Calcifediol: Difference between revisions

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'''Calcifediol''', also known as '''calcidiol''', '''25-hydroxycholecalciferol''', or '''25-hydroxyvitamin D3''' (abbreviated '''25(OH)D3'''), is a form of [[vitamin D]] produced in the [[liver]] by [[hydroxylation]] of [[vitamin D3|vitamin D3]] (cholecalciferol) by the enzyme [[vitamin D 25-hydroxylase]]. Calcifediol can be further hydroxylated by the [[enzyme]] [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|25(OH)D-1α-hydroxylase]], primarily in the kidney, to form [[calcitriol]] (1,25-(OH)2D3), which is the active hormonal form of vitamin D.

Calcifediol is strongly bound in blood by the [[vitamin D-binding protein]].Measurement of serum calcifediol is the usual test performed to determine a person's vitamin D status, to show [[vitamin D deficiency]] or sufficiency. Calcifediol is available as an oral medication in some countries to supplement vitamin D status.~~<ref name="NIH-ODS-2020"/>~~

Calcifediol is strongly bound in blood by the [[vitamin D-binding protein]].Measurement of serum calcifediol is the usual test performed to determine a person's vitamin D status, to show [[vitamin D deficiency]] or sufficiency. Calcifediol is available as an oral medication in some countries to supplement vitamin D status.

==Biology==

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Calcifediol is further hydroxylated at the 1-alpha-position in the kidneys to form 1,25-(OH)2D3, calcitriol. This enzymatic [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|25(OH)D-1α-hydroxylase]] reaction is performed exclusively by [[CYP27B1]], which is highly expressed in the kidneys where it is principally regulated by [[parathyroid hormone]], but also by [[FGF23]] and calcitriol itself. CYP27B1 is also expressed in a number of other tissues, including [[macrophages]], [[monocytes]], [[keratinocytes]], [[placenta]] and [[parathyroid gland]] and extra-renal synthesis of calcitriol from calcifediol has been shown to have biological effects in these tissues.

Calcifediol is also converted into [[24,25-dihydroxycholecalciferol]] by 24-hydroxylation. This enzymatic reaction is performed by [[CYP24A1]] which is expressed in many vitamin D target tissues including kidney, and is induced by calcitriol.~~<ref name=Bikle2014/>~~ This will inactivate calcitriol to [[calcitroic acid]], but 24,25-(OH)2D3 may have some biological actions itself.

Calcifediol is also converted into [[24,25-dihydroxycholecalciferol]] by 24-hydroxylation. This enzymatic reaction is performed by [[CYP24A1]] which is expressed in many vitamin D target tissues including kidney, and is induced by calcitriol. This will inactivate calcitriol to [[calcitroic acid]], but 24,25-(OH)2D3 may have some biological actions itself.

==Blood test for vitamin D deficiency==

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==Supplementation==

Calcifediol supplements have been used in some studies to improve vitamin D status.~~<ref name="NIH-ODS-2020"/>~~ Indications for their use include vitamin D deficiency or insufficiency, refractory rickets ([[vitamin D resistant rickets]]), [[familial hypophosphatemia]], [[hypoparathyroidism]], hypocalcemia and [[renal osteodystrophy]] and, with calcium, in primary or corticosteroid-induced [[osteoporosis]].

Calcifediol supplements have been used in some studies to improve vitamin D status. Indications for their use include vitamin D deficiency or insufficiency, refractory rickets ([[vitamin D resistant rickets]]), [[familial hypophosphatemia]], [[hypoparathyroidism]], hypocalcemia and [[renal osteodystrophy]] and, with calcium, in primary or corticosteroid-induced [[osteoporosis]].

Calcifediol may have advantages over cholecalciferol for the correction of vitamin D deficiency states. A review of the results of nine [[randomized control trials]] which compared oral doses of both, found that calcifediol was 3.2-fold more potent than cholecalciferol. Calcifediol is better absorbed from the intestine and has greater affinity for the vitamin-D-binding protein, both of which increase its bioavailability. Orally administered calcifediol has a much shorter half-life with faster elimination. These properties may be beneficial in people with intestinal [[malabsorption]], obesity, or treated with certain other medications.

@@ Line 89: / Line 89: @@
 '''Calcifediol''', also known as '''calcidiol''', '''25-hydroxycholecalciferol''', or '''25-hydroxyvitamin D<sub>3</sub>''' (abbreviated '''25(OH)D<sub>3</sub>'''), is a form of [[vitamin D]] produced in the [[liver]] by [[hydroxylation]] of [[vitamin D3|vitamin D<sub>3</sub>]] (cholecalciferol) by the enzyme [[vitamin D 25-hydroxylase]]. Calcifediol can be further hydroxylated by the [[enzyme]] [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|25(OH)D-1α-hydroxylase]], primarily in the kidney, to form [[calcitriol]] (1,25-(OH)<sub>2</sub>D<sub>3</sub>), which is the active hormonal form of vitamin D.
-Calcifediol is strongly bound in blood by the [[vitamin D-binding protein]].Measurement of serum calcifediol is the usual test performed to determine a person's vitamin D status, to show [[vitamin D deficiency]] or sufficiency. Calcifediol is available as an oral medication in some countries to supplement vitamin D status.<ref name="NIH-ODS-2020"/>
+Calcifediol is strongly bound in blood by the [[vitamin D-binding protein]].Measurement of serum calcifediol is the usual test performed to determine a person's vitamin D status, to show [[vitamin D deficiency]] or sufficiency. Calcifediol is available as an oral medication in some countries to supplement vitamin D status.
 ==Biology==
@@ Line 98: / Line 98: @@
 Calcifediol is further hydroxylated at the 1-alpha-position in the kidneys to form 1,25-(OH)<sub>2</sub>D<sub>3</sub>, calcitriol. This enzymatic [[25-Hydroxyvitamin D3 1-alpha-hydroxylase|25(OH)D-1α-hydroxylase]] reaction is performed exclusively by [[CYP27B1]], which is highly expressed in the kidneys where it is principally regulated by [[parathyroid hormone]], but also by [[FGF23]] and calcitriol itself. CYP27B1 is also expressed in a number of other tissues, including [[macrophages]], [[monocytes]], [[keratinocytes]], [[placenta]] and [[parathyroid gland]] and extra-renal synthesis of calcitriol from calcifediol has been shown to have biological effects in these tissues.
-Calcifediol is also converted into [[24,25-dihydroxycholecalciferol]] by 24-hydroxylation. This enzymatic reaction is performed by [[CYP24A1]] which is expressed in many vitamin D target tissues including kidney, and is induced by calcitriol.<ref name=Bikle2014/>  This will inactivate calcitriol to [[calcitroic acid]], but 24,25-(OH)<sub>2</sub>D<sub>3</sub> may have some biological actions itself.
+Calcifediol is also converted into [[24,25-dihydroxycholecalciferol]] by 24-hydroxylation. This enzymatic reaction is performed by [[CYP24A1]] which is expressed in many vitamin D target tissues including kidney, and is induced by calcitriol. This will inactivate calcitriol to [[calcitroic acid]], but 24,25-(OH)<sub>2</sub>D<sub>3</sub> may have some biological actions itself.
 ==Blood test for vitamin D deficiency==
@@ Line 114: / Line 114: @@
 ==Supplementation==
-Calcifediol supplements have been used in some studies to improve vitamin D status.<ref name="NIH-ODS-2020"/>  Indications for their use include vitamin D deficiency or insufficiency, refractory rickets ([[vitamin D resistant rickets]]), [[familial hypophosphatemia]], [[hypoparathyroidism]], hypocalcemia and [[renal osteodystrophy]] and, with calcium, in primary or corticosteroid-induced [[osteoporosis]].
+Calcifediol supplements have been used in some studies to improve vitamin D status. Indications for their use include vitamin D deficiency or insufficiency, refractory rickets ([[vitamin D resistant rickets]]), [[familial hypophosphatemia]], [[hypoparathyroidism]], hypocalcemia and [[renal osteodystrophy]] and, with calcium, in primary or corticosteroid-induced [[osteoporosis]].
 Calcifediol may have advantages over cholecalciferol for the correction of vitamin D deficiency states. A review of the results of nine [[randomized control trials]] which compared oral doses of both, found that calcifediol was 3.2-fold more potent than cholecalciferol.  Calcifediol is better absorbed from the intestine and has greater affinity for the vitamin-D-binding protein, both of which increase its bioavailability. Orally administered calcifediol has a much shorter half-life with faster elimination. These properties may be beneficial in people with intestinal [[malabsorption]], obesity, or treated with certain other medications.