Biotin: Difference between revisions

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{|class="wikitable"

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!Source~~<ref name=Staggs2004/>~~

!Source

!Amount (μg / 100 g)

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The large intestine [[microbiota]] synthesize amounts of biotin estimated to be similar to the amount taken in the diet, and a significant portion of this biotin exists in the free (protein-unbound) form and, thus, is available for absorption. How much is absorbed in humans is unknown, although a review did report that human epithelial cells of the colon in vitro demonstrated an ability to uptake biotin.

Once absorbed, [[sodium-dependent multivitamin transporter]] (SMVT) mediates biotin uptake into the liver.~~<ref name=PKIN2020Biotin />~~ SMVT also binds [[pantothenic acid]], so high intakes of either of these vitamins can interfere with transport of the other.

Once absorbed, [[sodium-dependent multivitamin transporter]] (SMVT) mediates biotin uptake into the liver. SMVT also binds [[pantothenic acid]], so high intakes of either of these vitamins can interfere with transport of the other.

===Metabolism and excretion===

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[[Biotinidase deficiency]] is a deficiency of the enzyme that recycles biotin, the consequence of an inherited genetic mutation. Biotinidase catalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. It is also important in freeing biotin from dietary protein-bound biotin. Neonatal screening for biotinidase deficiency started in the United States in 1984, which as of 2017 was reported as required in more than 30 countries.

Profound biotinidase deficiency, defined as less than 10% of normal serum enzyme activity, which has been reported as 7.1 nmol/min/mL, has an incidence of 1 in 40,000 to 1 in 60,000, but with rates as high as 1 in 10,000 in countries with high incidence of consanguineous marriages (second cousin or closer). Partial biotinidase deficiency is defined as 10% to 30% of normal serum activity. Incidence data stems from government mandated newborn screening. For profound deficiency, treatment is oral dosing with 5 to 20 mg per day. Seizures are reported as resolving in hours to days, with other symptoms resolving within weeks.~~<ref name=Canda2020/>~~ Treatment of partial biotinidase deficiency is also recommended even though some untreated people never manifest symptoms.~~<ref name=Canda2020 />~~ Lifelong treatment with supplemental biotin is recommended for both profound and partial biotinidase deficiency.

Profound biotinidase deficiency, defined as less than 10% of normal serum enzyme activity, which has been reported as 7.1 nmol/min/mL, has an incidence of 1 in 40,000 to 1 in 60,000, but with rates as high as 1 in 10,000 in countries with high incidence of consanguineous marriages (second cousin or closer). Partial biotinidase deficiency is defined as 10% to 30% of normal serum activity. Incidence data stems from government mandated newborn screening. For profound deficiency, treatment is oral dosing with 5 to 20 mg per day. Seizures are reported as resolving in hours to days, with other symptoms resolving within weeks. Treatment of partial biotinidase deficiency is also recommended even though some untreated people never manifest symptoms. Lifelong treatment with supplemental biotin is recommended for both profound and partial biotinidase deficiency.

Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed [[multiple carboxylase deficiency]]. These include deficiencies in the enzymes [[holocarboxylase synthetase]]. [[Holocarboxylase synthetase deficiency]] prevents the body's cells from using biotin effectively and thus interferes with multiple carboxylase reactions. There can also be a genetic defect affecting the sodium-dependent multivitamin transporter protein.

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==Use in biotechnology==

Chemically modified versions of biotin are widely used throughout the [[biotechnology]] industry to isolate proteins and non-protein compounds for biochemical [[assay]]s. Because egg-derived [[avidin]] binds strongly to biotin with a [[dissociation constant]] ''K''d ≈ 10−15 M, biotinylated compounds of interest can be isolated from a sample by exploiting this highly stable interaction. First, the chemically modified biotin reagents are bound to the targeted compounds in a solution via a process called biotinylation. The choice of which chemical modification to use is responsible for the biotin reagent binding to a specific protein.~~<ref name=ThermoFisher />~~ Second, the sample is incubated with avidin bound to beads, then rinsed, removing all unbound proteins, while leaving only the biotinylated protein bound to avidin. Last, the biotinylated protein can be eluted from the beads with excess free biotin. The process can also utilize bacteria-derived [[streptavidin]] bound to beads, but because it has a higher dissociation constant than avidin, very harsh conditions are needed to elute the biotinylated protein from the beads, which often will denature the protein of interest.

Chemically modified versions of biotin are widely used throughout the [[biotechnology]] industry to isolate proteins and non-protein compounds for biochemical [[assay]]s. Because egg-derived [[avidin]] binds strongly to biotin with a [[dissociation constant]] ''K''d ≈ 10−15 M, biotinylated compounds of interest can be isolated from a sample by exploiting this highly stable interaction. First, the chemically modified biotin reagents are bound to the targeted compounds in a solution via a process called biotinylation. The choice of which chemical modification to use is responsible for the biotin reagent binding to a specific protein. Second, the sample is incubated with avidin bound to beads, then rinsed, removing all unbound proteins, while leaving only the biotinylated protein bound to avidin. Last, the biotinylated protein can be eluted from the beads with excess free biotin. The process can also utilize bacteria-derived [[streptavidin]] bound to beads, but because it has a higher dissociation constant than avidin, very harsh conditions are needed to elute the biotinylated protein from the beads, which often will denature the protein of interest.

==Interference with medical laboratory results==

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===Multiple sclerosis===

High-dose biotin (300 mg/day = 10,000 times [[Dietary Reference Intake|adequate intake]]) has been used in [[clinical trial]]s for treatment of [[multiple sclerosis]], a demyelinating autoimmune disease.~~<ref name=Tryfonow2019/><ref name=Sedel2016/>~~ The hypothesis is that biotin may promote remyelination of the [[myelin]] sheath of nerve cells, slowing or even reversing neurodegeneration. The proposed mechanisms are that biotin activates acetyl-coA carboxylase, which is a key rate-limiting enzyme during the synthesis of myelin, and by reducing axonal hypoxia through enhanced energy production. Clinical trial results are mixed; a 2019 review concluded that a further investigation of the association between multiple sclerosis symptoms and biotin should be undertaken,~~<ref name=Tryfonow2019/>~~ whereas two 2020 reviews of a larger number of clinical trials reported no consistent evidence for benefits, and some evidence for increased disease activity and higher risk of relapse.

High-dose biotin (300 mg/day = 10,000 times [[Dietary Reference Intake|adequate intake]]) has been used in [[clinical trial]]s for treatment of [[multiple sclerosis]], a demyelinating autoimmune disease. The hypothesis is that biotin may promote remyelination of the [[myelin]] sheath of nerve cells, slowing or even reversing neurodegeneration. The proposed mechanisms are that biotin activates acetyl-coA carboxylase, which is a key rate-limiting enzyme during the synthesis of myelin, and by reducing axonal hypoxia through enhanced energy production. Clinical trial results are mixed; a 2019 review concluded that a further investigation of the association between multiple sclerosis symptoms and biotin should be undertaken, whereas two 2020 reviews of a larger number of clinical trials reported no consistent evidence for benefits, and some evidence for increased disease activity and higher risk of relapse.

===Hair, nails, skin===

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==Animals==

In cattle, biotin is necessary for hoof health. Lameness due to hoof problems is common, with herd prevalence estimated at 10 to 35%.~~{{citation needed|date=October 2021}}~~ Consequences of lameness include less food consumption, lower milk production, and increased veterinary treatment costs. Results after 4–6 months from supplementing biotin at 20 mg/day into daily diet reduces the risk of lameness. A review of controlled trials reported that supplementation at 20 mg/day increased milk yield by 4.8%. The discussion speculated that this could be an indirect consequence of improved hoof health or a direct effect on milk production.

In cattle, biotin is necessary for hoof health. Lameness due to hoof problems is common, with herd prevalence estimated at 10 to 35%. Consequences of lameness include less food consumption, lower milk production, and increased veterinary treatment costs. Results after 4–6 months from supplementing biotin at 20 mg/day into daily diet reduces the risk of lameness. A review of controlled trials reported that supplementation at 20 mg/day increased milk yield by 4.8%. The discussion speculated that this could be an indirect consequence of improved hoof health or a direct effect on milk production.

For horses, conditions such as chronic laminitis, cracked hooves, or dry, brittle feet incapable of holding shoes are a common problem. Biotin is a popular nutritional supplement. There are recommendations that horses need 15 to 25 mg/day. Studies report biotin improves the growth of new hoof horn rather than improving the status of existing hoof, so months of supplementation are needed for the hoof wall to be completely replaced.

@@ Line 128: / Line 128: @@
 {|class="wikitable"
   |-
-!Source<ref name=Staggs2004/>
+!Source
 !Amount<br /> (μg / 100 g)
 |-
@@ Line 161: / Line 161: @@
 The large intestine [[microbiota]] synthesize amounts of biotin estimated to be similar to the amount taken in the diet, and a significant portion of this biotin exists in the free (protein-unbound) form and, thus, is available for absorption. How much is absorbed in humans is unknown, although a review did report that human epithelial cells of the colon in vitro demonstrated an ability to uptake biotin.
-Once absorbed, [[sodium-dependent multivitamin transporter]] (SMVT) mediates biotin uptake into the liver.<ref name=PKIN2020Biotin /> SMVT also binds [[pantothenic acid]], so high intakes of either of these vitamins can interfere with transport of the other.
+Once absorbed, [[sodium-dependent multivitamin transporter]] (SMVT) mediates biotin uptake into the liver. SMVT also binds [[pantothenic acid]], so high intakes of either of these vitamins can interfere with transport of the other.
 ===Metabolism and excretion===
@@ Line 198: / Line 198: @@
 [[Biotinidase deficiency]] is a deficiency of the enzyme that recycles biotin, the consequence of an inherited genetic mutation. Biotinidase catalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. It is also important in freeing biotin from dietary protein-bound biotin. Neonatal screening for biotinidase deficiency started in the United States in 1984, which as of 2017 was reported as required in more than 30 countries.
-Profound biotinidase deficiency, defined as less than 10% of normal serum enzyme activity, which has been reported as 7.1 nmol/min/mL, has an incidence of 1 in 40,000 to 1 in 60,000, but with rates as high as 1 in 10,000 in countries with high incidence of consanguineous marriages (second cousin or closer). Partial biotinidase deficiency is defined as 10% to 30% of normal serum activity. Incidence data stems from government mandated newborn screening. For profound deficiency, treatment is oral dosing with 5 to 20&nbsp;mg per day. Seizures are reported as resolving in hours to days, with other symptoms resolving within weeks.<ref name=Canda2020/> Treatment of partial biotinidase deficiency is also recommended even though some untreated people never manifest symptoms.<ref name=Canda2020 /> Lifelong treatment with supplemental biotin is recommended for both profound and partial biotinidase deficiency.
+Profound biotinidase deficiency, defined as less than 10% of normal serum enzyme activity, which has been reported as 7.1 nmol/min/mL, has an incidence of 1 in 40,000 to 1 in 60,000, but with rates as high as 1 in 10,000 in countries with high incidence of consanguineous marriages (second cousin or closer). Partial biotinidase deficiency is defined as 10% to 30% of normal serum activity. Incidence data stems from government mandated newborn screening. For profound deficiency, treatment is oral dosing with 5 to 20&nbsp;mg per day. Seizures are reported as resolving in hours to days, with other symptoms resolving within weeks. Treatment of partial biotinidase deficiency is also recommended even though some untreated people never manifest symptoms. Lifelong treatment with supplemental biotin is recommended for both profound and partial biotinidase deficiency.
 Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed [[multiple carboxylase deficiency]]. These include deficiencies in the enzymes [[holocarboxylase synthetase]]. [[Holocarboxylase synthetase deficiency]] prevents the body's cells from using biotin effectively and thus interferes with multiple carboxylase reactions. There can also be a genetic defect affecting the  sodium-dependent multivitamin transporter protein.
@@ Line 205: / Line 205: @@
 ==Use in biotechnology==
-Chemically modified versions of biotin are widely used throughout the [[biotechnology]] industry to isolate proteins and non-protein compounds for biochemical [[assay]]s. Because egg-derived [[avidin]] binds strongly to biotin with a [[dissociation constant]] ''K''<sub>d</sub> ≈ 10<sup>−15</sup>&nbsp;M, biotinylated compounds of interest can be isolated from a sample by exploiting this highly stable interaction. First, the chemically modified biotin reagents are bound to the targeted compounds in a solution via a process called biotinylation. The choice of which chemical modification to use is responsible for the biotin reagent binding to a specific protein.<ref name=ThermoFisher /> Second, the sample is incubated with avidin bound to beads, then rinsed, removing all unbound proteins, while leaving only the biotinylated protein bound to avidin. Last, the biotinylated protein can be eluted from the beads with excess free biotin. The process can also utilize bacteria-derived [[streptavidin]] bound to beads, but because it has a higher dissociation constant than avidin, very harsh conditions are needed to elute the biotinylated protein from the beads, which often will denature the protein of interest.
+Chemically modified versions of biotin are widely used throughout the [[biotechnology]] industry to isolate proteins and non-protein compounds for biochemical [[assay]]s. Because egg-derived [[avidin]] binds strongly to biotin with a [[dissociation constant]] ''K''<sub>d</sub> ≈ 10<sup>−15</sup>&nbsp;M, biotinylated compounds of interest can be isolated from a sample by exploiting this highly stable interaction. First, the chemically modified biotin reagents are bound to the targeted compounds in a solution via a process called biotinylation. The choice of which chemical modification to use is responsible for the biotin reagent binding to a specific protein. Second, the sample is incubated with avidin bound to beads, then rinsed, removing all unbound proteins, while leaving only the biotinylated protein bound to avidin. Last, the biotinylated protein can be eluted from the beads with excess free biotin. The process can also utilize bacteria-derived [[streptavidin]] bound to beads, but because it has a higher dissociation constant than avidin, very harsh conditions are needed to elute the biotinylated protein from the beads, which often will denature the protein of interest.
 ==Interference with medical laboratory results==
@@ Line 221: / Line 221: @@
 ===Multiple sclerosis===
-High-dose biotin (300&nbsp;mg/day = 10,000 times [[Dietary Reference Intake|adequate intake]]) has been used in [[clinical trial]]s for treatment of [[multiple sclerosis]], a demyelinating autoimmune disease.<ref name=Tryfonow2019/><ref name=Sedel2016/> The hypothesis is that biotin may promote remyelination of the [[myelin]] sheath of nerve cells, slowing or even reversing neurodegeneration. The proposed mechanisms are that biotin activates acetyl-coA carboxylase, which is a key rate-limiting enzyme during the synthesis of myelin, and by reducing axonal hypoxia through enhanced energy production. Clinical trial results are mixed; a 2019 review concluded that a further investigation of the association between multiple sclerosis symptoms and biotin should be undertaken,<ref name=Tryfonow2019/> whereas two 2020 reviews of a larger number of clinical trials reported no consistent evidence for benefits, and some evidence for increased disease activity and higher risk of relapse.
+High-dose biotin (300&nbsp;mg/day = 10,000 times [[Dietary Reference Intake|adequate intake]]) has been used in [[clinical trial]]s for treatment of [[multiple sclerosis]], a demyelinating autoimmune disease. The hypothesis is that biotin may promote remyelination of the [[myelin]] sheath of nerve cells, slowing or even reversing neurodegeneration. The proposed mechanisms are that biotin activates acetyl-coA carboxylase, which is a key rate-limiting enzyme during the synthesis of myelin, and by reducing axonal hypoxia through enhanced energy production. Clinical trial results are mixed; a 2019 review concluded that a further investigation of the association between multiple sclerosis symptoms and biotin should be undertaken, whereas two 2020 reviews of a larger number of clinical trials reported no consistent evidence for benefits, and some evidence for increased disease activity and higher risk of relapse.
 ===Hair, nails, skin===
@@ Line 229: / Line 229: @@
 ==Animals==
-In cattle, biotin is necessary for hoof health. Lameness due to hoof problems is common, with herd prevalence estimated at 10 to 35%.{{citation needed|date=October 2021}} Consequences of lameness include less food consumption, lower milk production, and increased veterinary treatment costs. Results after 4–6 months from supplementing biotin at 20&nbsp;mg/day into daily diet reduces the risk of lameness. A review of controlled trials reported that supplementation at 20&nbsp;mg/day increased milk yield by 4.8%. The discussion speculated that this could be an indirect consequence of improved hoof health or a direct effect on milk production.
+In cattle, biotin is necessary for hoof health. Lameness due to hoof problems is common, with herd prevalence estimated at 10 to 35%. Consequences of lameness include less food consumption, lower milk production, and increased veterinary treatment costs. Results after 4–6 months from supplementing biotin at 20&nbsp;mg/day into daily diet reduces the risk of lameness. A review of controlled trials reported that supplementation at 20&nbsp;mg/day increased milk yield by 4.8%. The discussion speculated that this could be an indirect consequence of improved hoof health or a direct effect on milk production.
 For horses, conditions such as chronic laminitis, cracked hooves, or dry, brittle feet incapable of holding shoes are a common problem. Biotin is a popular nutritional supplement. There are recommendations that horses need 15 to 25&nbsp;mg/day. Studies report biotin improves the growth of new hoof horn rather than improving the status of existing hoof, so months of supplementation are needed for the hoof wall to be completely replaced.