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DRI Dietary Reference Intakes: For Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline
the ears and perineal orifices are affected. The resultant rash is similar in appearance to that of cutaneous candidiasis (so termed because Candida can usually be cultured from the lesions) and is quite similar to that seen in zinc deficiency.
Hair loss has been noted in infants after 6 to 9 months of TPN; two infants evaluated had lost all hair, including eyelashes and eyebrows, within 3 to 6 months of the onset of hair loss (Mock, 1996). In biotin-deficient infants, hypotonia, lethargy, and developmental delay, along with a peculiar withdrawn behavior, are all characteristic of a neurological disorder resulting from a lack of biotin; it is thought that the withdrawn behavior may represent the equivalent of depression seen in adults that is due to central nervous system dysfunction.
SELECTION OF INDICATORS FOR ESTIMATING THE REQUIREMENT FOR BIOTIN
The most useful information concerning indicators of the adequacy of biotin intake arises from (1) clinical observations of patients receiving biotin-free intravenous nutrition, individuals with inborn errors of metabolism, and persons who consume large amounts of raw egg white; (2) 2 studies in which biotin deficiency was experimentally induced by feeding raw egg white; and (3) fewer than 10 studies of biotin bioavailability and pharmacokinetics.
Biotin and 3-Hydroxyisovalerate Excretion
The indicators of biotin status that have been validated to the greatest extent are an abnormally decreased urinary excretion of biotin and an abnormally increased urinary excretion of 3-hydroxyisovaleric acid (NI Mock et al., 1997). The urinary excretion of biotin decreased dramatically with time in normal subjects on a raw egg white diet, reaching markedly abnormal values in 9 of 10 subjects by day 20. Bisnorbiotin excretion declined in parallel, providing evidence for regulated catabolism of biotin. By day 14 of egg white feeding, 3-hydroxyisovalerate acid excretion was abnormally increased (greater than 195 µmol/day) in all 10 subjects, providing evidence that biotin depletion decreased the activity of β-methylcrotonyl-coenzyme A (CoA) and altered leucine metabolism relatively early in biotin deficiency (NI Mock et al., 1997). Normal values are 77 to 195 µmol/day (112 ± 38 [standard deviation]); at day 10 the values for the deficient people were 272 ± 92 µmol/day. Abnormally decreased excretion of biotin, abnormally increased excretion