WHAT FOODS THESE MORSELS BE: NUTRITIONAL ASSESSMENT Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition The University of Georgia

The American Animal Hospital Association released the Guidelines for Nutritional Assessment (July/August JAAHA 2010). Utilizing the two-step iterative process, a screening assessment is made and if concerns are found, then a more detailed assessment is made. Following assessment, data are analyzed, a plan formulated and initiated, and repeated evaluation and modification of the plan is made. The American College of Veterinary Nutrition recommends a two-step iterative process in making nutritional recommendations where the first step is ASSESSMENT. During this step, assess the ANIMAL, the DIET, and the FEEDING factors. ANIMAL FACTORS assessed include gathering historical information, performing physical examination, body condition and muscle condition scoring, and evaluating laboratory and imaging results if indicated. Gather information on any health or disease-related conditions, medications (including over-the-counter and nutraceuticals/supplements), reason for visit, and other household members. A thorough physical examination is performed and a body condition score assigned. There are 5- and 9- point body condition scoring systems; either can be used. In either scale, the middle number of the scale represents ideal body condition and a body fat content of 15-25%; numbers lower than this correspond to lower body condition and less body fat (0-15%) while numbers higher than this correspond to higher body condition and greater body fat (≥ 35%). Assigning a body condition score provides more information than body weight alone and can be used with a muscle condition scoring system where 3 = adequate muscle mass, 2 = decreased muscle mass, and 1 = severe muscle wasting (sarcopenia). DIETARY FACTORS include gathering information on dietary intake and inspection of the food, if needed. Take the dietary history from the person that actually feeds the pet(s) asking for type of food, amount fed, frequency of feeding, table food or treats, access to other food (garbage, outside, etc), supplements, and medications (including over-the-counter). If necessary, inspect a sample of the food or send a sample for analysis. Pet foods can be purchased in a variety of forms – dry, canned, semi-moist, semi-dry, liquid, and frozen. Reading the food label is also beneficial. The food label can be roughly divided into a principal display panel and an information panel. The PRINCIPAL DISPLAY PANEL contains information directed towards the consumer including the product name, species for which the food is intended, net weight of product, and descriptive words and/or pictures (e.g. “new and improved”, picture of a famous cat, etc). The INFORMATION PANEL contains the important information including ingredient list, guaranteed analysis, feeding guidelines, contact information, and the nutritional adequacy statement. Although often maligned and not as complete as labels for human foods, there is useful information. Ingredients are listed in descending order according to pre-processing weight and names are set by AAFCO (e.g. by-product, etc); this means that ingredients containing moisture that weigh more will be listed first. Unfortunately, this does not give information as to the quality or exact amount of each ingredient; also, different forms of the same type of ingredient are listed separately. Chemical sounding ingredients are typically vitamins, minerals, and preservatives. Feeding guidelines are provided that are suitable for most, but not all, dogs or cats that consume the diet. The manufacturer’s or distributer’s name and address is required; they should be able and willing to provide answers. When contacting them, several questions should be asked: 1. Do you have a Veterinary Nutritionist or some equivalent on staff in your company? Are they available for

consultation or questions? 2. Who formulates your diets and what are their credentials? 3. Which of your diet(s) is AAFCO Feed Trial tested? Which of your diets have been analyzed? 4. What specific quality control measures do you use to assure the consistency and quality of your product line? 5. Where are your diets produced and manufactured? Can this plant be visited? 6. Can you provide a complete product nutrient analysis of your bestselling canine and feline pet food including

digestibility values? 7. Can you give me the caloric value per can or cup of your diets? The guaranteed analysis provides information regarding the 4 major components of a pet food as percentages of the diet as fed including minimum amount of crude protein, minimum amount of crude fat, maximum amount of crude fiber, and maximum amount of moisture. “Crude” refers to the analytical procedure and does not refer to the quality of the ingredient. The nutritional adequacy statement must be included and is designed to ensure that the product, when fed as the sole source of nutrition, is complete and balanced for one or more life stages, including how this adequacy was verified. The four recognized life stages by AAFCO are pregnancy, lactation, growth, and adult maintenance, and nutritional adequacy can be determined by feeding trials or by calculation. The calculation method involves determining the amount of nutrients in the diet and comparing to AAFCO nutrient profiles for that/those life

 

stage(s). Feeding trials are performed by feeding the diet to the animals in that/those life stage(s) following AAFCO protocol. Feeding trials, while not perfect, provide indirectly information on bioavailability of nutrients and is preferred method for validation of nutritional adequacy. Therapeutic diets, supplements, and treats often do not carry a nutritional adequacy statement. Therapeutic diets are formulated for specific non-healthy conditions, which are not recognized by AAFCO and for which no nutrient profiles exist (e.g. renal failure, liver failure, etc); they usually carry a statement such as “intended for intermittent use” or “use only under the supervision or direction of a veterinarian”. Snacks and treats are not formulated or intended to be the sole source of nutrition; therefore, they are not required to carry a nutritional adequacy statement. The label often contains other information, much of which do not have official definitions. According to AAFCO, “natural” is “…only acceptable in reference to the product as a whole when all of the ingredients and components of ingredients meet the definition….the use of ‘natural’ is false and misleading if any chemically synthesized ingredients are present in the product; however, AAFCO recommends that exceptions be made in the cases when chemically synthesized vitamins, minerals, or other trace nutrients are present as ingredients in the product, provided that the product is not a dietary supplement and that a disclaimer is used to inform the consumer that the vitamins, minerals, or other trace minerals are not natural. For example, ‘Natural with added vitamins, minerals, and other trace minerals.’” AAFCO defines “natural” as “a feed or ingredient derived solely from plant, animal, or mixed sources, either in its unprocessed state or having been subject to physical processing, heat processing, rendering, purification, extraction, hydrolysis, enzymolysis, or fermentation, but not having been produced by or subject to a chemically synthetic process and not containing any additives or processing aids that are chemically synthetic except in amounts as might occur unavoidably in good manufacturing processes.” “Organic” refers to processing, “organic (process): a formula or a specific ingredient within a formula feed that has been produced and handled in compliance with the requirements of the USDA national Organic Program (7 CFR Part 205).” The USDA National Organic Program (NOP) “develops, implements, and administers national production, handling, and labeling standards for organic agricultural products. The NOP also accredits the certifying agents (foreign and domestic) who inspect organic production and handling operations to certify that they meet USDA standards.” There is no definition of “human grade” food and many ingredients used in pet foods are suitable for human consumption. “The U.S. Food and Drug Administration (FDA) Center for Veterinary Medicine has taken the position that if every ingredient in a product is edible, meaning that it was processed according to rules of sanitation required of food sold to people, then the product may be labeled “human grade”. However, an edible ingredient becomes inedible when you add it to other inedible ingredients.” - Dr. William Burkholder, veterinary medical officer for the FDA CVM (January 2009). Other designators such as “premium” and “gourmet” also have no official definitions. TYPES OF DIETS. There are basically 3 types of diets available for pets: (1) commercial, over-the-counter diets, (2) therapeutic diets, and (3) homemade diets. These arbitrary designations are becoming somewhat blurred as there are commercial raw food diets and commercially available feed mixes that provide all nutrients except for the protein source, which the pet owner adds a protein source whether cooked or raw. Over-the-counter (OTC) diets are regulated through several different agencies. The Association of American Feed Control Officials (AAFCO) is not a regulatory agency but sets nutritional standards for life stages and defines ingredients. The FDA specifies and regulates health claims in addition to ensuring safety. The USDA regulates ingredients and inspects facilities. The State Department of Agriculture enforces animal food regulations. AAFCO sets nutritional standards so that if the food is fed as a sole source of nutrition it meets or exceeds known nutritional requirements. OTC foods are convenient and can be cost effective and they are easy to feed especially dry foods. There are potential disadvantages, though, including the minimal regulatory requirements, lack of additional AAFCO lifestages (e.g. is a 15 year old Chihuahua the same as a 3 year old Great Dane?), pet food labels provide a minimal amount of information and give no indication of food quality, and there is a wide range of diets available that vary in composition and ingredients. Therapeutic diets have more defined formulations and are primarily produced by larger companies who maintain better control over formulation, production, and distribution. Therapeutic diets are formulated primarily for non-healthy states (e.g. chronic kidney failure and obesity); however, some can be fed to healthy pets. Larger companies usually maintain control of the process and have better quality control and formulations are more defined. Therapeutic diets are available for food elimination, but OTC diets may claim to contain “novel” ingredients. There is one study of 4 OTC venison dry dog food diets that showed that none of the diets would be suitable for an elimination food trial because they contained common pet food proteins some of which were identified on the label while others were not but were detected in the diet. If these diets represent a majority of OTC products then OTC diets should not be used for a diagnostic elimination trial. In another study of “soy free” diets, 4 of 4 OTC diets contained soy while 1 of 7 therapeutic diets contained soy. There are some disadvantages of therapeutic diets including public perception of large pet food companies, some of the therapeutic diets have been recalled (especially the melamine/cyanuric acid recall in 2007 due to specialized formulated diets containing wheat gluten), often pets are transitioned onto therapeutic diets when they are sick and so do not eat, and many therapeutic diets are formulated for specific disease states and

 

so may not be suitable for all pets in the household (e.g a weight reduction diet for an obese pet would not be advisable for a lean healthy pet and an alkalinizing renal diet would not be suitable for a pet during growth). Some joint diets, dermatology diets, and GI diets are suitable for healthy pets including large breed growth (e.g. some joint diets). Some owners prefer to prepare homemade foods – feel less guilty and have impression of preparing a “real meal” that is “more natural” and “more traditional”. Many dogs and cats in the US consume table foods at some time in their lives. Majority of dogs and cats in US receive >90% of calories from commercial foods. When a client wants to prepare pet foods at home, it is important to understand the client’s reasons and motivation. In many cases it is possible to address their concerns and to recommend an appropriate commercial food. If they still wish to cook, then proper guidance can be provided. Some owners wish to cook homemade diets in order to provide a natural or organic food. Pet owners may also want to prepare vegetarian food for their dog or cat because they are vegetarian or vegan. Because cats are true carnivores, vegetarian cooking should be discouraged. Other owners wish to prepare homemade diets in order to avoid additives, preservatives, and contaminants. Pet food labels may be difficult to read and understand and they do not contain as much information as human food labels; therefore, some choose to home cook because they are more comfortable with being in control. Some pets will only eat table foods because it has become a habit. Lastly, homemade diets may be used for dietary elimination trials and for medical situations where a commercial diet is not available (e.g. a dog with chronic kidney disease and pancreatitis). Homemade diets are often very palatable and so may be useful with sick patients. It is possible to achieve the same nutrient balance with a homemade food as with a commercially prepared food. However, this largely depends on the accuracy and competence of the person formulating the food, and on the compliance and discipline of the owner. Unfortunately, some homemade recipes are flawed even when followed exactly and consistently. In one survey, 90% of homemade elimination diets prescribed by 116 veterinarians in North America were not nutritionally adequate for adult dog or cat maintenance. Few of the recipes available in books, magazines, and on-line have been tested to document the nutritional adequacy of the diet. Preparing homemade diets take time and some owners cannot afford the time. There are common nutrient problems in many homemade foods. Many formulations contain excessive protein, but are deficient in calories, calcium, vitamins, and micro-minerals. Commonly used meat and carbohydrate sources contain more phosphorous than calcium resulting in inverse calcium: phosphorous ratio. Foods designed by clients are commonly deficient in fat and energy density or contain an unpalatable fat source (vegetable oil). Homemade foods are rarely balanced for micro-minerals and vitamins because veterinary vitamin-mineral supplements are not complete nor are the nutrients well balanced within the product. People are taught that eating a variety of foods is nutritionally sound. Clients often extend this principle to their pet’s nutrition. Pet owners perceive that feeding a variety of foods is their best defense against malnutrition. Likewise, many owners feed a homemade diet because they can use a variety of ingredients. Some owners choose meat and carbohydrate sources for their pet’s food based on their own preferences, product availability, or affordability. Other pets are fed “leftovers” such as fat trimmings, bones, vegetable skins, crusts, and condiments. Some owners feed their pets according to guidelines for humans not realizing that dogs and cats have different requirements. A common problem with homemade diets is that the vitamin-mineral supplement is left out because of inconvenience, expense, or failure to understand its importance – after all, many humans do not take vitamins. Lastly, some homemade diets use raw ingredients. Veterinarians encounter a wide variety of pet food recipes from breeders and the popular press. Some owners want an opinion as to whether the recipe is good and others want to alter the recipe. Homemade diets can be checked for nutritional adequacy using the “quick check” guidelines: 1. Do five food groups appear in the recipe?

a. Carbohydrate/fiber source from a cooked cereal grain b. A protein source, preferably of animal origin, or if more than one protein source is used, one source should

be of animal origin c. Fat source d. Source of minerals, particularly calcium e. Multivitamin and trace mineral source

2. Is the carbohydrate source a cooked cereal and present in a higher or equal quantity than the meat source? a. Carbohydrate to protein ratio should be at least 1:1 to 2:1 for cat foods and 2:1 to 3:1 for dog foods b. Sources are cereal such as cooked corn, rice, wheat, potato, or barley c. These sources have similar caloric contributions, but some carbohydrates contribute a substantial amount of

protein, fiber, and fat 3. What is the type and quantity of the primary protein source?

a. Overall protein quality of the diet can be improved by substituting an animal-derived protein source for a vegetable protein

b. Skeletal muscle protein from different species have similar amino acid profiles

 

c. Final food should contain 25-30% cooked meat for dogs (1 part meat to 2-3 parts carbohydrate) and 35-50% cooked meat for cats (1 part meat to 1-2 parts carbohydrate)

d. Providing some liver in the meat portion is recommended once a week or no more than ½ of the meat portion on a regular basis – corrects most potential amino acid deficiencies and contributes fatty acids, cholesterol, energy, vitamins, and microminerals

e. If owner requests an ovo-lacto-vegetarian food, eggs are best f. If vegan food is requested, soybeans are the next best, but incomplete, amino acid profile

4. Is the primary protein source lean or fatty? a. Lean protein sources require addition of an animal, vegetable, or fish fat source at 2% of the formula

weight for dogs and 5% of the formula weight for cats b. If a homemade food lacks sufficient caloric density, addition of cooked beef or chicken fat, poultry skins,

vegetable or fish oils can markedly increase caloric density without adding other nutrients 5. Is a source of calcium and other minerals provided?

a. An absolute calcium deficiency is common b. Cottage cheese, cheese or milk added in small quantities does not provide adequate calcium c. Most foods require a specific calcium supplement

i. When the protein fraction equals or is greater than the carbohydrate fraction, usually only calcium carbonate is added (0.5 g/4.5 kg cat/d and at least 2.0 g/15 kg/dog/d).

ii. Calcium and phosphorous supplementation may be necessary when the protein fraction is less than the carbohydrate fraction. Steamed bone meal, dicalcium phosphate, and certain proprietary mineral supplements contain @ 27% calcium and 16% phosphorous (about 2:1) and micro-minerals

6. Is a source of vitamins and other nutrients provided? a. A human adult over-the-counter vitamin-mineral tablet that contains no more than 20% of the

recommended daily allowances for people works well for dogs and cats at ½-1 tablet per day (1 gm/tablet). b. One tablet per day of a human adult product will not over-supplement pets with calcium, phosphorous,

magnesium, vitamins A, D, and E, iron, copper, zinc, iodine, and selenium according to AAFCO maximum allowances for canine and feline foods.

c. Most veterinary supplements provide between 0-300% of vitamin-mineral requirements of dogs and cats FEEDING FACTORS to be assessed include how the nutrition is provided and must take into account owner and animal factors. Simply filling a bowl within reach of the animal is not enough; the appropriate diet must be provided in the appropriate amount. Obesity is the most common nutritional disorder of dogs and cats and, in part, is due to overfeeding. “One cup” of food refers to the amount of food contained in one 8-ounce measuring cup. Ask specifically for the size of the cup used and the size of the bowl that is filled up. Many owners feed free choice – “drive-by feeders” - without regard to amount. The amount of energy required by the pet can be determined using one of two formulae: Linear: [(30 x BWkg) + 70] or Exponential: 70 x (BWkg

0.75). This provides the RESTING ENERGY REQUIREMENT and this result is multiplied by a life stage or activity factor depending on the individual. The second step is FORMULATION AND INITIATION OF A FEEDING PLAN. The nutritional plan is formulated based on the assessment phase and initiated. It is important that this plan is re-evaluated periodically (iterative process) and adjustments made based on what is found during assessment. Recommendations for the feeding plan are made based on life stage and physiological or pathological condition of the pet as well as the life style of the owner. Working within the constraints placed by the owner helps to ensure compliance; otherwise, recommendations will not be followed. There is no “one best” diet available for healthy pets or for pets that suffer from a disease. Oftentimes, many options exist including homemade diets. Today’s health care providers, veterinarians and technicians, need to be able to assess a pet, evaluate diets, and make recommendations on diets and feeding. Knowledge of assessment and formulation of a nutritional plan should be part of a patient’s health care. Use body condition scoring in addition to weight to assess nutritional status.

FOOD FOR ‘PHRONS: NUTRITION AND CHRONIC KIDNEY DISEASE Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition The University of Georgia

Chronic kidney disease (CKD) implies irreversible failure that remains stable for a period of time but is ultimately progressive over some period of time. CKD may occur at any age, but incidence increases with increasing age. The kidneys are involved with homeostasis; therefore, CKD affects many organ systems. Clinical signs involve primarily change in water balance (polyuria and polydipsia), gastrointestinal signs (anorexia, hyporexia, halitosis, vomiting), and evidence of chronicity (weight loss, loss of body condition and muscle mass, unkempt appearance). Physical examination may reveal oral ulceration and halitosis, decreased muscle mass and body weight, dehydration, and small, irregular kidneys. Laboratory evaluation reveals azotemia, inappropriately dilute urine, hyperphosphatemia, metabolic acidosis, and possibly hypokalemia, non-regenerative anemia, and calcium imbalance. Bacterial urinary tract infection may be present but is often not associated with active urine sediment. Systemic arterial hypertension occurs in 65-80% of patients. Proteinuria may also be present. INTERNATIONAL RENAL INSUFFICIENCY SOCIETY (IRIS) STAGING The International Renal Insufficiency Society (http://www.IRIS-kidney.com) has developed staging system for animals with CKD and treatment based on staging. The staging system is designed for use with dogs and cats with CKD. A diagnosis of CKD is made first and staging is accomplished by evaluating 2 serum creatinine values when patient is well hydrated, 2 to 3 urine protein-creatinine ratios (UPC), and 2 to 3 indirect arterial blood pressure determinations. CKD is staged by magnitude of renal dysfunction and further modified (sub-staged) by presence or absence of proteinuria and/or hypertension. Proteinuria ONLY refers to renal proteinuria and not pre-renal (e.g. hyperglobulinemia) or post-renal (e.g. urinary tract infection, hematuria, etc.), and is based on UPC. Blood pressure determination should be performed several times in order to account for a “white coat” effect using a standard protocol.

Stage Plasma creatinine µmol/l mg/dl

Comments

Dogs Cats

1 <125 <1.4

<140 <1.6

Non-azotemic Some other renal abnormality present e.g. inadequate concentrating ability without identifiable non-renal cause; abnormal renal palpation and/or abnormal renal imaging findings; proteinuria of renal origin; abnormal renal biopsy results

2 125 - 179 1.4 - 2.0

140 - 249 1.6 - 2.8

Mild renal azotemia [lower end of the range lies within the reference range for many labs but the insensitivity of creatinine as a screening test means that animals with creatinine values close to the upper limit of normality often have excretory failure] Clinical signs usually mild or absent

3 180 - 439 2.1 - 5.0

250 - 439 2.9 – 5.0

Moderate renal azotaemia Many systemic clinical signs may be present

4 >440 >5.0

>440 >5.0

Severe renal azotaemia Many extra-renal clinical signs present

UPC value Substage

Dogs Cats <0.2 <0.2 Non-proteinuric (NP)

0.2 to 0.5 0.2 to 0.4 Borderline proteinuric (BP) >0.5 >0.4 Proteinuric (P)

Systolic BP mm Hg Diastolic BP mm Hg Adaptation when breed-specific

reference range is available * Substage

<150 <95 <10 mm Hg above reference range AP0: Minimal Risk (N) 150 – 159 95 - 99 10 – 20 mm Hg above reference range AP1: Low Risk (L) 160 – 179 100 - 119 20 – 40 mm Hg above reference range AP2: Moderate Risk (M)

> 180 > 120 > 40 mm Hg above reference range AP3: High Risk (H)

No evidence of end organ damage/complications No complications (nc) Evidence of end organ damage/complications Complications (c) Blood pressure not measured Risk not determined (RND) In addition to standard laboratory evaluation, a new test is or will soon be available that may be beneficial in evaluating pets with CKD. This measures symmetric dimethylarginine (SDMA), which has been shown to correlate with GFR and changes with loss of 20-45% of nephrons, which is earlier than creatinine concentration changes. Therefore, it may detect decreasing renal function before the onset of azotemia. MANAGEMENT OF CKD Goal of management of CKD is to minimize excesses and deficiencies associated with CKD in order to improve quality and quantity of patient’s life NUTRITION - Maintain adequate to optimal body condition and adequate muscle condition. Anorexia and nausea occur with CKD (uremic gastroenteritis). Feed a highly palatable diet that is calorically dense. Increasing the palatability of the diet can be done by adding water or flavoring agents and warming it to near body temperature. Small frequent meals may be required. Treat uremic gastroenteritis by restricting dietary protein and administering histamine-2-receptor blockers (e.g. ranitidine and famotidine: 1-2 mg/kg PO q12h). Sucralfate (Dogs: 0.5-1 gm PO q8-12h; Cats: 0.25-0.5 gm PO q8-12h) may be used with gastric ulcer disease and is an antacid and phosphate binder. An anti-emetic, such as Maropitant (2-4 mg/kg PO q24h), may be used. Appetite may also be stimulated pharmacologically (e.g. mirtazapine: Dogs: 15-30 mg PO q24h; Cats: 1.875-3.75 mg PO q72h). If necessary, a feeding tube may be used. Feeding diets containing high omega-3 fatty acids (n3FA) are beneficial in dogs. An extract of medicinal rhubarb and a proprietary mixture of amino acids and peptides are available; however, no data exists as to benefit or not. ELECTROLYTES - Hypokalemia may occur especially in cats with CKD due to hyporexia, increased urinary and fecal losses, metabolic acidosis, and activation of the renin-angiotensin-aldosterone system (RAAS). Clinical signs of hypokalemia include polymyopathy, anorexia, and worsening azotemia. Treatment involves feeding a potassium replete diet, adding potassium to fluids (do not exceed 20 mEq/L with potassium chloride for SQ fluids), and oral supplementation using potassium citrate (preferred at initial dose of 75 mg/kg PO q12h) or potassium gluconate. Moderate dietary sodium restriction is beneficial with CKD and in one study feeding a diet containing 1.2% sodium chloride to cats with CKD was associated with more severe azotemia. METABOLIC ACIDOSIS - Metabolic acidosis occurs commonly and is usually associated with a high anion gap. Treatment involves dietary protein restriction, feeding an alkalinizing diet, and administering an alkalinizing agent (e.g. potassium citrate), if needed. PROTEINURIA - Proteinuria appears to be nephrotoxic and to promote progression of CKD. Treatment involves dietary protein restriction, administration of an angiotensin converting enzyme inhibitor (ACEI; enalapril or benazepril: 0.25-1.0 mg/kg PO q12-24h), and n3FA (300 mg of EPA + DHA per 10 pounds body weight PO q24h) supplementation. Angiotensin receptor blockers (ARBs: losartan, irbesartan, telmisartan) may be used instead of or in addition to an ACEI. There is evidence that in cats with experimentally induced CKD, ARBs may be more effective than ACEI for reducing blood pressure and proteinuria. Cost of ARBs vary depending on generation of ARB. For example, a month’s worth of ARB for a 25 pound dog are: (a) Losartan – 1 mg/kg PO q24h – 25 mg =

$8, (b) Azilsartan – 0.1-1.0 mg/kg PO q12h – 40 mg = $140, (c) Irbesartan – 5 mg/kg PO q12-24h – 75 mg = $115, (d) Telmisartan – 5-10 mg/kg PO q24h = $40, (e) Valsartan – 80-160 mg PO q24h = $60-100. HYDRATION - CKD is associated with water imbalance and dehydration may occur especially in cats. Treatment involves providing clean and fresh water, adding water to diet, or feeding a canned food. Supplemental SQ fluids may be administered. Water may be administered through a feeding tube if one is used. RETENTION OF WASTES - Azotemia occurs with CKD and restricting dietary protein decreases the blood urea nitrogen (BUN) concentration. Prebiotics (e.g. dietary fiber) and probiotics may be administered in an attempt to eliminate nitrogen through the GI tract (so-called nitrogen trapping). This does occur, but the amount of nitrogen excreted by this manner is minimal. AVOID OTHER RENAL INSULTS – Administration of potentially nephrotoxic drugs (e.g. NSAIDs, aminoglycosides) should be avoided or done cautiously. Indiscriminant administration of antimicrobial agents may result in a multi-drug resistant bacterial UTI. There is evidence in cats; however, that NSAIDs, specifically Meloxicam, is NOT associated with progression or worsening of azotemia in 3 studies and may actually be beneficial in slowing progression of feline CKD when administered at 0.015-0.033 mg/kg/d PO. NEUROENDOCRINE FUNCTION – Three common neuroendocrine abnormalities include renal secondary hyperparathyroidism, non-regenerative anemia, and systemic arterial hypertension. Renal secondary hyperparathyroidism – Hyperphosphatemia and decreased 1,25-vitamin D production result in renal secondary hyperparathyroidism. Goal of treatment is to achieve a normal serum phosphorous concentration. This may achieved by feeding a low phosphorous diet administering a phosphate binder if needed (e.g. aluminum hydroxide: 15-45 mg/kg PO q12h with food, calcium acetate: 60-90 mg/kg PO q12h with food or carbonate, chitosan: 1 g/kg PO q12h; 3-5kg: 1 scoop; 10kg: 2 scoops; 15kg: 3 scoops; 20kg: 4 scoops PO q12h, sevelamer hydrochloride: 400-1600 mg PO q12h with food, or lanthanum carbonate: Dogs: 5-20 mg/kg PO q12h; Cats: 1 ml (1 pump) PO q12h (Renalzin)), or administering 1,25-vitamin D. Vitamin D replacement therapy (initial:2-2.5 ng/kg PO q24h; maximum: 5 ng/kg PO q24h) has been shown to improve survival in dogs with CKD but not cats. Serum phosphorous must be normalized when administering vitamin D. Non-regenerative anemia – A normocytic, nonregenerative anemia may occur with CKD due to decreased renal production of erythropoietin, decreased nutritional status, and GI blood loss associated with uremic gastroenteritis. Treatment includes maintaining good nutritional status, minimizing GI blood loss, and stimulating red blood cell production using erythropoietin (100 ug/kg SQ 3X/week initially) or darbepoetin (1.5 ug/kg SQ 1X/week initially). Darbepoetin appears to be less likely to induce antibody production and so is more efficacious and safe. Iron should be supplemented with hormonal replacement therapy. Systemic arterial hypertension – Systemic arterial hypertension occurs commonly with CKD and risk of hypertensive related complications is high when systolic blood pressure (sBP) is greater than 180mmHg. The goal is a sBP of less than 150 mmHg. Hypertensive related complications include retinal vascular damage and hemorrhage, left ventricular hypertrophy, ischemic encephalopathy, proteinuria, and progression of CKD. Treatment involves administration of anti-hypertensive drugs. Calcium channel blockers (CCB; e.g. amlodipine: Dogs: 0.1-0.4 mg/kg PO q24h; Cats: 0.625-1.25 mg PO q24h) decrease sBP by an average of 50mmHg and are the most effective. Complications are unusual. ACEI decrease sBP by an average of 10mmHg but also decrease degree of proteinuria. Benazapril has been reported to slow progression of CKD; however, 1 study failed to show benefit in cats with CKD unless they were also proteinuric. Angiotensin receptor blockers (ARB; e.g. Losartan: 1 mg/kg PO q12h initially) have similar effect to ACEI. When an ACEI and an ARB are used together there is a 60-fold synergistic effect in human beings. RENAL TRANSPLANTATION – Renal transplantation has been reported; however, consistent long term success has not been reported. In the most recent clinical study, an approximate 2 year survival was achieved in 50% of cats.

STEM CELL THERAPY – There is scarce data that intrarenal administration of mesenchymal stem cells may be beneficial with CKD. The mechanism is not likely regeneration of new tissue from stem cells but rather growth factor production induced by the stem cells and slowing or halting of fibrosis. Benefits are yet to be determined. SERIAL MONITORING – CKD is progressive; therefore, periodic monitoring of body weight and condition, blood pressure, blood work, and UPC is important. Additionally, UTI may occur and may result in progression if it involves the kidneys. Despite treatment, CKD is progressive. Early detection and intervention could have profound implications. WHEN SHOULD DIET BE CHANGED WITH CKD? Dietary modification can offset many deficiencies and excesses that occur with CKD. Dietary modification includes more than just dietary protein restriction as renal failure diets are more calorically dense, may contain n3 fatty acids, may contain soluble fiber, low phosphorous, low sodium, potassium replete, alkalinizing, and water soluble vitamin replete. For these reasons, I believe diet should be changed when a patient is diagnosed with CKD. Changing the diet early in the course of CKD results in better acceptance of the diet and may provide a better quality and longer quantity of life.

 

MEALS FOR WHEELS: NUTRITION AND OSTEOARTHRITIS Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition The University of Georgia

Osteoarthritis (OA) is a common syndrome having multiple etiologies and characterized by pathologic change of synovial or diarthrodial joint accompanied by clinical signs of pain and disability. Prevalence of musculoskeletal disorders for all dogs has been reported to be approximately one in four. In dogs < 1 year of age, prevalence is 22%, with 20% of these possibly having a nutrition-related cause. There have been few controlled studies evaluating nutrition and OA in dogs although nutrition plays a role in prevention of and management of dogs and cats with OA. ROLE OF NUTRITION IN THE PREVENTION OF MUSCULOSKELETAL DISEASE Developmental Orthopedic Disease (DOD). DOD refers to a group of skeletal abnormalities that affect primarily rapidly growing, large- and giant-breed dogs. Nutrient excess (calcium and energy) and rapid growth (overfeeding and excess energy) are known risk factors for DOD in dogs that have genetic risk. Restricting food intake during growth slows growth rate without significantly reducing adult body size and is associated with decreased incidence of DOD. Dietary calcium greater than 3% on a dry matter basis is associated with increased risk despite an appropriate calcium-to-phosphorous ratio. Even if the diet contains less calcium than this, excess calcium intake can occur if owners provide supplemental calcium. Limited meal-feeding and limiting rate of growth also decrease DOD. For large- and giant-breed dogs during growth, recommended dietary composition includes: Energy: 3.2-4.1 kcal/kg of diet (lower end of range if at risk for DOD or if clients use free-choice feeding); Crude fat: 8.5-11% on a dry matter basis; Docosahexaenoic acid: 0.02% on a dry matter basis; Protein: 27% on a dry matter basis; Calcium: 0.8-1.2% ( 3% on a dry matter basis) with a calcium-to-phosphorous ratio of 1.1-2.0:1.0 Obesity. Obesity can be defined as accumulation of body fat exceeding ideal body weight by 15-20% or more. Obesity may contribute to development and progression of OA because of excess forces placed on joints and articular cartilage, which may lead to inactivity and further development of obesity. Additionally, adipose tissue is recognized as being metabolically active and pro-inflammatory; therefore, obesity may contribute to inflammation. Several studies have demonstrated a relationship between obesity and OA; however, a cause and effect has not been determined. A long term study was performed of 48 Labrador retrievers from 7 litters divided into 2 dietary groups. One group was fed an adult maintenance dog food and the second group was fed the same diet at 75% of the amount. Restricted fed dogs lived on average 1.8 years longer, weighed less, had better body condition scores and had longer delay to treatment of chronic disease including OA. Maintaining optimal or slightly lean body condition may be associated with lower risk of developing OA, development of less severe OA if it occurs, and delay of onset of clinical signs of OA in dogs. ROLE OF NUTRITION IN THE TREATMENT OF MUSCULOSKELETAL DISEASE Non-traumatized surgical patients. Patients undergoing surgery that are healthy and in optimal body and muscle condition require no further intervention nutritionally other than to continue feeding the current diet at the same amount and frequency. Patients are not fed 8-12 hours prior to anesthesia and surgery, but can resume normal feeding pattern once recovered from the procedure. It may be necessary to add flavoring agents or feed a different diet to stimulate appetite in the post-operative period. Patients should be assessed daily following surgery to insure they are eating adequately and that no adverse events occur either from the procedure or from post-operative medications such as analgesics and sedatives. As the patient becomes more active or as a rehabilitation program is initiated, energy requirements will increase. In many instances, surgery in these patients is elective; therefore, depending on the urgency of the surgical procedure, consideration should be given to weight reduction prior to surgery in patients that are obese. Reducing body weight to the optimal weight decreases anesthetic risk, improves immune function, and allows patients to more easily undergo post-surgical physical rehabilitation. Traumatized surgical patients. Patients with surgical musculoskeletal disease associated with trauma may or may not have increased nutritional requirements depending on the degree of trauma. If the trauma is less severe, then energy requirements are similar to non-traumatized surgical patients, and energy requirements approximate resting energy requirements. Severely injured patients or those with closed head injuries typically have energy requirements exceeding resting energy requirements due to the extent of the injuries or to activation of the sympathetic nervous system, in part. In these patients, energy requirements may exceed two times the estimated resting energy requirements. Likewise, protein requirements may exceed that required for maintenance in order to facilitate recovery, immune function, and wound healing. With trauma or strenuous exercise, protein requirements may exceed these by 50-100%. Some patients may require facilitated nutritional support enterally or parenterally. Nutritional support in these patients should be individualized and intensive monitoring is required in order to maximize recovery and

 

response to supportive care. Convalescent diets that are formulated to contain higher levels of protein and fat, are more calorically dense, highly palatable, and have a homogeneous texture suitable for feeding tubes are available. Nutrition and Rehabilitation. Research into nutritional needs of patients undergoing various rehabilitation programs is non-existent. Individuals developing rehabilitation programs should have knowledge of nutrition. Rehabilitation can include simple strengthening to extensive long-term physical rehabilitation; therefore, the nutritional plan for a patient must adjunctively meet the goals set during therapy and after goals are met. Nutritional plans should be included as part of the rehabilitation therapy. Water is the most essential nutrient. During rehabilitation, excitement, fear, pain, and other stress factors affect the simplest of nutritional needs, water and electrolytes. Water intake for healthy dogs approximates 50-60 ml/kg/day, but may be more with rehabilitation. Energy is a primary nutrient for maintenance, life-stage, and the therapy program. Energy requirements correlate to work intensity, duration, and frequency, with intensity being the primary determinant. Sprinters, such as greyhounds that are running with maximum intensity, have low energy requirements because of the short race duration and low frequency of training. These dogs use mainly carbohydrates to meet energy requirements. Studies of endurance sled dog with long durations of work are at the other extreme, requiring high energy intake. High fat diets are fed to meet these high-energy requirements. Exercise intensity has not been quantified in rehabilitation, unlike performance and working dogs. Therapy is likely an intermediate level of exercise, which has not been well defined. Intensity, duration, and frequency of exercise are highly variable; therefore, it is difficult to predict energy needs of these patients. Consideration of historical exercise level combined with current patient and diet assessment may provide some insight into energy needs. In a study of well-conditioned beagles running on a treadmill, time to exhaustion correlated with fat intake, diet digestibility, and energy concentration of the diet. Increasing fat intake improves performance of dogs with extreme energy requirements. In rehabilitation therapy, the level of exercise is unlikely to equate to the extreme energy requirements of sled dogs. Fat intake should still be considered when a patient is in therapy. If we use the example of a sprinting Greyhound, dogs in therapy may have similar fat requirements with fat providing 20 to 30% of the total energy requirement. This equates to a diet with a fat content of 8-10% on a dry matter basis. Protein is required for structure and function, and to a lesser extent, energy. Current recommendations with exercise are to increase protein 5 to 15% regardless of the level of exercise, with dietary protein providing approximately 25% of the energy needs. Dietary protein is the most important nutrient with regard to muscle protein and exercise increases protein requirements. Many of the goals of canine physical rehabilitation require increased muscle tissue. Exercise increases protein synthesis and breakdown with the net result of decreased muscle protein. Ingestion of amino acids stimulates muscle protein synthesis, exceeding the rate of breakdown, and muscle mass increases. Exercise combined with amino acid intake produces a greater response regarding muscle synthesis than response to individual treatments. This suggests exercise can prime the muscle response to the anabolic effects of amino acids or exercise activates muscle synthesis, but adequate amino acid precursors are needed to increase muscle mass. Studies of protein nutrition often evaluate total dietary protein content instead of amino acid composition. Investigation to optimize amino acid profiles for specific benefits has identified ‘slow’ and ‘fast’ proteins. This classification is determined by rate a protein exits the stomach, is hydrolyzed into peptides and amino acids, and absorbed. Plasma amino acid profiles of fast and slow proteins have shown that ‘blends’ produce maximal amino acid concentration for optimal protein synthesis. Identifying and using protein blends for maximal muscle synthesis and strength during physical rehabilitation may be a reasonable goal with these current studies. Obesity. Three uncontrolled clinical studies of obese dogs with OA demonstrated improvement in mobility. In one study of nine dogs, with body condition score of 5 out of 5 and coxofemoral OA, obesity management resulted in loss of 11-18% of body weight, a decrease in body condition to optimal, and improvement in severity of subjective hind limb lameness scores. In the second study of 16 dogs with coxofemoral OA, weight loss of 13-29% of body weight and decrease of body condition to optimal resulted in improvement of ground reactive forces and improvement in subjective mobility and clinical signs of OA. In the third study, 14 client-owned dogs with clinical and radiographic signs of OA participated in an open prospective clinical trial. Results indicate that body weight reduction causes a significant decrease in lameness with a weight loss of 6.10% or more. Kinetic gait analysis supported the results with a body weight reduction of 8.85% or more. These results confirm that weight loss should be presented as an important treatment modality to owners of obese dogs with OA and that noticeable improvement may be seen after modest weight loss of 6.10 - 8.85% body weight. Weight loss is beneficial when used in combination with rehabilitation and physical rehabilitation in dogs. In a non-blinded prospective randomized clinical trial, 29 adult dogs that were overweight or obese (body condition score of 4/5 or 5/5) having clinical and radiographic signs of OA were evaluated. All dogs underwent weight loss. One group received caloric restriction and a home-based physical rehabilitation program and the other group received an identical dietetic protocol and an intensive physical rehabilitation program including transcutaneous electrical nerve stimulation. Significant weight loss and improved mobility were achieved

 

in both groups; however, greater weight reduction and better mobility was obtained in the group receiving intensive physical rehabilitation. DIETS FOR OSTEOARTHRITIS IN DOGS AND CATS There are several commercially available diets formulated for management of dogs with OA. These diets contain higher levels of omega-3 fatty acids and may contain chondromodulators and antioxidants. A controlled experimental study in dogs where the cruciate ligament was transected demonstrated a beneficial effect of pre-feeding a diet containing high omega-3 fatty acids with less severe radiographic and functional joint disease. Available “joint” diets also contain antioxidants that may be beneficial in decreasing free radical induced injury with OA. Chondromodulating agents are also often included in “joint” diets. The amount of these compounds in commercial diets is less than recommended for treatment of OA; therefore, they may be beneficial in prevention or management of early disease but probably less effective in more advanced disease. OA occurs commonly in cats; however, there is a paucity of information regarding nutrition or nutritional compounds in management. In a prospective, blinded, parallel group study evaluating a diet high in n-3 fatty acids and supplemented with green-lipped mussel extract and glucosamine/chondroitin fed to cats with OA over 9 weeks, there was an improvement in mobility of cats fed the supplemented diet and a decline in cats fed the control diet. Although other nutritional compounds are used in cats with OA, none have been evaluated in a controlled manner. NUTRACEUTICALS / SUPPLEMENTS Chondromodulating agents. Nutraceuticals for OA are classified as antioxidants and chondromodulating agents that are purported to slow or alter the progression of osteoarthritis. Chondromodulating agents can be further divided into agents approved by the US Food and Drug Administration, such as polysulfated glycosaminoglycan, which can have label claims of clinical effect, or nutritional supplements, which are not regulated, and legally cannot claim any medical benefit. These oral nutraceuticals include glucosamine and chondroitin sulfate. Glucosamine is an amino sugar and precursor for biochemical synthesis of glycosaminoglycans, proteoglycans, and glycolipids. Glycosaminoglycans are a major component of joint cartilage; therefore, it is believed that supplemental glucosamine may rebuild cartilage. In vitro studies support this claim although these studies use concentrations not achieved in serum or plasma after oral administration. Results of studies of chondromodulants both in veterinary and human literature are mixed due to product used (glucosamine alone, glucosamine/chondroitin sulfate), dose administration, subjective and objective measurements of outcome, and length of trials. In a randomized, double blind, placebo controlled clinical trial comparing glucosamine/chondroitin sulfate to carprofen in 35 dogs with OA, carprofen treated dogs had improvement in 5 subjective measures while dogs treated with the glucosamine/chondroitin sulfate improved in 3 of 5 measures, but only after final assessment at 70 days. A 60-day, prospective, randomized, double blind, placebo controlled trial of 71 dogs comparing carprofen, meloxicam, glucosamine/chondroitin, and placebo demonstrated significant improvement in objective measurements with carprofen and meloxicam but not with the nutraceutical or placebo. Finally a large multicenter clinical trial compared an NSAID with glucosamine alone, chondroitin sulfate alone, and a glucosamine/chondroitin sulfate combination in patients stifle OA. Patients with moderate to severe stifle OA showed significant improvement in clinical function using the combination of glucosamine/chondroitin sulfate. Based on these studies and others the clinical evidence of these chondromodulants seems weak and will most likely be dependent on content, amount of disease, dosing, and length of treatment. Another natural source of glycosaminoglycans, the New Zealand green lipped mussel (Perna canaliculus), is marketed for its chondromodulating effects. Numerous publications reporting the results of uncontrolled studies have been published with promising results. One randomized controlled clinical study added green lipped mussel powder to diet (0.3%) and the dogs receiving the supplemented diet vs. control had significant improvement in subjective arthritic scores. Another randomized double blinded clinical study with 45 dogs showed improvement in mobility compared to placebo, but not as effective as carprofen. An uncontrolled study of 85 dogs with presumptive OA, using green-lipped mussel supplemental diet for 50 days showed a reduction in a composite arthritic score when compared with baseline scores on various diets the dogs were consuming. In reviewing the studies of green lipped mussel extract as beneficial in treating canine OA, results seem promising, but there are uncertainties with the scientific quality of the data published. Omega 3 (n-3) fatty acids. The potential of modifying the inflammatory components of osteoarthritis using nutritional components is another approach of nutraceutical therapy. Arachidonic acid, an n-6 fatty acid, is incorporated into cell membranes and when metabolized, yields the 2 and 4 series of prostaglandins, leukotrienes and thromboxanes. These proinflammatory pathways are where conventional drugs are used to control OA inflammation. Substituting n-3 fatty acids into cell membranes may decrease inflammation with biosynthesis of eicosanoids of the 3 and 5 series, which are less proinflammatory. In addition to modulating cytokines, n-3 fatty acids have been shown to reduce expression

 

of cyclooxgenase 2- lipoxygenase-5, aggrecanase, matrix metalloproteinase 3 and 13, interleukin 1α and 1β, and tumor necrosis factor α. Interestingly n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to decrease inflammatory exudates in tissues through production of oxygenated products called Resolvins (resolution phase interaction products) and docosatrienes. There is growing data showing the positive effects of n-3 fatty acids supplementation on cartilage metabolism with degradative enzymes and reducing inflammatory responses elicited by chondrocytes and joint matrix during the progression of OA. An unpublished study was performed in dogs evaluating omega 3 fatty acids and experimentally induced stifle OA. Dogs were randomly assigned to isocalcoric diet groups containing 21.4% fat (dry matter basis, DMB) differing only in fatty acid composition: a diet with an n-6 to n-3 ratio of 28:1, 8.7:1(control diet) and a diet with an n-6 to n-3 ratio of 0.7:1. Dogs began the new diet 3 months prior to surgical transection of the left cruciate ligament, were continued on the diet for 6 more months prior to surgical repair, and maintained for 12 months following repair. When compared to the high n-6 diet and control diet, the high n-3 diet was associated with lower serum cholesterol, triglycerides, and phospholipids, lower synovial concentration of prostaglandin E2, better ground reaction forces, and less radiographic changes of OA. A study of 127 dogs with OA fed a diet with a 31-fold increase in total n-3 fatty acid content and 34- fold decrease in n-6 to n-3 ratio had improved ability to rise from a resting position and play for 6 months when compared to dogs fed a control diet. Peak vertical force values and subjective lameness parameters improved with a randomized, double blinded controlled clinical trial of 38 dogs with OA fed a high (3.5%) n-3fatty acids for 90 days. A randomized, controlled clinical trial with 131 dogs with stable OA treated with carprofen over 12 weeks fed a diet supplemented with n-3 fatty acids provided a significantly faster carprofen dose reduction compared to a control diet. A recent study using a veterinary therapeutic diet (VTD) rich in n- 3 fatty acids (total n-3 fatty acid 1.47% DMB) compared to a control diet (CTR, total n-3 fatty acid 0.18% DMB) over 13 weeks with 30 dogs with naturally occurring OA evaluated peak of the vertical oriented ground reaction force (PVF) using a force platform and activity scores provided by owners. The VTD fed dogs showed significant improvement in PVF at both week 7 and week 13 compared to CTD fed dogs. These studies provide a rationale for n-3 fatty acid supplementation or feeding diets with high n-3 fatty acid content. Recommendations for n-3 supplementation for canine OA has been reported as 310mg/ (kg 0.75) or 1745 mg EPA + DHA per 10kg body weight for the dog. Zeel®. Zeel® is an over-the-counter highly diluted proprietary formulation of herbs, metabolites, minerals, and antioxidants preparation that has been evaluated in 2 controlled studies in dogs. In a study of 68 dogs > 1 year of age diagnosed with OA, it was compared with carprofen in a multicenter, prospective, observational open-label cohort study in 12 German veterinary clinics. In another study in dogs (n=44), greater than one year of age diagnosed with OA, it was compared with carprofen and a placebo. Clinical signs and several measures of OA improved significantly with treatment in both studies; however, in one study, it was not as effective as carprofen. The composition of the products and the dosage of Zeel® differed between the two studies, confounding interpretation of results. Boswellia serrata. Boswellia, also known as Boswellin or Indian frankincense, comes from the Indian Boswellia serrata tree. Resin from the bark of this tree is purported to have anti-inflammatory properties derived primarily from 3-O-acetyl-11-keto-β-boswellic acid (AKBA), which inhibits 5-lipoxygenase and matrix metalloproteinases, and decreases tumor necrosis factor and interleukin 1β. Boswellia resin has been shown to improve clinical signs and pain in humans in controlled studies. Boswellia resin has been evaluated in 24 dogs in an open multi-center study. Improvement in clinical signs, lameness, and pain was found in 17 of 24 dogs. Avocado/Soybean Unsaponifiables. Avocado/soybean unsaponifiables (ASU) are composed of the unsaponifiable fractions of avocado and soybean oils in a 1/3 to 2/3 proportion. ASU has anti-OA properties by inhibiting interlukin-1 and stimulating collagen synthesis in cartilage cultures. Human clinical trials have shown some beneficial effects of ASU on clinical symptoms of OA, but conflicting data in other studies found no long term benefits. In one study of dogs, OA was induced by anterior cruciate ligament transection. Dogs then received placebo or ASU (10 mg/kg/24h). The size of macroscopic lesions of the tibial plateau, severity of cartilage lesions, synovial cellular infiltration, and inducible nitric oxide synthase were decreased significantly and there was reduced loss of subchondral bone volume and calcified cartilage thickness in the group receiving ASU.

 

REACTIONS BY CONSUMERS: ADVERSE FOOD REACTIONS Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition The University of Georgia

Inflammatory bowel disease (IBD) is a collective term for a group of chronic enteropathies that are

common in cats and dogs. IBD is a complex interaction among the intestinal microbiome, dietary constituents, the immune system, host genetics, and environmental triggers of intestinal inflammation. An adverse reaction to food is defined as a clinically abnormal response attributed to an ingested food substance, and may be further categorized as immunologic or non-immunologic in nature. Food allergy is an immunologically mediated, reaction to ingested food. This is different than food intolerance, which is a non-immunologically mediated adverse reaction including toxic reactions, pharmacological reactions, metabolic reactions, and idiosyncratic reactions. IBD DIAGNOSIS

The accurate diagnosis of IBD involves a systematic integration of signalment, medical and dietary history, physical findings, clinicopathologic testing, diagnostic imaging, and intestinal histopathology. This evaluation permits exclusion of non-IBD conditions causing similar clinical signs, including gastrointestinal infections (endoparasites and enteric pathogens), exocrine pancreatic insufficiency, hypoadrenocorticism, hepatopathies, gastrointestinal obstructions, and cancers. During the initial diagnostic evaluation, often prior to obtaining a definitive diagnosis, therapeutic and prognostic information can be obtained. The clinical severity of the disease process can be estimated by calculating the canine IBD activity index (CIBDAI) and/or measuring serum C-reactive protein (CRP) levels. These parameters are also helpful as a baseline when evaluating response to treatment. Detecting hypoalbuminemia, low serum cobalamin concentration (< 200 ng/L), and/or elevated pancreatic lipase immunoreactivity (PLI) concentrations has been associated with a poor prognosis. In patients with hypoalbuminemia secondary to a protein-losing enteropathy (PLE), screening hemostatic function (in particular thromboelastography) is recommended to detect and, if abnormal, guide treatment of hypo- or hypercoagulability. Fecal alpha1-proteinase inhibitor (α1-PI) is a valuable test in dogs with suspected PLE, in particular prior to overt clinical signs (i.e., vomiting, diarrhea, weight loss) or in dogs with intestinal disease and concurrent renal or hepatic disease.

Abdominal ultrasound is an important tool during the diagnostic evaluation of cats and dogs suspected to have IBD. It provides a rapid, noninvasive method to screen for gastrointestinal obstructions and masses and concurrent conditions, including pancreatitis, gall bladder or hepatic disorders. During evaluation of the gastrointestinal tract, the wall thickness, appearance of wall layers including layer distinction, peristaltic activity, luminal contents and diameter, adjacent lymph nodes, peri-intestinal echogenicity, and presence of free fluid are evaluated. The degree and distribution (focal, multifocal, or diffuse) of disease are described. Five distinct layers are visible in the wall of the stomach and intestine (luminal to peripheral - bright hyperechoic mucosal-luminal interface, hypoechoic mucosal layer, thin hyperechoic submucosa, thin hypoechoic muscularis layer, outermost hyperechoic serosa). Normal peristaltic activity for the stomach and small intestines is 3–5 contractions per minute. Ultrasound abnormalities reported with IBD include diffuse or multifocal, mild to moderate, transmural thickening of the intestinal wall with preserved wall layering and no to mild mesenteric lymphadenopathy; however, intestinal wall thickness, wall layer definition, or mesenteric lymph node size have not been reported to be specific or sensitive for diagnosis of IBD. Increased prominence of the muscularis layer (equal or greater in thickness to the mucosal layer) has been reported with IBD, in particular in cats. Mucosal echogenicity has been suggested to be a more sensitive indicator of IBD. The presence of hyperechoic striations, but not hyperechoic speckles, in the jejunum had a sensitivity of 75% and a specificity of 96% for dogs with protein-losing enteropathy. A complete loss of wall layer definition and wall thickness > 1.5 cm are considered more specific indicators of gastrointestinal neoplasia. Definitive differentiation of IBD, cancer, or other chronic enteropathies is not possible with ultrasound.

Intestinal biopsies, acquired endoscopically or surgically, are indicated in patients with suspected IBD that have failed empirical therapy to confirm the diagnosis, classify the type of IBD, and to eliminate non-IBD disorders, in particular neoplastic or infectious enteropathies or lymphangiectasia. Some authors prefer diagnostic endoscopy to procure samples in patients without an indication for surgery (i.e., gastrointestinal obstructions, intestinal masses, perforation, and/or indication for hepatic/pancreatic biopsies). In some but not all studies, the endoscopic appearance of the small intestines provides better prognostic information than the histopathology. Suggested indications for surgical biopsies is apparent involvement of the submucosa or muscularis, often inferred from ultrasound studies, concern for intestinal leiomyositis, and/or prior endoscopic biopsy findings that do not correlate with the clinical picture. If ileal involvement is suspected based on low cobalamin levels and/or ultrasonographic findings, transcolonic ileoscopy, in addition to standard upper GI tract endoscopic examination, should be performed.

 

Independent of localization of the small intestinal disease, ileal biopsies should be considered to screen for small-cell lymphoma (LSA). In one retrospective study, 44% of cats were diagnosed with LSA based solely on ileal histopathology without involvement of the duodenum. The quality and number of endoscopic biopsies and tissue processing at the histopathology laboratory significantly impacts identifying certain intestinal lesions and potentially a diagnosis of IBD. Although requiring future research, reasonable goals for the number and quality of endoscopic biopsies in dogs are 13 marginal/7 adequate gastric and 10–15 marginal/6 adequate duodenal samples and for cats are 6 marginal/adequate gastric or duodenal samples.

The emphasis of gastrointestinal histopathologic evaluation in patients with IBD is a semiquantitative estimate of the type and degree of cellular accumulation in the lamina propria. The type of inflammation is based on the primary cell type - eosinophilic, neutrophilic, lymphoplasmacytic, and granulomatous - and the extent of the inflammation ranges from focal to diffuse and is subjectively categorized as normal, mild, moderate, or severe. Mucosal architecture findings (villous morphology, lymphatic dilatation, goblet cell mucus content, and crypt lesions) correlate with clinical severity and proinflammatory cytokines and may prove to be a more accurate categorization for IBD. For example, in cats with GI disease, villous atrophy and fusion in the duodenal mucosa correlated with the severity of clinical signs, and in dogs, loss of mucus and goblet cells correlated with the severity of lymphoplasmacytic colitis. To more accurately define certain abnormalities noted on standard light microscopy, additional studies should be considered. Neutrophilic and/or granulomatous inflammation raises the possibility of an infectious process, and cultures (mucosal biopsies, intestinal lymph nodes), cytochemical 'special' stains (Gomori methenamine silver, periodic acid-Schiff, Gram, and modified Steiner stains) and/or fluorescent in situ hybridization with a probe directed against eubacterial 16S ribosomal RNA (FISH) are indicated. Imaging of the chest and retinal examination can be considered to screen for systemic infections. Differentiation of severe IBD and intestinal lymphoma (enteropathy-associated T-cell lymphoma) can be challenging based on histopathology alone, especially when only endoscopic biopsies are available. To improve the accuracy of the diagnosis, a stepwise diagnostic approach has been suggested. Histopathology is the first step, followed by immunohistochemistry (CD3, CD20, and Ki-67) and polymerase chain reaction (PCR) for antigen receptor rearrangement (T-cell clonality). POTENTIAL COMPLICATIONS WITH IBD

There are several potential complications and comorbidities associated with IBD including hypoalbuminemia and pancreatitis. Hypoalbuminemia (< 20 g/L) has been established as a negative prognostic indicator and higher likelihood of refractoriness to treatment in dogs and cats with IBD. Hypoalbuminemia secondary to a protein-losing enteropathy (PLE) may be due to a reduction in intestinal surface area, such as with villus atrophy or fibrosis, hemorrhage or exudation of protein into the gastrointestinal tract, and/or increased intestinal permeability. The loss of protein in PLE is independent of the molecular weight - therefore, panhypoproteinemia would be expected; however, there are cases in which only hypoalbuminemia is present. Primary therapy for hypoalbuminemia/PLE is the treatment of the underlying intestinal pathology with medical and dietary therapy. Patients with hypoalbuminemia should be screened for pleural effusions, prior to anesthesia or when displaying tachypnea or labored breathing. Therapeutic thoracocentesis is indicated in patients with moderate to severe pleural effusions. Abdominocentesis is typically reserved for patients with moderate to severe volumes of ascites associated with apparent discomfort and inappetence. Hypoalbuminemia can contribute to other lifethreatening complications including hypotension, hypovolemia, and pulmonary edema. Colloid therapy has been recommended to restore colloid osmotic pressure (if documented or decreased oncotic pressure is suspected or when the total protein is < 3.5 mg/L [or albumin is < 1.5 g/L]) and blood volume; however, the choice of colloid therapy has been debated in human and veterinary medicine. Synthetic colloids (hydroxyethyl starch [dogs up to 20 mL/kg/24 h, divide into 5 mL/kg boluses to effect; cats 10–20 mL/kg/24 h, 2.5–3 mL/kg boluses to effect]) are typically the first line of therapy. Although synthetic colloids increase osmotic pressure and help to maintain fluid in the intravascular space, they do not appreciably change total solids as measured by refractometry. A large, retrospective study demonstrated it appeared safe to administer 5% human serum albumin (2 mL/kg/h for 10 h/day [total volume 20 mL/kg/d] until albumin reached 20 g/L) to critically ill hypoalbuminemic cats and dogs. In this study, a majority of the patients (75% dogs, 72% cats) survived to discharge, and no signs of severe hypersensitivity reactions such as anaphylaxis, angioedema, and urticaria were detected. Human serum albumin is costly, and the therapeutic benefit in dogs and cats with PLE has not been determined. The author rarely uses human albumin in dogs or cats with PLE. Plasma transfusions are not typically effective in raising albumin levels due to the relatively low albumin levels in plasma. Rarely, total parental nutrition is considered in the management of severe PLE patients that are intolerant of enteral nutrition. One of the more potentially severe complications of PLE is hypercoagulability and thromboembolic complications, both venous and arterial. Protocols for the treatment of TE and for primary thromboprophylaxis in dogs and cats have not been definitively established. Anticoagulants are the mainstay of management for confirmed or suspected venous TE, to prevent thrombus extension and rethrombosis

 

(secondary thromboprophylaxis). Unfractionated heparin (UFH) therapy is best achieved using a heparin nomogram. UFH is initiated with bolus injection (80–100 U/kg IV), followed by a continuousrate infusion of 18–20 U/kg/h. Because of the unpredictability of UFH bioavailability and response, monitoring and titration are essential. An aPTT is monitored q 6 h, and the infusion rate titrated to maintain an aPTT of 1.5–2.0 x pretreatment. A nomogram has not been established for cats, and aPTT monitoring in this species appears to be unreliable. In humans, LMWHs have shown to be of at least equivalent efficacy, but do not require monitoring in most cases. No evidence exists in small animals comparing UFH and LMWH regimens for TE therapy. The LMWH, dalteparin can be administered in dogs at 150 U/kg SC q 8 h and in cats at 180 U/kg SC q 6 h. Enoxaparin at 0.8 mg/kg SC q 6 h has been demonstrated to maintain target levels of anti-Xa in healthy greyhounds. In cats, an enoxaparin dose of 1.25 mg/kg SC q 6 h has been recommended. The frequency of dosing is based on pharmacokinetic studies in these species. More recent venous stasis models, however, imply that adequate anticoagulation does not require maintenance of target anti-Xa levels, and in humans the dose is based on the achievement only of a peak anti-Xa in the target range. For these reasons, and anecdotal experience, some veterinary clinicians recommend enoxaparin at 1.0 mg/kg q 8–12 h. Because LMWH regimens are not well validated in small animals, the author recommends measurement of anti-Xa activity at peak (2–3 h in the cat, 3–4 h in the dog) and dose adjustment as needed to achieve therapeutic target range (0.5–1.0 U/ml). Intermittent, subcutaneous UFH is not considered ideal for secondary thromboprophylaxis due to the difficulty in achieving a therapeutic effect in a timely fashion. If it is to be used, a dose of 250–300 U/kg SC q 6 h is recommended. Dose titration based on frequent aPTT monitoring is essential due to the huge variability and unpredictability of response. If AT is decreased, administration of fresh-frozen plasma (FFP, 6–10 ml/kg) may be of benefit. The addition of an antiplatelet drug to the therapeutic protocol has merit - for arterial thromboprophylaxis as well as a potential synergistic effect with the anticoagulant for venous thromboprophylaxis. This can be achieved with low-dose aspirin (dogs 0.5–1.0 mg/kg PO q 12 h, cats 5 mg/cat PO q 72 h). Clopidogrel bisulfate (dogs 2 mg/kg q 24 h, cats 18.75 mg PO q 24 h) is an alternative option for patients that have failed, or do not tolerate, aspirin therapy. It should be noted that the onset of effect is delayed, 5–7 days. An association between feline and canine IBD and pancreatitis has been suggested based on limited histopathologic studies involving small numbers of patients, and larger (but still relatively limited) serologic studies utilizing pancreatic lipase immunoreactivity (PLI) concentrations. It is unknown if there is a common underlying cause for the apparent association; however, there does appear to be a clinical significance of concurrent IBD and pancreatitis (based on elevated PLI concentrations). Dogs with IBD and increased serum cPLI concentrations have worse outcome and increased risk of euthanasia compared to dogs with IBD and normal cPLI concentrations. Increased fPLI concentrations did not significantly affect survival outcome in cats with IBD; however, hypoalbuminemia and hypocobalaminemia were observed more frequently with serum fPLI concentrations of ≥ 12.0 μg/l. IBD MANAGEMENT

The global therapeutic approach to biopsy-confirmed IBD (enteritis) is directed at counteracting inflammation and dysbiosis and correcting nutritional deficiencies (i.e., cobalamin and/or folate deficiency). Empirical anthelmintic therapy (i.e., fenbendazole 50 mg/kg PO q 24 h for 5 days) for Giardia and antibiotic therapy (i.e., tylosin 10–15 mg/kg PO q 8 h, oxytetracycline 20 mg/kg PO q 8 h, or metronidazole 10 mg/kg PO q 12 h for 14–28 days) are often administered, if not already initiated. In patients with a positive response to antibiotics (antibiotic-responsive enteropathy), transition to a probiotic (i.e., VSL #3) can be considered. In dogs with IBD, combination therapy including VSL#3 demonstrated a protective effect with a significant decrease in clinical and histological scores and CD3+ T-cell infiltration. Cobalamin deficiency has traditionally been treated with parenterally administered vitamin B12; however, oral therapy (cyanocobalamin 1-mg tablets, dogs with a bodyweight of 1–10 kg ¼ tablet, > 10–20 kg ½ tablet, and > 20 kg 1 tablet PO q 24 h) has been shown to be effective. Granulomatous or Neutrophilic IBD

The initial focus is screening (see above) for underlying infectious causes - i.e., bacterial (E. coli - GC in boxers), Streptococcus, Campylobacter, Yersinia, and Mycobacterium; fungal (i.e., Histoplasma); or algal (i.e., Prototheca) infections. Signalment, historical findings (i.e., raw food diet), or travel history assists in prioritizing pathogen screening. Therapy is directed at the underlying infectious agent. Immunosuppression should not be considered until infectious agents have been excluded. The prognosis for idiopathic granulomatous or neutrophilic IBD is considered poor. Lymphoplasmacytic IBD

The mainstay of therapy remains a combination of corticosteroids, antibiotics, and dietary therapy. Multiple studies have evaluated the management of IBD; however, many of these studies have evaluated multiple parameters (different immunosuppressive therapies and/or diets) or mixed IBD types (i.e., lymphoplasmacytic or eosinophilic or presumptive IBD). Greater than 80% of dogs with IBD have been reported to go into remission, based on a > 75%

 

decrease in CIBDAI score, with prednisone (1 mg/kg PO q 12 h) alone and prednisone with metronidazole (10 mg/kg PO q 12 h). However, a different retrospective study including dogs treated with prednisolone, sulfasalazine, metronidazole ± tylosin, suggested a much lower rate of remission (26% complete, 50% intermittent signs, 4% uncontrolled, 13% euthanized [GI], 7% euthanized [non-GI]).

A sequential therapeutic approach has been suggested, adjusted based on clinical disease activity, histopathologic severity, and presence of hypoalbuminemia. In patients with mild to moderate clinical disease activity and intestinal histopathology and serum albumin levels > 2 g/L, a dietary and antibiotic trial is initiated first and if an incomplete response, followed by immunosuppression with glucocorticoids. If a poor response, escalating immunosuppression is then considered. In patients with moderate to severe clinical disease activity and intestinal histopathology (atrophy, fusion) and serum albumin levels < 2 g/L, immunosuppression is started concurrently. Considering the dietary studies as a whole, a positive response to diet is reported in approximately 50% of dogs with chronic GI signs and IBD. The descriptive terms 'food responsive' or 'dietary intolerant' have been suggested as a more appropriate term than food allergy or intolerance since many patients do not relapse on rechallenge with the original diet. The focuses of dietary therapies are antigenic modification (antigen-restricted/novel protein source or protein hydrolysate) or optimized assimilation (highly digestible, fat restricted and/or restricted fiber). In patients with lymphoplasmacytic IBD and a poor response to immunosuppression with prednisone, it is important to reappraise all aspects of the diagnosis and therapy. Screening for concurrent or newly developed conditions to explain the clinical signs should be considered and treated if detected. Prior to implementing escalation of immunosuppression, switching from oral prednisone to injectable dexamethasone can be considered. Budesonide (3–7 kg: 1 mg PO q 24 h; 7.1–15 kg: 2 mg PO q 24 h; 15.1–30 kg: 3 mg PO q 24 h; > 30 kg: 5 mg PO q 24 h) has been suggested to reduce the side effects of prednisone and has been reported to have a similar remission rate of 78%, based on > 75% decrease in CIBDAI score; however, the frequency of adverse effects was similar to prednisone. In a small study of dogs with steroid-refractory IBD (n = 14), cyclosporine therapy (5 mg/kg PO q 24 h) was reported to be effective therapy. Improvement in clinical activity score, infiltrating lymphocytes and T cells were noted in 86% of the dogs. Masitinib, azathioprine, and mycophenolate have all been suggested in the management of these patients. Elemental diets and partial parenteral nutrition may be indicated in dogs with prednisone-resistant, severe proteinlosing enteropathy. Eosinophilic IBD

An immunologic reaction to diet or parasites is speculated to result in eosinophilic IBD. Repeated zinc-sulfate fecal centrifugation evaluation, potentially with PCR pathogen screening, should be considered to screen for parasites. A prophylactic anthelmintic therapy (i.e., fenbendazole 50 mg/kg PO q 24 h for 5 days) is warranted. Some patients respond to diet therapy (antigen-restricted or protein hydrolysate diets), and those failing diet therapy often improvewith immunosuppressive therapy (prednisone/prednisolone 1 mg/kg PO q 12 h or 2 mg/kg PO q 24 h). OTHER THERAPIES

Glucocorticoids – either systemic (e.g. prednisone: 1-2 mg/kg PO q24h or divided q12h) or topical (e.g. budesonide: 3 mg/m2 q24-48h (dogs), 1 mg/cat PO q24h (cats)). Glucocorticoids are often very effective if eosinophilic component. Azathioprine – a purine analog that is immunosuppressive. Used primarily in dogs and has been reported that cats are very sensitive to toxicity. There may be a lag phase between initiation and response; however, newer data suggests that it is not necessarily more than 1 week or so. In dogs, there are a couple of protocols: 2 mg/kg PO q24h x 2-4weeks, then either 1 mg/kg PO q24h or 2 mg/kg PO q48h, then 1 mg/kg PO q48h until decide to stop. It can be used indefinitely if patient tolerates. May induce bone marrow suppression, liver disease, and pancreatitis Chlorambucil – an alkylating agent also used as a chemotherapeutic drug. Dosages include: Dogs: 6 mg/m2 PO q48h for 2-4 weeks then taper or 0.25-0.33 mg/kg PO q72h for 2-4 weeks then taper; Cats: 2 mg/cat PO q48h for 2-4 weeks then taper or 2 mg/cat PO q72h for 2-4 weeks then taper. Can be myelosuppressive. Cyclosporin A – inhibits T cell function; therefore, may be more effective with lymphocytic IBD. Dose: 5 mg/kg PO q24h. May be associated with renal and liver toxicity, myelotoxicity, and increased infections. Mycophenolate – also a purine analog. Dosage: Dogs: 10-20 mg/kg PO q12h; Cats: 10 mg/kg PO q12h. Seems to be well tolerated. Main side effects are GI signs. Antimicrobial agents – Recently, enteroinvasive E coli has been found in some boxers with ulcerative colitis. Enteroinvasive bacteria may play a role in other intestinal diseases. This may explain why some patients are “anti-microbial responsive” despite lack of evidence for SIBO. Tylosin: 10-20 mg/kg q 8 h for 21 days, 20-40 mg/kg q 12 h, tapered to lowest effective dose, 40-80 mg/kg/day po (cats). Metronidazole: 10-20 mg/kg q 12 h for 10-14 days, then q 24 h for 10-14 days; 10 mg/kg po q 12 h or 25 mg/kg/day po for 5 days (cats); Enrofloxacin: 10-20 mg/kg PO q24h; Oxytetracycline: 10-20 mg/kg q 8 h

 

Vitamin B12 (cobalamin): patients with small intestinal disease even if not SIBO may have systemic B12 deficiency. With GI disease, oral replacement is not effective; therefore, parenteral therapy is required. Treatment includes: 1000 mcg SQ q 2-3 weeks, dogs/cats; Cats and dogs <5kg 250 mcg SQ q 7 days for 6 weeks, then q 2 weeks for 6 weeks, then q 4 weeks; Dogs 5-15 kg, 500 mcg/injection; Dogs > 15 kg, 1000mcg/injection Probiotics – there are many probiotics available for use. Although some are “veterinary specific”, there are not actually species specific probiotics. As a general rule: “more is better” – more bugs of more types in more numbers. For comparison: VSL#3 has 450 billion organisms of 8 strains, Culturelle has 10 billion organisms of 1 strain, Proviable has 5 billion organisms of 7 strains, ProstoraMaxx has 100 million organisms of 1 strain, and Fortiflora has 10 million organisms of 1 strain. Probiotics may help with GI disease by altering the gut microflora, competing with pathogenic enteric organisms, and by producing beneficial substances while metabolizing potentially harmful ones.

Anti-inflammatories – sulfasalazine, which is salicylate bound to a sulfa antibiotic, is a good anti-inflammatory agent for colitis. The bond prevents metabolism prior to entering the large bowel where bacteria cleave the bond releasing the salicylate to act locally. Sulfasalazine: 20-30 mg/kg q 8-12 h, 10-25 mg/kg q 8 h for 6 weeks, then taper; 10-20 mg/kg po q 8-24 h for up to 10 days (cats). Olsalazine: 10-15 mg/kg q 8-12 h, 5-10 mg/kg q 8 h for 6 weeks, then taper. Side-effects may include KCS due to the sulfa drug Omega-3 fatty acids – exert anti-inflammatory effects by substituting into cell membranes where metabolism results in cytokines of the odd series. The dose is based on the amount of EPA and DHA in the product not the total amount of omega-3 fatty acids: 300 mg EPA + DHA per 10 pounds PO q24h. Motility modifiers – Motility disorders occur with GI disease and modification of abnormal motility may help with diarrhea. These are typically opioids. Loperamide (Imodium): 0.1 - 0.2 mg/kg q8 - 12h PO (dog), 0.08 – 0.16 mg/kg q24h PO (cat – cautiously); Diphenoxylate (Lomotil): 0.05 – 0.2 mg/kg q8 - 12h PO (dog), 0.05 – 0.1 mg/kg q12h PO

Anti-emetics – vomiting is often a component of diffuse GI disease and anti-emetics may aid with appetite as well as owner compliance to other treatments. H2 receptor blockers have minimal anti-emetic effect and are used more as antacids. Serotonin antagonists are more potent anti-emetics. Ondansetron (Zofran): 0.5-1 mg/kg PO q12-24h. Dolasetron (Anzemet): 0.5 mg/kg SC, PO q24h. Mirtazapine (Remeron): 15 – 30 mg PO q24h (dog), 1.875 – 3.75 mg PO q72h (cat) Pancreatic enzyme replacement – while we typically use pancreatic enzymes with exocrine pancreatic insufficiency, patients with diffuse gastrointestinal disease may exhibit some degree of malassimilation. Feeding highly digestible diets and pre-digesting food with pancreatic enzymes may improve stool quality by increasing digestion and absorption. FOOD ASSOCIATED ILLNESS AND TOXICITY FDA: http://www.fda.gov FDA – report a problem: http://www.fda.gov/Safety/ReportaProblem/default.htm AVMA: http://www.avma.org – specifically, this link for reporting adverse events with drugs, vaccines, and pet food: http://www.avma.org/animal_health/reporting_adverse_events.asp Here is a listing if interested in a nutritional consult: The ACVN (http://www.acvn.org); Cornell University Veterinary Specialists: http://www.cuvs.org; Michigan State 517 / 432 – 7782; North Carolina State 919 / 513 – 6871 http://www.cvm.ncsu.edu/vhc/vhwc/nutrition; Ohio State 614 / 292 – 1221 http://www.vet.ohio-state.edu/nssvet.htm; Tufts University 839–5395ext84 696; UC Davis 530 / 752 – 1387 http://www.vmth.ucdavis.edu/vmth/services/nutrition/nutrition.html; University of Missouri http://www.vmth.missouri.edu/clin_nu.htm; University of Tennessee 865 / 974 – 8387 utvns@utk.edu; Veterinary Information Network http://www.vin.com

INFLAMMATORY BOWEL DISEASE: NUTRITIONAL AND INTEGRATIVE THERAPIES

Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition

The University of Georgia

INTRODUCTION - NUTRITION

Canine and feline IBD is a heterogeneous group of chronic enteropathies characterized by persistent or recurrent

gastrointestinal signs with inflammatory infiltrate. The infiltration is most often lymphoplasmacytic, but may include

eosinophilic and neutrophilic and may be associated with crypt abscessation and/or lacteal dilation with protein losing

enteropathy (PLE). Patients with IBD may respond to diet (food responsive), antimicrobial agents, and/or immunosuppressive

agents. Clinical signs include vomiting, diarrhea, and/or changes in appetite and often patients have variable degrees of weight

loss. Inflammation may involve stomach, small intestine, and or large intestine; however, PLE usually involves only the small

intestine. The cause(s) of IBD is/are unknown in dogs and cats but likely involves interactions between the GI microbiota and

dysregulated responses in a genetically susceptible individual. The genetic basis of IBD in certain breeds of dogs is recognized.

The role of dysbiosis and abnormal innate immunity have also been recognized. Dysbiosis is an important component of IBD as

evidenced by response to metronidazole, tylosin, or quinolones.

How is IBD diagnosed? IBD is diagnosed based on historical information and clinical examination findings in addition to

supporting laboratory evaluation (CBC, biochemistry, B12, folate, TLI, PLI, etc.), imaging (radiography, ultrasonography), and

biopsy (endoscopic or surgical). There is an association between IBD and cutaneous and other intra-abdominal organ

inflammation. The role of biopsy is important as it not only provides a histologic diagnosis, but it can be submitted for

fluorescent in situ hybridization for examination of enteroinvasive pathogens. Additionally, there are clinical activity indices for

dogs and cats with chronic GI disease. Dietary modification is an important component in management of dogs and cats with

IBD. There are diagnostic tests available for determining serum allergen-specific IgE and salivary allergen-specific IgA.

Unfortunately, these tests have no validation as to their usefulness in diagnosing a dog or cat with a food allergy. Serum

allergen-specific testing may be sensitive but lack specificity. Additionally, serum allergen-specific IgG and IgE levels do not

change with feeding an elimination diet despite resolution of clinical signs. Conventionally, a food elimination trial with

challenge can be undertaken to evaluate for a food allergy; however, response to diet change does not confirm food allergy, only

that the patient has a food-responsive disorder. The most useful diagnostic test of dietary sensitivity is feeding an elimination

diet followed by challenge with a test meal. Elimination diets must be individualized based on previous dietary exposure. A

detailed study of the animal’s diet will allow identification of foods that have not been fed before and that could be used to

formulate a nutritionally balanced elimination diet. If it is not possible to formulate a suitable elimination diet, then a restricted

diet may be used that contains only one or two potential allergens, preferably ones that have not been eaten in the preceding

month. Many homemade diets used as elimination diets are not complete and balanced (e.g. cottage cheese and rice, or chicken

and rice). Supplementation with vitamins and minerals is encouraged, but avoid use of supplements that contain potentially

offending foodstuffs.

NUTRITION IN PATHOGENESIS OF IBD

Is dietary protein source a cause of IBD? Throughout life, animals are exposed to a variety of potential dietary allergens;

however, after a variable period of time, some may develop an immune response against a particular foodstuff that activates one

or more immunopathogenic pathways. After development of this response, subsequent ingestion of this foodstuff results in

clinical signs. These dietary antigens do not normally cause problems because the intestinal mucosa forms a barrier that limits

absorption of macromolecules. There is evidence that antigens are absorbed through both normal and abnormal gut as allergen

specific food antibodies are demonstrable in healthy individuals. Upon initial presentation of the antigen to the gut mucosa, there

is an immune response involving IgA. This reduces the amount of antigenic material absorbed. Immune complexes of antigen

and IgA antibody are transported across hepatocytes, into bile, and re-circulated to the intestine. This local IgA response may be

followed by a transitory systemic immune response, but immunologic tolerance follows. Thus, there is an apparent paradox of a

vigorous local immune response followed by a systemic tolerance. Absorption of macromolecules can be altered by local

immunity. Decreased uptake has been demonstrated experimentally following oral or parenteral immunization in rats and

increased absorption occurs in IgA-deficient human beings. Absorption is also enhanced by gut mucosal vasodilatation. In this

case, the patient becomes caught in an immunological vicious circle because local hypersensitivity reactions favor access of

allergens that in turn heightens the antibody response. Factors that lead to development of hypersensitivity to ingested antigens

are speculative. Those most frequently implicated are heat- and acid-stable glycoproteins with molecular weights of 18-30 kD.

Hypersensitivity reactions involved in food allergies have been shown to involve types I, III, and IV reactions. Some studies

indicate that IgE is implicated in some instances and the reactions involved include both classic, immediate Type I reaction and

late-phase IgE-mediated reactions. What initiates the original immunologic reaction is not clear. If clinical or subclinical

gastrointestinal disease occurs altering mucosal integrity, absorption of antigenic proteins may occur which may initiate the

processes. Additionally, dysbiosis is being recognized as a common finding in patients with IBD.

What are advanced glycated end-products (AGE’s) and do they have a role in IBD? Many pets eat processed foods.

Temperature and residence time during processing are known to influence Maillard reactions in which a reducing sugar binds to

a free reactive amino group of an amino acid blocking its reactive site. In intact proteins, the -amino group of lysine is the most

abundant free amino group. The reaction results in Amadori compound leading eventually to decreased lysine bioavailability

and Maillard reaction products (MRP’s) that are also advanced glycation end-products (ABE’s). During formation, AGE’s can

covalently cross-link tissue protein and modify structural and functional properties. Tissue AGE’s are associated with various

diseases such as diabetes mellitus, cataract formation, osteoarthritis, and pro-inflammatory responses. Dietary MRP’s can be

absorbed and contribute to the body’s AGE pool and possibly to associated diseases. While no studies have evaluated the role,

if any, of MRP’s with animal diseases, one study showed that dogs may ingest up to 122 times more MRP when consuming an

average extruded dog food than the calculated average for adult human beings and up to 36 times more MRP compared to

human infants. Likewise, cats consuming an average extruded cat food may ingest up to 38 times more MPR compared to adult

human beings and 11 times more MRP compared to human infants. Those fed canned pelleted diets are more likely to ingest

higher amount of MRP compared to extruded diet.

NUTRITION IN MANAGEMENT OF IBD

Treatment of canine and feline IBD is empirical and consists of dietary and pharmacological therapy. There are several

options for dietary trials: (1) global modification: switch to a different diet or a different manufacturer, (2) optimize assimilation:

highly digestible (usually rice based), fat restricted (< 15% dry matter basis), easy-to digest fats, restricted fiber, (3) antigen

modification: antigen-restricted novel protein source, protein hydrolysate, (4) immunomodulation: altered fat composition (e.g.

omega 3 fatty acids), prebiotics (e.g. inulin, fructooligosaccharides, etc.), (5) homemade complete and balanced diets. The

rationale for dietary therapy of IBD is that restricting exposure to antigens will mitigate clinical signs and prevent recurrence.

Does switching to a different diet work? There are no specific studies that have evaluated changing from one commercial diet

to another commercial diet without utilizing a novel protein or hydrolyzed protein source. A non-therapeutic diet that has a

different nutrient composition than the diet presumed to be associated with removing the offending dietary component

responsible for clinical signs. Food or food ingredients reported to cause adverse reactions in 330 dogs included in descending

order: beef, dairy, chicken, wheat, chicken egg, soy, lamb, port, fish, corn, turkey, rice, and duck; while in 56 cats they included:

beef, dairy, fish, chicken, corn/corn gluten, lamb, wheat, and chicken egg. Unfortunately, the references for these data are from

2007 or before. However, choosing a diet based on previous exposure and this information could allow for selection of a

commercial non-therapeutic diet. Recommendations of choosing diets for elimination trial is concerning as there have been

publications documenting protein sources analyzed using species specific DNA being present in pet foods and therapeutics that

were not specifically listed including 3 studies where 14 of 17 samples, 20 of 52 samples, and 4 of 4 samples were mislabeled,

and one study of therapeutics where 4 of 7 products were mislabeled. Additionally soy may be present in diets that are claimed

to be soy free and in one study 3 of 4 such over the counter diets contained appreciable amounts of soy protein.

What are easily assimilated diets? Easily assimilated diets refer to easily digestible diets that are moderate in protein, lower in

fat, low in fiber, and moderate in carbohydrates. There are no studies on the amount of dietary protein in management of IBD in

dogs and cats. While providing a higher protein diet would seem logical, a study of human beings with ulcerative colitis

demonstrated that feeding a higher protein diet was associated with 3-fold risk of relapse when compared with patients fed a

lower protein diet. One possible explanation is related to increased amounts of some deleterious amino acid derived metabolites

produced from undigested protein in the large intestine lumen by microbiota. In one study of cats with IBD, cobalamin

deficiency was associated with decreased fat digestibility. Dietary fat restriction has been shown to be beneficial in dogs with

PLE. In human beings with ulcerative colitis, increased dietary total fat, animal fat, omega-6 fatty acids, and omega-6-to-omega-

3 fatty acid ratios were associated with increased incidence. Carbohydrate maldigestion is a feature of feline IBD; however, it

has not been shown to contribute to clinical signs. Gluten likely does not play a role in most patients with IBD except for Irish

Setters with known gluten sensitivity. In addition to macronutrients, micronutrients such as vitamin and mineral deficiency have

been reported including vitamins B12 and D and calcium.

Are novel protein diets beneficial in treating IBD? Feeding a novel protein diet assumes several things: (1) a knowledge of

dietary protein exposure, (2) clinical signs are due to the dietary protein serving as an allergen, and (3) the novel protein diet

chosen contains only the protein listed. What constitutes an ideal novel protein is unknown and likely variable depending on the

patient’s previous exposure. There are no published studies that have compared response of dogs or cats with IBD to an intact

novel protein diet with a hydrolyzed protein diet. Response to controlled dietary change using intact proteins is good ranging

from 50-100%. Dogs with food responsive IBD tend to be younger in age and have less severe clinical signs than in dogs

requiring immunosuppressive therapy. In one study, dogs with food responsive IBD responded to an elimination diet of intact

protein and response occurred in 10-14 days. The diet was fed for 14 weeks and 31 of 39 dogs were able to be transitioned to

their original diet while 8 required continued dietary modification. A similar result was found in two other studies. In a study of

55 cats with chronic GI signs, 27 were diagnosed as food responsive or food allergic based on response to a diet utilizing intact

proteins and 11 of these cats could be converted to their original diet. In a study approximately 50% of cats with

lymphocytic/plasmacytic gastroenteritis responded to a change in intact protein diets. In another retrospective study, 100% of

cats responded to dietary change using a different intact protein with or without additional pharmacologic therapy.

Are protein hydrolysate diets beneficial in treating IBD? The primary aim of hydrolyzing proteins for specialized diets is to

sufficiently disrupt the protein structure within the diet to remove any existing allergens and allergenic epitopes and thereby

prevent immune recognition by patients already sensitized to the intact protein. Because proteins with molecular weights over

18,000 Daltons are incriminated as being antigenic, modification of proteins to compounds having lower molecular weight may

be of benefit. Reducing the average weight of the protein molecule to less than 18,000 Daltons can result in a protein that may

be truly hypoallergenic. There are a few studies demonstrating 50-100% efficacy of hydrolyzed protein diets in managing IBD

in dogs and cats; however, some patients may have increased cutaneous signs. Available commercial hydrolyzed protein diets

are complete and balanced for adult dogs or cats. Consumption of protein hydrolysates may result in a more rapid uptake of

amino acids when compared with whole proteins or amino acids in mixtures. Soy hydrolysate diets have been shown to be

tolerated in dogs with known soy hypersensitivity.

Are homemade diets beneficial in treating IBD? Homemade diets allow promote control over ingredients and truly novel

ingredient diets may be formulated. Because some dietary ingredients may become antigenic due to processing, feeding a whole

ingredient or raw food diet means there is no processing. Homemade diets are typically more digestible and smaller quantities

may be fed. In one survey, 90% of homemade elimination diets prescribed by 116 veterinarians in North America were not

nutritionally adequate for adult dog or cat maintenance. Few of the recipes available in books, magazines, and on-line have been

tested to document the nutritional adequacy of the diet. There are common nutrient problems in many homemade foods. Many

formulations are deficient in calories, calcium, vitamins, and micro-minerals. Nutritionally complete and balanced diets can be

formulated by board-certified veterinary nutritionists and a listing can be found at the American College of Veterinary Nutrition

website: http://www.acvn.org.

Are there other nutritional modifications that may be useful with IBD? Prebiotics are Probiotics are live microbial feed

supplement that beneficially affects the host by improving the intestinal microbial balance and so correct dysbiosis that occurs

with IBD. Prebiotics are indigestible fibrous products that selectively promote the growth or activity of commensal

microorganisms that improve the well-being of the host. Prebiotics are carbohydrates that are not digestible in monogastric

animals but are selectively fermented by commensal bacteria (e.g. Bifidobacteria) including inulin, fructooligosaccharides,

mannanoligosacharides and resistant starch. Their fermentation produces short-chain fatty acids that have anti-inflammatory

properties, promotes colonic epithelial integrity and healing, reduces neoplasia, and more. Their use has been minimally

evaluated in dogs and cats but have shown benefit in dogs with large bowel diarrhea and in altering small intestinal bacterial

population. Probiotics have been shown to be beneficial in dogs with IBD. Omega-3 fatty acids modulate the immune response

and exerts an anti-inflammatory effect. There use in documented in human beings with IBD; however, there are no studies in

dogs and cats evaluating their effect.

INTRODUCTION – INTEGRATIVE THERAPIES

In 2014 the National Center for Complementary and Integrative Care (NCCIH) stated that complementary approaches

are no longer considered an ‘alternative’ to conventional medical care, but are used in combination to provide what is defined as

integrative health care. Complementary approaches include herbs, dietary supplements, acupuncture and other modalities that

are rational and supported by evidence to alleviate physical symptoms, improve quality of life (QOL) and prevent disease.

There is consumer demand for the integrative health care and we challenged to understand these nontraditional therapies. The

NCCIH states that despite widespread use of integrative health care scientific evidence for many complementary approaches is

still needed. A survey of adults attending an outpatient GI clinic reported the prevalence of complementary medicine (CM) use

was 44%, more often in females and those dissatisfied with conventional treatments. Among those using CM, 54% reported

taking a supplement or dietary modification, citing “they wish to feel better” (68%) as the most common reason for CM use. In

this study 30% of patients stated they did not discuss CM with their physicians citing the primary reason was the physician did

not ask (82%). It was concluded that a discussion of CM should be part of a GI office visit and gastroenterologists should have

a greater awareness of CM to identify potential side effects and promote a more holistic, patient-centered approach to health.

Another study surveyed the American Gastroenterological Association reported that although gastroenterologists lacked formal

training in CM (65%) they were receptive to its use and most felt it had a role in the treatment of IBD without necessarily

compromising conventional therapy. Considering the complex bond between owners and pets, it would be logical that owners

of pets with GI disease will apply complementary approaches to the treatment of their pets. This would be especially applicable

in patients where conventional treatment is not eliminating all symptoms such as with IBD. Herbs and dietary supplements

(HDS) are the most accessible form of complementary medicine. In 2014, pet owners spent approximately $191 million for

dietary supplements for their companion animals. Owners reported wanting not only supplements for joints, but supplements

for digestive issues. The evidence base for the use of relevant HDS for IBD was assessed via literature searches for dog/cat,

human or in vitro cell lines. No meta- analysis and only a few randomized controlled clinical trials (RCCT) using HDS in canine

IBD were found. There is a paucity of research in feline IBD.

TRANSLATIONAL RESEARCH

Human idiopathic IBD may be similar to canine IBD. Numerous studies of IBD in the veterinary literature compare

and contrast results to human IBD including gene expression, helper T lymphocyte (Th) profiles, histopathology, biological

markers, and response to treatments. Studies using high-throughput DNA sequencing techniques have determined fecal

microbial phylogeny (e.g. predominance of Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria) and their functional

capacity (e.g. related to carbohydrate, protein, DNA, vitamin metabolism, virulence factors) of the canine and feline gut are

similar to what has been found in the human gut. Canine IBD represents a potential model to study human IBD and parallel

studies could lead to more information in man while providing better therapeutics in canine IBD. Acknowledging the

translational and clinical science role of this disorder, the evidence base for the use of relevant HDS for human IBD was

assessed. Over a hundred randomized controlled clinical trials (RCCT) using HDS in human IBD were found.

THE INTESTINAL MICROBIOTA

IBD is an idiopathic cause of chronic gastrointestinal disease in dogs, cats and humans. Three main factors are

considered fundamental to the pathogenesis of idiopathic IBD: the interactions between the mucosal immune system, host

genetic susceptibility, and environmental factors which include nutrition and the intestinal microbiota. As noted in human

idiopathic IBD there is an ‘intestinal dysbiosis’ with a decrease in bacterial diversity; this same phenomenon has been reported

in companion animal IBD. Human idiopathic IBD is mainly defined as either ulcerative colitis (UC) or Crohn’s disease (CD).

The gut microbiota shows little temporal change in healthy individuals, whereas the microbiota of the IBD patient is unstable

differing between active and quiescent stages. A longitudinally human study showed the microbiota in IBD patients remained

unstable even in patients with UC in remission. Before relapses normal anaerobes are decreased and the intestinal microbiota is

reduced. It is controversial whether dysbiosis is a cause or consequence of intestinal inflammation in IBD, but currently the

literature favors the former. Studies in twins, affected and unaffected relatives and studies of NOD2 and ATG18L, two major

CD susceptibility genes, suggest dysbiosis is caused by genetics and environmental factors rather than a consequence of chronic

inflammation. In canine IBD, affected dogs have a lower abundance of Bacteroidetes and Firmicutes and higher abundance of

Proteobacteria when compared to healthy dogs. The role of the intestinal microbiota in the pathogenesis of idiopathic IBD is

supported by both human and animal studies and direct modulation of the intestinal microbiota may potentially be a treatment.

DIETARY SUPPLEMENTS IN MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

Probiotics. The most common HDS noted in PubMed searches were the use of probiotics. Probiotics are defined as live

microorganisms that, when administered in adequate amounts confer a health benefit(s) to the host. In the human literature, two

meta-analyses of IBD found some benefit in probiotics in inducing and maintaining remission in UC, especially when combined

with conventional therapies. Meta-analysis in patients with CD did not find a significant benefit of probiotics in preventing

post-operative recurrences, decreasing relapses or maintaining remission. Probiotic studies in the veterinary literature have

looked at probiotic in acute diarrhea or chronic enteropathies such as canine food responsive diarrhea with only one study, Rossi

et al evaluating probiotic in 20 dogs with idiopathic IBD. This randomized 90 day open label study compared the effects of the

probiotic SIVOY (VSL Pharmaceuticals, Inc. Gaithersburg, MD, USA), a high- dose multi-strain probiotic product containing

four strains of viable lyophilized bacteria to combination therapy with prednisone and metronidazole in canine IBD. The

probiotic is a pet product using bacteria strains from VSL#3 which has shown some efficacy in humans for the prevention,

treatment and maintenance of remission of pouchitis and ulcerative colitis in adults and children. The probiotic group (D-

VSL#3; n=10) received 112-225 billion bacteria per 10 kg; the combination drug therapy (D-CT; n=10) received a combination

of 20 mg/kg q 12h metronidazole and 1mg/kg/day prednisone for 60 days. Tissue sampling for histological scores, CIBDAI and

TGF-β+, FoxP3+, and CD3+ T-cell expression were determined after enrollment (time point T0) and 30 days after completing

60 days of treatment(T1) in both groups. The study reported a decrease in duodenal histological scores, CIBDAI and infiltration

with mucosal CD3+ in both treatment groups with no significant effect between treatments. TGF-β+ increased in both groups,

but the magnitude of this increase was greater in the D-VSL#3 dogs. FoxP3+ increased in the D-VSL#3 group after treatment,

but not in the D-CT group. Microbiota analysis showed that at T0 all dogs showed a statically decreased abundance of

Faecalibacterium spp. and Turicibacter spp. when compared to 10 healthy dogs (one time only). Faecalibacterium spp.

increased significantly in the D-VSL#3 dogs as well as with a trend to increase in the D-CT. This bacterium has been reported

to increase with conventional therapies in IBD dogs and could be an indicator of normalization of dysbiosis. The study

suggested that the enhancement of the regulator T-cell markers (FoxP3+ and TGF-β+) along with normalization of dysbiosis

may indicate a protective effect of the probiotic as compared to combination therapy. It was concluded probiotics induced

differential anti-inflammatory responses when compared to conventional combination treatment. This was not a superiority

study as there was no placebo group, but findings complement other studies of how probiotics may affect the mucosal immune

system. Other studies of probiotics have demonstrated increases in anti-inflammatory cytokines IL-10 as well as TGF-β+ by

modulation of NF-B pathway and influencing the cross talk between natural killer cells and dendritic cells. Although study

limitations exist, this study suggests a role for probiotics in canine IBD.

Prebiotics & Symbiotics. Prebiotics are defined as selectively fermentable ingredients that result in specific changes in the

composition and/or activity of the GI microbiota, thus conferring benefit(s) upon host health. When prebiotics reach the colon

they are rapidly fermented to short chain fatty acids (SCFA) acetate, propionic, and butyrate by resident bacteria. These SCFA

especially butyrate activate nuclear peroxisome-proliferator- activated receptor γ which antagonizes inflammatory pathways.

Studies using fructo-oligosaccharide (FOS) and oligofructose-enriched inulin in CD patients did not show any significant

benefits. One small study in CD and prebiotic reported a decrease in activity scores and increased Bifidobacteria species. A

symbiotic, defined as the combination of a probiotic and prebiotic, was shown to improve symptoms, pro-inflammatory

cytokines and increased Bifidobacteria content in active CD patients. The role of prebiotics and IBD in veterinary medicine has

been minimally investigated.

Fecal Microbiota Transplantation. Fecal microbiota transplantation (FMT) has emerged as a treatment for severe, recurrent

human Clostridium difficile infection (CDI). It is not a new therapy, first reported in 4th century China and 17th century used in

veterinary medicine, both orally and rectally and termed transfaunation. Systematic review and meta- analysis of FMT in IBD

determined more RCT’s are needed. Weese et al. reported using stool transplantation enemas in a dog with eosinophilic IBD

and a cat with refractory GI symptoms.

Omega-3 fatty acids (fish oil) Omega 3 fatty acids contained in marine life oil have anti-inflammatory effects by substituting

in the cell membrane for arachidonic acid. The equivalent n3 fatty acid is eicosapentaenoic acid (EPA). Dosing n3 fatty acids is

based on the amount of the sum of EPA and DHA and is dosed at 300 mg of EPA+DHA per 10 pounds of body weight per day.

This should be initiated at approximately ½ of this dosage as GI upset and diarrhea may occur. If tolerated after 2 weeks then

increase the dose to the desired amount.

Vitamin B12 (cobalamin) Low serum cobalamin concentrations (< 200 ng/L) has a wide-ranging reported prevalence (6–73%) and

has been associated with refractoriness to treatment in cats and dogs with chronic enteropathies. In dogs with PLE, it has been

correlated with the serum albumin levels. Hypocobalaminemia can be detected in combination with hyperfolatemia. Absorption of

cobalamin in cats and dogs is a complex, multistep process mediated by carrier proteins and intrinsic factor (IF). IF is produced by the

stomach and pancreas in dogs and by the pancreas, but not the stomach, in the cat. The cobalamin-IF complex is absorbed in the ileum

by receptors; however, in humans a small amount (1%) of unbounded cobalamin is absorbed along the entire intestine. Suggested

causes of hypocobalaminemia in patients with chronic enteropathies include damage to the ileal mucosal receptors for binding

cobalamin-IF complexes or decreased amounts of cobalamin available for absorption due to bacterial competition of nutrients.

Hypocobalaminemia can cause inappetence, weight loss, villous atrophy, malabsorption of other vitamins and nutrients, central and

peripheral neuropathies, and immunodeficiency. Cobalamin supplementation has traditionally been with a repeated, parentally

administered, vitamin B12 injection protocol (500 to 1500 mg/dog depending on the size; 250 mg/cat). This protocol was based on the

pathophysiologic justification that oral vitamin B12 would be poorly absorbed and would not normalize hypocobalaminemia. Several

studies in humans and a Cochrane review suggested oral cobalamin might be as effective as parenteral administration in various

conditions, including gastrointestinal disorders. A retrospective study in dogs with chronic enteropathies and hypocobalaminemia

(cobalamin concentration of ≤ 270 ng/L used) demonstrated oral cobalamin supplementation can restore normocobalaminemia.

Cyanocobalamin 1-mg tablets (dogs with a bodyweight of 1–10 kg ¼ tablet, > 10–20 kg ½ tablet, and > 20 kg 1 tablet PO q 24 h)

were shown to be effective. Daily, oral cobalamin supplementation has been suggested to be a likely cheaper, simpler, and pain-free

alternative to parental cobalamin injections. Cobalamin supplementation can be started while pending vitamin B12 levels and based on

a study suggesting cobalamin deficiency on a cellular level (increased methylmalonic acid [MMA]) with vitamin B12 in the lower end

of the reference interval, therapy can be considered even with low-normal measurements. Despite therapy with parental vitamin B12

supplementation for 6 weeks, a prior study suggested hypocobalaminemia remains a negative prognostic indictor and associated with

an increased risk of euthanasia.

Vitamin D. Studies in the human literature have investigated the role of specific nutrients and IBD including omega three fatty

acids, fat soluble vitamins (A, D, E, K), ascorbic acid, B12, folate, iron, and zinc. Prevalence of vitamin A and D deficiency has

been reported as 26-93% (UC), 11-50% (CD) and 35% (UC), 75% (CD) respectively. Iron deficiency has been reported to have

a prevalence of 81% in UC and 39% in CD. As most dogs and cats are fed complete and balanced diets concerns for overt

nutrient deficiencies in disease states has not been intensely investigated including canine and feline IBD. Studies of the role

vitamin D in human idiopathic IBD including prevalence, optimal levels, prevention, quality of life and genomic technologies

are abundant and would suggest a need for further investigation in vitamin D levels in canine and feline IBD. A recent study

evaluated vitamin D status in hospitalized cats. It was reported that the odds ratio of mortality within 30 days was 8.27 (95%

confidence interval 2.54-31.52) for cats with a serum vitamin D in the lower quarttile. Dietary levels of vitamin D in pet diets

are adequate to prevent nutritional rickets however the amounts that correspond to adequate serum levels for cellular health have

not been established. Sharp et al. has defined sufficient serum vitamin D levels to be greater than 100 ng/ml and evaluated

serum vitamin D levels in dogs fed commercial dog food, homemade diets or combination. Serum concentrations varied in all

diets, ranging from 9.5 to 249.2 ng/ml. It was concluded that serum vitamin D concentrations in dogs vary widely likely as a

consequence of dietary intake. Gow et al. reported dogs with IBD and hypoalbuminemia frequently have ionized elevated

calcium, high PTH and low serum vitamin D concentrations. It could not be determined whether low serum vitamin D was due

to low dietary intake from inappetence or increase loss of vitamin D through the GI tract. The authors favored the latter

explanation, but concluded further studies were indicated to establish the pathogenesis of this IBD complication. A recent study

evaluated the relationship between vitamin D and markers of systemic and gastrointestinal inflammation in a cohort of dogs with

CE. This study concluded serum vitamin D concentrations were inversely associated with systemic markers of inflammation in

dogs with CE and with severity of inflammatory changes seen in histopathological samples. The authors reported that although

hypovitaminosis D can be seen with intestinal disease, newer information to identify its contribution to the initiation and

perpetuation of intestinal inflammation needs to be determined. The role of vitamin A status in human IBD and intestinal

inflammation has been similarly questioned. It is known that retinoic acid induces FoxP3+ T cells which regulate intestinal

inflammation. Low levels of both carotene, a vitamin A precursor and vitamin A, serum retinol have been reported in CD.

These findings suggest despite the concept of complete and balanced commercial pet diets, there is a need to assess vitamin D

status in canine and feline IBD where inappetence, vomiting, diarrhea, and malabsorption together with diet variation may affect

serum vitamin D levels similar to human IBD. The diet study also noted higher serum vitamin D in dogs given salmon oil. As

vitamin D is fat soluble and absorption is enhanced with fat intake, IBD patients with severe disease and low fat diet may be

more at risk of hypovitaminosis D. Studies in the role of vitamin D and canine and feline IBD suggest vitamin D status should

be assessed, treated and monitored. It should be noted that parental vitamin A and D solutions can be easily administered orally,

subcutaneously and have been used safely for other companion animal disease states.

Iron In the human IBD literature, it is noteworthy that anemia is considered the most common systemic complication and extra

intestinal manifestation of IBD. Consensus statements recommend prevention of anemia and maintenance of iron stores in IBD

patients as the impact of anemia on QOL, ability to work, hospitalization and health care costs is substantial. The major forms

of anemia of IBD are defined as iron deficiency anemia (IDA), anemia of chronic disease (ACD) and anemia of mixed origin.

Numerous studies evaluating diagnosis, prevention and treatment of IBD associated anemia abound in the human literature. The

concept of our pets’ daily consumption of a complete and balanced diet may have slowed translational research and investigation

into the role of IDA in canine and feline IBD. As the diagnostics of anemia and iron metabolism in dogs and cats are being

reevaluated, it would be timely to reassess the role of anemia in veterinary IBD patients. Parental iron has been used in suspect

cases of IDA in canine IBD with positive outcomes.

HERBS AND THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

A review of complementary therapies compared to conventional treatments assessed the level of evidence based on

Strength of Recommendation Taxonomy (SORT) as follows: Grade A based on consistent, good-quality oriented evidence such

as systematic reviews or meta-analysis or high quality patient orientated RCCT, Grade B is based on inconsistent or limited-

quality patient-oriented evidence, and Grade C is based on consensus, usual practice, opinion, or disease-oriented evidence.

This comparison also assessed level of risk of each therapy. Curcumin and Boswellia were given a SORT rating of B, with level

of risk rated low for Boswellia. Corticosteroid, aminosalicylates, and Infliximab had a SORT of A, but level of risk was high.

Similar results are noted in other systematic reviews of studies of the use of curcumin and Boswellia in IBD.

RAW OR WAR: HOMEMADE AND RAW FOOD DIETS Joe Bartges, DVM, PhD, DACVIM, DACVN

Professor of Medicine and Nutrition The University of Georgia

HOMEMADE DIETS

Some owners prefer to prepare homemade foods – feel less guilty and have impression of preparing a “real meal” that is “more natural” and “more traditional”. Nearly all dogs and cats in the US consume table foods at some time in their lives. Majority of dogs and cats in US receive >90% of calories from commercial foods. When a client wants to prepare pet foods at home, it is important for veterinarians to understand the client’s reasons and motivation. In many cases it is possible to address their concerns and to recommend an appropriate commercial food. If they still wish to cook, then proper guidance can be provided.

Some owners wish to cook homemade diets in order to provide a natural or organic food. Remember, there is no legal definition for the terms “natural” and “organic”. Pet owners may also want to prepare vegetarian food for their dog or cat because they are vegetarian or vegan. Because cats are true carnivores, vegetarian cooking should be discouraged. Other owners wish to prepare homemade diets in order to avoid additives, preservatives, and contaminants. Pet food labels may be difficult to read and understand and they do not contain as much information as human food labels; therefore, some choose to home cook because they are more comfortable with being in control. Some pets will only eat table foods because it has become a habit. Lastly, homemade diets may be used for dietary elimination trials.

It is possible to achieve the same nutrient balance with a homemade food as with a commercially prepared food. However, this largely depends on the accuracy and competence of the person formulating the food, and on the compliance and discipline of the owner. Unfortunately, some homemade recipes are flawed even when followed exactly and consistently. IN one survey, 90% of homemade elimination diets prescribed by 116 veterinarians in North America were not nutritionally adequate for adult dog or cat maintenance. Few of the recipes available in books, magazines, and on-line have been tested to document the nutritional adequacy of the diet.

There are common nutrient problems in many homemade foods. Many formulations contain excessive protein, but are deficient in calories, calcium, vitamins, and micro-minerals. Commonly used meat and carbohydrate sources contain more phosphorous than calcium resulting in inverse calcium: phosphorous ratio. Foods designed by clients are commonly deficient in fat and energy density or contain an unpalatable fat source (vegetable oil). Homemade foods are rarely balanced for micro-minerals and vitamins because veterinary vitamin-mineral supplements are not complete nor are the nutrients well balanced within the product.

People are taught that eating a variety of foods is nutritionally sound. Clients often extend this principle to their pet’s nutrition. Pet owners perceive that feeding a variety of foods is their best defense against malnutrition. Likewise, many owners feed a homemade diet because they can use a variety of ingredients. Some owners choose meat and carbohydrate sources for their pet’s food based on their own preferences, product availability, or affordability. Other pets are fed “leftovers” such as fat trimmings, bones, vegetable skins, crusts, and condiments. Some owners feed their pets according to guidelines for humans not realizing that dogs and cats have different requirements. A common problem with homemade diets is that the vitamin-mineral supplement is left out because of inconvenience, expense, or failure to understand its importance – after all, many humans do not take vitamins. Lastly, some homemade diets use raw ingredients – we will talk more about these in a little bit

Veterinarians encounter a wide variety of pet food recipes from breeders and the popular press. Some owners want an opinion as to whether the recipe is good and others want to alter the recipe. Homemade formulations can be checked for nutritional adequacy and adjusted using the “quick check” guidelines: 1. Do five food groups appear in the recipe?

a. Carbohydrate/fiber source from a cooked cereal grain b. A protein source, preferably of animal origin, or if more than one protein source is used, one source should

be of animal origin c. Fat source d. Source of minerals, particularly calcium e. Multivitamin and trace mineral source

2. Is the carbohydrate source a cooked cereal and present in a higher or equal quantity than the meat source? a. Carbohydrate to protein ratio should be at least 1:1 to 2:1 for cat foods and 2:1 to 3:1 for dog foods b. Sources are cereal such as cooked corn, rice, wheat, potato, or barley c. These sources have similar caloric contributions, but some carbohydrates contribute a substantial amount of

protein, fiber, and fat

3. What is the type and quantity of the primary protein source? a. Overall protein quality of the diet can be improved by substituting an animal-derived protein source for a

vegetable protein b. Skeletal muscle protein from different species have similar amino acid profiles c. Final food should contain 25-30% cooked meat for dogs (1 part meat to 2-3 parts carbohydrate) and 35-

50% cooked meat for cats (1 part meat to 1-2 parts carbohydrate) d. Providing some liver in the meat portion is recommended once a week or no more than ½ of the meat

portion on a regular basis – corrects most potential amino acid deficiencies and contributes fatty acids, cholesterol, energy, vitamins, and microminerals

e. If owner requests an ovo-lacto-vegetarian food, eggs are best f. If vegan food is requested, soybeans are the next best, but incomplete, amino acid profile

4. Is the primary protein source lean or fatty? a. Lean protein sources require addition of an animal, vegetable, or fish fat source at 2% of the formula

weight for dogs and 5% of the formula weight for cats b. If a homemade food lacks sufficient caloric density, addition of cooked beef or chicken fat, poultry skins,

vegetable or fish oils can markedly increase caloric density without adding other nutrients 5. Is a source of calcium and other minerals provided?

a. An absolute calcium deficiency is common b. Many owners erroneously assume cottage cheese, cheese or milk added in small quantities provides

adequate calcium c. Most foods require a specific calcium supplement

i. When the protein fraction equals or is greater than the carbohydrate fraction, usually only calcium carbonate is added (0.5 g/4.5 kg cat/d and at least 2.0 g/15 kg/dog/d).

ii. Calcium and phosphorous supplementation may be necessary when the protein fraction is less than the carbohydrate fraction. Steamed bone meal, dicalcium phosphate, and certain proprietary mineral supplements contain @ 27% calcium and 16% phosphorous (about 2:1) and micro-minerals

6. Is a source of vitamins and other nutrients provided? a. A human adult over-the-counter vitamin-mineral tablet that contains no more than 20% of the

recommended daily allowances for people works well for both dogs and cats at ½ to 1 tablet per day (@ 1 gm/tablet).

b. One tablet per day of a human adult product will not over-supplement pets with calcium, phosphorous, magnesium, vitamins A, D, and E, iron, copper, zinc, iodine, and selenium according to AAFCO maximum allowances for canine and feline foods.

c. In general, veterinary supplements provide between 0-300% of vitamin-mineral requirements of dogs and cats Substitution of ingredients can be done, but should be researched as to the equivalent amounts. One protein

source is not the same as another. Other instructions that should be given owners include those for preparation, storage, and feeding. Emphasis should be made to not eliminate an ingredient or indiscriminately substitute ingredients. Owners that wish to use raw eggs and meats should be informed that there is a risk for infectious diseases. Animal ingredients should be cooked for at least 10 minutes at 180F. Vegetable ingredients should be washed or rinsed and cooked if increased digestibility is desired. Since antioxidants are not usually added to homemade diets, storage in airtight containers at refrigeration temperature can be done for 7 day stretches. Large quantities can be frozen. Owners should check appearance and odor daily to make sure rancidity or contamination has not occurred. Starches should be cooked to increase digestibility; however, they should be cooked separately from the protein source. Carbohydrate sources require a longer cooking time; meat and liver should not be overcooked or protein denaturation will occur

Pets should be evaluated routinely whether they are being fed commercial food or homemade food. Stools should be formed although they may contain more water. Body condition and weight should be maintained. If problems are encountered, then either the homemade diet should be re-evaluated and modified or use of a commercially available diet should be encouraged.

RAW FOOD DIETS (BONES AND RAW FOOD OR BIOLOGICALLY ACTIVE RAW FOODS) Veterinarians deal with pet owners who have access to a large body of information on small animal nutrition. Food is something that everyone relates to because it is one of the necessities of life. Food can have important effects on psychological well-being. Diet is something that an owner can control. Nutritional therapy is viewed as natural and holistic as opposed to surgical and pharmacological management of disease. For these

reasons, there are a growing number of homemade diet recipes available through the internet and published sources that tout health benefits. An example of a non-traditional pet food is raw food diets. Proponents of raw food diets claim numerous benefits such as improvement in coat and skin; elimination of breath, body, and fecal odor; improvement in amount of energy and behavior; improvement in overall health and immune function; and reduction of the incidence of many medical conditions including allergies, arthritis, pancreatitis, and parasitism. The rationale for use of raw food is simple. Dogs and cats are carnivores that evolved eating raw foods. In addition, commercial foods are heat processed which alters or destroys nutrients and essential enzymes. Therefore, commercial foods may not be a natural or nutritionally sound diet for dogs and cats. There are three major categories of raw food diets: 1) Commercially available raw food diets. These diets are intended to be complete and balanced without the need

for additional supplements. These diets are typically sold in frozen form. 2) Homemade complete raw food diets. Many recipes for homemade raw food diets are available in books and

articles as well as on the internet. The three most popular homemade raw food diets are the bones and raw food (BARF) diet, the Ultimate diet, and the Volhard diet.

3) Combination diets. These consist of commercially available grain-and-supplement mixes. The grain mix is fed in combination with raw meat.

Although there are numerous health claims for these diets, there is no scientifically proven information, only testimonials. There are several serious potential drawbacks to these diets.

Nutritional imbalances. In one small study, raw food diets were found to have one or more of the following: an unbalanced calcium-to-phosphorous ratio, increased vitamin D levels, decreased potassium content, decreased manganese content, decreased or increased zinc content, decreased iron content, and increased vitamin E content.

Intestinal foreign bodies. There are sporadic reports of esophageal foreign body and obstruction due to ingestion of bones.

Infectious agents. Raw foods, especially meat, may contain infectious agents, many of which are zoonotic. Escherichia coli O147:H7 was cultured from one homemade raw food diet. In one study, approximately 50% of raw food diet contained non-type specific E coli while these were not found in commercial dry foods. In another study, E coli was identified in 15/25 (64%) diets; however, E. coli O157 was not detected. Salmonella spp. were detected in 5/25 (20%) diets. Clostridium perfringens was identified in 5/25 (20%) samples. A toxigenic strain of C. difficile was isolated from one diet. Staphylococcus aureus was isolated from 1/25 (4%) diets. Campylobacter spp. were not isolated from any of the diets. Raw pork may can contain Yersinia enterocolitica 4/O:3 and has been isolated from feces of dogs and cats fed raw pork. Listeria monocytogenes has also been isolated from raw pork and has been associated with disease in dogs including reproductive problems. Rendered raw meat has been shown to be contaminated with bacteria, including Salmonella spp, (in one study 80% of raw food diets cultured positive), Proteus spp, and Pseudomonas spp, that may also be carried by flies. Clostridium difficile has been isolated from feces from dogs and cats. In addition to bacteria, raw foods may contain Toxoplasmosis, trichinella, and other parasites including Echinococcus. These may pose health hazards to animals as well as to the humans who are preparing the food. One argument given by raw food proponents is that the bacteria do not cause disease in dogs or cats. One concern that is often overlooked is the role of dogs and cats to be carriers of potentially zoonotic infectious agents. For example, dogs have been shown to carry Escherichia coli that can cause non-enteric Escherichia coli infections in human beings. In addition, indiscriminate use of antimicrobials may result in antimicrobial resistance of enteric organisms, which, in turn, may find its way into human medicine. There are some publications mainly case reports concerning consumption of raw foods or raw food diets by dogs and cats and reviews expressing opinions concerning raw food consumption by dogs and cats. Cases and case series include: anestrous due to hyperthyroidism associated with consumption of raw meat, hyperthyroidism and associated signs due to consumption of raw meat and glands, hypervitamonisis A in cats resulting in cervical ankylosing spondylosis and hepatic fibrosis, septicemic Salmonellosis in cats fed a raw chicken diet, and diarrhea associated with Salmonella in cats fed raw meat. However, there is a controlled study of growth in kittens fed a homemade raw diet, commercial raw diet, and commercial heat-processed diet that showed decreased stool volume and improved fecal consistency, better overall weight and body composition gain, and no adverse effects including infections in kittens fed the raw chicken homemade diet. There are other known or potential benefits of homemade especially raw food diets: they are typically limited ingredient diets and so may help with food allergies or intolerances, they are more digestible and so decrease on amount of food fed as well as amount of fecal matter produced, they are not processed and so may be beneficial in certain situations as processed foods have been linked

to certain diseases and clinical conditions in humans, and owners have a sense of control over what they feed their pet.

So what kind of recommendation do we make to clients? There are two issues that require resolving when dealing with raw food diets and clients who wish to feed them. First, we must decide whether we believe in their use and feel comfortable in providing advice concerning their use and preparation. Second, we must provide competent advice on their use. These issues extend beyond health issues for dogs and cats to health issues with the human beings that share the same environment and prepare the food. Clients should be made aware of the potential for problems especially infectious diseases associated with raw food diets and hygiene should be emphasized. Raw food diets should be kept on a bottom shelf in the freezer or refrigerator to prevent contamination of other foods and if possible the raw pet food should be kept in a separate refrigerator. Separate food preparation bowls and utensils should be used and they should be washed as soon as possible after using. Homes with young children or immunocompromised adults should be strongly scrutinized concerning risk-benefit to the pet. Most important – good hygiene and common sense.

Standard Pet Formula - adequate for healthy dogs and cats over 6 months of age – from Veterinary Information

Network (Susan Wynn, Claudia Kirk, Joe Bartges, Craig Datz) 1 pound fresh boneless skinless chicken breast 2 and 2/3 cup cooked white rice 1 Tablespoon safflower oil 1/4 tsp Morton's lite salt 1/4 tsp iodinated salt 3 grams of calcium carbonate without vitamin D (regular Tums - check size) 1 Centrum adult multivitamin-mineral supplement (no special senior, ocular, women's or other versions) 1/4 tsp taurine powder (or 500 mg tablet) (taurine is optional for dogs - essential for cats) Sauté chopped chicken breast in oil until thoroughly cooked. Add rice and salt.Grind Tums (calcium carbonate), multi vitamin/mineral tab, and taurine supplement together. Add to cooled mixture. Store in refrigerator. Larger batches may be prepared in advance and stored in the freezer. Nutritional profile 40% protein (Dry matter basis (DMB)) 12% fat DMB 6% calcium DMB 4.3% phosphorus 1.4:1.0 calcium:phosphorus

Calories: 1046 kcal per batch or 1.12 kcal/gram Batch size: 932 grams

To feed, calculate caloric needs and divide into twice daily feeding. One recipe batch should provide adequate intake for a 40-45 pound dog for 1 day. Adjust intake to maintain ideal body weight There are many resources available that can be found at the American College of Veterinary Nutrition web site (http://www.acvn.org)