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==What is Vitamin D (Cholecalciferol)?==

==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 Overview - Nutrition|fat]] and absorbed by [[Diffusion - Physiology|diffusion]] across the mucosal surface of the [[Small Intestine Overview - Anatomy & Physiology|small intestine]]. Absorbed vitamin D is released into the [[Lymphatic System Overview - Anatomy & Physiology|lymphatics]] for transport to the [[Liver - Anatomy & Physiology|liver]], where it undergoes the first of two hydroxylation steps. From the liver, vitamin D is then transported to the [[Renal Anatomy - Anatomy & Physiology|kidney]] for the second and final hydroxylation step to form calcitriol. '''Calcitriol is the biologically active form of vitamin D that facilitates [[Calcium - Nutrition|calcium]] balance in the body'''.

Vitamin D is an '''[[Nutrition Glossary#Essential Nutrients|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 Overview - Nutrition|fat]] and absorbed by [[Diffusion - Physiology|diffusion]] across the mucosal surface of the [[Small Intestine Overview - Anatomy & Physiology|small intestine]]. Absorbed vitamin D is released into the [[Lymphatic System Overview - Anatomy & Physiology|lymphatics]] for transport to the [[Liver - Anatomy & Physiology|liver]], where it undergoes the first of two hydroxylation steps. From the liver, vitamin D is then transported to the [[Renal Anatomy - Anatomy & Physiology|kidney]] for the second and final hydroxylation step to form calcitriol. '''Calcitriol is the biologically active form of vitamin D that facilitates [[Calcium - Nutrition|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<ref>How KL, et al. Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D. Gen Comp Endocrinol 1994;96:12-18.</ref> due to high 7-dehydrocalciferol-Δ7 reductase activity<ref>Morris JG. Ineffective vitamin D synthesis in cats is reversed by an inhibitor of 7-dehydrocalciferol-Δ7 reductase. J Nutr 1999;129:903-909.</ref>.  

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<ref>How KL, et al. Dietary vitamin D dependence of cat and dog due to inadequate cutaneous synthesis of vitamin D. Gen Comp Endocrinol 1994;96:12-18.</ref> due to high 7-dehydrocalciferol-Δ7 reductase activity<ref>Morris JG. Ineffective vitamin D synthesis in cats is reversed by an inhibitor of 7-dehydrocalciferol-Δ7 reductase. J Nutr 1999;129:903-909.</ref>.

==Why is it Important?==

==Why is it Important?==

==Roles in the Body==

==Roles in the Body==

#'''Calcium Homeostasis<ref>Holick MF. Vitamin D. In Biochemical and physiological aspects of human nutrition. 2000 Philadelphia, PA: WB Saunders Company p.625-639.</ref><ref name="NRC">National Research Council (NRC). Vitamins. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.194-200.</ref>:''' 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 [[Nephron Microscopic Anatomy#Proximal Tubule|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 [[Calcium#Parathyroid Hormone (PTH)|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 [[Calcium#Calcitriol (Activated Vitamin D3)|calcitriol]]. Low circulating PTH concentration results in low 1α-25 hydroxylase activity. There are '''two primary target tissues for calcitriol: the intestinal epithelium and [[Bones - Anatomy & Physiology|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.

#'''[[Calcium#Calcium Homeostasis|Calcium Homeostasis]]<ref>Holick MF. Vitamin D. In Biochemical and physiological aspects of human nutrition. 2000 Philadelphia, PA: WB Saunders Company p.625-639.</ref><ref name="NRC">National Research Council (NRC). Vitamins. In Nutrient Requirements for Dogs and Cats. 2006 Washington, DC: National Academies Press p.194-200.</ref>:''' 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 [[Nephron Microscopic Anatomy#Proximal Tubule|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 [[Calcium#Parathyroid Hormone (PTH)|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 [[Calcium#Calcitriol (Activated Vitamin D3)|calcitriol]]. Low circulating PTH concentration results in low 1α-25 hydroxylase activity. There are '''two primary target tissues for calcitriol: the intestinal epithelium and [[Bones - Anatomy & Physiology|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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[[File:Canine vitamineD.jpg|500px|center|thumb|© Diffomédia/Masure]]

[[File:Canine vitamineD.jpg|500px|center|thumb|© Diffomédia/Masure]]

==Consequences of Vitamin D Deficiency==

==Consequences of Vitamin D Deficiency==

====Dogs:====  

====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'''<ref name="NRC"/><ref>Malik R, et al. Rickets in a litter of racing greyhounds. J Small Anim Pract 1997;38:109-114.</ref><ref>Taylor MB, et al. Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef. JAVMA 2009;234:1041-1048.</ref>. 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<ref>De Fornel-Thibaud P, et al. Unusual case of osteopenia associated with nutritional calcium and vitamin D deficiency in an adult dog. JAAHA 2007;43:52-60.</ref>.

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'''<ref name="NRC"/><ref>Malik R, et al. Rickets in a litter of racing greyhounds. J Small Anim Pract 1997;38:109-114.</ref><ref>Taylor MB, et al. Diffuse osteopenia and myelopathy in a puppy fed a diet composed of an organic premix and raw ground beef. JAVMA 2009;234:1041-1048.</ref>. 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<ref>De Fornel-Thibaud P, et al. Unusual case of osteopenia associated with nutritional calcium and vitamin D deficiency in an adult dog. JAAHA 2007;43:52-60.</ref>.

====Cats:====  

====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'''<ref>Gershoff SN, et al. The effect of vitamin D-deficient diets containing various Ca:P ratios on cats. J Nutr 1957;63:79-93.</ref><ref>Morris JG, et al. Vitamin D deficiency in kittens exposed to ultraviolet light or sunlight. FASEB J 1994;8:A190.</ref>.

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'''<ref>Gershoff SN, et al. The effect of vitamin D-deficient diets containing various Ca:P ratios on cats. J Nutr 1957;63:79-93.</ref><ref>Morris JG, et al. Vitamin D deficiency in kittens exposed to ultraviolet light or sunlight. FASEB J 1994;8:A190.</ref>.

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|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.

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|protein-losing enteropathy]]), '''[[Liver - Pathology|liver disease]]''' resulting in inadequate conversion of vitamin D to 25-hydroxyvitamin D, or with '''[[:Category:Kidney - Pathology|kidney disease]]''' and inadequate conversion of 25-hydroxyvitamin D to 1,25-hydroxyvitamin D.

==Toxicity==

==Toxicity==

==Dietary Sources==

==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.  

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.<br>

Commercial dog and cat foods intended to be complete and balanced are fortified with cholecalciferol to ensure adequate Vitamin D intake.  

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==

==Diagnosing Vitamin D Deficiency==

==References==

==References==

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[[Category:Vitamins]]

[[Category:Vitamins]]