Hydrolyzed Protein and Amino Acid–Based Diets for Management of Adverse Cutaneous or Gastrointestinal Food Reactions

“Let food be thy medicine and medicine be thy food.” This saying, attributed to Hippocrates, could also be the answer to managing patients with adverse food reactions (AFRs). AFRs, which are divided into food allergy or hypersensitivity (immunologic) or food intolerance (nonimmunologic) reactions, are typically characterized by either gastrointestinal (GI) signs such as inappetence, vomiting, bloating, and diarrhea or cutaneous signs such as pruritus, erythema, and altered hair growth in dogs and cats. AFRs can be clinically managed with a well-tolerated diet, often resulting in fewer medications needed to treat secondary infections or minimize clinical signs and, hopefully, in fewer flares and negative outcomes.

Diagnosis of an AFR requires a strict elimination diet trial using an appropriate diet. Such diets typically fall into 3 broad categories: veterinary therapeutic hydrolyzed protein diets, veterinary therapeutic limited-ingredient diets, and complete and balanced home-cooked diets. Each type of diet has benefits and drawbacks; the latter 2 categories require a very thorough diet history to ensure a novel protein and/or novel carbohydrate is used. Complete and balanced home-cooked diets also require a board-certified veterinary nutritionist to formulate the diet to ensure appropriateness for the patient, as well as strict client adherence to the recipe provided (BOX 1).

Given that completely accurate diet histories are not always possible, that successfully identifying truly novel protein and carbohydrate diets can be difficult, and that clients may not adhere to home-cooked recipes (“diet drift”),¹ veterinary therapeutic hydrolyzed protein diets can be excellent tools in the clinician’s diagnostic and treatment toolbox.

Hydrolyzed Protein Diets

The main goal of hydrolyzing a protein is to break it down to a size that removes existing allergens, thereby avoiding recognition by patients sensitized to the intact protein.² Briefly, hydrolysis is a reasonably reliable way to reduce antigenicity of a protein molecule by using proteolytic enzymes to cleave peptide bonds. The degree to which the resultant hydrolysate stimulates a response depends on the site of action within the peptide chain. In a hydrolyzed protein diet, all intact proteins and larger polypeptides are ideally processed into small peptides, typically < 13 kDa (low–molecular-weight proteins). TABLES 1 AND 2 list currently available commercial veterinary therapeutic hydrolyzed protein diets for dogs and cats, respectively.

While some protein sources are obvious (i.e., animal proteins), carbohydrate sources also contain protein (TABLE 3), and protein allergens from 67 to 145 kDA have even been detected in refined vegetable oils.³ Thus, the fat and carbohydrate sources in hydrolyzed protein diets may also contribute allergens, and all the ingredients in any diet should be considered when assessing clinical response. Some hydrolyzed diets are extensively hydrolyzed with the goal of ensuring fewer allergens and reduced clinical signs.^4,5 However, even these diets may retain allergens that cause AFRs in some individuals, at which point a trial using a different diet, often with a different protein source, is recommended.

In selecting an elimination trial diet, carbohydrate sources should also be considered. The most commonly reported sources of food allergies in dogs and cats include animal proteins and some carbohydrates (TABLE 4)⁶; therefore, it is worth noting that some hydrolyzed diets offer only the carbohydrate portion of the carbohydrate source (e.g., corn starch, tapioca starch, potato starch, rice starch). Even so, in human nutrition studies, maize zeins—proteins of 20 to 23 kDa—have been detected in an extensively hydrolyzed casein hydrolysate infant formula that used corn starch as the carbohydrate source.⁷

When selecting a hydrolyzed diet, the author prefers diets that use only hydrolyzed proteins (ideally single source) and either isolated carbohydrate sources or rice, as this limits potential confounding factors in the diagnostic process. Some hydrolyzed formulas include plant proteins, but these proteins should still be hydrolyzed to limit antigenicity; thus, some diet formulations that provide hydrolyzed animal protein sources and isolated (but not hydrolyzed) plant protein sources are less preferred by the author.

Amino Acid–Based Diets

In an effort to further minimize antigenicity, some diets provide protein in the form of individual amino acids rather than the small polypeptides in hydrolyzed diets (oligomeric) or intact proteins (polymeric) in other diets. The advent of these elemental (monomeric) diets in veterinary medicine stems from elemental diet use in human medicine.

Elemental diets have been used in human nutrition for more than 50 years to manage several disease processes, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel disease, small intestinal bacterial overgrowth, intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease.⁸ In veterinary nutrition, elemental diets have been used to improve clinical signs in chronic enteropathy and cutaneous AFRs and as prophylaxis for dogs undergoing pelvic radiation therapy.^9-11 However, elemental diets have been associated with palatability issues in both human and veterinary patients.

While human liquid elemental diets may be used in veterinary patients in short-term clinical settings, they are not complete and balanced for dogs and cats, and significant essential nutrient deficiencies could lead to poor and potentially fatal outcomes even with short-term use, depending on the human formulation. Supplementation of human products with at least taurine, arginine, and B vitamins is necessary when used longer term.

Use of a complete and balanced elemental diet appropriate for dogs and cats could help particularly sensitive patients that do not respond to hydrolyzed diets. However, only 1 amino acid–based complete and balanced veterinary diet currently exists on the market (Pro Plan Veterinary Diets EL Elemental dry dog food; Purina, proplanvetdirect.com), and there have been difficulties with its distribution and access.

Clinical Strategies for Diet Selection

Trial and error is often required to identify the cause of AFRs in patients with GI or cutaneous signs, and owners must be clearly informed that multiple attempts may be necessary to determine the best diet option. However, diagnosis and treatment can go hand in hand if diet selection is successful. In a successful diet trial, GI signs typically improve within 2 to 3 weeks, while cutaneous signs usually improve within 4 to 12 weeks.¹²

The following sections outline clinical strategies for selecting diets for patients with various conditions.

Cutaneous Adverse Food Reactions

Diet history can help guide hydrolyzed protein choice, as many clinicians prefer to choose proteins that are both novel and hydrolyzed (if possible) for elimination diet trials and long-term management. Patients with cutaneous AFRs may benefit from recipes with higher eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content (all other factors and comorbidities considered), as these omega-3 fatty acids provide anti-inflammatory support for skin health.

Clients should expect diet trials for patients with cutaneous AFRs to run at least 4 weeks and up to 8 to 12 weeks.¹² These patients typically take longer to respond even when the ideal trial diet is selected; thus, clients should be counseled to be consistent and follow through to at least 4 weeks. If no improvement in clinical signs is seen and secondary infection/inflammation has been addressed, an alternative diet should be trialed.

Gastrointestinal Adverse Food Reactions (Small Bowel)

Hydrolyzed or elemental diets with low total dietary fiber (TDF) content (8 to 20 g/1000 kcal) make good first-line trial options for patients with small bowel GI AFRs. If a diet history is available, a hydrolyzed formula of a protein known to be novel or tolerated should be considered. Some patients may respond to higher fiber content, and higher-fiber options can be tried gradually if low-residue recipes are unsuccessful.

Gastrointestinal Adverse Food Reactions (Large Bowel)

Hydrolyzed diets with high TDF content (> 25 g/1000 kcal) are good first-line trial options for patients with large bowel GI AFRs. Only 1 currently available commercial diet has very high fiber content (Canine Satiety + Hydrolyzed Protein; Royal Canin, royalcanin.com [110 g TDF/1000 kcal]). If a diet history is available, a hydrolyzed formula of a protein known to be novel or tolerated should be considered.

If a hydrolyzed diet is adequately tolerated but stool quality remains poor, additional supplementation of fiber (e.g., psyllium husk) may be beneficial (BOX 2). Fiber supplements should be introduced gradually, mixing 1 part fiber with at least 3 parts water. Fresh water should be available to the patient at all times. While specific dosing has not been established, varied inclusion rates have been found to be beneficial. In addition, not all fiber is created equally. Solubility, fermentability, and amount all affect each individual differently; thus, trial and error may be necessary and alternate fiber sources (e.g., insoluble fibers such as cellulose) may be considered as well. It is vital to communicate to clients that gradually increasing fiber supplementation to evaluate tolerance will allow for a more successful outcome. Mixing the fiber supplement into a small amount of unsweetened, unflavored applesauce can help with palatability and further increase moisture intake.

Fat Intolerance

For patients with pancreatitis, hyperlipidemia, or lymphangiectasia, formulas that are lower in fat compared with current diet/intake should be used. The best low-fat diet options have fat contents < 35 g/1000 kcal for cats and < 25 g/1000 kcal for dogs (although cats are less susceptible to fat content than dogs). Lower-fat hydrolyzed formulas are available in dry and canned formats. The available elemental diet is fat controlled but may not be adequately fat restricted.

Patients with lymphangiectasia usually require lower-fat recipes than are currently available in hydrolyzed or elemental diets and may benefit from a consultation with a board-certified veterinary nutritionist and an ultra–low-fat home-cooked diet (< 20 g/1000 kcal fat).

Chronic Kidney Disease

Specialized formulas designed to help with management of kidney disease have appropriate phosphorus restriction and controlled protein content. They also have additional renal-supportive nutrients, such as higher levels of anti-inflammatory omega-3 fatty acids (EPA and DHA). Currently, only dry hydrolyzed renal-appropriate diet formulas exist (e.g., Canine/Feline Renal Support + Hydrolyzed Protein; Royal Canin, royalcanin.com).

Struvite or Calcium Oxalate Urolithiasis

For patients with a history of struvite or calcium oxalate urolithiasis, formulas designed to reduce risk of stone recurrence should be considered. Feeding higher-moisture diets (moist, canned foods) and/or promoting water intake should be encouraged to achieve a urine specific gravity below 1.020 in dogs and 1.030 in cats.

Current formulas appropriate for dogs and cats with urolithiasis and AFRs include:

• Dogs: Royal Canin Veterinary Diet Urinary SO + Hydrolyzed Protein dry, Royal Canin Veterinary Diet Hydrolyzed Protein Small Dog dry, Hill’s Prescription Diet z/d dry and canned, Hill’s Prescription Diet z/d Low Fat dry and canned
• Cats: Royal Canin Veterinary Diet Feline Ultamino dry, Royal Canin Veterinary Diet Feline Hydrolyzed Protein HP dry, Royal Canin Veterinary Diet Feline Urinary SO + Hydrolyzed Protein dry, Royal Canin Veterinary Diet Feline Satiety + Hydrolyzed Protein dry, Purina Pro Plan Veterinary Diets HA Hydrolyzed Feline Formula dry, Hill’s Prescription Diet z/d dry and canned

Protein Intolerance

Patients with liver disease with hepatic encephalopathy (HE) or urate stones may benefit from plant-based recipes (e.g., hydrolyzed soy protein isolate) as well as those that are lower in protein (or purine, if indicated). Diets containing < 50 g protein/1000 kcal for dogs and < 70 g protein/1000 kcal for cats can be used as first-line options. Providing the most protein the patient can tolerate without clinical signs (HE or urate stone formation) is important; therefore, the lowest-protein diet available may not be necessary.

Obesity

Plans for active weight loss in pets require a diet that is appropriately fortified with nutrients and avoids essential nutrient deficiencies during caloric restriction. The goal should be to achieve 1% to 2% body weight loss (kg) per week for dogs, and 0.5% to 2% body weight loss (kg) per week for cats. Cats usually fall on the lower end of the weight-loss rate, and patients with comorbidities may benefit from a more conservative rate of weight loss of 0.5% to 1% body weight (kg) maximum per week.

Current formulas appropriate for active weight loss in dogs and cats with AFRs include:

• Dogs: Royal Canin Veterinary Diet Canine Satiety + Hydrolyzed Protein dry
• Cats: Royal Canin Veterinary Diet Feline Satiety + Hydrolyzed Protein dry

Puppies and Kittens

Formulations change with time; therefore, it is important to verify with the manufacturer that any current formula is appropriate for growth, particularly if the patient is a large-breed puppy (> 31.8 kg [70 lb] as an adult).

Current formulas appropriate for growth for puppies and kittens with AFRs include:

• Dogs: Royal Canin Veterinary Diet Hydrolyzed Protein Puppy dry, Purina Pro Plan Veterinary Diets EL Elemental dry, Purina Pro Plan Veterinary Diets HA Hydrolyzed Protein Chicken canned, Purina Pro Plan Veterinary Diets HA Hydrolyzed Protein Salmon dry
• Cats: Purina Pro Plan Veterinary Diets HA Hydrolyzed Feline Formula dry

Additional Considerations

Distribution and accessibility of specialized diets can influence successful management of AFRs. A diet that helps resolve clinical signs has limited therapeutic benefit if it is on backorder or unavailable, requiring alternative diets to be sourced in the meantime. Hydrolyzed diets are also typically considered more expensive and less palatable than veterinary therapeutic limited-ingredient novel protein diets; however, their cost and palatability are similar or preferable to those of the single currently available amino acid–based diet. Canned options for hydrolyzed diets are limited, as the manufacturing process makes the canned texture difficult to achieve, and those that exist may have variable palatability.

Summary

Tailored dietary strategies are crucial for managing patients with AFR, and many issues should be considered to determine which options are appropriate for each patient. Further research into amino acid–based diets may help better determine specific cases that might benefit from this therapeutic strategy and create a larger pool of therapeutic choices in the future.