Monday, July 13, 2015

Hypoallergenic Diets By Laura McKenny and Julia Neer

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Introduction

In human medicine, food allergy refers to adverse food reactions involving a humoral response mediated by immunoglobulin E (IgE). Other food hypersensitivities involve cellular immune responses mediated by T lymphocytes. Food intolerance, by contrast, is a non-immunologic adverse food reaction (Hillier and Griffin, 2001).
Figure 1: Classification of adverse reactions to food (Kennis, 2006).

Both Type I and Type IV hypersensitivity reactions have been reported in dogs. The ACVD task force recommends using the terms “adverse food reaction” in veterinary medicine to refer to an aberrant reaction after ingestion of food or additives since the true pathogenesis is often very difficult to determine (Hillier and Griffin, 2001).


The most common clinical signs of cutaneous adverse food reaction in dogs include year round pruritus or the face, feet, ears, axilla, forelegs or perianal regions, though dogs may present with chronic recurrent otitis or pyoderma. Cats may also develop pleomorphic skin disease. Owners may also report non-dermatologic signs such as vomiting, diarrhea, flatulence, change in stool consistency, anal sac disease and other non-specific gastrointestinal signs (Kennis, 2006). In terms of frequency allergic skin disease occurs in 76% of the canine population in Canada and cutaneous adverse food reaction is reported to be the cause of 32.7% of allergic skin disease. In both dogs and cats it is the third most common skin disease, ranking behind atopic dermatitis and flea bite allergy.

Diagnosis of food allergy can be difficult and usually requires an elimination diet. Although there are serum tests available to detect the level of specific circulating food allergen, they are very unreliable because the level of IgE in serum does not correspond to the severity of clinical presentation and cross-reactivity is common. Therefore the preferred method is a minimum 10 week elimination diet in which the pet is fed only one type of food and nothing else to see if the clinical signs improve. Often times the elimination diet is compromised by things owners do not consider as allergens, such as treats, rawhide bones, flavored medications or oral care products such as dental paste and rinses.


Usually harmless dietary proteins of animal or plant origin can cause allergic food reactions in humans. More than 90% of food allergies are caused by only a dozen food sources. The main food allergens identified in dogs are as follows: cow’s milk, beef, lamb, chicken and grains (Martin et al, 2004, Omori et al, 2007).  Major food allergens are heat-stable, water-soluble glycoproteins with molecular weights ranging from 10 to 60 kd (Kennis, 2006). However peptides as small as 3 to 5 kd can be allergenic. Proteins larger than 70 kd are not likely to be allergenic because they are too large to be absorbed intact across the gut mucosa.

The principal ingredients of pet foods are red meat, poultry, seafood and by-products, feed grains and meals. In Canada these products are widely produced through our agriculture system and thus our dietary preferences are reflected in what we feed to our pets. Since these products are common pet food ingredients it is not surprising that beef and dairy products are the most common pet allergens in Canada. Interestingly beef is not a common allergen in humans despite being a significant part of our diet. This further illustrates the species differences between humans and pet populations.

Dietary management of food allergies can be broad classified into two categories. Hypoallergenic commercial pet foods are marketed as either a hydrolyzed protein source, or a novel protein source. The science behind a hydrolysed protein diet is based on the success of hydrolyzed proteins in babies and children with food allergies.  Although these diets are shown to decrease allergenicity they do not completely eliminate all risk of sensitivity and there are different values in literature and pet food labels of what the smallest molecular weight should be that will not react with IgE. In contrast the logic behind a novel protein diet is that feeding a protein source that the immune system has never been exposed to should not recognized as an allergen.


The role of additives in adverse food reactions in humans and animals is not well defined.  Additives are commonly incriminated but very few studies exist to prove their involvement in adverse food reactions.  In one study, seven previously diagnosed dogs tolerating a home-cooked lamb and rice diet developed clinical signs again once the diet was switched back to a commercial lamb and rice kibble (White, 1986). Another study had similar results showing that the dogs on a homemade diet relapsed when switched to a processed diet (Jeffers et al, 1991).

Another possible cause of food intolerance is the presence of vasoactive amines such as histamine in foods, although their importance in animals is not fully known. Vasoactive amines can be found in high levels in spoiled scombroid fish such as tuna and mackerel. Adverse reactions to these fish have been seen in dogs and cats, and idiosyncratic intolerances to small quantities of histamine have been reported in humans and animals (Hand and Novotny, 2002).


Table 1: Elimination diet options to treat adverse food reactions
Diet Type
Novel Protein
Hydrolyzed Protein
Homemade
Owner Compliance
64-80%
73-97%
63%
Historical Use
First Generation
Next Generation
Gold Standard
Pros
Ease of use
Ease of use
Prescription Only
Digestibility
Free of additives
Cons
Cost

Identification of novel protein can be difficult

Multiple OTC Products
Cross-reactivity
Cost +

Occasional GI signs (hyperosmolar diarrhea)
Cost

Supplementation needed for long term maintenance

Often not nutritionally complete

Time-consuming preparation


Methodology

We have analyzed the label claims from various commercial hypo allergic diets manufactured by several different pet food companies: Purina, Hill’s Pet Nutrition, MediCal/Royal Canin and Iams/Eukanuba. We have investigated both prescription and over the counter diets offered for dogs and cats, listed below. These are not exhaustive lists of all the available hypoallergenic diets but we felt they are an adequate cross section of the major brands.

Table 2: Novel Protein Diets - Canine and Feline
Manufacturer
Brand
Species
Protein
Carbohydrate
Lipid
Treat
Grain Free?
Iams P&G
Veterinary Formulas Skin and Coat Response FP
Dogs
Herring
Catfish
Potato
Fish Oil

No
Yes
Iams P&G
Veterinary Formulas Skin and Coat Response KO
Dogs
Kangaroo
Oatmeal
Fish Oil

No
No
Eukanuba P&G
Sensitive Skin
Dogs
Catfish
Corn
Animal Fat
No
No
Hill’s
Prescription Diet d/d
Dogs
Duck
Potato
Pork Fat

No
Yes
Hill’s
Prescription Diet d/d
Cats
Duck
Potato
Pork Fat Soybean oil
No
Yes
MediCal
Hypoallergenic HP
Dogs
Duck

Rice, potato, oat
Vegetable oil
Yes
No

MediCal
Hypoallergenic HP 
Cats
Duck

Rice,
Potato (dry)

Fish Oil,
Vegetable oil
Yes
No

Royal Canin
Sensitivity RC
Dogs
Catfish
Rice
Poultry Fat
Soybean Oil
No
No

 Table 3: Hydrolyzed Protein Diets - Canine and Feline
Manufacturer
Brand
Species
Protein
Carbohydrate
Lipid
Treats
Grain Free?
Nestle Purina
HA
Dogs
Soy
Corn starch, cellulose, vegetable gums
Coconut oil, canola oil, corn oil
Yes
No
Hill’s
Prescription Diet z/d low allergen
Dogs
Cats
Chicken
Potato (canine)
Potato (canine)
Rice (feline)
Soybean oil
Yes
No
Hill’s
Prescription Diet z/d ultra allergen
Dogs
Cats
Chicken

Corn starch, cellulose
Soybean oil
Yes
No (hydrolyzed)
Hill’s
Prescription Diet z/d low allergen
Cats (canned only)
Chicken
Potato (canine)
Corn starch, cellulose
Soybean oil
Yes
No

Homemade diets are considered the gold standard for the initial elimination diet for diagnosis of food allergies. However, care must be taken to ensure these diets are balanced nutritionally, especially in young animals, as feeding an inadequate diet to a growing animal for more than 3 weeks can result in clinical disease (Hand and Novotny, 2002).


Canine Home Cooked Diet: Recipe for daily requirement of 10 kg dog
  1. Sweet Potato 133 g
  2. Pork meat 67 g
  3. Vegetable Oil 5.6 g
  4. Carrots 16.7 g
  5. Bone meal 2.2 g
  6. KCl 0.56 g
  7. ½ tablet human multivitamin
  8. Omega 3 Fatty Acid Supplement (2000 mg)
Feline Home Cooked Diet: Recipe for daily requirement of a 4.5 kg cat
  1. Sweet Potato 60 g
  2. Pork meat 20 g
  3. Pork liver 20 g (200-500 mg taurine/day)
  4. Vegetable Oil 10 g
  5. Bone meal 1.2 g
  6. KCl 1 g
  7. ½ tablet human multivitamin
  8. Omega 3 Fatty Acid Supplement



Directions: Cook meat and starch separately (do not overcook meat). Pulverize the bone meal. Mix well and serve immediately or refrigerate. Add multivitamin and omega 3 supplements with meal.



Results

Table 4: Canine Hypoallergenic Diet Comparison
Diet
Claims
Cost to feed 10kg dog /day (cents)
Protein
(g/100 Kcal)
Fat  (g/100 Kcal)
Carbohydrates (g/100 Kcal)
Crude Fibre (g/100 Kcal)
Protein (% dry matter)
Ingredients
NRC requirements


5.0
2.25


20

AAFCO requirements


6.5
2.25


26

Hills d/d Potato and Duck

·        Reduced protein
·        Single novel animal protein source (duck)
·        Highly digestible carbohydrate (potato)
143
4.84
4.49
15.3
0.457
18

Potato, Potato Starch, Duck, Potato Protein, Pork Fat, Soybean Oil,  Powdered Cellulose, Fish Oil, Duck By-Product Meal
Hills z/d Low Allergen
·        Hydrolyzed animal protein
·        Single highly digestible carbohydrate source (potato)
150
5.33
4.29
15.1
0.869
19.6

Dried Potato Product, Hydrolyzed Chicken Liver, Potato Starch, Soybean Oil, Hydrolyzed Chicken, Powdered Cellulose
Hills z/d Ultra Allergen Free
·        Hydrolyzed animal protein (avg. MW < 3,000 Daltons)
·        Refined highly digestible carbohydrate (starch)
198
5.1
3.73
15.9
0.725
19

Starch, Hydrolyzed Chicken Liver, Soybean Oil, Hydrolyzed Chicken, Powdered Cellulose
Science Diet Sensitive Skin
·        High quality protein
·        High fatty acid levels
·        Enhanced levels of vitamins (E and C)
·        Superior antioxidant formula
72
7.25
4.59
12.8
0.369
27.52

Brewers Rice, Ground Whole Grain Corn, Corn Gluten Meal, Pork Meal, Dried Egg Product, Soybean Oil, Flaxseed, Animal Fat

MediCal Hypoallergenic HP
·        Hydrolyzed protein: highly digestible and low antigenicity
·        Lactose and wheat gluten free
·        “skin barrier blend”: pantothenic acid, inositol, nicotinamide, choline and histidine to increase ceramide and lipid production
125
5.22
4.72
11.6
0.273
23.1 (min.)

Rice, Soy Protein Isolate Hydrolysate, Chicken Fat,  Dried Beet Pulp, Soybean Oil, Fish Oil, Fructo-Oligosaccharides
MediCal Sensitivity RC
·        Novel protein source (catfish)
·        Single carbohydrate source (rice)
·        Lactose and wheat gluten free
163
6.74
2.64
16.2
1.26
25.6 (min.)

Rice, Catfish Meal, Powdered Cellulose, Chicken Fat, Rice Gluten, Natural Flavour, Soya Bean Oil
Techni-Cal Sensitive Skin
·        Single protein source (lamb)
·        Single carbohydrate source (rice)
77
5.88
3.73
13.0
1.14
22 (min.)

Lamb Meal, Rice, Brown Rice, Chicken Fat, Beet Pulp, Rice Hulls, Flax Seed, Fructo Oligo Saccharides
Purina HA

·        Single hydrolyzed protein source (avg. MW < 12,000 Daltons)
·        Low allergen carbohydrate source
·        Vegetarian diet
·        High digestibility
124
5.17
2.56
14.4
0.38
21.33

Corn Starch, Hydrolyzed Soya Protein, Coconut Oil, Rapeseed Oil, Cellulose, Corn Oil
Pro-Plan Sensitive Skin and Stomach
·        Novel protein source (salmon)
·        Highly digestible carbohydrates (rice and oatmeal)
·        High levels of omega 3 fatty acids
53
7.89
4.87
12.8
1.20
26 (min.)

Salmon, Brewer’s Rice
Canola Meal,
Oat Meal, Fish Meal,
Animal Fat, Salmon Meal,
Pearled Barley




Iams Skin and Coat Response FP
·        Novel protein source (fish)
·        Single carbohydrate source (potato)
·        Highly digestible
·        Reduced omega-6: omega-3 FA ratio to manage inflammation
99
6.62
3.59
13.5
0.702
22 (min.)

Potato, Herring Meal, Catfish, Animal Fat, Dried Beet Pulp
Iams Skin and Coat Response KO
·        Novel protein sources (kangaroo and canola meal)
·        Novel carbohydrate source (Oat flour)
·        Highly digestible
100
5.9
3.65
13.6
1.05
19 (min.)

Oat Flour, Kangaroo, Canola Meal, Animal Fat, Dried Beet Pulp, Fish Oil
Eukanuba Sensitive Skin
·        Does not contain common allergens chicken, corn or wheat
·        Main protein source is ocean fish
·        Main carbohydrate source is rice
·        Optimal ratio of omega-6 to omega-3 fatty acids
89
6.2
3.5
13.3
1.35
23 (min.)

Ocean Fish, Brewer’s Rice, Ground Whole Grain Sorghum, Fish Meal, Ground Whole Grain Barley, Animal Fat, Dried Egg Product, Dried Beet Pulp





Table 5: Feline Hypoallergenic Diet Comparison
Diet
Claims
Cost to feed 4 kg cat/day (cents)
Protein
(g/100 Kcal)
Fat  (g/100 Kcal)
Carbohydrates (g/100 Kcal)
Crude Fibre (g/100 Kcal)
Protein (% dry matter)
Ingredients
Requirements (Average nutrient content of Natural Prey Diet)


15.1
5.5
0.9
62.8



Requirements (Low protein high fat diet)


7.5
8.7
0.8
40

Hills d/d Duck and Green Pea

·        Single novel animal protein source (duck)
·        Allergies to carbohydrate source (green peas) uncommon

90

8.33

6.22

7.42

2.32

32

Pea Protein Concentrate, Duck, Pea Bran Meal, Ground Green Peas, Pork Fat, Duck Meal, Soybean Oil, Fish Oil
Hills z/d Low Allergen
·        Hydrolyzed animal protein
·        Single highly digestible carbohydrate source (rice)

106

8.69

4.24

11.1

0.66

33

Brewer’s Rice, Hydrolyzed Chicken  Liver, Hydrolyzed Chicken, Soybean Oil, Powdered Cellulose
Hills z/d Ultra Allergen Free (canned)
·        Hydrolyzed animal protein (avg. MW < 3,000 Daltons)
·        Refined highly digestible carbohydrate ( corn starch)


365


31.8


17.2


38.2


1.41


33.7

Hydrolyzed Chicken Liver, Corn Starch, Soybean Oil, Powdered Cellulose
Science Diet Sensitive Skin
·        High quality protein
·        Digestible carbohydrates (rice)
·        Enhanced levels of vitamins (E and C)
·        Superior antioxidant formula
·        High levels of fatty acids


67


11.8


5.0


9.1


1.18


35.1

Brewer’s Rice, Corn Gluten Meal, Chicken By-Product Meal, Ground Whole Grain Corn, Pork Fat, Dried Egg Product, Soybean Oil, Fish Oil
MediCal Hypoallergenic HP
·        Hydrolyzed protein: highly digestible and low antigenicity
·        Lactose and wheat gluten free
·        “skin barrier blend”: pantothenic acid, inositol, nicotinamide, choline and histidine to increase ceramide and lipid production

83

6.07


4.9

10.7


0.874

27.17

Rice, Soy Protein Isolate Hydrolysate, Chicken Fat, Powdered Cellulose, Soya Bean Oil, Dried Beet Pulp, Fish Oil, Fructo-Oligosaccharides
MediCal Sensitivity RD
·        Novel protein source (duck)
·        Single carbohydrate source (rice)
·        Lactose and wheat gluten free
·        Highly digestible

82

8.4

3.57

12.5

0.88

34.24

Rice, Duck Meal, Rice Gluten, Chicken Fat, Powdered Cellulose, Soybean Oil
Holistic Select Duck Meal
·        Unique protein source (duck meal) enhanced with Chicken Meal

54


8.6

5.4

2.45

7.6

32 (min.)

Duck Meal, Ground Brown Rice, Chicken Meal, Chicken Fat, Oatmeal, Dried Egg Product, Flaxseed, Tomato Pomace, Dried Beet Pulp
Pro-Plan Sensitive Skin and Stomach
·        Alternative protein source (lamb)
·        Digestible carbohydrates (rice and oat meal)
·        High levels of fatty acids

45

11.8

5.0

7.94

1.18

40 (min.)

Lamb, Brewer’s Rice, Corn Gluten Meal, Dried Egg Product, Wheat Flour, Soy Protein Isolate, Fish Meal, Chicken Meal, Soybean Meal, Animal Fat, Oat Meal, Lamb Meal, Soybean Oil
Iams Skin and Coat Response LB (canned)
·        Single protein source (lamb)
·        Single carbohydrate source (barley)
·        Highly digestible
·        Reduced omega-6 to omega-3 ratio for skin and coat health

202

9.38

6.17

3.99

0.707

41 (min.)

Lamb Broth, Lamb Liver, Lamb Tripe, Lamb,  Ground Pearled Barley, Lamb Meal, Corn Oil, Dried Beet Pulp















Table 6: Canine Hypoallergenic Diets: Omega Fatty Acid Levels (mg/day based on 10 kg dog eating 600 kcal/day))
Diet
Omega 6 (mg)
Omega 3 (mg)
Omega 6:Omega 3 Ratio
Hills d/d Potato and Duck

na*
468
na
Hills z/d Low Allergen
7542
978
7.1:1
Hills z/d Ultra Allergen Free
7434
930
8:1
Science Diet Sensitive Skin
7440
2058
3.6:1
MediCal Hypoallergenic HP
na
na
na
MediCal Sensitivity RC
na
na
na
Techni-Cal Sensitive Skin
na
na
na
Purina HA

3241
521
6.2:1
Pro-Plan Sensitive Skin and Stomach
2535
1027
2.5:1
Iams Skin and Coat Response FP
2352
438
5.4:1
Iams Skin and Coat Response KO
4452
564
7.9:1
Eukanuba Sensitive Skin
3200
640
5:1
Supplements
Product
Omega 6 (mg)
Omega 3 (mg)
Manufacturer’s recommended dose for 10 kg dog (mg Omega 3/day)
Super Pure Omega 3 (1 capsule)
0
300
300
DermCaps Regular (1 capsule)
402
42
42
EFA Caps (1 capsule)
48
130
130
EFA Caps HP (1 capsule)
88
200
455
Pet-Derm OM Regular (1 capsule)
14
135
na

* na= Information not available.
**Clinical studies suggest an initial dose of 50 to 250 mg of n-3 fatty acids/kg body weight/day for patients with inflammatory disease (500 – 2500 mg/day for a 10 kg dog)




Table 7: Ingredients commonly associated with adverse food reactions (Hand and Novotny, 2002)
Dogs
Cats
68% of reported cases
25% of reported cases
89% of reported cases
Beef
Lamb
Beef
Dairy Products
Chicken egg
Dairy Products
Wheat
Chicken
Fish

Soy


Discussion
Most food allergens are thought to be glycoproteins; therefore, protein is the nutrient of greatest concern when dealing with adverse food reactions. The amount of protein, the digestibility of the protein, the number of protein sources and previous exposure to the protein are all important factors to be considered. A different method of decreasing protein antigenicity is the protein Hydrolysate diets. These diets contain proteins that have been hydrolyzed to decrease their molecular weight to below a certain molecular weight. The goal is to reduce the size of proteins until they are theoretically too small to elicit an immune-mediated response. In human medicine there is good evidence of reduced allergenicity of milk hydrolytes in infants (Cave, 2006). Furthermore, the process of hydroxylation eliminates the need for novel or reduced proteins. However, Loeffler et al. (2006) suggest that hydrolyzed protein diets are probably most useful for patients not allergic to the ingredient in their native form.
Hand and Novotny (1998) quote an ideal molecular weight of less than 10,000 Daltons, while Cave (2006) states that if the protein size is reduced to less than 6,000 Daltons in size it should reduce binding to IgE and increase digestibility. However, Verlinden et al (2006), states that peptides over 4,500 Daltons could still be capable of starting the immunologic reaction which contributes to the allergic reaction.

Of the canine hydrolyzed diets, Hill’s z/d Low Allergen has an average molecular weight below 6,000 Daltons while the Hill’s z/d ULTRA Allergen Free has an average molecular weight below 3,000 Daltons. Purina HA has a higher average molecular weight at less than 12,200 Daltons. Medi-cal’s Hypoallergenic HP label claims the soy protein isolate Hydrolysate is “composed of low molecular weight peptides” but information on the average molecular weight was unavailable. Hills z/d Low Allergen does not contain any intact animal proteins but does contain intact plant proteins (potato). Their z/d ULTRA Allergen Free diet does not contain any intact animal or plant protein sources. Medi-cal Hypoallergenic HP contains no intact animal proteins but does contain intact plant protein (rice). Iams/Eukanuba does not produce a hydrolyzed diet.

Of the hydrolyzed feline diets we examined, Hill’s z/d Low Allergen and z/d ULTRA Allergen Free are similar to the canine diets in that the Low Allergen diet contains no intact animal proteins but does contain intact plant proteins (rice), and the ULTRA Allergen Free diet contains no intact animal or plant proteins. The feline Medi-cal Hypoallergenic HP also contains no intact animal proteins but does contain intact plant protein (rice). Purina does not produce a feline hydrolyzed diet for sale in Canada, nor does Iams/Eukanuba.

In non-hydrolyzed hypoallergenic diets, another desirable characteristic is high protein digestibility. When proteins are adequately digested (>87%), free amino acids and small peptides are produced, which are poor antigens (Hand and Novotny, 2002). Most of the diets we examined claimed to be highly digestible, but very few had information available on the percent digestibility of their diets.

Reducing protein content is only beneficial in non-allergic reactions, as even small amounts of an allergenic protein would cause a clinical reaction in a food allergic animal. However, it has been suggested that reducing protein may be useful in delayed type III reactions (Verlinden et al, 2006). For animals with dermatologic conditions, Hand and Novotny (2002) suggest limiting dietary protein to 16-20% on a dry matter basis (DMB) for dogs and 30-45% DMB for cats. The lower limit of the recommendation for canines is below AAFCO standards.
AAFCO has established protein requirements for cats and dogs based on both extremely high quality protein sources and commonly used protein sources in commercial foods. For commonly used protein sources, adult canine maintenance diets should contain at least 18% protein on a DMB, and foods for growth should contain at least 22% protein. Cats, being obligate carnivores require higher protein levels and should receive at least 26% protein on a DMB and kittens should receive at least 30% protein.
All of the canine and feline diets we examined met AAFCO standards for minimum protein levels. Of the canine diets we examined, all of the Hill’s diets (d/d, z/d low allergen and z/d ultra) had low protein levels (18%, 19.6% and 19% dry matter respectively) but only the d/d diet had a label claim of reduced protein. Iams skin and coat response KO formula had a minimum protein content of 19% on a DMB, but average analysis was not available. Of the feline diets we examined, only Medi-cal’s Hypoallergenic HP diet had low protein content (27.17 % dry matter).
Several diets limit the number of animal protein sources to reduce the number of possible allergens. Most of the diets also contain a “novel” protein source, one that is not commonly associated with adverse food reactions and that the animal has likely not been previously exposed to. Novel protein diets are widely available, including several over-the-counter brands, but few have undergone clinical trials on animals with food allergies. One such study found that novel protein diets were 70-80% efficacious for the long term treatment of food allergic dogs (Verlinden et al, 2006). Although not as useful as a properly prepared homemade diet, novel protein diets are useful for those clients that do not have the time or desire to cook for their dogs, or for large breed dogs, for which a homemade diet can be quite expensive.

Of the non-hydrolyzed canine diets we examined, Iams Skin and Coat Response KO contained a single novel animal protein source of Kangaroo. Iams Skin and Coat Response FP contain multiple novel animal protein sources, herring meal, catfish and fish digest. The comparable over-the-counter (OTC) diet, Eukanuba Sensitive Skin, contains multiple animal proteins (ocean fish, fish meal and dried egg product). Ocean fish and fish meal would be considered novel protein sources, but egg is an ingredient commonly associated with adverse food reactions in dogs (Table 7). Hill’s Science Diet Sensitive Skin Formula also contains dried egg product, an inappropriate protein source for a hypoallergenic diet.
Medi-cal’s Sensitivity RC contains catfish as the single animal protein source and as a novel protein. Medi-cal’s OTC hypoallergenic diet, Techni-Cal Lamb and Rice Sensitive Skin, contains lamb as the single animal protein source. The label claims that there is a single animal protein source to “limit your dog’s exposure to food allergens”. Lamb, however, is associated with 25% of reported cases of adverse food reactions, along with chicken, egg and soy (Table 7). Lamb is also a common ingredient in commercial dog foods, so would not likely be useful as a novel protein source. Hills d/d Duck and Potato formula contained a single novel animal protein source (duck). 
Of the non-hydrolyzed feline diets we examined, Iams Skin and Coat Response LB contained a single, novel protein source (lamb) as did Royal Canin Sensitivity RD (duck) and Hill’s d/d Duck and Green Pea Formula (duck).  Purina’s Pro Plan Sensitive Skin and Stomach Formula contain several animal protein sources (lamb, egg, fish and chicken) including fish which is recognized as one of the top allergens in cats. Medi-cal’s comparable OTC diet, made by Waltham’s is Holistic Select Duck Meal Formula, which like the Medi-cal Sensitivity RD formula contains rice and duck meal, but contains two additional animal protein sources: dried egg product and chicken meal, which is not a novel protein source. Hills comparable OTC diet, Science Diet Sensitive Skin also contains dried egg product and chicken as animal protein sources.

The role of carbohydrate and lipid allergens in humans, dogs and cats is controversial and poorly defined. Numerous studies in the literature report incidences of wheat, corn and oat allergies in dogs (Kennis, 2006). Rice is a commonly used carbohydrate source in hypoallergenic diets; however its role as an allergen is controversial. Of the canine diets we looked at, the majority of the diets used rice as the main, or the sole source of carbohydrates. Two products, Purina ProPlan Sensitive Skin and Stomach and Iams Skin and Coat Response KO used oat products as the carbohydrate source. Perhaps a more appropriate source of carbohydrates is potato, which is used in Hill’s z/d Low Allergen, Hill’s d/d Potato and Duck Formula and Iams Skin and Coat Response FP. Hill’s z/d ULTRA Allergen Free diet circumvents the need for a low allergen carbohydrate by also hydrolyzing its carbohydrate source.

In cats, barley and wheat have been implicated as food allergens (Verlinden et al, 2006). Of the diets we examined, two of the diets utilized these ingredients: Purina’s ProPlan Sensitive Skin and Stomach Formula contain wheat flour, and Iams Skin and Coat Response LB contains barley. The majority of the other diets use rice as their main or sole carbohydrate source, with the exception of Hill’s d/d Duck and Green Pea Formula, which uses ground green peas, and Hill’s ULTRA Allergen Free which uses a hydrolyzed carbohydrate source.

Another factor in the choice of carbohydrate sources in pet foods is the impact of the pet food associated renal failure outbreaks due to contaminated wheat/corn gluten or rice protein with melamine. This event has shaken public trust in pet food companies and caused owners to demand a grain-free product.

Dogs and cats are unable to synthesize linoleic acid (an omega-6 fatty acid), making this an essential fatty acid requiring a dietary source. In addition, cats require a dietary source of arachadonic acid, as they are deficient in the enzyme required to synthesize arachadonic acid from linoleic acid. Essential fatty acids have several important roles: they serve a structural role in cell membranes, act as precursors for eicosanoids such as prostaglandins and leukotrienes, and are vital for maintaining normal skin structure and function (Watson, 1998).

Omega-3 fatty acids, on the other hand, have not been demonstrated to be essential in companion animal nutrition, however there may be a requirement for these fatty acids in certain physiological states. Controlled studies have found a benefit of high doses on n-3 fatty acids in the treatment of pruritic skin diseases. There is some evidence that a specific ratio of n-6:n-3 fatty acids is most useful for treatment of inflammatory diseases while others suggest it is the absolute amount of n-3 fatty acids that is of the most importance
(Watson, 1998). In humans, a ratio of 2-3:1 has been found to suppress inflammation in rheumatoid arthritis while a ratio of 5:1 was beneficial to patients with asthma. It has therefore been suggested that the ideal n-6: n-3 ratio depends on the disease process (Simopoulos, 2002).

Pet food ingredients that serve as a source of linoleic acid (an omega-6 fatty acid) include vegetable oils such as soy oil, corn oil, safflower oil and canola oil. Gamma-linoleic acid, another omega-6 fatty acid, can be found in black currant oil, borage oil, and evening primrose oil. Of the omega-3 fatty acids, alpha-linoleic acid (ALA) is found in flax and flax oil, and Eicosapentaenoic acid (EPA) and Docosahexaenoic acid (DHA) are both found in fishmeal and cold water marine oils (Hand and Novotny, 2002).
Conditions that may respond to essential fatty acid supplementation include canine atopy, flea-allergic dermatitis and feline miliary eczema. The problem remains that optimal concentrations and ratios of fatty acids have not been established for dogs and cats. However, based on clinical studies, an initial dose of n-3 fatty acids for patients with inflammatory disease has been suggested of 50-250 mg/kg body weight/day (Hand and Novotny, 2002). Of the diets we examined, all but Hill’s d/d and Iams Skin and Coat Response FP surpass the lower end of this dose range, while only Hill’s Science Diet Sensitive Skin approaches the upper end of the dose range. The fatty acid supplements we looked at are surprisingly low in n-3 fatty acids. At the manufacturer’s recommended dose, none of the supplements reached the lower end of the suggested dose range, and only the concentrated form of EFA caps came close (Table 6).

Only Hills and Iams provide information on their websites about omega 3 and 6 fatty acid levels in their veterinary diets and their over the counter diets (Science Diet and Eukanuba respectively). When contacted, Medi-cal representatives said this information was unavailable for their products. Information on Purina products was available through their company representatives.
Scientific Studies

Loeffler et al. (2004) Dietary trials with a commercial chicken hyolysate diet in 63 pruritic dogs. Veterinary Record 154, 519-522.
The authors evaluated Hill’s z/d Ultra Allergen-Free in a dietary trial consisting of 63 pruritic dogs presented to a veterinary dermatologist. The purpose of the study was to investigate the efficacy of the diet in diagnoses and treatment of adverse food reactions.  Of these dogs 19.6% were diagnosed with cutaneous adverse food reaction but it is unknown if the patients were allergic to the native non-hydrolyzed chicken protein. Furthermore some of the dogs were treated with oral prednisone during the trial to alleviate pruritus, and other dogs were still on antibiotic therapy during the trial, which could affect results pertaining to GI signs. Pruritus scores were based on the owner’s assessment and thus were not standardized among the participants. Potential problems with the Hill’s z/d diet brought up in the study include cost (two owners with larger breed dogs dropped out due to the expense of the diet) and palatability (four dogs refused to eat the diet).
                                                              
Biourge et al. (2004) Diagnosis of Adverse Reactions to Food in Dogs: Efficacy of Soy-Isolate Hydrolysate-Based Diet. Journal of Nutrition, 134: 2062-2064
 The authors evaluated the Royal Canin Hypoallergenic diet to assess the efficacy of a hydrolyzed soy and rice diet in diagnosis of adverse food reactions in dogs. Sixty dogs with suspected skin hypersensitivity were recruited for the study after presentation at a dermatology specialist practice
The study design provided good inclusion criteria (localized or generalized pruritus, self-trauma, erythema, seborrhea and recurrent pyoderma) and excluded dogs with the presence of ectoparasites or underlying disease and the concomitant use of corticosteroid therapy.  Participants were asked to return to a veterinary dermatologist at the end of the trial period to reassess the pruritus score.  Of these dogs 62.1% were diagnosed with cutaneous adverse food reaction and the authors report a 94% success rate with the hydrolyzed soy diet. The authors feel the high success rate is due to stringent exclusion criteria and correct diagnosis of adverse food reaction. Some of the dogs that did not respond to the diet were shown to have concurrent atopy. The authors also admit that  some dogs may not respond to certain elimination diets, but will respond to others and therefore the lack of a positive response to a dietary trial does not eliminate the possibility of food hypersensitivity.

Jackson et al. 2003. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy Hydrolysate diet in dogs with spontaneous food allergy. Veterinary Dermatology 14: 181–187
The authors evaluated the Purina HA diet to assess the efficacy of a limited antigen duck and rice diet in dogs with known clinical hypersensitivity to soy and corn. The dogs were maintained on Purina HA until cutaneous manifestations of pruritus were minimal (78 days). Then the dogs were sequentially re-challenged with oral cornstarch, corn and soy. The authors report a statistically significant increase in pruritus after oral challenge with the allergens, but no significant increase when the dogs we challenged with hydrolyzed soy in 11 out of 14 dogs. These findings suggest that a hydrolyzed diet can be fed to most dogs (79%) that are sensitive to the native non-hydrolyzed soy but a minority (21%) will still react to the hydrolyzed diet.


Beale, K.M., Laflamme, D.P. Comparison of a hydrolyzed soy protein diet containing cornstarch with a positive and negative control diet on corn or soy sensitive dogs. [Abstract] Veterinary Dermatology 2001: 237.
Another study evaluating the efficacy of Purina HA was performed. The authors used 10 allergic dogs (soy or corn) and performed a randomized blinded study. The trial involved one positive control diet (consisting of the native non-hydrolyzed soy), one negative control diet (free of allergens) and the Purina HA diet. The authors report a 50% reduction in pruritus in six soy allergic dogs, and an 80% reduction in pruritus in four corn allergic dogs (not statistically significant).

Conclusions
On the whole, the diets we examined met their label claims. All of the veterinary diets used appropriate animal proteins, i.e. a limited number of protein sources, proteins that are likely novel and proteins that are not known to be common food allergens. The over-the-counter (OTC) diets that had ingredients that were questionable as novel or low antigenicity animal protein sources did not make these specific claims. For example, for the canine Techni-cal Lamb and Rice Sensitive Skin Formula, the label claim is only that there is a single source of protein, not that it is novel or of low allergenicity. Similarly, for the feline Pro Plan Sensitive Skin and Stomach Formula, which contains fish meal, a common food allergen in cats, the only label claim related to protein is that real lamb is the number one ingredient. Eukanuba’s website states that its canine Sensitive Skin product contains “no wheat or corn: No ingredients that may cause itching and scratching in some dogs with sensitive skin”. However this product contains egg, a known food allergen in dogs (Hand and Novotny, 2002). Hill’s canine Science Diet Sensitive Skin Formula also contains egg, and has a label claim that simply states for use in “dogs with skin problems due to adverse reactions to food”.
All of the companies, with the exception of Hill’s, failed to provide information on the percent digestibility of their diets, despite claiming high digestibility on labels.
Where it is less clear as to whether companies are living up to label claims is with regards to Omega-3 fatty acid content. Several diets make label claims that they contain high levels of n-3 fatty acids. However, since the level of n-3’s needed for the treatment of inflammatory skin diseases has not been definitively established, it is difficult to assess whether the companies are living up to this claim. Based on the initial dose of 50-250 mg/kg/day (Hand and Novotny, 2002), only Hill’s Science Diet Sensitive Skin formula approaches a high level of n-3 fatty acids (Table 6). Furthermore, the majority of omega fatty acid supplements on the market do not come close to even the lower end of the recommended dose range for treatment of inflammatory skin diseases, when given at the manufacturer’s recommended dose. Veterinarians prescribing fatty acid supplements for their patients with inflammatory skin diseases would be prudent to prescribe doses higher than the label instructions.
Although not all of the diets examined are completely appropriate for use as elimination diets in the treatment of food allergens in cats and dogs, for the most part, the companies lived up to their label claims.
Overall, the veterinary hypoallergenic diets are all appropriate elimination diets. All of the diets are nutritionally balanced and appropriate for long term use in adult animals, with the possible exception of the diets with reduced protein levels.  According to the NRC minimum protein requirement of 20% on a DMB, all three of the canine Hill’s diets (z/d Low Allergen, z/d ULTRA Allergen Free and d/d Duck and Potato) as well as the Iams Skin and Coat Response KO formula are too low in protein. If the AAFCO minimum requirement for protein levels is used, all of the diets are deficient in protein. Theses diets also have insufficient protein levels to be used in growing animals.
Of the feline OTC diets we looked at, we feel that Hill’s Science Diet Sensitive Skin and Waltham’s Holistic Select Duck Meal are the most appropriate elimination diets as neither contain any of the common allergens known in cats. Both of these diets are priced lower that the veterinary diets, at 67 and 54 cents per day to feed a 4 kg cat respectively. Much less appropriate is Purina’s Pro Plan Sensitive Skin and Stomach which contains both fish meal and wheat, as well as seven different protein sources.
Of the canine OTC diets, we felt that Purina’s Pro Plan Sensitive Skin and Stomach was the most appropriate elimination diet, as it contained only novel proteins (salmon and fish) whereas the three other companies’ diets contained either dried egg product or lamb. Pro Plan also had the second highest n-3 fatty acid level of all the diets, at 1027mg/day for a 10 kg dog. Cost-wise, Purina Pro Plan is also the least expensive of all the diets at 54 cents per day to feed a 10 kg dog (Table 4).
While researching the diets for this paper, most of our frustrations centered on the difficulty in gaining easy access to complete nutritional information in a consistent format. Each company presented their nutritional information in different units, and with different types of analyses (typical vs. guaranteed). There were also inevitably missing pieces of information from each of the companies’ websites, which required phone contact with company representatives. Most representatives were very helpful; however certain information was apparently not available, such as the fatty acid content of Medi-cal diets. Information on fatty acid content for feline diets was even more lacking, prompting us to omit this data from our paper.


References
Beale, K.M., Laflamme, D.P. Comparison of a hydrolyzed soy protein diet containing cornstarch with a positive and negative control diet on corn or soy sensitive dogs. [Abstract] Veterinary Dermatology 2001: 237.
Biourge et al. 2004 Diagnosis of Adverse Reactions to Food in Dogs: Efficacy of Soy-Isolate Hydrolysate-Based Diet.  Journal of Nutrition, 134: 2062-2064
Cave. 2006. Hydrolyzed Protein Diets for Dogs and Cats. Vet Clin Small Anim 36 (2006) 1251–1268
Hand, M.S. and B.J. Novotny. 2002. Pocket Companion to Small Animal Clinical Nutrition. 4th Edition. Mark Morris Institute. pp328-348, 809-816.
Hillier and Griffin. 2001. The ACVD task force on canine atopic dermatitis (X): is there a relationship between canine atopic dermatitis and cutaneous adverse food reaction? Veterinary Immunology and Immunopathology 81: 227-231.
Ishida  et al. 2004. Lymphocyte blastogenic responses to inciting food allergens in dogs with food hypersensitivity. J Vet Intern Med 18(1):25-30
Ishida et al. 2003. Antigen-specific histamine release in dogs with food hypersensitivity J Vet Med Sci 65(3):435-8.
Jackson et al. 2003. Evaluation of the clinical and allergen specific serum immunoglobulin E responses to oral challenge with cornstarch, corn, soy and a soy hydrolysate diet in dogs with spontaneous food allergy. Veterinary Dermatology 14: 181–187
Jeffers et al. 1991. Diagnostic testing of dogs for food hypersensitivity.  JAVMA 198: 245-250.
Kennis, R.A. Food Allergies: Update of Pathogenesis, Diagnoses, and Management. Vet Clin Small Animal 36 (2006): 175-184.
Loeffler et al. 2004 Dietary trials with a commercial chicken hyrolysate diet in 63 pruritic dogs. Veterinary Record 154, 519-522.
Martin et al. 2004. Identification of allergens responsible for canine cutaneous adverse food reactions to lamb, beef and cow's milk. Vet Derm 15(6):349-356
 Ohmori et al. 2007. Identification of bovine serum albumin as an IgE-reactive beef component in a dog with food hypersensitivity against beef. J Vet Med Sci 69(8):865-7.
Simopoulos, A.P. 2002. The importance of the ratio of Omega-6 to Omega-3 essential fatty acids. Biomed Pharmacother. 58(8): 365-379.
Verlinden et al. 2006. Food Allergy in Dogs and Cats: A Review. Critical Reviews in Food Science and Nutrition 46:259-273
Watson, T. 1998. Diet and Skin Disease in Dogs and Cats. Waltham Centre for Pet Nutrition, Waltham-on-the-Wolds, Melton
White SD. 1986. Food hypersensitivity in 30 dogs.  JAVMA 188: 695-698.

www.pgpetwellness.com        Iams/Eukanuba
www.hillspet.com                  Hills/Science Diet
www.purina.ca                        Purina
www.royalcanin.ca                 Medi-cal/Royal Canin/Techni-Cal
www.holisticselect.com         Waltham’s Holistic Select

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