Biotin

Biotin, also called vitamin B7, is one of the B vitamins.[1][2][3] It is involved in a wide range of
metabolic processes, both in humans and in other organisms, primarily related to the utilization
of fats, carbohydrates, and amino acids.[4] The name biotin derives from the Greek word “bios”
(to live) and the suffix “-in” (a general chemical suffix used in organic chemistry).[5]
 Biotin

Names

Preferred IUPAC name

5-[(3aS,4S,6aR)-2-Oxohexahydro-1H-thieno[3,4-
d]imidazol-4-yl]pentanoic acid

Other names
Vitamin B7; Vitamin H; Coenzyme R; Biopeiderm

Identifiers

CAS Number 58-85-5 (https://commonchemistry.cas.org/detai

l?cas_rn=58-85-5)  

3D model (JSmol) Interactive image (https://chemapps.stolaf.edu/j

mol/jmol.php?model=O%3DC1N%5BC%40%40H%
5D2%5BC%40%40H%5D%28SC%5BC%40%40H%5
D2N1%29CCCCC%28%3DO%29O)

Interactive image (https://chemapps.stolaf.edu/j

mol/jmol.php?model=C1%5BC%40H%5D2%5BC%
40%40H%5D%28%5BC%40%40H%5D%28S1%29C
CCCC%28%3DO%29O%29NC%28%3DO%29N2)

ChEBI CHEBI:15956 (https://www.ebi.ac.uk/chebi/searc

hId.do?chebiId=15956)  

ChEMBL ChEMBL857 (https://www.ebi.ac.uk/chembldb/in

 dex.php/compound/inspect/ChEMBL857)  
ChemSpider 149962 (http://www.chemspider.com/Chemical-S
tructure.149962.html)  

DrugBank DB00121 (https://www.drugbank.ca/drugs/DB0

0121)  

ECHA InfoCard 100.000.363 (https://echa.europa.eu/substance-i

nformation/-/substanceinfo/100.000.363)

IUPHAR/BPS 4787 (http://www.guidetopharmacology.org/GRA

C/LigandDisplayForward?tab=summary&ligandId=
4787)

KEGG D00029 (https://www.kegg.jp/entry/D00029)  

PubChem CID 171548 (https://pubchem.ncbi.nlm.nih.gov/comp

ound/171548)

UNII 6SO6U10H04 (https://fdasis.nlm.nih.gov/srs/srsd

irect.jsp?regno=6SO6U10H04)  

CompTox Dashboard (EPA) DTXSID7022679 (https://comptox.epa.gov/dashb

oard/DTXSID7022679)

InChI
InChI=1S/C10H16N2O3S/c13-8(14)4-2-1-3-7-9-6(5-16-7)11-10(15)12-9/h6-7,9H,1-5H2,(H,13,14)(H2,11,1
2,15)/t6-,7-,9-/m0/s1 
Key: YBJHBAHKTGYVGT-ZKWXMUAHSA-N 
InChI=1/C10H16N2O3S/c13-8(14)4-2-1-3-7-9-6(5-16-7)11-10(15)12-9/h6-7,9H,1-5H2,(H,13,14)(H2,11,12,
15)/t6-,7-,9-/m0/s1
Key: YBJHBAHKTGYVGT-ZKWXMUAHBB

SMILES
O=C1N[C@@H]2[C@@H](SC[C@@H]2N1)CCCCC(=O)O
C1[C@H]2[C@@H]([C@@H](S1)CCCCC(=O)O)NC(=O)N2

Properties

Chemical formula C10H16N2O3S

Molar mass 244.31 g·mol−1

Appearance White crystalline needles

Melting point 232 to 233 °C (450 to 451 °F; 505 to 506 K)

Solubility in water 22 mg/100 mL

 Pharmacology

ATC code A11HA05 (WHO (https://www.whocc.no/atc_ddd_

index/?code=A11HA05) )

Hazards

NFPA 704 (fire diamond)

1
1 0

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F],
100 kPa).

 verify (https://en.wikipedia.org/w/index.php?title=Special:ComparePages&rev1=443307462&page2=
Biotin) (what is   ?)

Infobox references

Biotin deficiency can be caused by inadequate dietary intake (rare) or inheritance of one or more
inborn genetic disorders that affect biotin metabolism. The most common among these is
biotinidase deficiency. Low activity of this enzyme causes a failure to recycle biotin from
biocytin. Rarer are carboxylase and biotin transporter deficiences.[4][6] Subclinical deficiency can
cause mild symptoms, such as hair thinning, brittle fingernails, or skin rash, typically on the
face.[2][4] Neonatal screening for biotinidase deficiency started in the United States in 1984, with
many countries now also testing for this genetic disorder at birth. Treatment is lifelong dietary
supplement with biotin.[1]

Definition

Biotin is a water-soluble B-vitamin. It is composed of a ureido ring fused with a

tetrahydrothiophene ring. The ureido ring containing the –N–CO–N– group acts as the carbon
dioxide carrier in carboxylation reactions.[7] A valeric acid substituent is attached to one of the
carbon atoms of the tetrahydrothiophene ring. Biotin is a coenzyme for five carboxylase
enzymes, which are involved in the digestion of carbohydrates, synthesis of fatty acids, and
gluconeogenesis.[3][4] Biotinylation of histone proteins in nuclear chromatin plays a role in
chromatin stability and gene expression.[4][8]
Dietary recommendations

The US National Academy of Medicine updated Dietary Reference Intakes for many vitamins in
1998. At that time there was insufficient information to establish estimated average requirement
or recommended dietary allowance, terms that exist for most vitamins. In instances such as
this, the Academy sets adequate intakes (AIs) with the understanding that at some later date,
when the physiological effects of biotin are better understood, AIs will be replaced by more
exact information. The biotin AIs for both males and females are: 5 μg/day of biotin for 0-to-6-
month-olds, 6 μg/day of biotin for 7-to-12-month-olds, 8 μg/day of biotin for 1-to-3-year-olds,
12 μg/day of biotin for 4-to-8-year-olds, 20 μg/day of biotin for 9-to-13-year-olds, 25 μg/day of
biotin for 14-to-18-year-olds, and 30 μg/day of biotin for those 19 years old and older. The biotin
AIs for females who are either pregnant or lactating, respectively, are: 30 μg/day of biotin for
pregnant females 14-to-50-years old and 35 μg/day of biotin for lactating females 14-to-50-years
old.[2] Australia and New Zealand set AIs similar to the US.[9]

The European Food Safety Authority (EFSA) also identifies AIs, setting values at 40 μg/day for
adults, pregnancy at 40 μg/day, and breastfeeding at 45 μg/day. For children ages 1–17 years,
the AIs increase with age from 20 to 35 μg/day.[10]

Safety

The US National Academy of Medicine estimates upper limits (ULs) for vitamins and minerals
when evidence for a true limit is sufficient. For biotin, however, there is no UL because adverse
effects of high biotin intake have not been determined.[2] The EFSA also reviewed safety and
reached the same conclusion as in the United States.[11]

Labeling regulations

For US food and dietary supplement labeling purposes the amount in a serving is expressed as a
percent of daily value. For biotin labeling purposes 100% of the daily value was 300 μg/day, but
as of May 27, 2016 it was revised to 30 μg/day to bring it into an agreement with the adequate
intake.[12][13] Compliance with the updated labeling regulations was required by 1 January 2020
for manufacturers with US$10 million or more in annual food sales, and by 1 January 2021 for
manufacturers with lower volume food sales.[14][15] A table of the old and new adult daily values
is provided at Reference Daily Intake.
Sources

Amount
Amount

Source[16] Source[16]
(μg / 100 g) (μg / 100 g)

Chicken liver 187 Peanuts, roasted 17.5

Beef liver 42 Sunflower seeds, roasted 7.8

Eggs 21 Almonds, roasted 4.4

Egg white 5.8 Sweet potato 1.5

Egg yolk 27 Broccoli 0.9

Salmon, canned in water 5.9 Tomato 0.7

Pork chop 4.5 Strawberry 1.5

Turkey breast 0.7 Avocado 1.0

Tuna, white, canned 0.7 Corn, canned 0.05

Amount

Source[16]
(μg / 100 g)

Cheese 1.4

Milk 0.1

Corn flakes cereal 0.1

Oatmeal 0.1

Bread 0.1

French fries 0.3

Wine 0.1

Beer 0.1

Potatoes, mashed 0.1

Biotin is stable at room temperature and is not destroyed by cooking. The dietary biotin intake in
Western populations has been estimated to be in the range of 35 to 70 μg/day. Nursing infants
ingest about 6 μg/day.[4] Biotin is available in dietary supplements, individually or as an
ingredient in multivitamins.[1][3]

No government fortification programs

According to the Global Fortification Data Exchange, biotin deficiency is so rare that no countries
require that foods be fortified.[17]

Physiology

Biotin is a water-soluble B vitamin. Consumption of large amounts as a dietary supplement

results in absorption, followed by excretion into urine as biotin. Consumption of biotin as part of
a normal diet results in urinary excretion of biotin and biotin metabolites.[4]

Absorption

Biotin in food is bound to proteins. Digestive enzymes reduce the proteins to biotin-bound
peptides. The intestinal enzyme biotinidase, found in pancreatic secretions and in the brush
border membranes of all three parts of the small intestine, frees biotin, which is then absorbed
from the small intestine.[4] When consumed as a biotin dietary supplement, absorption is
nonsaturable, meaning that even very high amounts are absorbed effectively. Transport across
the jejunum is faster than across the ileum.[4]

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.[18]

Once absorbed, sodium-dependent multivitamin transporter (SMVT) mediates biotin uptake into
the liver.[4] SMVT also binds pantothenic acid, so high intakes of either of these vitamins can
interfere with transport of the other.[19]

Metabolism and excretion

Biotin catabolism occurs via two pathways. In one, the valeric acid sidechain is cleaved,
resulting in bisnorbiotin. In the other pathway, the sulfur is oxidized, resulting in biotin sulfoxide.
Urine content is proportionally about half biotin, plus bisnorbiotin, biotin sulfoxide, and small
amounts of other metabolites.[4]

Factors that affect biotin requirements

Chronic alcohol use is associated with a significant reduction in plasma biotin.[20] Intestinal
biotin uptake also appears to be sensitive to the effect of the anti-epilepsy drugs carbamazepine
and primidone.[20] Relatively low levels of biotin have also been reported in the urine or plasma
of patients who have had a partial gastrectomy or have other causes of achlorhydria, burn
patients, elderly individuals, and athletes.[21] Pregnancy and lactation may be associated with an
increased demand for biotin. In pregnancy, this may be due to a possible acceleration of biotin
catabolism, whereas, in lactation, the higher demand has yet to be elucidated. Recent studies
have shown marginal biotin deficiency can be present in human gestation, as evidenced by
increased urinary excretion of 3-hydroxyisovaleric acid, decreased urinary excretion of biotin and
bisnorbiotin, and decreased plasma concentration of biotin.[4]

Biosynthesis

Biotin is a heterocyclic, sulfur-containing monocarboxylic acid with two rings fused together via
one of their sides (figure). The two rings are ureido and tetrahydrothiophene moieties.[22] Biotin,
synthesized in plants, is essential to plant growth and development.[23] Bacteria also synthesize
biotin,[24] and it is thought that bacteria resident in the large intestine may synthesize biotin that
is absorbed and utilized by the host organism.[18]

Synthesis starts from two precursors, alanine and pimeloyl-CoA. These form 7-Keto-8-
aminopelargonic acid (KAPA). KAPA is transported from plant peroxisomes to mitochondria
where it is converted to 7,8-Diaminopelargonic acid (DAPA). The enzyme dethiobiotin synthetase
catalyzes the formation of the ureido ring via a DAPA carbamate activated with ATP, creating
dethiobiotin, which is then converted into biotin. The last step is catalyzed by biotin
synthase.[22][23]

Cofactor biochemistry
The enzyme holocarboxylase synthetase covalently attaches biotin to five human carboxylase
enzymes:[4]

Acetyl-CoA carboxylase alpha (ACC1)

Acetyl-CoA carboxylase beta (ACC2)

Pyruvate carboxylase (PC)

Methylcrotonyl-CoA carboxylase (MCC)

Propionyl-CoA carboxylase (PCC)

For the first two, biotin serves as a cofactor responsible for transfer of bicarbonate to acetyl-
CoA, converting it to malonyl-CoA for fatty acid synthesis. PC participates in gluconeogenesis.
MCC catalyzes a step in leucine metabolism. PCC catalyzes a step in the metabolism of
propionyl-CoA.[1][3][4] Metabolic degradation of the biotinylated carboxylases leads to the
formation of biocytin. This compound is further degraded by biotinidase to release biotin, which
is then reutilized by holocarboxylase synthetase.[4]

Histone biochemistry

Histones are highly basic proteins found in eukaryotic cell nuclei, the chief protein components
of chromatin, that compact and order nuclear DNA into structural units called nucleosomes and
play a role in gene regulation.[25] Biotinylation of histone proteins in nuclear chromatin is a
posttranslational modification that plays a role in chromatin stability and gene expression.[4][8]

Deficiency

Primary biotin deficiency, meaning deficiency as a consequence of too little biotin in the diet, is
rare, because biotin is contained in so many foods. Signs of biotin deficiency have been
described in people who were receiving all nutrition intravenously without biotin, also people
regularly consuming raw or incompletely cooked egg whites, because egg whites contain avidin,
a biotin-binding protein. Deficiency symptoms include: brittle and thin fingernails, hair loss
(alopecia), conjunctivitis, dermatitis in the form of a scaly, red rash around the eyes, nose,
mouth, and genital area, plus neurological symptoms such as depression, lethargy, hallucination,
and numbness and tingling of the extremities[4] The neurological and psychological symptoms
can occur with only mild deficiencies. Dermatitis, conjunctivitis, and hair loss will generally occur
only when deficiency becomes more severe. Individuals with hereditary disorders of biotin
deficiency have evidence of impaired immune system function, including increased
susceptibility to bacterial and fungal infections.[3]

Diagnosis

Low serum and urine biotin are not sensitive indicators of inadequate biotin intake.[4] However,
serum testing can be useful for confirmation of consumption of biotin-containing dietary
supplements, and whether a period of refraining from supplement use is long enough to
eliminate the potential for interfering with drug tests.[26][27] Indirect measures depend on the
biotin requirement for carboxylases. 3-Methylcrotonyl-CoA is an intermediate step in the
catabolism of the amino acid leucine. In the absence of biotin, the pathway diverts to 3-
hydroxyisovaleric acid. Urinary excretion of this compound is an early and sensitive indicator of
biotin deficiency.[2][4]

Deficiency as a result of metabolic disorders

Biotinidase deficiency is a deficiency of the enzyme that recycles biotin, the consequence of an
inherited genetic mutation.[1] Biotinidase catalyzes the cleavage of biotin from biocytin and
biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby
recycles biotin.[2] It is also important in freeing biotin from dietary protein-bound biotin.[28]
Neonatal screening for biotinidase deficiency started in the United States in 1984,[29] which as of
2017 was reported as required in more than 30 countries.[30]

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.[29] Incidence data stems from government mandated newborn screening.[30] 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.[29] Treatment of partial
biotinidase deficiency is also recommended even though some untreated people never manifest
symptoms.[29] Lifelong treatment with supplmental biotin is recommended for both profound
and partial biotinidase deficiency.[1]

Inherited metabolic disorders characterized by deficient activities of biotin-dependent

carboxylases are termed multiple carboxylase deficiency. These include deficiencies in the
enzymes holocarboxylase synthetase.[1] Holocarboxylase synthetase deficiency prevents the
body's cells from using biotin effectively and thus interferes with multiple carboxylase
reactions.[28] There can also be a genetic defect affecting the sodium-dependent multivitamin
transporter protein.[6]

Biochemical and clinical manifestations of any of these metabolic disorders can include
ketolactic acidosis, organic aciduria, hyperammonemia, rash, hypotonia, seizures, developmental
delay, alopecia and coma.[4]

Use in biotechnology

Chemically modified versions of biotin are widely used throughout the biotechnology industry to
isolate proteins and non-protein compounds for biochemical assays.[31] Because egg-derived
avidin binds strongly to biotin with a dissociation constant Kd of ≈10−15 M,[32] 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.[31] 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.[33] 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.[32]

Interference with medical laboratory results

When people are ingesting high levels of biotin in dietary supplements, a consequence can be
clinically significant interference with diagnostic blood tests that use biotin-streptavidin
technology. This methodology is commonly used to measure levels of hormones such as thyroid
hormones, and other analytes such as 25-hydroxyvitamin D. Biotin interference can produce both
falsely normal and falsely abnormal results.[1][34] In the US, biotin as a non-prescription dietary
supplement is sold in amounts of 1 to 10 mg per serving, with claims for supporting hair and nail
health, and as 300 mg per day as a possibly effective treatment for multiple sclerosis[35][36] (see
Research). Overconsumption of 5 mg/day or higher causes elevated concentration in plasma
that interferes with biotin-streptavidin immunoassays in an unpredictable manner.[26][27]
Healthcare professionals are advised to instruct patients to stop taking biotin supplements for
48 h or even up to weeks before the test, depending on the specific test, dose, and frequency of
biotin uptake.[26] Guidance for laboratory staff is proposed to detect and manage biotin
interference.[27]

History

In 1916, W.G. Bateman observed that a diet high in raw egg whites caused toxic symptoms in
dogs, cats, rabbits, and humans.[37] By 1927, scientists such as Margarete Boas and Helen
Parsons had performed experiments demonstrating the symptoms associated with "egg-white
injury." They had found that rats fed large amounts of egg-white as their only protein source
exhibited neurological dysfunction, hair loss, dermatitis, and eventually, death.[38][39]

In 1936, Fritz Kögl and Benno Tönnis documented isolating a yeast growth factor in a journal
article titled "Darstellung von krystallisiertem biotin aus eigelb." (Representation of crystallized
biotin from egg yolk).[40] The name "biotin" derives from the Greek word “bios” (to live) and the
suffix “-in” (a general chemical suffix used in organic chemistry).[5] Other research groups,
working independently, had isolated the same compound under different names. Hungarian
scientist Paul Gyorgy began investigating the factor responsible for egg-white injury in 1933 and
in 1939, was successful identifying what he called "Vitamin H" (the H represents Haar und Haut,
German for hair and skin).[41][42] Further chemical characterization of vitamin H revealed that it
was water-soluble and present in high amounts in the liver.[43] After experiments performed with
yeast and Rhizobium trifolii, West and Wilson isolated a compound they called co-enzyme
R.[44][45] By 1940, it was recognized that all three compounds were identical and were collectively
given the name: biotin.[46] Gyorgy continued his work on biotin and in 1941 published a paper
demonstrating that egg-white injury was caused by the binding of biotin by avidin.[47][48] Unlike
for many vitamins, there is insufficient information to establish a recommended dietary
allowance, so dietary guidelines identify an "adequate intake" based on best available science
with the understanding that at some later date this will be replaced by more exact
information.[2][9][10]

Using E. coli, a biosynthesis pathway was proposed by Rolfe and Eisenberg in 1968. The initial
step was described as a condensation of pimelyl-CoA and alanine to form 7-oxo-8-
aminopelargonic acid. From there, they described three-step process, the last being introducing
a sulfur atom to form the tetrahydrothiophene ring.[49]

Research
Multiple sclerosis

High-dose biotin (300 mg/day = 10,000 times adequate intake) has been used in clinical trials
for treatment of multiple sclerosis, a demyelinating autoimmune disease.[35][36] 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.[35][36] 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,[35] whereas two 2020 reviews of a larger number of
clinical trials reported no consistent evidence for benefits,[50] and some evidence for increased
disease activity and higher risk of relapse.[51]

Hair, nails, skin

In the United States, biotin is promoted as a dietary supplement for strengthening hair and
fingernails, though scientific data supporting these outcomes in humans are very weak.[3][52][53]
A review of the fingernails literature reported brittle nail improvement as evidence from two pre-
1990 clinical trials that had administered an oral dietary supplement of 2.5 mg/day for several
months, without a placebo control comparison group. There is no more recent clinical trial
literature.[52] A review of biotin as treatment for hair loss identified case studies of infants and
young children with genetic defect biotin deficiency having improved hair growth after
supplementation, but went on to report that "there have been no randomized, controlled trials to
prove efficacy of supplementation with biotin in normal, healthy individuals."[53] Biotin is also
incorporated into topical hair and skin products with similar claims.[54]

The Dietary Supplement Health and Education Act of 1994 states that the US Food and Drug
Administration must allow on the product label what are described as "Structure:Function" (S:F)
health claims that ingredient(s) are essential for health. For example: Biotin helps maintain
healthy skin, hair and nails. If a S:F claim is made, the label must include the disclaimer "This
statement has not been evaluated by the Food and Drug Administration. This product is not
intended to diagnose, treat, cure, or prevent any disease."[55]

Animals

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. Dietary
supplementation biotin at 20 mg/day reduces the risk of lameness.[56] 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.[57]

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.[58]

See also

Biotinylation

Multiple carboxylase deficiency

NeutrAvidin

Photobiotin

References

1. "Biotin – Fact Sheet for Health Professionals" (https://ods.od.nih.gov/factsheets/Biotin-HealthProfessi

onal/) . Office of Dietary Supplements, US National Institutes of Health. 8 December 2017. Retrieved
25 February 2018.

2. Institute of Medicine (1998). "Biotin" (http://www.nap.edu/openbook.php?record_id=6015&page=374) .

Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic
Acid, Biotin, and Choline. Washington, DC: The National Academies Press. pp. 374–389. ISBN 0-309-
06554-2. Retrieved 2017-08-29.

3. "Biotin" (http://lpi.oregonstate.edu/mic/vitamins/biotin) . Micronutrient Information Center, Linus

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4. Penberthy WT, Sadri M, Zempleni J (2020). "Biotin". In BP Marriott, DF Birt, VA Stallings, AA Yates (eds.).
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5. "biotin | Origin and meaning of biotin by Online Etymology Dictionary" (https://www.etymonline.com/wor

d/biotin) . www.etymonline.com. Retrieved 2020-11-14.
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cbi.nlm.nih.gov/pmc/articles/PMC2726758) . Expert Review of Endocrinology & Metabolism. 3 (6):
715–24. doi:10.1586/17446651.3.6.715 (https://doi.org/10.1586%2F17446651.3.6.715) .
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bmed.ncbi.nlm.nih.gov/19727438) .

7. Waldrop GL, Holden HM, St Maurice M (November 2012). "The enzymes of biotin dependent CO₂
metabolism: what structures reveal about their reaction mechanisms" (https://www.ncbi.nlm.nih.gov/pm
c/articles/PMC3527699) . Protein Science. 21 (11): 1597–619. doi:10.1002/pro.2156 (https://doi.org/1
0.1002%2Fpro.2156) . PMC 3527699 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527699) .
PMID 22969052 (https://pubmed.ncbi.nlm.nih.gov/22969052) .

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blications/synopses/n35.pdf) (PDF). Archived from the original (http://www.nhmrc.gov.au/_files_nhmr
c/file/publications/synopses/n35.pdf) (PDF) on 2017-01-21. Retrieved 2010-02-19.

10. "Overview on Dietary Reference Values for the EU population as derived by the EFSA Panel on Dietetic
Products, Nutrition and Allergies" (https://www.efsa.europa.eu/sites/default/files/assets/DRV_Summary
_tables_jan_17.pdf) (PDF). 2017.

11. "Tolerable Upper Intake Levels For Vitamins And Minerals" (http://www.efsa.europa.eu/sites/default/file
s/efsa_rep/blobserver_assets/ndatolerableuil.pdf) (PDF). European Food Safety Authority. 2006.

12. "Federal Register May 27, 2016 Food Labeling: Revision of the Nutrition and Supplement Facts Labels" (ht
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