Biotin

Biotin, also known as vitamin B₇ or vitamin H, is a water-soluble member of the B-vitamin complex involved in numerous fundamental metabolic pathways. It functions chiefly in the utilisation of fats, carbohydrates, and amino acids across a wide range of organisms. As a term, biotin originates from German usage, itself derived from the Ancient Greek word for “life”, combined with a common chemical suffix.
Biotin occurs as a white, crystalline, needle-like solid and is chemically classified as a heterocyclic compound. Its structure features a sulfur-containing tetrahydrothiophene ring fused to a ureido group, from which a C₅ carboxylic acid side chain extends. This architecture is central to its biological activity, particularly its role as a carbon dioxide carrier in carboxylation reactions.

Chemical Description and Biological Functions

In cellular biochemistry, biotin serves as a coenzyme for five essential carboxylase enzymes that participate in amino-acid catabolism, fatty-acid metabolism, fatty-acid synthesis, and gluconeogenesis. These enzymes include acetyl-CoA carboxylase 1 and 2 (ACC1 and ACC2), pyruvate carboxylase (PC), methylcrotonyl-CoA carboxylase (MCC), and propionyl-CoA carboxylase (PCC). Attachment of biotin to these enzymes is facilitated by holocarboxylase synthetase.
Biotinylation also has epigenetic implications: the covalent modification of histone proteins supports chromatin stability and influences gene expression.

Dietary Recommendations

In 1998, the US National Academy of Medicine established adequate intakes (AIs) for biotin rather than recommended dietary allowances because available evidence was insufficient for formal requirement estimates. Adult AIs apply equally to men and women. Australia and New Zealand set comparable values. The European Food Safety Authority recommends 40 µg per day for adults, 40 µg per day in pregnancy, and 45 µg per day during lactation, with children’s requirements scaled by age from 20–35 µg per day.

Safety

No tolerable upper intake level has been set in the United States or by the European Food Safety Authority, as adverse effects from high biotin intakes have not been conclusively identified. Changes to US labelling regulations in 2016 revised the daily value for biotin from 300 µg to 30 µg, with compliance deadlines phased in by early 2021.

Dietary Sources

Biotin is stable under typical food-preparation conditions, and cooking does not degrade it. Estimated intake in Western diets ranges from 35 to 70 µg per day, with breastfed infants consuming approximately 6 µg per day. Biotin is available as a stand-alone supplement or as part of multivitamin preparations. Globally, food-fortification policies do not include biotin because deficiency is exceedingly rare.

Physiology of Absorption and Transport

Dietary biotin is generally bound to proteins and must be released by digestive processes. Proteolytic enzymes reduce biotin-bound proteins to peptides, after which the enzyme biotinidase—present in pancreatic secretions and along the small-intestinal brush border—liberates free biotin for absorption.
When ingested as a supplement, biotin is absorbed efficiently and without saturation. Transport across the jejunum occurs more rapidly than across the ileum. The large-intestinal microbiota also synthesises free biotin, but the proportion absorbed in humans remains uncertain.
Once absorbed, the sodium-dependent multivitamin transporter (SMVT) mediates uptake into the liver. Because SMVT also transports pantothenic acid, high intakes of this vitamin can influence biotin transport and vice versa.

Metabolism and Excretion

Biotin catabolism proceeds through two major pathways. One cleaves the valeric-acid side chain to generate bisnorbiotin; the other oxidises the sulfur atom to produce biotin sulfoxide. Approximately half of urinary excretion comprises unmetabolised biotin and these major metabolites.

Factors Increasing Biotin Requirements

Several physiological and pharmacological factors influence circulating biotin concentrations:

• Chronic alcohol consumption can reduce plasma biotin.
• Certain antiepileptic medications, such as carbamazepine and primidone, impair intestinal uptake.
• Low levels have been reported in individuals with achlorhydria, partial gastrectomy, severe burns, or very high athletic activity.
• Pregnancy increases biotin turnover, potentially accelerating its catabolism; lactation appears to raise biotin requirements, although the mechanism is not yet clear.

Marginal deficiency during pregnancy has been suggested through biomarkers such as altered urinary excretion of biotin and its metabolites.

Biosynthesis

Biotin biosynthesis occurs in plants and bacteria and is essential for plant development. In bacteria and plants, biosynthesis begins with alanine and pimelic acid-CoA, producing 7-keto-8-aminopelargonic acid (KAPA). KAPA is transported to mitochondria and converted into 7,8-diaminopelargonic acid (DAPA) via the enzyme BioA. The enzyme dethiobiotin synthetase (BioD) catalyses ureido-ring formation, generating dethiobiotin, which is then converted into biotin by BioB (biotin synthase), a radical SAM enzyme employing a 2Fe–2S ferredoxin to supply sulfur. Multiple pathway variations exist across bacterial species.

Cofactor Biochemistry

Biotin functions as a covalently bound cofactor attached by holocarboxylase synthetase to its target carboxylases. In fatty-acid synthesis, ACC1 and ACC2 utilise biotin to transfer bicarbonate to acetyl-CoA. PC enables the gluconeogenic conversion of pyruvate to oxaloacetate. MCC manages a step in leucine catabolism, while PCC participates in propionyl-CoA metabolism. Degradation of biotinylated enzymes yields biocytin, which is subsequently cleaved by biotinidase, enabling biotin recycling.

Deficiency

Primary biotin deficiency due solely to low dietary intake is exceptionally uncommon, as biotin is present in numerous foods and synthesised by gut microbiota. Mild or subclinical deficiency may manifest as thinning hair, brittle nails, or facial rash. Rarely, genetic disorders affecting biotin metabolism result in clinically significant deficiency. These conditions disrupt enzymes such as biotinidase or holocarboxylase synthetase, leading to impaired biotin recycling or utilisation.