Cholecalciferol: Difference between revisions

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Cholecalciferol can be taken as an oral dietary supplement to prevent [[vitamin D deficiency]] or as a medication to treat associated diseases, including [[rickets]]. It is also used for [[familial hypophosphatemia]], [[hypoparathyroidism]] that is causing [[low blood calcium]], and [[Fanconi syndrome]]. Vitamin-D supplements may not be effective in people with severe [[kidney disease]]. Excessive doses in humans can result in vomiting, constipation, weakness, and confusion. Other risks include [[kidney stones]].~~<ref name=UK2016/>~~ Doses greater than 40,000{{nbsp}}[[International unit|IU]] (1,000{{nbsp}}μg) per day are generally required before [[high blood calcium]] occurs. Normal doses, 800–2000 IU per day, are safe in [[pregnancy]].

Cholecalciferol can be taken as an oral dietary supplement to prevent [[vitamin D deficiency]] or as a medication to treat associated diseases, including [[rickets]]. It is also used for [[familial hypophosphatemia]], [[hypoparathyroidism]] that is causing [[low blood calcium]], and [[Fanconi syndrome]]. Vitamin-D supplements may not be effective in people with severe [[kidney disease]]. Excessive doses in humans can result in vomiting, constipation, weakness, and confusion. Other risks include [[kidney stones]]. Doses greater than 40,000{{nbsp}}[[International unit|IU]] (1,000{{nbsp}}μg) per day are generally required before [[high blood calcium]] occurs. Normal doses, 800–2000 IU per day, are safe in [[pregnancy]].

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===Vitamin D deficiency===

Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to [[calcitriol]]. This is important for maintaining calcium levels and promoting bone health and development.~~<ref name=Norman/>~~ As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is 40,000,000 (40x106) [[International unit|IU]], equivalently 1 IU is 0.025 μg or 25 ng. Dietary reference intake values for vitamin D ([[ergocalciferol]] which is D2 and/or cholecalciferol which is D3) have been established and recommendations vary depending on the country:

Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to [[calcitriol]]. This is important for maintaining calcium levels and promoting bone health and development. As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is 40,000,000 (40x106) [[International unit|IU]], equivalently 1 IU is 0.025 μg or 25 ng. Dietary reference intake values for vitamin D ([[ergocalciferol]] which is D2 and/or cholecalciferol which is D3) have been established and recommendations vary depending on the country:

*In the US: 15 μg/d (600 IU per day) for all individuals (males, females, pregnant/lactating women) between the ages of 1 and 70 years old, inclusive. For all individuals older than 70 years, 20 μg/d (800 IU per day) is recommended.

*In the EU: 15 μg/d (600 IU per day) for all people older than 1 year and 10 μg/d (400 IU per day) for infants aged 7–11 months, assuming minimal cutaneous vitamin D synthesis.

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==Biochemistry==

=== Structure ===

Cholecalciferol is one of the five forms of [[vitamin D]].~~<ref>{{DorlandsDict|two/000020436|cholecalciferol}}</ref>~~ Cholecalciferol is a [[secosteroid]], that is, a steroid molecule with one ring open.

Cholecalciferol is one of the five forms of [[vitamin D]]. Cholecalciferol is a [[secosteroid]], that is, a steroid molecule with one ring open.

===Mechanism of action===

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Cholecalciferol can be produced in skin from the light emitted by the UV lamps in [[tanning bed]]s, which produce ultraviolet primarily in the [[Ultraviolet light#Subtypes|UVA]] spectrum, but typically produce 4% to 10% of the total UV emissions as UVB. Levels in blood are higher in frequent users of tanning salons.

Whether cholecalciferol and all forms of vitamin D are by definition "[[vitamins]]" can be disputed, since the definition of vitamins includes that the substance cannot be synthesized by the body and must be ingested. Cholecalciferol ''is'' synthesized by the body during UVB radiation exposure.~~<ref name=Norman/>~~

Whether cholecalciferol and all forms of vitamin D are by definition "[[vitamins]]" can be disputed, since the definition of vitamins includes that the substance cannot be synthesized by the body and must be ingested. Cholecalciferol ''is'' synthesized by the body during UVB radiation exposure.

The three steps in the synthesis and activation of vitamin D3 are regulated as follows:

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The mechanism of high dose cholecalciferol is that it can produce "[[hypercalcemia]], which results in systemic calcification of soft tissue, leading to [[kidney failure]], [[cardiac]] abnormalities, [[hypertension]], CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, [[loss of appetite]], [[polyuria]], and [[polydipsia]]." High-dose cholecalciferol will tend to rapidly accumulate in [[adipose]] tissue yet release more slowly which will tend to delay time of death for several days from the time that high-dose bait is introduced.

In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits. The [[Median lethal dose|LD50]] is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait. Kidneys and heart are target organs. LD50 of 4.4 mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15 mg/kg.<ref name=henderson2000>R. J. Henderson and C. T. Eason (2000), [https://www.publish.csiro.au/wr/wr99048 Acute toxicity of cholecalciferol and gliftor baits to the European rabbit, Oryctolagus cuniculus], Wildlife Research 27(3) 297-300.</ref> Toxicity has been reported across a wide range of cholecalciferol dosages, with LD50 as high as 88 mg/kg or LDLo as low as 2 mg/kg reported for dogs.

In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits. The [[Median lethal dose|LD50]] is 16.8 mg/kg, but only 9.8 mg/kg if calcium carbonate is added to the bait. Kidneys and heart are target organs. LD50 of 4.4 mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15 mg/kg. Toxicity has been reported across a wide range of cholecalciferol dosages, with LD50 as high as 88 mg/kg or LDLo as low as 2 mg/kg reported for dogs.

Researchers have reported that the compound is less toxic to non-target species than earlier generations of anticoagulant rodenticides ([[Warfarin]] and [[Congener (chemistry)|congeners]]) or [[Bromethalin]], and that [[Relay toxicity|relay toxicosis]] (poisoning by eating a poisoned animal) has not been documented. Nevertheless, the same source reports that use of cholecalciferol in [[rodenticide]]s may still pose a significant hazard to other animals, such as dogs and cats, when rodenticide bait or other forms of cholecalciferol are directly ingested.

@@ Line 91: / Line 91: @@
 <!-- Use as a medication -->
-Cholecalciferol can be taken as an oral dietary supplement to prevent [[vitamin D deficiency]] or as a medication to treat associated diseases, including [[rickets]]. It is also used for [[familial hypophosphatemia]], [[hypoparathyroidism]] that is causing [[low blood calcium]], and [[Fanconi syndrome]]. Vitamin-D supplements may not be effective in people with severe [[kidney disease]]. Excessive doses in humans can result in vomiting, constipation, weakness, and confusion. Other risks include [[kidney stones]].<ref name=UK2016/> Doses greater than 40,000{{nbsp}}[[International unit|IU]] (1,000{{nbsp}}μg) per day are generally required before [[high blood calcium]] occurs. Normal doses, 800–2000 IU per day, are safe in [[pregnancy]].
+Cholecalciferol can be taken as an oral dietary supplement to prevent [[vitamin D deficiency]] or as a medication to treat associated diseases, including [[rickets]]. It is also used for [[familial hypophosphatemia]], [[hypoparathyroidism]] that is causing [[low blood calcium]], and [[Fanconi syndrome]]. Vitamin-D supplements may not be effective in people with severe [[kidney disease]]. Excessive doses in humans can result in vomiting, constipation, weakness, and confusion. Other risks include [[kidney stones]]. Doses greater than 40,000{{nbsp}}[[International unit|IU]] (1,000{{nbsp}}μg) per day are generally required before [[high blood calcium]] occurs. Normal doses, 800–2000 IU per day, are safe in [[pregnancy]].
 <!-- History and culture -->
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 ===Vitamin D deficiency===
 {{Main|Vitamin D deficiency}}
-Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to [[calcitriol]]. This is important for maintaining calcium levels and promoting bone health and development.<ref name=Norman/> As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is 40,000,000 (40x10<sup>6</sup>) [[International unit|IU]], equivalently 1 IU is 0.025&nbsp;μg or 25 ng. Dietary reference intake values for vitamin D ([[ergocalciferol]] which is D<sub>2</sub> and/or cholecalciferol which is D<sub>3</sub>) have been established and recommendations vary depending on the country:
+Cholecalciferol is a form of vitamin D which is naturally synthesized in skin and functions as a pro-hormone, being converted to [[calcitriol]]. This is important for maintaining calcium levels and promoting bone health and development. As a medication, cholecalciferol may be taken as a dietary supplement to prevent or to treat vitamin D deficiency. One gram is 40,000,000 (40x10<sup>6</sup>) [[International unit|IU]], equivalently 1 IU is 0.025&nbsp;μg or 25 ng. Dietary reference intake values for vitamin D ([[ergocalciferol]] which is D<sub>2</sub> and/or cholecalciferol which is D<sub>3</sub>) have been established and recommendations vary depending on the country:
 *In the US: 15&nbsp;μg/d (600 IU per day) for all individuals (males, females, pregnant/lactating women) between the ages of 1 and 70 years old, inclusive. For all individuals older than 70 years, 20&nbsp;μg/d (800 IU per day) is recommended.
 *In the EU: 15&nbsp;μg/d (600 IU per day) for all people older than 1 year and 10&nbsp;μg/d (400 IU per day) for infants aged 7–11 months, assuming minimal cutaneous vitamin D synthesis.
@@ Line 123: / Line 123: @@
 ==Biochemistry==
 === Structure ===
-Cholecalciferol is one of the five forms of [[vitamin D]].<ref>{{DorlandsDict|two/000020436|cholecalciferol}}</ref> Cholecalciferol is a [[secosteroid]], that is, a steroid molecule with one ring open.
+Cholecalciferol is one of the five forms of [[vitamin D]]. Cholecalciferol is a [[secosteroid]], that is, a steroid molecule with one ring open.
 ===Mechanism of action===
@@ Line 138: / Line 138: @@
 Cholecalciferol can be produced in skin from the light emitted by the UV lamps in [[tanning bed]]s, which produce ultraviolet primarily in the [[Ultraviolet light#Subtypes|UVA]] spectrum, but typically produce 4% to 10% of the total UV emissions as UVB. Levels in blood are higher in frequent users of tanning salons.
-Whether cholecalciferol and all forms of vitamin D are by definition "[[vitamins]]" can be disputed, since the definition of vitamins includes that the substance cannot be synthesized by the body and must be ingested. Cholecalciferol ''is'' synthesized by the body during UVB radiation exposure.<ref name=Norman/>
+Whether cholecalciferol and all forms of vitamin D are by definition "[[vitamins]]" can be disputed, since the definition of vitamins includes that the substance cannot be synthesized by the body and must be ingested. Cholecalciferol ''is'' synthesized by the body during UVB radiation exposure.
 The three steps in the synthesis and activation of vitamin D<sub>3</sub> are regulated as follows:
@@ Line 160: / Line 160: @@
 The mechanism of high dose cholecalciferol is that it can produce "[[hypercalcemia]], which results in systemic calcification of soft tissue, leading to [[kidney failure]], [[cardiac]] abnormalities, [[hypertension]], CNS depression, and GI upset. Signs generally develop within 18-36 hr of ingestion and can include depression, [[loss of appetite]], [[polyuria]], and [[polydipsia]]." High-dose cholecalciferol will tend to rapidly accumulate in [[adipose]] tissue yet release more slowly which will tend to delay time of death for several days from the time that high-dose bait is introduced.
-In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits. The [[Median lethal dose|LD<sub>50</sub>]] is 16.8&nbsp;mg/kg, but only 9.8&nbsp;mg/kg if calcium carbonate is added to the bait. Kidneys and heart are target organs. LD<sub>50</sub> of 4.4&nbsp;mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15&nbsp;mg/kg.<ref name=henderson2000>R. J. Henderson and C. T. Eason (2000), [https://www.publish.csiro.au/wr/wr99048 Acute toxicity of cholecalciferol and gliftor baits to the European rabbit, Oryctolagus cuniculus], Wildlife Research 27(3) 297-300.</ref> Toxicity has been reported across a wide range of cholecalciferol dosages, with LD<sub>50</sub> as high as 88&nbsp;mg/kg or LD<sub>Lo</sub> as low as 2&nbsp;mg/kg reported for dogs.
+In New Zealand, [[Common brushtail possum|possums]] have become a significant pest animal. For possum control, cholecalciferol has been used as the active ingredient in lethal baits. The [[Median lethal dose|LD<sub>50</sub>]] is 16.8&nbsp;mg/kg, but only 9.8&nbsp;mg/kg if calcium carbonate is added to the bait. Kidneys and heart are target organs. LD<sub>50</sub> of 4.4&nbsp;mg/kg has been reported in rabbits, with lethality to almost all rabbits ingesting doses greater than 15&nbsp;mg/kg. Toxicity has been reported across a wide range of cholecalciferol dosages, with LD<sub>50</sub> as high as 88&nbsp;mg/kg or LD<sub>Lo</sub> as low as 2&nbsp;mg/kg reported for dogs.
 Researchers have reported that the compound is less toxic to non-target species than earlier generations of anticoagulant rodenticides ([[Warfarin]] and [[Congener (chemistry)|congeners]]) or [[Bromethalin]], and that [[Relay toxicity|relay toxicosis]] (poisoning by eating a poisoned animal) has not been documented. Nevertheless, the same source reports that use of cholecalciferol in [[rodenticide]]s may still pose a significant hazard to other animals, such as dogs and cats, when rodenticide bait or other forms of cholecalciferol are directly ingested.