Biotin (vitamin B7, also called vitamin H) is the water-soluble vitamin that is the essential cofactor for the five biotin-dependent carboxylases in the human body — the pyruvate carboxylase (which is essential for the gluconeogenesis and for the refilling of the TCA cycle with the oxaloacetate), the acetyl-CoA carboxylase 1 and 2 (which are essential for the fatty acid synthesis and for the regulation of the malonyl-CoA levels in the cytoplasm and in the mitochondria), the methylcrotonyl-CoA carboxylase (which is essential for the leucine catabolism), the propionyl-CoA carboxylase (which is essential for the catabolism of the odd-chain fatty acids, of the isoleucine, of the methionine, and of the threonine), and the geranyl-CoA carboxylase (which is essential for the cholesterol synthesis). The biotin is covalently attached to the epsilon-amino group of the lysine residue of these carboxylases (forming the biotinyl-lysine or biocytin), and it functions as the mobile carboxyl carrier — shuttling the bicarbonate-derived CO2 between the active sites of the carboxylase reactions. Without adequate biotin and functional biotin-dependent carboxylases, all of these metabolic pathways are compromised, and the neurological dysfunction, the dermatological manifestations, and the growth failure develop — the hallmark of the biotin deficiency. The typical dietary biotin intake is 30-100mcg daily (from the egg yolks, the liver, the nuts, the seeds, and the vegetables), and the estimated safe and adequate intake is 30-100mcg daily for adults — but the biotin deficiency is more common than generally recognised, particularly in people with the alcoholism, with the malabsorption, with the MTHFR polymorphism, and in infants (who have a high biotin requirement for the rapid growth). The biotinidase is the enzyme that recycles the biotin from the biocytin and from the dietary protein-bound biotin — and the biotinidase deficiency is one of the most common inherited metabolic disorders, affecting approximately 1 in 60,000 newborns.
Biotin-Dependent Carboxylases and the Central Metabolism
The five biotin-dependent carboxylases are essential for the central metabolic pathways — the pyruvate carboxylase is essential for the gluconeogenesis (it carboxylates the pyruvate to the oxaloacetate, which is the first step in the synthesis of the new glucose from the non-carbohydrate precursors), the acetyl-CoA carboxylase is essential for the fatty acid synthesis (it carboxylates the acetyl-CoA to the malonyl-CoA, which is the two-carbon donor for the fatty acid chain elongation), the methylcrotonyl-CoA carboxylase is essential for the leucine catabolism (it carboxylates the methylcrotonyl-CoA to the methylglutaconyl-CoA), the propionyl-CoA carboxylase is essential for the catabolism of the odd-chain fatty acids and of the branched-chain amino acids (it carboxylates the propionyl-CoA to the methylmalonyl-CoA, which is then isomerised to the succinyl-CoA by the B12-dependent methylmalonyl-CoA mutase), and the geranyl-CoA carboxylase is essential for the cholesterol synthesis (it carboxylates the geranyl-CoA to the geranylmalonyl-CoA). Without adequate biotin, all of these carboxylase reactions are impaired, and the metabolic pathways that depend on them are compromised — producing the accumulation of the toxic intermediates (including the methylcrotonyl-CoA, the propionyl-CoA, and the odd-chain fatty acids), the impaired energy production, and the neurological dysfunction.
The clinical importance of the biotin for the carboxylase function is underscored by the observation that the biotin supplementation rapidly reverses the clinical manifestations of the biotin deficiency. A study in 10 patients with the biotinidase deficiency found that the biotin supplementation at 10mg daily completely reversed the dermatitis, the alopecia, and the neurological dysfunction within 2-4 weeks — demonstrating the remarkable efficacy of the biotin replacement for the biotin deficiency.
Biotin and the Skin Health
Biotin is essential for the health of the skin, the hair, and the nails — it is required for the fatty acid synthesis, for the cholesterol synthesis, and for the keratin protein synthesis, all of which are essential for the integrity of the skin lipid barrier, for the production of the sebum (the natural oil that lubricates the skin and hair), and for the structure of the hair and nails. The biotin deficiency produces the characteristic dermatological manifestations — the scaly erythematous dermatitis (particularly around the eyes, nose, mouth, and genitals), the alopecia (hair loss), and the brittle nails — which are the most visible and most recognisable signs of the biotin deficiency and which are rapidly reversed by the biotin supplementation. The biotin is one of the most commonly used supplements for the skin, hair, and nail health — with an estimated market size of over $100 million annually in the United States alone — but the evidence for the efficacy of the biotin supplementation in people who are not biotin deficient is limited, and the supplementation is most effective in people with the biotin deficiency or with the biotinidase deficiency.
Practical Application
For general biotin supplementation for the skin, hair, and nail health, the evidence-based approach is to supplement with 30-100mcg of biotin daily (as biotin or as the more bioavailable d-biotin form, which is the naturally occurring stereoisomer). Most people achieve adequate biotin from a varied diet — biotin is found in egg yolks, liver, nuts, seeds, sweet potatoes, and spinach. The therapeutic doses for the biotin deficiency and for the biotinidase deficiency are much higher (5-20mg daily), and the therapeutic use of the high-dose biotin has also been studied for the treatment of the multiple sclerosis (where the high-dose biotin is thought to promote the remyelination of the nerve fibres) and for the treatment of the brittle nail syndrome. For comprehensive skin, hair, and nail support, biotin pairs well with the zinc (which is required for the keratin synthesis and for the skin healing), with the vitamin D (which has immunomodulatory effects and which is important for the skin barrier function), with the omega-3 fatty acids (which have anti-inflammatory effects in the skin and which support the skin lipid barrier), and with the silica (which is required for the collagen synthesis and for the nail strength).
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