Biotin

Biotin

• “Egg white injury”

• Eating raw egg whites → hair loss, dermatitis, neuromuscular problems

• Szent-Gyorgyi: substance (biotin) in liver could cure and prevent “egg white injury”

Sources

• Widely distributed in foods

• Made by bacteria in large intestine

• Commonly found free or bound to proteins

• Avidin (glycoprotein) in raw egg whites binds biotin and prevent its absorption

• Supplements: free form

• Single-nutrient: 10 mg

Biotin Digestion

• Protein-bound biotin digested by pepsin and intestinal proteases → free biotin and some biocytin (biotin bound to lysine)

• Biocytin (biotin + lysine) may be absorbed intact by a peptide carriers or hydrolyzed by biotinidase

• Biotinidase found in intestinal brush border, pancreatic and intestinal juices, in the plasma, and intracellularly

• Genetic mutation → biotinidase deficiency • Lethargy, hypotonia, seizures, ataxia, dermatitis, and alopecia

• Treatment: 5-20 mg biotin daily

Biotin Absorption

• Free biotin absorbed primarily in proximal small intestine

• Pharmacologic doses: passive diffusion

• Physiological intakes: SMVT in small intestine

• Regulated by [biotin]

• Negatively affected by alcohol

• Biotin synthesized by colonic bacteria absorbed in proximal and transverse colon (SMVT)

• Transport across the basolateral membrane is carriermediated

• 100% of oral free biotin is absorbed

Biotin Transport

• In plasma 80% is free biotin, 20% bound to proteins (albumin, globulins, and biotinidase)

• Blood [biotin]: 200 - 750 pg/mL

Biotin Uptake

• Liver and probably other tissues: SMVT and monocarboxylate transporter (MCT) 1

Biotin Storage

• Small quantities stored in muscle, liver, brain

Biotin Functions & Mechanisms of Action

• Coenzyme roles: holocarboxylase

• Genetic mutation → holocarboxylase synthetase

• Vomiting, lethargy, hypotonia, acidosis, and seizures

• Treatment: 10 - 200 mg oral biotin daily

• Non-coenzyme roles • Biotinylation

• Histones and nonhistone proteins

• Biotinylation of histones allow transcription factors to affect gene expression

Biotin Metabolism & Excretion

• Small amounts of biotin and biocytin found in urine

• Biocytin degraded to lysine & biotin (biotinidase)

• Biotin is usually further degraded

• Metabolites excreted in urine

• Biotin that was synthesized by colonic bacteria, but not absorbed, is excreted in feces

Biotin Adequate Intake

• Adults: 30 µg/day

• Pregnancy: 30 µg/day

• Lactation: 35 µg/day

Biotin Deficiency (Rare but serious)

• Excessive consumption of raw egg whites

• Lethargy, paresthesia, hypotonia, depression, hallucinations, dermatitis (red, dry, scaly), anorexia, nausea, brittle nails, alopecia, and muscle pain

• 10 mg daily

Biotin At Risk for Deficiency

• Those consuming excess raw egg whites

• Those with GI disorders

• Pregnant and lactating women

• People who consume excess alcohol

• Those on anticonvulsant drug therapies

Biotin Toxicity

• None reported, no UL

• Up to 200 mg without side effects (inherited disorders of biotin metabolism)

Biotin Assessment of Nutriture

• Blood concentrations do not accurately reflect intake or status

• Decreased urinary biotin excretion (< 6 μg/day) is a sensitive and early indicator of biotin deficiency

• A diet devoid of biotin can decrease [biotin] in plasma and urine in ~2-4 weeks