Biotin
Biotin is one of the B vitamins - a group of essential dietary micronutrients. Present in every living cell, it is involved as a cofactor for enzymes in numerous metabolic processes, both in humans and in other organisms, primarily related to the biochemistry of fats, carbohydrates, and amino acids.
When isolated, biotin is a white, needle-like crystalline solid. Biotin is obtained from foods, particularly meats and liver, and is sold as a dietary supplement.
The name biotin, borrowed from the German biotin, derives from the Ancient Greek word and the suffix "-in".
Chemical description
Biotin is classified as a heterocyclic compound, with a sulfur-containing tetrahydrothiophene ring fused to a ureido group. A C5-carboxylic acid side chain is appended to the former ring. The ureido ring, containing the −N−CO−N− group, serves as the carbon dioxide carrier in carboxylation reactions. Biotin is a coenzyme for five carboxylase enzymes, which are involved in the catabolism of amino acids and fatty acids, synthesis of fatty acids, and gluconeogenesis. Biotinylation of histone proteins in nuclear chromatin plays a role in chromatin stability and gene expression.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 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 appear below.| Age group | Biotin AI |
| 0 to 6 months | 5 |
| 7 to 12 months | 6 |
| 1 to 3 years | 8 |
| 4 to 8 years | 12 |
| 9 to 13 years | 20 |
| 14 to 18 years | 25 |
| 19 years and older | 30 |
| Pregnant females | 30 |
| Lactating females | 35 |
Australia and New Zealand set AIs similar to the US.
The European Food Safety Authority 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.
Safety
The US National Academy of Medicine estimates upper limits for vitamins and minerals when evidence for a true limit is sufficient. For biotin, however, there is no upper limit because the adverse effects of high biotin intake have not been determined. The EFSA also reviewed safety and reached the same conclusion as in the United States.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 agree with the adequate intake. Compliance with the updated labeling regulations was required by January 1, 2020, for manufacturers with US$10 million or more in annual food sales, and by January 1, 2021, for manufacturers with lower volume food sales.Food sources
| Source | Amount |
| Beef liver | 31 |
| Whole eggs | 10 |
| Salmon, pink, canned in water | 5 |
| Pork chop | 4 |
| Hamburger patty | 4 |
| Sunflower seeds, roasted | 3 |
| Sweet potato, cooked | 2 |
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. Biotin is available in dietary supplements, individually or as an ingredient in multivitamins.
According to the Global Fortification Data Exchange, biotin deficiency is so rare that no countries require that foods be fortified.
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.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. 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.The large intestine microbiota synthesizes 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 form and, thus, is available for absorption. How much is absorbed in humans is unknown, although a review did report that human colon epithelial cells in vitro demonstrated an ability to uptake biotin.
Once absorbed, sodium-dependent multivitamin transporter mediates biotin uptake into the liver. SMVT also binds pantothenic acid, so high intakes of either of these vitamins can interfere with the transport of the other.
Metabolism and excretion
Biotin catabolism occurs via two pathways. In one, the valeric acid sidechain is cleaved, resulting in bisnorbiotin. In the other path, 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.Factors that affect biotin requirements
Chronic alcohol use is associated with a significant reduction in plasma biotin. Intestinal biotin uptake also appears to be sensitive to the effect of the anti-epilepsy drugs carbamazepine and primidone. 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, as well as burn patients, elderly individuals, and athletes. 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.Biosynthesis
Biotin, synthesized in plants, is essential to plant growth and development. Bacteria also synthesize biotin, and it is thought that bacteria resident in the large intestine may synthesize biotin that is absorbed and utilized by the host organism.Biosynthesis starts from two precursors, alanine and pimeloyl-CoA. These form 7-keto-8-aminopelargonic acid. KAPA is transported from plant peroxisomes to mitochondria where it is converted to 7,8-diaminopelargonic acid with the help of the enzyme, BioA. The enzyme dethiobiotin synthetase catalyzes the formation of the ureido ring via a DAPA carbamate activated with ATP, creating dethiobiotin with the help of the enzyme, BioD, which is then converted into biotin which is catalyzed by BioB. The last step is catalyzed by biotin synthase, a radical SAM enzyme. The sulfur is donated by an unusual ferredoxin. Depending on the species of bacteria, Biotin can be synthesized via multiple pathways.
Cofactor biochemistry
The enzyme holocarboxylase synthetase covalently attaches biotin to five human carboxylase enzymes:- Acetyl-CoA carboxylase alpha
- Acetyl-CoA carboxylase beta
- Pyruvate carboxylase
- Methylcrotonyl-CoA carboxylase
- Propionyl-CoA carboxylase
Biotinylation of histone proteins in nuclear chromatin is a posttranslational modification that plays a role in chromatin stability and gene expression.
Deficiency
Primary biotin deficiency, meaning deficiency due to too little biotin in the diet, is rare because biotin is contained in many foods. Subclinical deficiency can cause mild symptoms, such as hair thinning, brittle fingernails, or skin rash, typically on the face.Aside from inadequate dietary intake, biotin deficiency can be caused by a genetic disorder that affects 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 deficiencies. 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 a lifelong dietary supplement with biotin. If biotinidase deficiency goes untreated, it can be fatal.