Abstract
“Our goal this year was to reach out to people in the feline world,” said Forum organizer Dorothy Laflamme, DVM, PhD, DACVN, Nestle Purina PetCare. “There has been some outstanding research in feline nutrition, and this was the perfect venue to showcase that information.”
Nestle Purina has graciously allowed us to print a summary of Drs. Morris and Rogers lecture from the Forum.
Some Highlights in Elucidating the Peculiar Nutritional Needs of Cats
Quinton R. Rogers, PhD, Hon Dipl ACVN and James G. Morris, PhD, Hon Dipl ACVN
Dr. Quinton R. Rogers (left) and Dr. James G. Morris (right)
A strict carnivorous diet is high in protein, moderately high in fat and very low in carbohydrates. This diet also contains the essential vitamins and minerals (if the skeleton is consumed) and fatty acids to provide a complete diet. One can debate what constitutes a strict dietary carnivore. Certainly raptors and carnivorous fish such as salmonids belong in this category. While cats share many of the same characteristics of these carnivores, cats can also utilize starch. It would appear in the evolution of cats this capability has been maintained while it has either been lost or did not exist in raptors and carnivorous fish.
Food Intake
It was not until the 1950s that purified diets were developed that supported near normal growth in cats. A major obstacle to the study of feline nutrition was a lack of control of respiratory and other viral diseases in colony cats so it was not until specific pathogen free colonies were developed that fully controlled studies could be undertaken.
Another stumbling block was the feeding behavior of cats which had often been referred to as finicky. Besides being particularly sensitive to flavor, texture of the diet is very important for cats. Various research groups were able to improve consumption of purified diets by increasing the water content of the diet using gelatin or agar diets or formulating the diet as a mash. It has been consistently found in various laboratories that weanling kittens more readily adapt to purified diets than adult cats. Although proteins, per se, are neither selected nor avoided, amino acids, peptides and nucleotides show positive palatability for cats.
Protein and Amino Acids
A key difference between the nutritional needs of cats and omnivores (e.g., rats and dogs) is the quantitatively higher crude protein (CP) requirement of cats for maintenance and the higher requirements for arginine, sulfur amino acids, and aromatic amino acids. Cats also show a greater tolerance for excess crude protein and several essential amino acids; and a lesser tolerance for glutamic acid than other animals. Cats also require taurine and niacin which can be synthesized by most animals from cysteine and tryptophan respectively.
The minimum requirement of bioavailable CP for the adult cat is about 160 g/kg diet whereas that of the dog is about one-half as much. The high CP requirement of adult cats is reflected by the quantity of protein in all commercial diets formulated for maintenance of cats, which has for several decades generally contained at least 280-300 g CP/kg diet. However, the minimum crude protein requirements of growing kittens, rats and puppies are 180, 150 and 180 g/kg diet, respectively. Cats have the least difference between maintenance and growth requirements due to having a considerably higher CP requirement for maintenance. This is consistent with the rates of growth of post weanling kittens, rats and puppies of about 1.5–2, 5–10, and 2–5 % of body weight/day, respectively. Thus, the increased need for CP by growing rats and puppies is due to the higher rate of growth in these species, which also results in a higher percentage of the dietary nitrogen being used for protein synthesis than for kittens. The reason for the high CP requirement of adult cats for maintenance appears to be the metabolic profile of the nitrogen catabolic enzymes, those moving nitrogen into the liver for the urea cycle and those involved in synthesizing urea per se. These enzymes in the cat do not downregulate when they are given low-protein diets as occurs in omnivores and herbivores and therefore cats cannot conserve nitrogen to the same extent as these species. While cats do not adapt to low protein diets, cats adapt well to diets containing medium to high protein. Adaptation is brought about by increasing flow through enzyme systems including the urea cycle via substrate regulation, allosteric regulation, and increasing metabolic intermediates (e.g., ornithine in the urea cycle), all without the necessity of increasing enzyme activities. This lower ability of cats to conserve nitrogen results in an obligatory urinary nitrogen loss of 360 mg/kg body weight3/4/day in adult cats fed a protein-free diet which is higher than what occurs in rats or dogs. Long-term food deprivation also causes a much higher urinary nitrogen loss in cats than it does in omnivores. This same lack of down-regulation of nitrogen catabolic enzymes results in the protein-efficiency ratio (PER) and net protein utilization (NPU) for the same proteins being much lower for kittens, about one-half or less, than for rats.
When we began our work on the amino acid requirements in cats neither the essentially nor the requirement for dietary amino acids had been determined. We began by showing which amino acids were essential for the cat. As you might expect, since all animals studied from the single-cell animals to higher animals had been shown to require 8 amino acids: leucine, isoleucine, valine, methionine, threonine, phenylalanine, lysine and tryptophan, we found these essential for cats. Not surprisingly, we also found histidine and arginine to be essential. Most surprising were some of the clinical signs of the deficiencies that we observed. Arginine deficiency produced the most dramatic effect, in that when near adult cats were food deprived overnight and fed a single meal of 4–11 g of an arginine-free diet, within 2 hours all cats exhibited emesis and lethargy. Shortly thereafter they also vocalized and exhibited frothing at the mouth, ataxia, emprosthotonos and exposed claws. One cat, which had eaten 8 g of diet showed bradyp-nea, cyanosis and died in apnea. These clinical signs were caused by severe hyperammonemia as the result of a lack of ornithine, an essential intermediate in the urea cycle, thus shutting down urea synthesis. Normally, under these conditions, ornithine is produced from dietary arginine via liver arginase. Acute short term deficiencies of any one essential amino acid of a week or less, except for arginine, resulted in no overt clinical signs except a gradual decrease in food intake and a corresponding weight loss. During the second week of feeding a diet mildly deficient in threonine (4 g/kg diet), neurological signs appeared, including slight tremor, jerky head and leg movements, a stiff rear gait, difficulty maintaining equilibrium and weakness in the front wrist joints such that upon standing the cats looked bowlegged. These clinical signs appeared to be of cerebellar dysfunction and all disappeared after supplementation with adequate threonine (6 g/kg diet).
Severe histidine deficiency for one month resulted in crusty exudates around their eyes and nostrils, whereas an even more prolonged sub-clinical deficiency for 4–5 months resulted in the development of cataracts in some of the kittens. Examination of the eyes revealed changes in the outer fibers of the lens, with no abnormalities seen in the retina.
It was not uncommon for dried secretions to accumulate around the eyes, nose and/or mouth of kittens after prolonged ingestion of diets deficient in an essential amino acid. For example, prolonged ingestion of an isoleucine deficient diet results in crusty exudates around the eyes of kittens. Apparently this condition is due to infection by common dermal staphylococcal species which indicates that isoleucine deficiency impairs the normal resistance to these dermal microorganisms. The infections resolved after isoleucine supplementation without antibiotic treatment.
Another example is the dermal lesions seen around the mouth and paws as a result of feeding a methionine deficient diet. These lesions are intensified by excess dietary cystine and are similar to those seen under similar dietary treatment of poults and dogs. These lesions quickly disappear upon adding sufficient methionine to the diet.
Methionine is of special interest in cat nutrition in that there are unusual and quantitative differences in pathways of its metabolism. Very little taurine is synthesized in cats, whereas both isovalthine and felinine, branched chain sulfur amino acids, are found in cat urine. More work has been done on felinine, which is considered to be primarily for territorial marking. Felinine is highly odorous and is the precursor to other highly odorous sulfur compounds which are products of the decomposition of felinine. It is now known that felinine is synthesized from cysteine in the liver similar to the synthesis of glutathione. It is transported to the kidney where it is hydrolyzed to release felinylglycine and free felinine which are excreted in the urine. Testosterone is known to enhance the synthesis and excretion of felinine.
Other interesting differences between cats and omnivores such as the rat and chick in amino acid nutrition are the lower tolerances for glutamic acid and the higher tolerances for most of the essential amino acids except methionine. The upper limit for dietary glutamic acid for the kitten is about 5–6 % of the energy. When more than 7 % of energy from glutamic acid was given to kittens, occasional emesis occurred and kittens given only their normal requirement of thiamine (4.4 mg thiamine/kg diet) also became thiamine deficient. With higher dietary thiamine or lower glutamic acid, the kittens grew normally and exhibited no observable clinical signs. Among the essential amino acids, the lowest tolerance is for methionine which is about 1.5 % of energy. An example of higher tolerance is that of the branched chain amino acids. Kittens tolerated 10 % leucine without a depression in food intake or weight gain. Also, kittens chose the high leucine diet even when isoleucine was limiting.
The phenylalanine plus tyrosine requirement of cats is interesting in that only about 7 g/kg diet is required for maximal growth and yet even in adult animals, at least twice this amount is required to produce enough eumelanin, in hair that is normally black, to maximize the black color.
All these differences in the cat's nutrition and metabolism vs. omnivores can be explained on the basis of cats being strict carnivores and having evolved eating small prey that is medium in fat and high in protein that contain less glutamic acid than that found in cereal proteins. The low tolerance of methionine that we have found in kittens fed purified diets may seem to contradict this evolutionary explanation. However, a diet of meat containing 65 % of the energy from protein and 35 % from fat and carbohydrate would provide right at this upper limit. It is known that cats eating high protein, low carbohydrate diets seldom if ever become obese. Perhaps it is the methionine tolerance that limits food intake in these animals.
Taurine
In 1975 Hayes and coworkers reported that feline central retinal degeneration was caused by taurine deficiency. Another highlight involving taurine in the nutrition of cats was the recognition in 1987 that taurine deficiency also resulted in dilated cardiomyopathy (DCM). In between these dates other clinical signs of taurine deficiency were described. They included reproductive and developmental problems as well as neurological, osmoregulatory and immunological defects. The puzzling part of the finding of DCM in cats was that the cats were normally eating diets containing 1200–1400 mg taurine/kg dry matter when the requirement had been determined, using purified diets, to be 400 mg/kg. After much research it was found that the cause of the higher requirement was the lower digestibility of protein and/or Maillard reaction products in most commercial diets (especially canned diets), compared to the purified diets. These diets resulted in bacterial overgrowth in the ileum which resulted in sufficient cholyl hydrolase in the bacteria to cause the hydrolysis of taurocholic acid and the further destruction of taurine, thus interfering with the enterohepatic reutilization of taurocholic acid. Thus, it was not a problem of bioavailability in the sense of absorption of dietary taurine, but in the efficiency of reutilization of taurocholic acid. This was supported by the use of dietary antibiotics which resulted in a restoration of taurine homeostasis in cats given such a diet. Thus, there is no single requirement for taurine for cats, but a variable requirement between 300 and 2000 mg/kg diet, depending on the composition and nature of the diet and its processing.
Carbohydrate Utilization
As a diet of animal tissue contains only low concentrations of carbohydrate, primarily glycogen, a question arises whether cats have the ability to utilize plant carbohydrates. Digestion studies on cats show that starch disappears from the gut, and may be more highly digested by cats than dogs even when uncooked. About four isoenzymes occur in mammalian liver that catalyze the formation of glucose-6 phosphate from glucose. The major liver hexokinase in most animals is hexokinase D or type IV, often referred to as glucokinase. Glucokinase is absent in the liver of cats which is consistent with the low glucose loads cats experience from an all-animal tissue diet. Glucokinase is also absent from the cat leukocytes, but is present in dog leukocytes. The expression pattern of glucose sensing proteins in feline liver differs from dogs, humans and rodents, but pancreatic expression of these proteins was similar in cats to these other species.
The absence of glucokinase in the liver of cats limits the cafs ability to handle high glucose loads but does not pose a problem unless cats ingest a high-carbohydrate diet. Even then, the normal eating behavior pattern of cats, which results in the ingestion of a number of small meals would tend to smooth out the glucose load. Despite the absence of glucokinase a number of enzymes related to glucose metabolism (hexokinase, fructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, fructose-1, 6-bisphophatase and glucose-6-phosphatase) are higher in feline than canine liver.
High intakes of sucrose in cats results in fructosemia and fructosuria. This observation indicates that although fructokinase activity in the liver of cats is higher than dogs, there is an impediment in the metabolism of fructose beyond fructose-1-phosphate. Normally, fructose-1-phosphate is catalyzed to dihydroxyacetone and glyceraldehyde by the enzyme fructose-1-phosphate aldolase, of which there are three isozymes of aldolase A, B, C. Aldolase B is expressed exclusively in the liver, kidney, and intestine. The evidence suggests that aldolase B activity is probably low in cat liver, but does not seem to have been measured. In humans, hereditary fructose intolerance is caused by a deficiency of aldolase B and over 25 enzyme impairing mutations of the aldolase B enzyme have been identified. There is a high probability cats have an inactive aldolase B which impedes the metabolism of fructose. A consequence of the poor utilization of fructose by cats is diarrhea and diuresis that follows ingestion of either aqueous solutions of sucrose or diets containing high amounts of sucrose. Providing only sucrose containing solutions to cats can result in death. Although sucrose improves the physical texture of purified diets for cats, compared to starch and glucose which produce more powdery diets, the amount in the diet should be restricted.
Vitamins
Major differences also occur in the vitamin requirements between cats and other animals. Subsequent to the discovery of the role of taurine in production of central retinal degeneration, the preformed vitamin A requirement of cats was shown to be not dissimilar to other mammals. However, it is in the utilization of the vitamin A precursor carotenoids where cats are different from most other animals including dogs. Carotenoids require cleavage to retinal, the aldehyde form of vitamin A, and it has been unequivocally proven that the major, if not the sole, pathway of beta-carotene cleavage to vitamin A is by oxidative cleavage of the central ethylenic bond of beta-carotene to yield two molecules of retinal. The enzyme undertaking this cleavage is a cytosolic enzyme located in the duodenal mucosa and to some extent in the liver of animals undertaking the carotene conversion. While the enzyme has been cloned from chicken and humans to our knowledge no studies have been done with cats to determine whether the enzyme is present, or if so, what factors prevent its activity.
Vitamin A has a key role in development and in the maturation of tissues. In all species of animals including cats, excessive dietary intakes of vitamin A produce pathological changes in fetal and adult tissues. Animals that obtain their vitamin A from carotenoids have the ability to protect against excess vitamin A by down regulation of the enzyme converting carotene to vitamin A. This step does not occur in cats as all the vitamin A is absorbed from tissues that contain retinol and retinyl esters which could increase the susceptibility of cats to vitamin A toxicity. However, cats, both as kittens and adults, can tolerate intakes of vitamin A that would induce toxicity in other species. The tolerance of cats appears to be a combination of two factors: the cafs ability to sequester larger quantities of vitamin A in the liver with no apparent adverse effect and the form of circulating retinoids in plasma which is predominately retinyl stearate rather than retinol. The liver of cats given high vitamin A diets contains concentrations of vitamin A in excess of those recorded in animals such as polar bears which is often cited as an animal storing such large quantities of vitamin A in the liver that it is toxic when eaten by humans and dogs.
Most animals are independent of a dietary source of vitamin D through ultraviolet activation of 7-dehydrocholesterol in the skin. However, cats and dogs are unable to synthesize adequate vitamin D even when shaved and subjected to UV radiation. Cats and dogs synthesize 7-dehydrocolesterol which is also a precursor of both vitamin D and cholesterol but cat and dog skin contain only low concentrations compared to animals that can undertake vitamin D synthesis. When cats are given an inhibitor of the enzyme that converts 7-dehydrocholesterol to cholesterol the concentration of 7-dehydrocholesterol in the skin is elevated and when cats are exposed to UV radiation they synthesize vitamin D, and have adequate concentrations of 25-hydroxyvitamin D in the plasma. Therefore, the peculiarity of cats in regard to vitamin D synthesis is high activity of the enzyme that depletes the precursor pool for synthesis, not that the enzyme(s) of the synthetic pathway are absent.
Most animals are able to supply their needs for nicotinic acid by the metabolism of tryptophan that is present in excess of that required for protein synthesis. The catabolic pathway of tryptophan to nicotinic acid has an intermediate: cx-amino-ffcarboxymuconic-e-semialdehyde which can either proceed to nicotinic acid synthesis or be metabolized to acetyl CoA and C02 by the enzyme picolinic carboxylase. The activity of picolinic carboxylase is so high in cats that virtually none of the intermediate is available for nicotinic acid synthesis, but is metabolized to acetyl CoA and C02 which renders niacin a dietary requirement. Therefore, while cats have the necessary pathway for nicotinic acid synthesis, the activity of an enzyme (picolinic carboxylase) is so high, that it diverts the intermediate for synthesis along an alternate pathway; a situation analogous to the cat's inability to synthesize vitamin D. It has been speculated that because animal tissue is a good source of nicotinamides there was no evolutionary pressure to maintain synthesis. No other major specific peculiarities in the cafs vitamin requirements have been identified with the possible exception of thiamin discussed in the section on amino acids. Similarly, the propensity of cats to exhibit clinical signs of vitamin E deficiency is more a reflection of the diet than a difference of requirement. Before leaving the vitamins, it may be added that, to our knowledge, the essentiality of dietary inositol has not been tested in cats. Under specific conditions of high saturated fat diets (coconut oil) inositol is required by female gerbils to prevent fatty infiltration of the liver and intestines.
Fats And Essential Fatty Acids
Fats play a significant role in the attractiveness of food for cats as well as being an important source of energy. Cats exhibit a distinct preference for some animal fats over other fats e.g. chicken fat is preferred to beef tallow which in turn is preferred to butter fat. The cat has an aversion to medium chain triglycerides.
Cats, like other mammals, require preformed n-3 and n-6 long chain essential fatty acids (EFA) in their diet, as they are unable to introduce double bonds (desaturate) to precursor fatty acids beyond carbon 9. These EFAs, through chain elongation and desaturation, result in families of highly active metabolic eicosanoids such as prostaglandins, prostacyclines, leucotrienes and thromboxanes. There is general consensus that cats, in common with other animals, require linoleate (an n-6 FA) in the diet along with n-3 fatty acids, but the exact requirements of cats for long chain fatty acids has not been well defined. For most animals, arachidonate (an n-6 FA) is not essential in the diet, as the metabolic need for arachidonate can be met through chain elongation and desaturation of linoleate. There is general consensus that cats have a limited capacity to synthesize arachidonate which is attributed to low desaturase activity of cat liver. Arachidonate-free diets permit similar growth rates in kittens and reproductive success in males when they achieve adulthood as toms given diets containing arachidonate. The essentiality of arachidonate in the diet for multiple litters in queens is somewhat equivocal. Limited numbers of litters have been reported in queens receiving linoleate and no arachidonate in the diet. It has been suggested that some of the problems encountered with purified diets may be due to the balance of n-3 to n-6 fatty acids. In view of the above, the addition of a source of arachidonate in the diet of breeding queens is prudent.
Minerals
Dietary selection based on minerals is relatively rare. In contrast to herbivores, cats show no preference or aversion to sodium salts. Even when severely depleted of sodium and given a choice of diets, cats do not choose a diet containing adequate sodium over a sodium-deficient diet. It would appear that as animal tissue always contains adequate sodium, the redundant neura! pathways required for detection of sodium either did not develop or have not been maintained in cats.
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