After vitamin A, vitamin D is the vitamin next most likely to be consumed in concentrations toxic to animals. Although vitamin D is toxic at high concentrations, short-term administration of as much as 100 times the requirement level may be tolerated. For most species, the presumed maximal safe level of vitamin D3 for long-term feeding conditions (more than 60 days) is four to 10 times the dietary requirement. Studies in a number of species indicate that vitamin D3 is 10 to 20 times more toxic than vitamin D2 when provided in excessive amounts (NRC, 1987).
Excessive intake of vitamin D produces a variety of effects, all associated with abnormal elevation of blood calcium. Elevated blood calcium is caused by greatly stimulated bone resorption, as well as increased intestinal calcium absorption. The main pathological effect of ingestion of massive doses of vitamin D is widespread calcification of soft tissues. Pathological changes in these tissues are observed to be inflammation, cellular degeneration, and calcification. Diffuse calcification affects joints, synovial membranes, kidneys, myocardium, pulmonary alveoli, parathyroids, pancreas, lymph glands, arteries, conjunctivae, and corneas. More advanced cases interfere with cartilage growth. As would be expected, the skeletal system undergoes a simultaneous demineralization that results in the thinning of bones. Other common observations of vitamin D toxicity are loss of appetite, extensive weight loss, elevated blood calcium, and lowered blood phosphate. Vitamin D toxicity is enhanced by elevated supplies of dietary calcium and phosphorus and is reduced when the diet is low in calcium.
Toxicity caused by excess vitamin D administration is also associated with plasma 25-OHD; concentrations of more than 400 ng per ml are reported (Hughes et al., 1976). Patients suffering from hypervitaminosis D have been shown to exhibit a 15-fold increase in plasma 25-OHD concentration as compared with normal individuals.
Morgan et al. (1947) administered a single oral dose of 314,000 to 530,000 IU vitamin D as irradiated ergosterol per kg (142,727 to 240,090 IU per lb) of body weight to 4- to 5-week-old puppies. All exhibited anorexia, polyuria, bloody diarrhea, polydipsia, and prostration. Three were dead within two weeks and a fourth was moribund in five weeks. Extensive calcification was found in the lungs of these dogs, and moderate calcification in the hearts and kidneys. In the dogs that survived, malocclusion, pitting, irregular placement, and poor development of the teeth were seen. Hendricks et al. (1947) fed 10,000 IU vitamin D daily per kg (4,545 IU per lb) of body weight to weaned cocker spaniel puppies. Anorexia developed, growth was retarded, serum calcium was variably increased, jaws and teeth were deformed and soft tissues were calcified–particularly the lungs, kidneys, and stomach.
Effects of overdosage of vitamin D were observed at necropsy in a cat that had been given 5 million IU of vitamin D3 and 2.5 million IU of vitamin A by mouth over a six-month period. The cat received these vitamins as treatment for a skin ailment, but gradually lost weight and died suddenly. The great vessels, including the aorta and the carotid arteries, and the adrenals were heavily calcified, and calcium was deposited in the stomach wall and parathyroids (Suter, 1957).
Feeding a milk replacer to Airedale puppies resulted in poor development and condition, impaired moving capacity, retarded change of teeth and pathological changes in the kidney (renal calcification and sclerosis, fibrosis of glomerula, dilation of the tubuli). The supplement contained excess vitamin D at 3.45 million IU per kg (1.57 million IU per lb).
Historically, vitamin D toxicosis was rarely considered in dogs, and was generally associated with chronic dietary or therapeutic oversupplementation. Recently, however, acute vitamin D poisoning has become more common through the ingestion of vitamin D3 rodenticides containing 0.075% cholecalciferol (Livezey and Dorman, 1991; Garlock et al., 1991). Toxicosis due to the ingestion of these products must therefore be included in the differential diagnosis for hypercalcemia in dogs and cats.
Cholecalciferol (vitamin D3) rodenticides have caused significant toxicity in dogs at a fraction of the manufacturer's reported LD50 for dog, 88 mg pure cholecalciferol per kg (40 mg per lb) (Garlock et al., 1991). These researchers described a dog estimated to have consumed 1.5 to 3.0 mg per kg (0.68 to 1.36 mg per lb) of body weight of pure cholecalciferol. Clinical signs most commonly associated with the resultant hypercalcemia are polyuria, polydipsia, depression, anorexia, weakness, and vomiting.
Caution for vitamin D toxicity must also be used when formulating home diets for dogs and cats or when enhancing the palatability of commercial diets with higher levels of liver or fish oil, which are all rich sources of vitamin D. Strombeck (1999) hypothesizes that the high incidence of kidney disease in dogs and cats may be related to commercial pet foods that contain excess vitamin D.
