Evaluation of Two Diets in the Nutritional Management of Cats with Naturally Occurring Chronic Diarrhea*

Evaluation of Two Diets in the Nutritional Management of Cats with Naturally Occurring Chronic Diarrhea* Dorothy S. Laflamme, DVM, PhD, DACVN Grace M. Long, DVM, MS, MBA Nestlé Purina PetCare Company Checkerboard Square St. Louis, MO 63164 CLINICAL RELEVANCE Feeding either a highly digestible, moderate-carbohydrate diet or a highly digestible, high-protein, low-carbohydrate diet resulted in significant (P <.05) improvements in fecal scores in 71% of cats with chronic, nonspecific diarrhea. Approximately 58% of the cats improved on either diet, with no significant differences between the two diets regarding the percentage of cats responding or the degree of response. These results suggest that dietary management may be helpful in cats with chronic diarrhea. If cats do not respond within 1 month, an alternative diet should be considered. *Funding for this study was provided by Nestlé Purina PetCare Company, St. Louis, MO. INTRODUCTION Dietary management of gastrointestinal (GI) disease is an adjunct to specific or symptomatic management to control clinical signs, such as diarrhea. The appropriate dietary modifications depend on the type and expression of the disease and on which parts of the GI tract or other associated organs are affected. It may also depend on which species is affected. Highly digestible, high-carbohydrate, restricted-fat diets have been advocated as appropriate for canine patients with GI disease and diarrhea for many years. Results in dogs have been extrapolated to include cats with some forms of diarrhea. 1 However, more recent recommendations suggest diets with higher fat content for cats with diarrhea. 2 4 Apparently, no data have been published supporting either recommendation for feline diarrhea. Current publications recommend a highly digestible, moderate-fat diet (i.e., 15% to 25% fat, dry basis) for cats with diarrhea due to small intestinal problems. 3,4 Along with higher fat, several authors have suggested that cats with diarrhea should avoid high-carbohydrate diets. 2,3,5,6 It has been suggested that these cats may have diarrhea secondary to maldigestion or malabsorption of carbohydrate. The disaccharidases that complete the digestion of carbohydrates are located in the intestinal brush border, which may be damaged due to enteritis from any cause. 3,5 Fur- 43

Veterinary Therapeutics Vol. 5, No. 1, Spring 2004 thermore, cats are metabolically adapted for higher metabolism of protein and lower utilization of carbohydrate compared with dogs or other omnivores. 7 Cats have lower pancreatic amylase activity compared with dogs. 8,9 Cats also may have less intestinal disaccharidase activity, 6,9 although other investigators found the opposite. 10 Anecdotal observations in recent years have indicated that many diabetic cats with nonspecific chronic diarrhea showed clinical improvement when fed a high-protein, low-carbohydrate diet for the nutritional management of their diabetes. Follow-up evaluations in the authors research colony demonstrated that chronic diarrhea in many cats suspected of having inflammatory bowel disease also improved when they were fed such a diet. These empiric observations suggested the need for a controlled clinical trial to determine whether these responses could be confirmed. The objective of this study was to evaluate the clinical responses of cats with chronic diarrhea of nonspecific causes to dietary management using either a high-protein, low-carbohydrate diet or a highly digestible, moderate-carbohydrate diet. A popular brand of feline intestinal diet was selected as the control diet for this study. A high-protein, low-carbohydrate diet currently marketed for the nutritional management of cats with diabetes mellitus was selected as the low-carbohydrate diet. Both commercially available diets were highly digestible and had moderate fat levels, so the primary macronutrient differences were the carbohydrate and protein contents. MATERIALS AND METHODS Animals Pet cats with chronic diarrhea were recruited through primary care veterinary practices. Cats were solicited for the study if they had experienced a minimum of three episodes of diarrhea per week for at least 1 month before entry into the study. Cats also must have shown an inadequate response (defined as continued or recurrent diarrhea) to prior therapy with a fullspectrum intestinal parasiticide, including treatment for Giardia. Cats were excluded from the study if they had an infectious disease (e.g., feline leukemia virus, feline immunodeficiency virus, panleukopenia, feline infectious peritonitis) or if they had evidence of a systemic disease that could cause diarrhea or GI signs (e.g., renal failure, hyperthyroidism, pancreatic or hepatic disease, malignancy). Cats also were excluded if their clinical condition was such that they required immediate medical care to control the diarrhea or its effects, such as those with hypoproteinemia or with recent weight loss in excess of 10% of their body weight or chronic, undesired weight loss in excess of 25% of any previous adult body weight. Finally, cats also were excluded if they had been treated with a long-acting corticosteroid within the past 6 weeks or with an oral steroid within the past 2 weeks. Experimental Design Cats entered into the study were randomly assigned to receive either Diet A or Diet B as the sole diet for 1 month. During the course of the study, cats were to receive no corticosteroids, GI motility modifiers, oral antibiotics, parasiticides, or other medications. Cats that did not improve adequately during the first month on the assigned diet were switched to the alternate diet for an additional month. Cats that did improve during the first period were continued on the same diet for a second month. Adequate improvement was defined as a reduction of 50% or more in vomiting frequency, and/or reduction of 30% or more in defecation frequency, and/or either a mean fecal score of 66 or higher or a 25% or greater increase in fecal score, whichever was greater, 44

during the 7 days before an examination. Fecal scores were determined using the Nestlé Purina illustrated scoring system (very watery diarrhea = 0 and very firm, dry feces = 100). Diets Two commercially available, dry diets were evaluated. Diet A was a highly digestible, moderate-fat, moderate-carbohydrate diet (Hill s Prescription Diet Feline i/d; Hill s Pet Nutrition). Diet B was a high-protein, moderate-fat, low-carbohydrate diet (Purina Veterinary Diets DM Diabetes Management brand Feline Formula; Nestlé Purina PetCare Company) (Table 1). Diets were repackaged into plain white bags so that neither the veterinarians nor the cat owners knew the identity of either food. TABLE 1. Nutrient Profile of Diets Evaluated in Cats with Naturally Occurring Diarrhea* Moderate-Carbohydrate Diet (A) Low-Carbohydrate Diet (B) % Dry g/100 kcal % Dry g/100 kcal Matter ME Matter ME Protein 40.0 9.5 57.9 12.9 Fat 20.4 4.8 17.9 4.0 Carbohydrate 31.7 7.5 15.0 3.4 Crude fiber 1.3 0.3 1.3 0.3 Source Percentage Percentage of Calories of Calories of Calories Protein 34.3 51.7 Fat 40.8 37.0 Carbohydrate 25.9 11.2 *Nutrient information obtained from respective manufacturers product guides. Calculated as 3.5 kcal/g for protein and carbohydrate and 8.5 kcal/g for fat, using average nutrient content provided in the manufacturer s product guide. Diet A = Hill s Prescription Diet Feline i/d; Diet B = Purina Veterinary Diets DM Diabetes Management brand Feline Formula. ME = metabolizable energy. Evaluations A complete physical examination was performed before initiation of the study. Other evaluations at baseline included body weight, body condition score, serum biochemical profile, hematology, urinalysis, feline leukemia virus antigen and feline immunodeficiency virus antibody testing, serum folate and cobalamin concentrations, and serum trypsin-like immunoreactivity (TLI). Fecal samples were analyzed for the presence of intestinal parasites using a standard fecal smear, a fecal flotation test, and a zinc sulfate centrifugation test to detect Giardia. A detailed medical and dietary history was obtained to include the frequency, duration, and character of vomiting and diarrhea. Clients were provided with the Nestlé Purina illustrated fecal scoring system to facilitate fecal scoring. Client recall of fecal scores and frequency of defecations for the 3 days immediately prior to the initial evaluation were recorded as baseline values. During each of the two feeding periods, clients were required to maintain a daily diary to record the incidence of vomiting (if any) and a fecal score for each defecation, which would provide an indication of the frequency of defecation as well as an assessment of the character of the feces. Clients also were to record their assessment of their cat s appetite and activity each day. At the end of each feeding period, cats were reevaluated by the attending veterinarian. Body weight and body condition score were recorded, and response to diet was assessed. At the completion of the 45

Veterinary Therapeutics Vol. 5, No. 1, Spring 2004 TABLE 2. Scoring of Clinical Signs of Gastrointestinal Disease and Diet Acceptance in Cats with Naturally Occurring, Nonspecific Diarrhea Vomiting Frequency Defecation Frequency Diet Acceptance Client Rating Score Client Rating Score Client Rating Score None 0 <1/day 1 Poor 1 <1/wk 1 1 2/day 2 Fair 2 1 3/wk 2 3 4/day 3 Good 3 5 7/wk 3 4 6/day 4 Excellent 4 1 2/day 4 >6/day 5 >2/day 5 second feeding period, serum biochemistry, folate, cobalamin, TLI, and urinalysis tests were repeated. Data Analysis Key outcome parameters included changes in vomiting frequency, defecation frequency, and fecal score. Secondary outcome parameters included changes in body weight, body condition score, and diet acceptance. Frequency of defecation and vomiting and diet acceptance were converted from the client-recorded frequencies or assessments into numeric scores for data evaluation (Table 2). For normally distributed data, paired t-tests were used to determine differences from baseline. When this criterion failed, a Wilcoxon signed rank test was performed. Between-diet differences were determined using two-way analysis of variance to account for any interactions within the feeding period. Cats were only switched to the alternate diet if they had not demonstrated adequate clinical improvement; therefore, the baseline evaluation TABLE 3. Fecal Score and Frequency of Defecation of Cats with Naturally Occurring, Nonspecific Diarrhea Remaining on Initial Diet for 2 Months Initial Month 1 Month 2 Fecal Score* Diet A 29.0 ± 8.0 78.8 ± 16.3 78.8 ± 16.3 (n = 4) (n = 4) Diet B 36.4 ± 17.9 74.6 ± 8.5 66.2 ± 11.7 (n = 6) (n = 5) Fecal Frequency Diet A 2.3 ± 1.3 2.0 ± 0.0 2.0 ± 0.0 Diet B 3.0 ± 1.2 2.2 ± 0.4 2.2 ± 0.4 *Based on visual score from 0 (watery) to 100 (very firm). Based on scores ranging from 1 (<1 defecation/day) to 5 (>6 defecations/ day). Diet A = Hill s Prescription Diet Feline i/d (moderate-carbohydrate diet); Diet B = Purina Veterinary Diets DM Diabetes Management brand Feline Formula (low-carbohydrate diet). Data are expressed as mean ± standard deviation. was assumed to remain valid as the initial measure for both feeding periods. The exceptions to this included data from cats that remained on the same diet for two periods. For those cats, changes from baseline parameters were not evaluated for the second feeding period. A z- test of proportions was used to detect dietary 46

TABLE 4. Response of Diarrhea or Vomiting in Cats with Naturally Occurring, Nonspecific Diarrhea to a Dietary Change During First Month on Each Diet Moderate-Carbohydrate Diet (A) (n = 24) Low-Carbohydrate Diet (B) (n = 26) Baseline End Baseline End Vomiting frequency* 0.4 ± 0.8 0.5 ± 0.7 0.4 ± 0.8 0.6 ± 0.8 Fecal frequency 2.4 ± 0.9 2.4 ± 0.8 2.7 ± 1.0 2.5 ± 0.8 Fecal score 33.0 ± 22.3 a 53.2 ± 23.0 b 35.6 ± 21.2 a 54.5 ± 25.3 b Diet acceptance NA 3.2 ± 0.7 NA 3.0 ± 1.0 *Based on scores ranging from 0 (none) to 5 (>2 times/day). Based on scores ranging from 1 (<1 defecation/day) to 5 (>6 defecations/day). Based on scores ranging from 0 (watery) to 100 (very firm). Based on scores ranging from 1 (poor) to 4 (excellent). a,b Means with different superscripts for an observation within diet are significantly different (P <.05). Diet A = Hill s Prescription Diet Feline i/d; Diet B = Purina Veterinary Diets DM Diabetes Management brand Feline Formula. NA = not applicable. Data are shown as mean ± standard deviation. differences in proportion of cats maintained on the same diet. Probability values of.05 or less were considered significant. RESULTS Forty-two cats were recruited into the study. Of these, 11 were excluded based on the predetermined criteria or withdrawn due to client preferences or noncompliance. For two of the remaining 31 cats, data were only available for Period 1 due to client noncompliance or administration of medications in the second period. All other cats (n = 29) completed both feeding periods. Nineteen cats were fed Diet A in Period 1. Of these, four (21.1%) remained on Diet A during the second month. Twelve cats were fed Diet B in Period 1. Of these, six (50.0%) remained on Diet B during the second month (P =.199 for diet effect; Table 3). Frequency of defecation was not affected by diet. Initial fecal scores for all cats averaged 33.6 ± 20.6 at entry, increasing to 53.2 ± 23.0 after Diet A and 54.5 ± 25.3 after Diet B (Table 4). Fourteen of 24 (58.3%) cats on Diet A and 15 of 26 (57.7%) cats on diet B showed a significant (P <.05) improvement in fecal score. Of the eight cats that showed no response to Diet A during the initial month of feeding, two improved when switched to Diet B. Of the five cats not responding to Diet B during the first month, two improved on Diet A and one was withdrawn before completing the second month of evaluation. No significant period effects were observed, and there were no significant differences between the two diets for the percentage of cats responding or the degree of response (Table 5). Overall, 22 (71.0%) of the cats showed a positive response to at least one of the diets. Among cats showing a positive response, the average fecal score more than doubled, whereas the average fecal score of nonresponders decreased (Table 6). Initial fecal scores were lower for responders than for nonresponders. Vomiting was uncommon in these cats, averaging an occurrence less than once a week 47

Veterinary Therapeutics Vol. 5, No. 1, Spring 2004 TABLE 5. Effect of Period and Diet on Fecal Score in Cats with Naturally Occurring, Nonspecific Diarrhea Fecal Scores* Month 1 Month 2 Baseline After Diet Baseline After Diet Diet A 31.3 ± 21.2 a 52.3 ± 22.3 b 39.6 ± 27.6 56.4 ± 28.0 No. of cats 19 19 5 5 Diet B 37.2 ± 20.0 a 55.9 ± 24.3 b 34.2 ± 22.9 a 53.4 ± 27.0 b No. of cats 12 12 14 14 *Based on visual score from 0 (watery) to 100 (very firm). a,b Means before and after diet within a period having different superscript letters are significantly different (P <.05). Diet A = Hill s Prescription Diet Feline i/d (moderate-carbohydrate diet); Diet B = Purina Veterinary Diets DM Diabetes Management brand Feline Formula (low-carbohydrate diet). Data are expressed as mean ± standard deviation. TABLE 6. Differences Between Responding and Nonresponding Cases for Fecal Scores in Cats with Naturally Occurring, Nonspecific Diarrhea Baseline After Diet Responders Responders Nonresponders Responders Nonresponders on Diet A on Diet B No. of cats 9 22 9 14 15 Fecal score* 45.9 ± 16.1 a 28.5 ± 20.5 b 41.5 ± 15.3 a 62.7 ± 23.8 b 68.0 ± 17.3 b Change in fecal score 7.6 ± 10.1 a 37.9 ± 15.1 b 38.3 b ± 17.0 b *Based on visual score from 0 (watery) to 100 (very firm). a,b Means having different superscripts within a time period are significantly different (P <.05). Diet A = Hill s Prescription Diet Feline i/d (moderate-carbohydrate diet); Diet B = Purina Veterinary Diets DM Diabetes Management brand Feline Formula (low-carbohydrate diet). Data includes scores only from first period on a given diet. Data are expressed as mean ± standard deviation. throughout the study regardless of diet. Descriptions provided by the owners implied most of these were a consequence of hairballs. There were no patterns for abnormal laboratory values among cats (data not shown). The most common laboratory abnormalities were proteinuria and low platelet counts. No patterns in key assays of digestive function (TLI, serum cobal- amin, and folate) were observed between responders and nonresponders (Table 7). DISCUSSION The majority of cats in this study with nonspecific chronic diarrhea responded to one or both of the diets tested with an improvement in fecal score. However, there were no differ- 48

TABLE 7. Baseline Blood Values for Variables Reflective of Digestive Function in Cats with Naturally Occurring, Nonspecific Diarrhea That Responded to Diet and Those That Did Not Component Reference Range Responders (n = 22) Nonresponders (n = 9) Trypsin-like immunoreactivity 12 82 105 (29 500) 51 (38 111) (ng/ml) Cobalamin (pg/ml) 290 1,500 822 (146 1,200) 1004 (253 1,200) Folate (ng/ml) 9.7 21.6 18.0 (9.3 24) 17.3 (13.2 24) ences in response rates between the two diets. Only nine cats out of 31 showed no improvement on either diet. There was no evidence from the data collected to determine why these cats did not respond, nor was there any indication as to why some cats responded to one diet but not the other. Neither endoscopic evaluation with biopsies nor other intestinal function tests were performed during this study. Had these been done, it may have been possible to postulate which conditions would more likely respond to dietary management and to which type of diet. The hypothesis of this study was that a lowcarbohydrate diet would be superior to a highly digestible, moderate-carbohydrate diet for the nutritional management of chronic diarrhea in cats. Cats are considered obligate carnivores. As such, it has been suggested that they may have difficulty digesting and metabolizing dietary carbohydrates. 7,9 Cats have lower pancreatic amylase activity compared with dogs. 9 They also appear to have lower activity of intestinal brush border disaccharidases, which are critical to complete starch digestion. 6,11 Conversely, cats have been shown to readily digest and absorb properly cooked carbohydrates. 8,9,12 Most research indicating cats have only a limited capacity for carbohydrate digestion was conducted using simple disaccharides or raw starches, 13 15 which are not representative of properly processed and cooked carbohydrates found in complete commercial diets. Raw and cooked starches have very different effects in cats. Raw starch is poorly digested by most monogastric species. Fine-grinding or cooking increases the digestibility to well over 90% in cats. 8 In addition, cooked cornstarch enhanced protein digestibility, whereas raw starch decreased protein digestibility. 15 Thus, the effects of carbohydrates on digestion can differ considerably between sources and based on processing variables. Dietary changes of many types can induce physiologic adaptations within the GI tract. 16 24 A partial list of such changes includes intestinal mucosal hypertrophy, alterations in gastric emptying and GI transit rate, changes in nutrient and water absorption, changes in intestinal microflora, and altered production of short-chain fatty acids. Changing diets can alter the presentation of both dietary antigens and antigens from intestinal bacteria that may be involved in dietary hypersensitivity or inflammatory bowel diseases. 25 27 Which, if any, of these mechanisms played a role in the clinical responses observed in this study was not determined. Because definitive diagnoses were not made in these cats, comparison of the results of this study with findings in other studies is somewhat difficult. One publication reported the results from 60 cats with inflammatory bowel disease. 28 Fifty-two of the cats were included in a dietary trial with a controlled protein diet; only two cats, both with lymphoplasmacytic 49

Veterinary Therapeutics Vol. 5, No. 1, Spring 2004 colitis, responded to dietary change alone. In another study, 27 of 55 cats with idiopathic GI signs improved when fed a novel protein elimination diet. 29 Of these 27, 16 were diagnosed with food hypersensitivity based on response to subsequent dietary challenge. The percentage of cats responding to a dietary change in the current study (71%) was greater than that reported by Guilford et al (49%). 29 The diets used in the present study were not based on novel proteins. Both diets included poultry and numerous other protein sources. This study has documented a benefit of dietary management in nonspecific, chronic diarrhea in cats. Further research now is needed to determine the mechanism(s) involved in the provision of these benefits; what dietary modifications would be best for specific types or causes of diarrhea; and whether other nutrient modifications would be of benefit. CONCLUSIONS The majority of cats in this study with nonspecific chronic diarrhea responded to one or both of the diets tested with an increase (improvement) in fecal score. However, there were no differences between the diets tested regarding the percentage of cats responding or the degree of response. Both diets were well accepted by the cats. Thus, it appears that a dietary change could be appropriate for cats with chronic, nonspecific diarrhea. A highly digestible diet with either low or moderate carbohydrate levels may provide a favorable outcome. If cats do not respond within 1 month, an alternative diet should be tried. Additional research is needed to determine whether cats with specific dietary conditions will be more likely to respond to one diet or the other. ACKNOWLEDGMENTS The authors thank the veterinarians and staff at the veterinary practices participating in this study as well as Denni Day and the staff of Vetpharm for assistance in data collection. REFERENCES 1. Jergens AE: Feline idiopathic inflammatory bowel disease. Compend Contin Educ Pract Vet 14:509 518, 1992. 2. Jergens AE: Acute diarrhea, in Bonagura JD, Kirk RW (eds): Kirk s Current Veterinary Therapy, XII. Philadelphia, WB Saunders, 1995, pp 701 705. 3. Davenport DJ, Remillard RL, Simpson KW, Pidgeon GL: Gastrointestinal and exocrine pancreatic disease, in Hand MS, Thatcher CD, Remillard RL, Roudebush P (eds): Small Animal Clinical Nutrition, ed. 4. Marceline, MO, Walsworth Publishing, 2000, pp 725 810. 4. Marks SL, Fascetti AJ: Nutritional management of diarrheal diseases, in Bonagura JD (ed): Kirk s Current Veterinary Therapy, XII. Philadelphia, WB. Saunders, 2000, pp 653 658. 5. Hall E: Gastrointestinal problems, in Kelly NC, Wills JM (eds): BSAVA Manual of Companion Animal Nutrition & Feeding. Ames, Iowa State University Press, 1996, pp 144 152. 6. Hall EJ, Simpson KW: Diseases of the small intestine, in Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed. 5. Philadelphia, WB Saunders, 2000, pp 1182 1238. 7. Zoran DL: The carnivore connection to nutrition in cats. JAVMA 221:1559 1567, 2002. 8. Morris JG, Rogers QR: Comparative aspects of nutrition and metabolism of dogs and cats, in Burger IH, Rivers JPW (eds): Nutrition of the Dog and Cat. Waltham Symp 7. Cambridge, Cambridge University Press, 1989, pp 35 66. 9. Meyer H, Kienzle E: Dietary protein and carbohydrate: Relationship to clinical disease. Proc Purina Intern Nutr Symp (Eastern States Vet Conf) 13 36, 1991. 10. Hore P, Messer M: Studies on disaccharidease activities of the small intestine of the domestic cat and other carnivorous mammals. Comp Biochem Physiol 24:717 725, 1968. 11. Kienzle E: Carbohydrate digestion of the cat: 4. Activity of maltase, isomaltase, sucrase and lactase in the gastrointestinal tract in relation to age and diet. J Anim Physiol Anim Health 70:89 96, 1993. 12. Harper EJ, Turner CL: Age-related changes in apparent digestibility in growing kittens. Reprod Nutr Dev 40:249 260, 2000. 13. Kienzle E: Carbohydrate digestion of the cat: 2. Digestion of starch. J Anim Physiol Anim Health 69:102 114, 1993. 14. Kienzle E: Carbohydrate digestion of the cat: 3. Di- 50

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