Biotin bound to proteinsin the PDB
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^[1]

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^ ^abHigdon, Jane (2003). "Biotin". An evidence-based approach to vitamins and minerals. Thieme. ISBN 978-1-58890-124-8. 

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^ ^abOregon State University, Linus Pauling Institute, Micronutrient Research

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^Combs, Gerald F. Jr. (1998). The Vitamins: Fundamental Aspects in Nutrition and Health. Ithaca: Elsevier Academic Press. ISBN 0-12-183492-1. pg. 360

Animal studies have indicated few, if any, effects due to high level doses of biotin. This may provide evidence that both animals and humans could tolerate doses of at least an order of magnitude greater than each of their nutritional requirements. There are no reported cases of adverse effects from receiving high doses of the vitamin, in particular, when used in the treatment of metabolic disorders causing sebhorrheic dermatitisin infants.^[34]

Health and diet

Diabetes

Diabetics may benefit from biotin supplementation. In both insulin-dependent and insulin-independent diabetics deficient in biotin, supplementation with biotin can improve blood sugar control and help lower fasting blood glucose levels; in one study, the reduction in fasting glucose approached 50%.^[27]Biotin can also play a role in preventing the neuropathy often associated with diabetes, reducing both the numbness and tingling associated with poor glucose control.^[27][28]

Hair and nail problems

The signs and symptoms of biotin deficiency include hair loss, which progresses in severity to include loss of eyelashes and eyebrows in severely deficient subjects, as well as nails that break, chip, or flake easily.^[29]Biotin supplements are available in most pharmacies. The recommended dose to treat deficiency for adults varies from 3,000 mcg per day for brittle fingernails up to 7,000 to 15,000 mcg per day for diabetics.^[30]

Biotin  Palmoplantar pustulosis

Patients with palmoplantar pustulosishad metabolic derangements of glucose and fatty acids, as well as immune dysfunction derived from biotin deficiency, which led to abnormal manifestations of skin, bone and other tissues and organs. All of the clinical, metabolic and immune disorders were improved by biotin administration. These findings indicate biotin deficiency was implicated in the outbreak and exacerbation of the disease and its complications. Supplementary addition of a probiotic agent to the biotin treatment intensified the therapeutic effect of the vitamin. Additionally, patients with psoriasis vulgaris, systemic lupus erythematosus, atopic dermatitisor rheumatoid arthritisalso had biotin deficiency with the subsequent metabolic abnormalities and immune dysfunction, so the biotin treatment provided beneficial effects in the therapy of the diseases, as in the case of palmoplantar pustulosis.^[31]

Biotin Cradle cap (seborrheic dermatitis)

Children with a rare inherited metabolic disorder called phenylketonuria(PKU; in which one is unable to break down the amino acid phenylalanine) often develop skin conditions such as eczemaand seborrheic dermatitisin areas of the body other than the scalp. The scaly skin changes that occur in people with PKU may be related to poor ability to use biotin. Increasing dietary biotin has been known to improve seborrheic dermatitis^[32]in these cases.

Biotin Biotechnology

Biotin is widely used throughout the biotechnologyindustry to conjugateproteins for biochemical assays.^[33]Biotin's small size means the biological activity of the protein will most likely be unaffected. This process is called biotinylation. Because both streptavidinand avidinbind biotin with high affinity (K_d of 10⁻¹⁴mol/l to 10⁻¹⁵mol/l) and specificity, biotinylated proteins of interest can be isolated from a sample by exploiting this highly stable interaction. The sample is incubated with streptavidin/avidin beads, allowing capture of the biotinylated protein of interest. Any other proteins binding to the biotinylated molecule will also stay with the bead and all other unbound proteins can be washed away. However, due to the extremely strong streptavidin-biotin interaction, very harsh conditions are needed to elute the biotinylated protein from the beads (typically 6M guanidineHCl at pH 1.5), which often will denature the protein of interest. To circumvent this problem, beads conjugated to monomeric avidin can be used, which has a decreased biotin-binding affinity of ~10⁻⁸mol/l, allowing the biotinylated protein of interest to be eluted with excess free biotin.

ELISAsoften make use of biotinylated primary antibodies against the antigen of interest, followed by a detection step using streptavidin conjugated to a reporter molecule, such as horseradish peroxidase.

Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed multiple carboxylase deficiency. These include deficiencies in the enzymes holocarboxylase synthetaseor biotinidase. Holocarboxylase synthetase deficiencyprevents the body's cells from using biotin effectively, and thus interferes with multiple carboxylase reactions.^[25]Biochemical and clinical manifestations include: ketolactic acidosis, organic aciduria, hyperammonemia, skin rash, feeding problems, hypotonia, seizures, developmental delay, alopecia, and coma.

Biotinidase deficiencyis not due to inadequate biotin, but rather to a deficiency in the enzymesthat process it. Biotinidasecatalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. It is also important in freeing biotin from dietary protein-bound biotin.^[25]General symptoms include decreased appetiteand growth. Dermatologic symptoms include dermatitis, alopecia, and achromotrichia(absence or loss of pigment in the hair).^[26]Perosis(a shortening and thickening of bones) is seen in the skeleton. Fatty liver and kidney syndromeand hepatic steatosisalso can occur.^[20]

Biotin deficiencyis rare and mild, and can be addressed with supplementation. It is caused by the consumption of raw egg whites(two or more daily for several months) due the avidinthey contain, a protein which binds extremely strongly with biotin, making it unavailable. Such regimens have produced the only examples of biotin deficiency serious enough to produce symptoms.^[22]

The first demonstration of biotin deficiency in animals was observed in animals fed raw egg white. Rats fed egg white protein were found to develop dermatitis, alopecia,^[23]and neuromuscular dysfunction. This syndrome, called egg white injury, was discovered to be caused by a glycoprotein found in egg white, avidin.^{[citation needed]}Avidin denatures upon heating (cooking), while the biotin remains intact.

Symptoms of biotin deficiency include:

Hair loss (alopecia)

Conjunctivitis

Dermatitisin the form of a scaly, red rash around the eyes, nose, mouth, and genital area.

Neurological symptoms in adults, such as depression, lethargy, hallucination, and numbness and tingling of the extremities^[8]

The characteristic facial rash, together with an unusual facial fat distribution, has been termed the "biotin-deficient face" by some experts. Individuals with hereditary disorders of biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.^[24]

Pregnant women tend to have a high risk of biotin deficiency. Nearly half of pregnant women have abnormal increases of 3-hydroxyisovaleric acid, which reflects reduced status of biotin.^[24]Several studies have reported this possible biotin deficiency during the pregnancy may cause infants' congenital malformations, such as cleft palate. Mice fed with dried raw egg to induce biotin deficiency during the gestation resulted in up to 100% incidence of the infants' malnourishment. Infants and embryos are more sensitive to the biotin deficiency. Therefore, even a mild level of the mother's biotin deficiency that does not reach the appearance of physiological deficiency signs may cause a serious consequence in the infants.