Biotin

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Biotin (also known as vitamin B<sub>7</sub> and vitamin H) 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.

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.

Dietary recommendations

The US National Academy of Medicine updated Dietary Reference Intakes for many vitamins in 1998.

! Age group !! Biotin AI (μg/day)

| 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 (14 to 50 years) || 30

| Lactating females (14 to 50 years) || 35

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Australia and New Zealand set AIs similar to the US.

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.

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.

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

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Physiology

Biotin is a water-soluble B vitamin.

Once absorbed, sodium-dependent multivitamin transporter (SMVT) mediates biotin uptake into the liver.

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. Intestinal biotin uptake also appears to be sensitive to the effect of the anti-epilepsy drugs carbamazepine and primidone. 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. 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. The last step is catalyzed by biotin synthase, a radical SAM enzyme. The sulfur is donated by an unusual [2Fe-2S] ferredoxin. Depending on the species of bacteria, biotin can be synthesized via multiple pathways. 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.

Diagnosis

Low serum and urine biotin are not sensitive indicators of inadequate biotin intake. 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. There can also be a genetic defect affecting the sodium-dependent multivitamin transporter protein. Because egg-derived avidin binds strongly to biotin with a dissociation constant K<sub>d</sub> ≈ 10<sup>−15</sup> 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. 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. 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 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. 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 whites as their only protein source exhibited neurological dysfunction, hair loss, dermatitis, and eventually, death.

In 1936, Fritz Kögl and Benno Tönnis documented isolating a yeast growth factor in a journal article titled "." (Representation of crystallized biotin from egg yolk). The name biotin derives from the Greek word ('to live') and the suffix "-in" (a general chemical suffix used in organic chemistry). Further chemical characterization of vitamin H revealed that it was water-soluble and present in high amounts in the liver. After experiments performed with yeast and Rhizobium trifolii, West and Wilson isolated a compound they called co-enzyme R. By 1940, it was recognized that all three compounds were identical and were collectively given the name: biotin. 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. 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.

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. 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, and some evidence for increased disease activity and higher risk of relapse.

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 remains a subject of ongoing research. Biotin is also incorporated into topical hair and skin products with similar claims.

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. A more recent 2018 meta-review found that "biotin has been used to treat several nail conditions with promising results."

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."

Animals

In cattle, biotin is necessary for hoof health. Lameness due to hoof problems is common, with herd prevalence estimated at 10 to 35%. 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.