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TECHNICAL REPORT Purina Veterinary Diets® OM Overweight Management® brand canine dry formula and the Beneficial Role of Introduction Approximately 35% of adult dogs in the U.S. are overweight or obese1. A markedly greater incidence of overweight and obesity was observed in neutered male (59% higher) and female dogs (40% higher)1. Chronic obesity can increase the risk of, or complications from, several chronic diseases including diabetes, hypertension, pulmonary and , and degenerative joint disease2. Obesity produces chronic, mild inflammation and increases oxidative stress, which, in turn, contributes to the development of the above-mentioned chronic diseases.3,4 Therefore, reducing obesity and oxidative stress can promote a long life span and improved quality of life in dogs.

What are Soy Isoflavones? Figure 2: Soy Isoflavones Reduced Plasma Isoprostanes Soy isoflavones are a class of natural bioactive compounds in . Natural a Marker of Oxidative Stress soy isoflavones include three chemical compounds: daidzein, , 5 Plasma Isoprostanes (ng/ml) and . Many health benefits have been associated with regular consumption of soy products. In humans, soy has been found to reduce the 4 risk of cardiovascular disease and certain types of (breast and prostate cancer); relieve a number of problems in post menopausal women including 3 hot flashes, , and decline in cognitive function; reduce and triglycerides in plasma; improve symptoms of hypertension; and reduce 2 abdominal fat accumulation.5,6,7 1 Why Did Nestlé Purina 0 Control Isoflavones* Choose Isoflavones? *P<0.01 for Control vs. Isoflavones Soy isoflavones provide a number of benefits for managing dogs with obesity, and reducing rebound effects after weight loss. Nestlé Purina research Nestlé Purina Nutritional scientists considered a number of important factors. Research on Isoflavones in Dogs Recognizing the safety of soy and the benefits observed in other species, • Soy has a long history of safe use in both humans and animals, including Nestlé Purina began studying the benefits of soy isoflavones in dogs over dogs and cats, and is an approved AAFCO ingredient class. 5 years ago, using randomized, controlled studies. The following points • Research in beagles indicated that soy isoflavones are very safe for dogs8. highlight some of the key results from those studies. Compared to the control diet, the -containing diet: • Soy isoflavones have been proven to reduce weight gain and abdominal fat • Reduced oxidative stress in overweight dogs during weight loss (figure 2). accumulation in other species.7,9,10 • Improved insulin clearance in overweight dogs. • germ meal naturally contains high levels of daidzein and glycitein, • Reduced weight gain (figure 3) and body fat (figure 4) accumulation in the isoflavones found to be beneficial in healthy weight management11,12 neutered and spayed dogs that were allowed to overeat. (figure 1). • Increased metabolism in neutered male dogs (figure 5). • Soy isoflavones can be obtained from natural ingredients. The level of Figure 3: Soy Isoflavones Reduced Weight Gain isoflavones in soybean germ meal is approximately four times the level in in Overfed Dogs .13,14 6 Change in Body Weight (kg) 5 Figure 1: Comparison of Isoflavone Content in 4 Soybean Meal and Soybean Germ Meal * 3 * Isoflavones Soybean Meal Soybean Germ Meal 2 Daidzein 32% 52% 1 Genistein 66% 17% 0 Glycitein 3% 31% Total Isoflavones 1490 mg/kg 6260 mg/kg -1 Months 3 6 9 12 Control Isoflavones *Control vs. Isoflavones, P<0.05 at 9 and 12 months, respectively. THIS REPORT PROVIDED EXCLUSIVELY TO VETERINARIANS BY NESTLÉ PURINA PETCARE

VET 1755A-1207 Trademarks owned by Société des Produits Nestlé S.A., Vevey Switzerland Printed in U.S.A. TECHNICAL REPORT

Figure 4: Soy Isoflavones Reduced Fat Gain in Overfed Dogs Safety Studies on Soy 15 Change in Body Fat % Isoflavones The safety of soy isoflavones was also evaluated during these studies. During 10 long-term testing, no clinical evidence of adverse effects were observed. The isoflavone containing diet had no adverse effects on thyroid function, blood chemistry, or complete blood counts. As a result of these studies, Nestlé Purina 5 selected soy isoflavones as one of the key components in Purina Veterinary Diets® in the new OM Overweight Management® dry canine formula. 0 Guaranteed Levels of Isoflavones -5 The level of total soy isoflavones is guaranteed to be a minimum of Months 3 6 9 12 850 mg/kg diet. Control Isoflavones *Isoflavone group was significantly different (p<0.05) from control from 6 months on. Ingredient List for Purina Veterinary Diets® OM Overweight Management® Figure 5: Soy Isoflavones Increased Total INGREDIENTS: Whole grain corn, corn gluten meal, soybean hulls, soybean Energy Expenditure in Dogs germ meal, soybean meal, pea fiber, wheat gluten, poultry by-product meal, 50 Energy Expenditure(kcal/kg BW/Day) animal digest, powdered cellulose, tricalcium phosphate, animal fat preserved with mixed-tocopherols (form of Vitamin E), salt, choline chloride, sulfate, 40 ferrous sulfate, Vitamin E supplement, manganese sulfate, , Vitamin A supplement, calcium carbonate, sulfate, brewers dried yeast, calcium 30 pantothenate, garlic oil, pyridoxine hydrochloride, Vitamin B-12 supplement, thiamine mononitrate, Vitamin D-3 supplement, riboflavin supplement, 20 calcium iodate, menadione sodium bisulfite complex (source of Vitamin K activity), folic acid, biotin, sodium selenite. 10

0 Control Isoflavones* Purina Veterinary Diets OM Overweight Management is formulated to meet the nutritional levels established by the AAFCO Dog Food Nutrient Profiles for *P<0.05 for control vs. Isoflavones maintenance.

References 1. Lund EM, Armstrong PJ, Kirk CA, Klausner JS. Prevalence and Risk Factors for obesity in adult dogs from private US veterinary practices. Intern J Appl Res Vet Med. 2006, 4:177-181. 2. Laflamme DP, Kuhlman G, Lawler DF. Evaluation of weight loss protocols for dogs. J. Am. Anim. Hosp. Assoc. 1997, 33:253-259. 3. Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanism, mutation, and disease. FASEB J. 2003; 17: 1195-1214. 4. Urakawa H, Katsuki A, Sumida Y, Gabazza EC, Murashima S, Morioka K, Maruyama N, Kitagawa N, Tanaka T, Hori Y, Nakatani K, Yano Y, Adachi Y. Oxidative stress is associated with adiposity and insulin resistance in men. J Clin Endocrinol Metab. 2003; 88:4673-4676. 5. Kritz-Silverstein D, Von Muhlen D, Barrett-Connor E, Bressel MA. Isoflavones and cognitive function in older women: the Soy and Postmenopausal Health In Aging (SOPHIA) Study. . 2003;10:196-202. 6. Setchell KD, Cassidy A. Dietary isoflavones: Biological effects and relevance to human health, 1999; 129:758S-767S. 7. Sites C, Cooper B, Toth M, Gastaldelli A, Arabshahi A, Barnes S. Effect of a daily supplement of on body composition and insulin secretion in postmenopausal women. Fertility and Sterility, 2007 (in press). 8. NCI. Clinical Development Plan: Genistein. J. Cell. Biochem. 1996;26S:114-126. 9. Pan Y, Anthony M, Watson S, Clarkson TB. Soy improve radial arm maze performance in ovariectomized retired breeder rats and do not attenuate benefits of 17beta- treatment. Menopause. 2000;7:230-235. 10. Uesugi T, Toda T, Tsuji K, Ishida H. Comparative study on reduction of bone loss and lipid metabolism abnormality in ovariectomized rats by soy isoflavones, daidzein, genistein, and glycitein. Biol Pharm Bull. 2001; 24:368-372. 11. Pan YL. Use of soy isoflavones for weight management in spayed/neutered dogs. FASEB J 2006; 20:A854-A855. 12. Pan YL. Effects of isoflavones on body fat accumulation in neutered male and female dogs. FASEB J 2007; 21:551.20. 13. USDA-Iowa State University Database on the Isoflavone Content of Foods – 1999. 14. Pan Y.L., unpublished data, 2007.

THIS REPORT PROVIDED EXCLUSIVELY TO VETERINARIANS BY NESTLÉ PURINA PETCARE

VET 1755A-1207 Trademarks owned by Société des Produits Nestlé S.A., Vevey Switzerland Printed in U.S.A.