known if this is clinically important (Ayuso, et al. Allergy 2000). No similar studies have been conducted in pet animals. Q: What are the sources of ingredients used in the Hill s hydrolysate and novel protein foods? A: Lamb (wet food): lamb and lamb liver from U.S., New Zealand and Australian sources Salmon (wet, dry foods): salmon and salmon meal from U.S. source Venison (wet, dry foods): venison and venison meal from New Zealand source Duck (wet, dry foods): duck from U.S. source and duck meal from European source Rabbit (wet, dry foods): rabbit and rabbit meal from European source Chicken hydrolysate (wet, dry foods): chicken liver and chicken heart are used as the starting ingredients for the chicken hydrolysate in both feline and canine formulas Q: Several of the formulas contain pork fat. Why is this fat source used, and could it lead to allergic reactions in my patients? A: Pork fat is highly palatable and helps deliver appropriate fatty acid levels when combined with other fat sources. There are no data in the veterinary literature to show that allergic reactions to fat sources or oils occur. Hill s has conducted extensive testing on the new Hill s Prescription Diet d/d formulas containing pork fat and has found no evidence of pork protein in any finished products. Testing for pork allergens cannot be conducted because no specific pork allergen has been identified in people or animals (www.allergen.org). Q: What is the target urine ph of the Hill s Prescription Diet d/d and z/d formulas for cats? A: Cats consuming Prescription Diet d/d and z/d formulas typically produce urine with a ph of 6.2 to 6.4. This urine ph range helps prevent struvite crystal and urolith formation, and is considered oxalate-safe since urine ph is not a major factor in calcium oxalate stone formation. Q: Can Hill s Science Diet Sensitive Skin and Prescription Diet d/d and z/d formulas be fed long-term? A: All these formulas have undergone feeding tests using AAFCO procedures to substantiate that they provide adequate nutrition for maintenance of adult dogs and cats. Q: Why is it important to have both wet and dry formulas available? A: Research with dog and cat owners has shown that a large number of them prefer to feed both moist and dry foods to their pets. In fact, more than 40% of pet owners prefer to feed both moist and dry food to their dogs, and two-thirds of pet owners prefer to feed both moist and dry food to their cats. This emphasizes the importance of asking pet owners what forms of food they prefer to feed. Best compliance will occur when you make specific recommendations for moist food, dry food and treats for an individual animal. Q: What carbohydrate sources are used in the Prescription Diet d/d and z/d formulas? A: Carbohydrate sources include potato (venison, duck, salmon varieties) or rice (lamb, egg varieties) in the canine novel protein formulas and green pea (venison, duck, rabbit varieties) in the feline novel protein formulas. Carbohydrate sources in the hydrolysate-based foods include starch (z/d ULTRA formulas), potato (canine dry) or rice (feline dry). Q: Can the moist formulas of Prescription Diet z/d therapeutic foods be used with the dry formulas? A: Prescription Diet z/d therapeutic foods are available as canine and feline moist and dry formulas. All formulas provide complete and balanced nutrition for maintenance of adult animals. Moist forms can be fed as the sole source of food or, more commonly, mixed with the dry Prescription Diet z/d formulas. For dogs with suspected or confirmed adverse food reactions, Prescription Diet z/d Canine Canned can be fed with either Prescription Diet z/d ULTRA Allergen-Free Canine or Prescription Diet z/d Low Allergen Canine Dry formulas. For cats, Prescription Diet z/d Feline Canned can be fed with Prescription Diet z/d Feline Low Allergen Dry formula. Q: What antioxidants have been added or enhanced in the Hill s formulas? A: Hill s has conducted extensive research on use of antioxidants in foods for healthy dogs and cats and those with various disease conditions. Levels of vitamin E, vitamin C, betacarotene and selenium are enhanced in all our therapeutic products to help counteract oxidative stress associated with skin disease and other conditions. 38

Q: Can fatty acid supplementation be used in conjunction with food for managing pets with skin conditions? A: Fatty acid intake is usually much higher with specific therapeutic foods than by adding fatty acid supplements to the food already being consumed by the pet. See the accompanying material for more detailed information on fatty acids. Q: What food is best to use for pets with food allergy and other concurrent disease conditions such as lower urinary tract disease, chronic kidney disease or pancreatitis? A: You can get specific recommendations as well as product information and case management assistance from Hill s Veterinary Consultation Service (VCS). VCS is a group of 15 veterinarians and veterinary technicians who offer free case consultations. They have more than 150 years of combined veterinary and pet food industry experience. VCS clinicians and technicians handle more than 285 phone calls per day and can readily assist you in determining the best food for an animal with multiple disease conditions. Contact VCS by phone (1-800-548-VETS), fax (1-800-548-VFAX) or e-mail (vet_consult@hillspet.com). 39

/ Hill s, Prescription Diet, Science Diet, d/d, n/d, z/d, a/d, b/d, j/d and Evidence-Based Clinical Nutrition are trademarks owned by Hill s Pet Nutrition, Inc. Eukanuba, Eukanuba Veterinary Diets and Response are trademarks owned by The Iams Company. Royal Canin, Royal Canin Veterinary Diet, IVD, Limited Ingredient Diets, Skin Support SS21, Hypoallergenic HP19, Feline Hypoallergenic HP 23, Royal Canin Skin Care 30, Royal Canin Adult Fit 32, Royal Canin Indoor 27, Royal Canin Persian 30, Feline Sensitivity RD 30 and Sensitivity RC21 are trademarks of Royal Canin USA. Nutro and Nutro Ultra are trademarks of Nutro Products, Inc. Purina Veterinary Diets and LA Limited Antigen are trademarks of Société des Produits Nestlé S.A. 3V Caps and DermCaps are trademarks owned by DVM Pharmaceuticals. NutriVed is a trademark owned by Zinpro Company. EicosaDerm is a trademark owned by DermaPet. Welactin is a trademark owned by Nutramax Laboratories, Inc. Nordic Naturals is a trademark of Nordic Naturals, Inc. 2007 Hill s Pet Nutrition, Inc.