Biotin is also known as vitamin H and coenzyme R
(Hexahydro-2-oxo-1H-thienal[3,4-d]- imidazole-4-pentatonic acid). It is
found primarily in liver, kidney and muscle. Biotin functions as an
essential cofactor for four carboxylases that catalyze the incorporation
of cellular bicarbonate into the carbon backbone of organic compounds.
Acetyl-CoA carboxylase (ACC) is located in the cytosol where it catalyzes
the formation of malonyl-CoA which then serves as a substrate for fatty
acid elongation. The other three enzymes are located in the mitochondria.
Pyruvate carboxylase (PC) catalyzes the incorporation of bicarbonate into
pyruvate to form oxaloacetate, an intermediate in the tricarboxylic acid
cycle. In gluconeogenic tissues such as the liver and kidney, oxaloacetate
can be converted to glucose. Methcrotonyl-CoA carboxylase (MCC) catalyzes
the incorporation of bicarbonate into propionyl-CoA to form
methylmalonyl-CoA which, in turn, is metabolized to other compounds that
eventually enter the tricarboxylic acid cycle.
Deficiencies: Severe deficiency causes 1) thinning of
hair, loss of hair color, and eventually complete loss of hair; 2) a
scaly, red rash distributed around the openings of the eyes, nose, mouth,
and perineal area; and 3) central nervous system abnormalities such as
depression, lethargy, hallucinations, and paresthesias. In infants, the
neurologic findings include hypotonia, lethargy, and developmental delay,
as well as a peculiar withdrawn behavior. In patients on total or near
total intravenous feeding, an unusual distribution of facial fat coupled
with the rash and hair loss produces a distinct appearance called "biotin
deficiency facies."
Clinical uses: Biotin is routinely provided to
individuals receiving total intravenous feeding and is incorporated into
almost all nutritionally complete dietary supplements and infant formulas.
In larger doses, biotin is also used to treat inborn errors of metabolism
such as biotinidase deficiency, holocarboxylase synthetase deficiency, and
the isolated deficiencies of PC, PCC, and MCC. Marginal states of biotin
deficiency may develop during normal pregnancy, possibly due to
accelerated biotin breakdown. Adequate intakes for pregnancy may need to
be revised upward in the future; however, no untoward effects of marginal
biotin status in pregnancy have been proven to date. Marginal status has
also been detected in patients taking anticonvulsants; these
anticonvulsants appear to accelerate the rate of biotin breakdown and
interfere with biotin absorption.
Diet recommendations: The estimated safe and adequate
dietary intake values for biotin for different age groups are as follows:
5, 6, 8, 12, 20, 25 and 30 ug/day for ages of 0-0.5, 0.5-1, 1-3, 4-8,
9-13, 14-18 and >19 years, respectively. The values for pregnacy and
lactation were estimated to be 30 and 35 ug/day, respectively.
Food sources: Biotin is widely distributed in food
stuffs, but the amounts are small relative to other vitamins. Biotin
deficiency is rare in the absence of total intravenous feedings without
added biotin or the chronic ingestion of raw egg white.
Toxicity: Oral and intravenous doses up to 200 mg have
not produced frank toxicity in human subjects. In animal studies, even
higher doses per kilogram body weight have not produced toxicity.
Recent research: It has been demonstrated that there
are specific sodium coupled intestinal, renal, and hepatic transporters
for this vitamin. Mounting evidence suggest that these transporters can
also transport pantothenic acid (a compound of coenzyme A) or lipoic acid
or both.
