Dietary management of gastrointestinal (GI) disease

Transcription

1 J Vet Intern Med 2011;25: Effet of Diets Differing in Fat Content on Chroni Diarrhea in Cats D.P. Laflamme, H. Xu, and G.M. Long Bakground: Fat-restrited diets have been advoated for dogs with diarrhea for many years. Reommendations for ats with diarrhea have varied between low-fat and high-fat diets, but there have been no published studies to support either reommendation. Objetives: The objetive of this study was to ompare the linial responses of ats with hroni diarrhea to dietary management using either a high fat or a low fat, highly digestible diet. Animals: Sixty pet ats with hroni diarrhea were reruited; 55 ats ompleted the study. Methods: Randomized, double-blinded, ontrolled linial trial. Upon ompletion of baseline measures, ats were fed 1 of 2 diets for 6 weeks, during whih the owners reorded feal sores daily using an illustrated feal sore hart ranging from 0 (very watery) to 100 (firm and dry). After 6 weeks, ats were reevaluated by the attending veterinarians. Results: Feal sores improved signifiantly, with 78.2% of ats improving by at least 25 points on the 100-point sale or having a final feal sore of at least 66. Over one third of the ats developed normal stools. There were no differenes in linial responses between the diets. Clinial improvement was noted within the 1st week, and maximized within 3 weeks. Conlusions and Clinial Importane: These results show that dietary management an be helpful in ats with hroni diarrhea, but dietary fat ontent does not appear to affet the outome. Cats that do not respond within 3 weeks should be evaluated further. Key words: Cobalamin; Feal sore; Feline; Gastrointestinal trat. Dietary management of gastrointestinal (GI) disease is an adjunt to speifi or symptomati management to ontrol linial signs, suh as diarrhea. The appropriate dietary modifiations are dependent upon the type and expression of the disease, and on whih parts of the GI trat or whih assoiated organs are affeted. Reommendations also may depend on whih speies is affeted. Highly digestible, restrited-fat diets have been advoated as appropriate for dogs with GI disease and diarrhea for many years. 1 4 Compared with protein and arbohydrate, fat is the most omplex nutrient to digest and absorb. For omplete digestion, fat requires lipase, olipase, and phospholipase A2 from the panreas, as well as bile aids, whih are produed by the liver, then stored and released from the gall bladder. One inside the enteroyte, fatty aids and monoglyerides must be reformed into triglyerides. This is an ative, energyexpending proess, resulting in prodution of hylomirons, whih then enter into the intestinal lateals and are transported via the lymphati system to the systemi bloodstream. This differs from other nutrients, whih are transported diretly to the liver via the portal blood. Despite the omplexity, fat digestion is highly effiient so that most ingested fat is absorbed in healthy subjets. Yet, beause of the omplexity, fat digestion is easily From the Nestle Purina PetCare Researh (Laflamme), Nestle Purina PetCare Produt Tehnology Center (Xu), and the Nestle Purina PetCare Company (Long), Chekerboard Square, St Louis, MO. An abstrat from this study was presented at the 2007 Amerian College of Veterinary Internal Mediine Forum. Corresponding author: Dottie Laflamme, DVM, PhD, DACVN, Nestle Purina PetCare Researh, Chekerboard Square, 3S, St Louis, MO 63164; dorothy.laflamme@rdmo.nestle.om. Submitted August 24, 2010; Revised Otober 19, 2010; Aepted November 29, Copyright r 2011 by the Amerian College of Veterinary Internal Mediine /j x Abbreviations: B12 FeLV FIV FSa GI KOP TLI vitamin B12 or obalamin feline leukemia virus feline immunodefiieny virus feal sore average for week gastrointestinal key outome parameters trypsin-like immunoreativity ompromised. Fat malabsorption or maldigestion may our as a result of intestinal muosal damage or villus atrophy, panreati enzymati defiieny, or biliary defiieny. Severe fat malabsorption is evident as steatorrhea, but fat malabsorption may our in the absene of obvious steatorrhea. When fat digestion is inomplete, bateria in the olon an ferment the undigested fat, produing potent seretagogues and proinflammatory ompounds. 3 5 This results in a seretory diarrhea as well as intestinal inflammation. Thus, low-fat diets have long been reommended for patients with GI disease and diarrhea. 1 6 In ontrast to the reommendations ited above, reent reommendations suggest moderate to high (eg, 15 25% fat, dry basis) fat diets for ats with diarrhea. 7 9 Higher fat diets usually are higher in alories, allowing a lower volume of food intake to maintain energy intake. The dereased food intake ould, in theory, derease hyme volume and inrease digestive effiieny. To our knowledge, no studies have been published to support either the low-fat or high-fat reommendation for ats with diarrhea. Thus, the objetive of this study was to evaluate the linial responses of ats with hroni diarrhea of nonspeifi ause to dietary management using either a high fat (45.1% of alories from fat) or a low fat (23.8% of alories from fat), highly digestible diet. Key outome parameters (KOP) indiating linial responses

2 Chroni Diarrhea in Cats 231 inluded hanges in feal sore, feal frequeny, and vomiting frequeny. Materials and Methods Animals Sixty pet ats with hroni large bowel diarrhea, small bowel diarrhea, or a ombination of these were reruited by 4 primary are veterinary praties. All pet owners gave informed written onsent to partiipate in the study. Cats were soliited for the study if they had experiened at least 3 episodes of diarrhea per week for at least 1 month before entry into the study. Cats must also have shown inadequate response, defined as ontinued diarrhea or reurrene after treatment, to prior therapy with a full-spetrum intestinal parasitiide, inluding treatment for Giardia. Cats were exluded from the study if they had an infetious disease suh as feline leukemia virus (FeLV), feline immunodefiieny virus (FIV), panleukopenia virus, or feline infetious peritonitis, or if they had evidene of a systemi disease that may ause diarrhea or GI signs inluding, but not limited to, renal failure, hyperthyroidism, panreati or hepati disease, or malignany of any type. Cats were exluded if their linial ondition was suh that they required immediate medial are to ontrol the diarrhea or its effets, suh as those with hypoproteinemia, reent weight loss in exess of 10% of their body weight, or with hroni, undesired weight loss in exess of 25% of any previous adult body weight. Cats also were exluded if they had been treated with a long-ating ortiosteroid within the past 6 weeks or had reeived ortiosteroids PO within the past 2 weeks. No ortiosteroids, GI motility modifiers, oral antibiotis, parasitiides, or other mediations were allowed during the study. Diets Two experimental diets were prepared from the same ingredients, adjusted as neessary to reate diets as similar as possible exept for the dietary fat ontent (10 or 23%, dry basis; Table 1). Both diets were formulated to provide omplete nutrition and to be highly digestible. Diets were provided in plain bags, labeled to indiate Diet A or Diet B. Neither the veterinarian nor the owner knew whih diet was the low-fat ontrol or the high-fat test diet. Owners agreed to feed their ats the assigned diet, in amounts suffiient to maintain body weight, as the sole diet for 6 weeks. Study Design All aspets of this trial were onduted in aordane with Nestlé Purina s guidelines for animal welfare. Upon entry into the study, a separate random numbers table for eah study enter was used to assign ats to either Diet A or Diet B. During the ourse of the study, ats were to reeive no mediations. All ats underwent baseline evaluations to rule out systemi diseases, inluding a omplete physial examination with body weight and body ondition sore, serum biohemial profile, CBC, urinalysis, FeLV antigen and FIV antibody tests, serum folate and obalamin (B12) onentrations, and serum trypsin-like immunoreativity (TLI). Feal samples were analyzed for the presene of intestinal parasites using a standard feal smear and feal floatation; zin-sulfate entrifugation was used to detet Giardia. A detailed medial and dietary history was obtained to inlude the frequeny, duration, and harater of vomiting and diarrhea. Feal sores were determined using an illustrated soring system (Fig 1), whih ranked very watery diarrhea as zero (0) and firm, dry fees as 100. Client reall of feal sores and frequeny of defeations for the 3 days immediately before the initial evaluation were reorded as baseline. To measure the KOP of feal sore and frequeny during the 6- week feeding period, lients were required to maintain a daily diary to reord feal sores for eah defeation, thus also indiating the frequeny of defeations. Daily feal sores for the entire week were averaged (FSa) for eah at for weeks 1, 3, and 6. The ourrene and harateristis of vomitus, if any, also were reorded, and lients were to reord their at s aeptane of the diet (1 5 poor; 2 5 fair; 3 5 good; 4 5 exellent). At the end of the study, ats were reevaluated by the attending veterinarian. Statistial Analysis KOP inluded hanges in vomiting frequeny, defeation frequeny, and FSa. For eah at, a positive response in FSa was defined as an inrease of at least 25 points or an inrease to a FSa of at least 66 on the 100-point sale. For this study, normal FSa was defined as a sore of 80. Repeated measures analysis of variane was used to evaluate normally distributed data. For data that were not normally distributed, a Mann-Whitney rank-sum test was performed. Polynomial regression was used to determine the assoiation between feal sores and serum obalamin onentrations. Statistial analyses were performed by SigmaPlot a Data are shown as means standard deviation unless otherwise noted. Probability values of o.05 were onsidered signifiant. Results Sixty ats were reruited into the study: 5 were exluded based on the predetermined riteria or withdrawn beause of lient preferenes or nonompliane. Of the Table 1. Nutrient profile of diets a Diet A Diet B % Dry Matter gm/100 kal ME % Calories b % Dry Matter gm/100 kal ME % Calories b Protein Fat Carbohydrate Crude fiber (kal/g dry weight) (kal/g dry weight) Metabolizable energy kal ME, kiloalories of metabolizable energy. a Key ingredients for both diets: Soy flakes and soy protein isolate; turkey and turkey by-produt meal; orn starh; oat meal; oat fiber; beef tallow; vitamins and minerals. b Perent of alories alulated as 3.5 kal/g for protein and arbohydrate and 8.5 kal/g for fat, as a perentage of alulated metabolizable energy.

3 232 Laflamme, Xu, and Long Fig 1. Illustrated feal soring hart. ats ompleting the study, 28 were fed Diet A and 27 were fed Diet B. Both diets were well aepted, although the lients rating for Diet A was higher than for Diet B ( versus , respetively; P o.005). Baseline values for all KOP were similar between groups. Vomiting was unommon in these ats. Client diaries indiated vomiting or regurgitation at some point during the study for 20 ats, but desriptions implied most of these were hairballs. Only 4 ats vomited or regurgitated more than twie over the 6-week period. Mean feal frequeny did not differ signifiantly over time or between diets. Data on initial feal frequeny were not available for 3 ats. Among the other 52 ats, frequeny exeeded twie daily for only 5 ats at baseline, dereasing to 1 at by the end of the study. FSa inreased (P o.001) over time from at entry to by the end of the study, but did not differ between diets (P 4.10). As shown in Figure 2, FSa began to inrease within the 1st week, reahing a steady state by the end of 3 weeks. By the end of 6 weeks, FSa for 43 of 55 ats (78.2%) was 66 or above or had inreased at least 25 points. This result inluded 2 ats starting with a feal sore of 66 that did not improve further. Twenty ats (36%) had final FSa above 80. Among these 20 ats, equally split between Diets A and B, initial feal sores averaged and improved to an average of Serum TLI and folate onentration did not differ over time or between diets. Feal sores were signifiantly lower in ats (n 5 11) with low-serum B12 onentrations (Table 2). Despite this, the proportion of ats responding positively to the diets (77.3% for ats with normal B12 versus 63.6% for ats with low B12) was not signifiantly different, and the final FSa was only weakly (r , P 5.44) orrelated with lower B12 onentrations (Fig 3). Seven of the 11 ats with low B12 showed improvement in feal sores, although only 1 developed normal stools during this study. Among the 7 ats with lowserum B12 onentration fed Diet A, FSa improved in Feal Sore 100 Diet A Diet B a a b b Week 0 Week 1 Week 3 Week 6 Time Fig 2. Feal sores of ats with hroni diarrhea in response to dietary hange. Means (1standard deviation) are based on lientassigned sores based on the system shown in Figure 1. a, b,, means with different supersripts differ, P o.001.

4 Chroni Diarrhea in Cats 233 Table 2. Assoiation between serum B12 onentration and feal sores in ats with hroni diarrhea Group N Mean Median 25% 75% P-Value a Baseline B12 onentration (ng/l) Low B12 b Normal B o.001 Baseline feal sores Low B Normal B Final feal sores Low B Normal B B12, vitamin B12 or obalamin. a Mann-Whitney rank-sum nonparametri test performed as data were not normally distributed. b Laboratory values shown as 41,200 were entered as 1,200, and values shown as o100 were listed as 100 for statistial analysis. Cats with serum B12 onentrations of o290 ng/l were onsidered to have low B12. 5 ats, 1 had a weak positive response and 1 at did not respond, with an overall signifiant (Po.05) improvement over baseline in this group. Among the 4 ats with low-serum B12 onentrations fed Diet B, FSa improved in 2 and did not hange or beame worse in 2 ats. However, statistial omparison within this group was not appropriate beause of the small number of ats and lowstatistial power. Disussion This study assessed the effets of dietary fat in ats with hroni diarrhea. The majority of ats in this study responded to the diets tested with an obvious improvement in FSa. However, there were no differenes in response between the 2 diets, indiating that the amount of dietary fat does not appear to be an important fator in dietary management of ats with diarrhea. Feal Sore Serum B12 Fig 3. Regression showing relationship between serum B12 onentration and final feal sores in ats with hroni diarrhea. The dotted line shows the 95% onfidene interval. Best fit of the data was a third-order polynomial regression: y (0.329B12) ( B12 2 ) 1 ( B12 3 ); P 5.044, r Novel protein diets often are reommended for the management of diarrhea in ats. 4,10 Both diets used in this study were highly digestible and made with the same ingredients. The protein soures, soy and turkey, are ommonly used ingredients. The response to these diets suggests that novel protein diets may not be important in the majority of ats with diarrhea. An important observation in this study was the rapid response time. All ats that responded to the study diets began to do so within the 1st week, with maximum effet seen by the end of 3 weeks. This time frame is onsistent with other studies in ats with diarrhea. 11,12 Also onsistent with other studies is the proportion of ats showing exellent improvement and even omplete remission of diarrhea. 11,12,b In this study, 36% of ats developed normal stools, with FSa Suh observations highlight the importane of dietary hange for the management of feline diarrhea. Dietary hanges of many types an indue physiologi adaptations within the GI trat A partial list of suh hanges inludes intestinal muosal hypertrophy, alterations in gastri emptying and GI transit rate, hanges in nutrient and water absorption, hanges in intestinal miroflora, and altered prodution of short hain fatty aids. Changing diets an alter the presentation of both dietary antigens and antigens from intestinal bateria, whih may be involved in dietary hypersensitivity or inflammatory bowel disease Whih, if any, of these mehanisms played a role in the linial responses observed in the ats of this study was not determined. There was a weak, but signifiant, assoiation between low-serum B12 onentration and feal sores in this study. Twenty perent of the ats in this study had B12 onentrations below the normal referene range. This is similar to the 16.5% reported by Reed et al, 22 but onsiderably less than 61% reported by Simpson et al 23 in their studies of ats with GI diseases. The proportion of ats with low-serum B12 onentration responding to the diets was only slightly less than the response rate among ats with normal B12 onentrations (63.6% for ats with low B12 versus 77.3% for ats with normal B12), but the magnitude of improvement was dereased in ats with low-b12 onentrations. However, in a previous study of ats with diarrhea, the mean serum B12 onentration atually was greater in ats not responding to dietary hange than in ats that improved, 12 so the importane of a low-b12 onentration is unlear. When low-b12 onentration is beause of panreati or small intestinal disease, whih interferes with B12 absorption, serum onentrations are unlikely to improve unless the disease is ontrolled. Beause low-b12 onentration itself an ontribute to intestinal pathology, some ats may not improve until the metaboli B12 defiieny is orreted by parenteral B12 administration. Unfortunately, repeated measurements of B12 onentration were not taken in this study to see if it improved as the ats diarrhea resolved. Testing for and orreting low-serum B12 onentration may be important, espeially in ats that do not respond to other forms of management for their GI disease.

5 234 Laflamme, Xu, and Long Although vomiting is a ommon sign of GI disease in ats, 22,23 it was not ommon among the ats in this study. Thus, we were not able to determine whether a high- or low-fat diet might be benefiial in the management of vomiting in ats. A limitation of this study is that no final diagnosis for the ause of diarrhea was made in these ats. Neither endosopi evaluation with biopsies nor other intestinal funtion tests were performed during this study. It would have been of interest to determine if the nonresponders had different underlying auses of diarrhea ompared with those that improved. Another possible limitation is the range of dietary fat tested in this study. Although the fat ontent of most dry ommerial at foods falls within the range of the diets tested, 24,25 some foods do have higher or lower fat levels. The effets of dietary fat might be different at notably higher or lower onentrations. Conlusions The majority of ats in this study with nonspeifi hroni diarrhea responded to the diets tested with an inrease in FSa. Cats with low-serum obalamin onentrations at the beginning of the study had a slightly inreased risk of not responding, or not responding as well, to dietary hange. Feal sores began to improve within the 1st week, and ahieved a maximum response within 3 weeks. However, there were no differenes between the diets tested regarding the perentage of ats responding or the degree of response. Both diets were well aepted by the ats. Thus, it appears that a dietary hange an be an important part of management for ats with hroni diarrhea, but the amount of dietary fat does not seem to be an important onsideration. Footnotes a Systat Software In, San Jose, CA b Laflamme DP, Xu H, Cupp CJ, et al. Comparison of two anned diets designed for the management of feline diarrhea. J Vet Int Med 2010;24:724 (abstrat) Aknowledgments The authors thank the veterinarians, staff, and at owners at the veterinary praties partiipating in this study (Cats Only Veterinary Hospital, Paddok Park Animal Care Center, Brik City Cat Hospital, and The Cat Dotor) as well as Denni Day and the staff of Vet Pharm In for assistane in data olletion. This study was onduted and funded by Nestle Purina PetCare Company, (St Louis, MO), in partnership with Cats Only Veterinary Hospital (Fayetteville, NY), Paddok Park Animal Care Center (Oala, FL), Brik City Cat Hospital (Oala, FL), and The Cat Dotor (Thousand Oaks, CA), and VetPharm In (East Rohester, NY). Referenes 1. Strombek DR. Small Animal Gastroenterology. Davis, CA: Stonegate Publisher; 1979: Simpson JW. Role of nutrition in aetiology and treatment of diarrhoea. J Sm Anim Prat 1992;33: Guilford WG. Nutritional management of gastrointestinal trat diseases of dogs and ats. J Nutr 1994;124:S2663S S Zoran D. 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