All animals have a physiological requirement for active vitamin A (retinol). However, most mammals, including the dog but with the exception of the cat, have the ability to convert vitamin A precursors to active vitamin A (see Section 1, pp. 27-29). Carotenoid pigments, of which beta-carotene is the most important, are cleaved by a dioxygenase enzyme in the intestinal mucosa to yield vitamin A aldehyde (retinal). Retinal is then reduced by a second enzyme to form active vitamin A (retinol). Retinol is esterified to fatty acids and absorbed into the body along with dietary fat. ^{1. and 2.} The dioxygenase enzyme that is essential for the splitting of the beta-carotene molecule is either absent or grossly deficient in the domestic cat. Studies have shown that neither dietary nor intravenous beta-carotene can prevent the development of vitamin A deficiency in the domestic cat. ³ As a result, the cat must have a source of preformed vitamin A present in the diet.

The most common forms of preformed vitamin A in foods are derivatives of retinol, such as retinyl palmitate and retinyl acetate. The largest quantities of these compounds are found in fish liver oils and animal livers. Nutrient requirements for vitamin A and its content in pet foods are expressed either as international units (IUs) or retinol equivalents (RE). One IU of vitamin A is equal to 0.3 micrograms (μg) of retinol or 0.3 RE. The 2006 National Research Council (NRC) recommendations suggest an adequate intake (AI) for dogs, during all life stages, of 303 RE/1000 kilocalories (kcal) of diet and a recommended allowance of 379 RE/1000 kcal. ⁴ These values are equivalent to 1060 RE/kilogram (kg) and 1326 RE/kg in a food containing 3.5 kcal/gram (g). The 2008 Association of American Feed Control Officials (AAFCO) Nutrient Profiles for dog foods recommends that dog foods containing an energy density of 3.5 kcal/kg should include a minimum of 5000 IU/kg for growth, reproduction, and adult maintenance. ⁵ This value is equivalent to 1500 RE/kg diet.

Because cats cannot convert carotenoid pigments to active vitamin A, the requirement is expressed in units of retinol for cats. The NRC’s recommendations for cats suggests an AI of 200 μg retinol/1000 kcal of food for growing kittens and adult maintenance, and 400 μg/1000 kcal during pregnancy and lactation. ⁴ The recommended allowances are 250 μg and 500 μg, respectively. These recommended allowances are equivalent to 1000 μg/kg and 2000 μg/kg in a food with an ME of 4.0 kcal/g of dry matter (DM) (Table 13-1). The AAFCO Nutrient Profiles recommend a minimum of 5000 IU/kg of diet on a dry-matter basis (DMB) for adult maintenance and 9000 IU/kg for growth and reproduction in foods containing 4.0 kcal/kg. ⁵ These values are equivalent to 1500 μg and 2700 μg, respectively.

Vitamin A deficiency is rarely observed in dogs and cats because commercial pet foods contain adequate amounts and because dogs are able to convert the carotenoids found in plant matter into active vitamin A. Experimental vitamin A deficiency results in abnormal bone growth and neurological disorders in young animals. Stenosis of the neural foramina causes pinching of cranial and spinal nerves as they pass through the abnormally shaped bone. If the deficiency persists, shortening and thickening of the long bones occur, along with abnormal development of the bones of the skull. ⁶ Vitamin A deficiency in adult animals affects reproduction, vision, and functioning of the epithelium. Clinical signs include anorexia, xerophthalmia and conjunctivitis, corneal opacity and ulceration, skin lesions, and multiple disorders of the epithelial layers in the body. ⁷

Vitamin A toxicity is not common in the animal kingdom because the precursor for vitamin A, beta-carotene, is not a toxic substance. The intestinal mucosa regulates the hydrolysis of beta-carotene and the subsequent absorption of retinol into the body. In addition, the dog appears to have a relatively high tolerance for preformed vitamin A. ^{8. and 9.} The cat differs from the dog because it cannot use carotenoids and must consume all of its vitamin A as preformed retinyl palmitate or free retinol from animal tissues. The absorption of preformed vitamin A is not regulated by the intestinal mucosa, and high amounts of this vitamin are readily absorbed by the body. If cats are fed foods having a concentrated source of vitamin A, they are unable to protect themselves from absorbing toxic levels. These foods include organ meats, such as liver and kidney, and various fish oils. Vitamin A toxicosis in cats results in a disorder called deforming cervical spondylosis. The effects of excess vitamin A on bone growth and remodeling cause the development of bony exostoses (outgrowths) on the cervical vertebrae. These changes eventually cause pain, difficult movement, lameness, and crippling in severe cases (see Section 4, pp. 280-282 for a complete discussion).

Vitamin D is essential for normal calcium and phosphorus metabolism and homeostasis. The actions of vitamin D on the intestine, skeleton, and kidneys result in increased plasma levels of calcium and phosphorus. This facilitates normal mineralization and remodeling of bone and cartilage and maintains the concentration of calcium in the extracellular fluid that is necessary for normal muscle contraction and nervous tissue excitability. Many animals have the ability to synthesize vitamin D ₃ (cholecalciferol) from 7-dehydrocholesterol when the skin is exposed to ultraviolet (UV) radiation. However, dogs and cats have limited ability to convert 7-dehydrocholesterol in the skin to vitamin D ₃ and therefore are dependent upon a dietary source of this essential vitamin. ¹⁰ Studies with cats have found that this inability is caused by a high activity of the enzyme 7-dehydrocholesterol-delta-7-reductase, which catalyzes the conversion of 7-dehydrocholesterol to cholesterol. ¹¹ Because cats rapidly convert 7-dehydrocholesterol to cholesterol, they have limited capacity for synthesizing cholecalciferol and, ultimately, active vitamin D (see Section 1, pp. 29-31).

The level of dietary vitamin D that is needed by a dog or cat depends upon the calcium and phosphorus levels in the diet and the age of the animal. Recent studies with dogs also suggest that differences may occur in vitamin D ₃ metabolism and calcium homeostasis between large and small-breed dogs during periods of growth. ^{12. and 13.} Specifically, the well-documented increased susceptibility of large-breed dogs to developmental skeletal disease may be related to relationships between elevated concentrations of circulating growth hormone, insulin-like growth factor, and active vitamin D ₃ during growth (see Section 5, pp 496-497 for a complete discussion). Regardless of breed-size differences, all growing animals experience a high rate of skeletal calcification and so are more sensitive to dietary deficiency than are adult animals. The interrelationship between vitamin D, calcium, and phosphorus has been demonstrated by studies that have produced experimental vitamin D deficiencies in dogs and cats by limiting or imbalancing calcium and phosphorus levels. ^{14. and 15.} For example, studies with kittens found that clinical signs of vitamin D deficiency did not occur when the level of calcium in a vitamin D–deficient diet was increased from 7 g/kg to 12 g/kg. ¹⁶ However, plasma levels of 25-hydroxycholecalciferol were less than normal in these kittens and increased significantly when the kittens were switched to a diet containing 124 IUs of vitamin D/kg. Normal plasma levels of 25-hydroxycholecalciferol were maintained when the diet’s vitamin D content was further increased to 250 IU/kg. The current AAFCO Nutrient Profiles advise that dog foods and adult maintenance cat foods contain a minimum of 500 IU/kg of vitamin D. The recommendation for kitten diets is 750 IU/kg.

As in other species, experimental induction of vitamin D deficiency in growing dogs and cats results in the development of rickets. ^{17. and 18.} Rickets is characterized by bone malformation caused by insufficient deposition of calcium and phosphorus. The long bones are affected, resulting in bowing of the legs and thickening of the joints. When the deficient diet is replaced with a food containing vitamin D, signs resolve, normal bone mineralization can occur, and circulating levels of vitamin D metabolites increase to normal values. Vitamin D deficiency has also been produced in kittens that were fed a diet containing no vitamin D and 1% calcium and phosphorus. ¹⁹ Deficiency signs were exacerbated when the diet’s phosphorus level was decreased to 0.65% and calcium was increased to 2%. Because practical ingredients that are included in commercially produced pet foods naturally contain vitamin D ₃, deficiency is rare in companion animals, and when observed is usually associated with either a strict vegetarian diet, the presence of disease, or an inborn error of metabolism.

Vitamin D deficiency in adult animals leads to osteomalacia. This disorder is caused by decalcification of bone and results in an increased tendency of the long bones to fracture. Cats with vitamin D deficiency become reluctant to move and show decreased inclination to groom themselves. A progressive posterior paralysis develops, eventually leading to quadriparesis in advanced cases. These neurological changes are associated with degeneration of the spinal cord caused by abnormal growth and remodeling of cervical vertebrae. In most animals, vitamin D deficiency develops concomitantly with deficiencies or imbalances in dietary calcium and phosphorus. Low levels or imbalances of these minerals exacerbate vitamin D deficiency and may precipitate the signs of rickets in growing animals or osteomalacia in adults.

Hypervitaminosis D caused by excess levels of dietary vitamin D is well documented and results in hypercalcemia and calcification of soft tissues. The most common cause in pet dogs and cats is not dietary, but rather occurs as a result of accidental cholecalciferol rodenticide poisoning. ^{20.21. and 22.} In addition, several cases of hypervitaminosis D were reported to occur in dogs in the United Kingdom and cats in Japan; these animals were fed commercial foods that mistakenly contained excessive levels of vitamin D. ^{23. and 24.} In both these cases, the commercial foods contained excessively high concentrations of vitamin D because of a manufacturing error that subsequently led to product recalls. A survey of commercial cat foods marketed in the United States found that none of the foods was deficient in vitamin D content, based upon an arbitrary minimum requirement of 250 IU/kg, but some did contain less than the AAFCO minimum of 500 IU/kg. ¹⁹ Conversely, 20 of the 49 foods sampled contained more than 7500 IU/kg, and 15 contained more than 10,000 IU/kg, levels that are well above the AAFCO’s maximum allowance of 5000 IU/kg. The sources of high vitamin D levels are generally ingredients such as fish meals and fish oils that contain naturally high concentrations of the vitamin, rather than supplemental vitamin D. Regardless of these findings, no reports of clinical vitamin D toxicity in cats have been reported in the United States, although there is some evidence of a connection between feline oral resorptive lesions and high dietary vitamin D (see Chapter 34, p. 447). The lack of toxicity reports may be in part due to evidence that cats appear to be relatively resistant to cholecalciferol toxicosis, when compared with other species. ²⁵

Vitamin E functions as a biological, chain-breaking antioxidant that neutralizes free radicals and prevents the peroxidation of lipids within cellular membranes. An animal’s requirement for vitamin E depends on dietary levels of polyunsaturated fatty acids (PUFAs) and selenium, a trace mineral. Vitamin E and selenium function synergistically. Although vitamin E protects cell membrane fatty acids by quenching the free radicals formed during oxidation, selenium (as a component of the enzyme glutathione peroxidase) reduces peroxide formation. This process further protects membrane fatty acids from oxidative damage (see Section 1, p. 31). Increasing the level of unsaturated fat in the diet causes an increase in an animal’s vitamin E requirement. In commercial pet foods, vitamin E also protects unsaturated dietary fats from destructive oxidation. The vitamin is preferentially oxidized before the unsaturated fatty acids, thus protecting them from rancidity. However, in this process, vitamin E is destroyed. Therefore, as the level of unsaturated fatty acids in a food increases, its concentration of vitamin E should also increase.

A naturally occurring deficiency of vitamin E is not common in dogs and cats. However, the ingestion of poorly prepared or poorly stored foods or supplementation with large amounts of PUFAs can precipitate a relative deficiency of this vitamin. ^{26. and 27.} Experimentally induced vitamin E deficiency in dogs results in skeletal muscle degeneration, decreased reproductive performance, retinal degeneration, and impaired immunological response. ^{28. and 29.} Supplementation with large amounts of vitamin E has been theorized to be beneficial in the treatment of some types of skin disorders in dogs, such as discoid lupus erythematosus, demodicosis, and acanthosis nigricans, with varying levels of success reported (see Section 5, pp. 384). ^{30. and 31.} However, these responses are believed to reflect a pharmacological response to high doses of vitamin E, rather than a response to a dietary deficiency state. Although study results have been conflicting, it has also been theorized that dogs engaging in prolonged or strenuous activity that results in oxidative stress may benefit from supplemental vitamin E, and that vitamin E may help to enhance the immune response (see Section 4, pp. 255-256 for a complete discussion). ³²

A condition called pansteatitis, or “yellow fat disease,” occurs in cats that are fed diets containing marginal or low levels of vitamin E and high amounts of unsaturated fatty acids. Signs of pansteatitis include anorexia, depression, pyrexia (fever), hyperesthesia of the thorax and abdomen, a reluctance to move, and the presence of “swollen fat.” ^{33. and 34.} A diet that contains high levels of fish oil may cause a threefold to fourfold increase in a cat’s daily requirement for vitamin E. Early cases of pansteatitis occurred almost exclusively in cats that were fed a canned, commercial, fish-based cat food, of which red tuna was the principal type of fish. Later cases of the disease occurred in cats that were fed diets consisting wholly or largely of canned red tuna, fish scraps, and, in two cases, an imbalanced homemade diet comprised almost completely of whole pig’s brain. ³⁵ Red tuna packed in oil contains high levels of PUFAs and low levels of vitamin E. The addition of large amounts of fish products to a cat’s diet appears to be the most common cause of this disease (see Section 4, p. 279).

Vitamin K includes a class of compounds known as quinones. This vitamin is necessary for normal blood coagulation because of its role in the synthesis of prothrombin (factor II) and several other clotting factors (see Section 1, p. 32). Evidence in both dogs and cats indicates very low dietary requirements for vitamin K, probably due to the ability of bacterial synthesis in the intestine to fully meet the animal’s need for this nutrient. However, interference with vitamin K synthesis or absorption can cause a deficiency, with signs of hemorrhage and decreased levels of prothrombin in the blood.

Naturally occurring vitamin K deficiency has not been reported in dogs and has only been reported anecdotally in case studies of cats consuming diets containing high amounts of fish. In two separate situations, cats fed canned commercial cat foods containing either salmon or tuna developed clinical signs of vitamin K deficiency. ³⁶ Signs included the development of gastric ulcers, increased coagulation times, and decreased serum concentrations of vitamin K–dependent clotting factors. Surprisingly, the vitamin K concentration in the diets was found to be 60 μg/kg diet, a level considered to be adequate for companion animals. Surviving animals responded positively to vitamin K supplementation and demonstrated normalized clotting times within 24 hours of vitamin K therapy. A subsequent series of studies by the same laboratory failed to induce vitamin K deficiency in cats fed various types of purified diets. The experimental diets contained low levels of vitamin K (4 to 30 μg/kg diet) and various factors with the potential to interfere with vitamin K synthesis or absorption. These results suggest that kittens fed purified diets have very low dietary vitamin K requirements and that there may be a factor present in some canned cat foods containing fish that interferes with vitamin K synthesis or absorption. Although this factor or underlying cause has not been identified, it is recommended that canned fish-based cat diets include supplemental vitamin K in the form of 1.0 milligrams (mg) menaquinone/kg food in a food containing 4000 kcal/kg. ⁴