Vitamin D (Cholecalciferol) - Nutrition

What is Vitamin D (Cholecalciferol)?

Vitamin D is an essential fat-soluble vitamin. It is found in the diet in one of two forms: animal-derived vitamin D₃ (cholecalciferol) or plant-derived vitamin D₂ (ergocalciferol). Both forms are incorporated into mixed micelles with dietary fat and absorbed by diffusion across the mucosal surface of the small intestine. Absorbed vitamin D is released into the lymphatics for transport to the liver, where it undergoes the first of two hydroxylation steps. From the liver, vitamin D is then transported to the kidney for the second and final hydroxylation step to form calcitriol. Calcitriol is the biologically active form of vitamin D that facilitates calcium balance in the body. Humans are able to synthesise vitamin D by conversion of 7-dehydrocalciferol (a precursor to cholesterol) to cholecalciferol when skin is exposed to ultraviolet (UV) radiation, but neither dogs or cats are able to synthesise adequate levels of vitamin D with UV exposure due to high 7-dehydrocalciferol-Δ7 reductase activity.

Why is it Important?

Vitamin D plays a key role in the regulation of Ca and P homeostasis.

Roles in the Body

1. Calcium Homeostasis: In the liver, dietary vitamin D is hydroxylated to 25-hydroxyvitamin D by the 25-hydroxylase enzyme. This is the first step in vitamin D activation and 25-hydroxyvitamin D is then bound to vitamin D binding protein and released into circulation. Protein-bound 25-hydroxyvitamin D is transported to the kidney for the second and final step in activation. Renal 1α-25 hydroxylase is located on the proximal tubule of the nephron and converts 25-hydroxyvitamin D to 1,25-hydroxyvitamin D (i.e. calcitriol). This renal enzyme is under control of PTH. During periods of low circulating ionized calcium concentrations the parathyroid gland releases PTH, which in turn stimulates 1α-25 hydroxylase activity to produce more calcitriol. Low circulating PTH concentration results in low 1α-25 hydroxylase activity. There are two primary target tissues for calcitriol: the intestinal epithelium and bone. In the enterocyte calcitriol stimulates production of a number of proteins, including the calcium binding protein calbindin, which facilitates uptake of dietary calcium. Receptors to calcitriol are also found on osteoblasts within bone. Binding of calcitriol to osteoblastic receptors stimulates production of cytokines that regulate mineral deposition and osteoclastic activity.

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Consequences of Vitamin D Deficiency

Dogs:

Puppies fed vitamin D deficient diets become lethargic, have poor muscle tone, develop bowing of the limbs (i.e. rickets), and diffuse osteopenia with pathologic fractures. In adult dogs, clinical signs of calcium deficiency (e.g. osteopenia and pathologic fractures) due to inadequate vitamin D intake may take years to develop and is typically associated with unbalanced home-prepared diets.

Cats:

Kittens fed vitamin D deficient diets have poor food intake, lose weight, develop generalized ataxia that progresses to caudal paralysis, and develop diffuse osteopenia with pathologic fractures. Vitamin D deficiencies can occur due to low dietary intake, but also as a result of intestinal diseases affecting absorption of dietary fat (e.g. protein-losing enteropathy), liver disease resulting in inadequate conversion of vitamin D to 25-hydroxyvitamin D, or with kidney disease and inadequate conversion of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D.

Toxicity

Vitamin D toxicity from ingestion of natural foodstuffs is uncommon in dogs and cats, but can be seen with accidental exposure to cholecalciferol rodenticides, excess supplementation of the diet, or from formulation errors in the manufacture of commercial pet foods. Clinical signs of vitamin D toxicity in both dogs and cats include vomiting, diarrhoea, polyuria, and polydipsia and are related to excess calcium absorption and resultant hypercalcaemia.

Dietary Sources

Cholecalciferol is found in animal liver, fatty fish (e.g. herring, salmon, and mackerel), and fish liver oils; dark green leafy vegetables (e.g. kale and spinach) contain ergocalciferol though at concentrations that are inadequate to meet daily requirements without supplementation. Vitamin D is supplemented into milk and milk products in the United States, but this is not consistent across the global milk industry.
Commercial dog and cat foods intended to be complete and balanced are fortified with cholecalciferol to ensure adequate Vitamin D intake.

Diagnosing Vitamin D Deficiency

Diagnosis of Vitamin D deficiency is based on measurement of low serum 25-hydroxycholecalcipherol concentration, low serum total and ionized calcium concentrations, and increased PTH concentration. Radiographs may be consistent with diffuse osteopenia and pathologic fractures. Clinical suspicion of a deficiency arises when there are clinical signs consistent with deficiency and evaluation of diet reveals inadequate vitamin D content.

References

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