Biotin functions in enzymatic processes (carboxylation) with key roles in the metabolism of lipids, glucose, some amino acids, and energy (1-3). It is also involved in the regulation of gene expression. Biotin has been shown to be necessary for the normal progression of cells through the cell cycle, with biotin-deficient cells arresting in the G1 phase.
Biotin deficiency manifests itself differently in different species, but most often involves dermatologic lesions to some extent. In addition to primary deficiencies of the vitamin, genetic disorders in biotin metabolism have been identified; some of these respond to large doses of biotin. A key feature of biotin metabolism is that it is recycled by the enzyme biotinidase. This recycling, and the prevalent hindgut microbial synthesis of the vitamin, allows quantitative dietary requirements for biotin to be relatively small (4). Nevertheless, inborn errors of metabolism have been identified which are associated with impaired absorption of, and increased need for, the vitamin.
Because biotin is rather widespread among foods and feedstuffs, and is synthesized by the intestinal microflora, simple deficiencies of biotin in animals or humans are rare. However, biotin deficiency can be induced by certain antagonists. Hence, few cases of biotin deficiency have been reported in humans. Most have involved nursing infants whose mother’s milk contained inadequate supplies of the vitamin or patients receiving incomplete parenteral nutrition. The signs and symptoms included dermatitis, anorexia, nausea, depression, hepatic and hypercholesterolemia. The impairments of lipid metabolism respond to biotin therapy (5).
The frequency of marginal biotin status (deficiency without clinical manifestation) is not known, but the incidence of low circulating biotin levels has been found to be substantially greater among alcoholics than the general population. Relatively low levels of biotin (vs. healthy controls) have also been reported in the plasma or urine of patients with partial gastrectomy or other causes of achlorhydria, burn patients, epileptics, elderly individuals, and athletes. Because animal products figure prominently as dietary sources of biotin, it has been suggested that vegetarians may be at risk for deficiency. Biotin catabolism also appears to be greater in smokers than non-smokers (6).
Because biotin is required in several aspects of intermediary metabolism, deficient individuals show abnormal metabolic profiles. Studies with validated biomarkers of biotin status indicate that subclinical biotin deficiency may be common in pregnancy – perhaps as frequent as one-third of pregnancies. The increases in the urinary excretion of biotin metabolites, suggests that pregnant women may experience marginal biotin deficiency due to increased catabolism of the vitamin.
The toxicity of biotin appears to be very low. No cases have been reported of adverse reactions by humans to high levels (doses as high as 200 mg orally or 20 mg intravenously) of the vitamin, as are used in treating seborrheic dermatitis in infants. Biotin excess appears to provide effective therapy to reduce the diabetic state, lowering postprandial glucose and improving glucose tolerance.
Genetic defects in all of the known biotin enzymes have been identified in humans (7). These are rare, affecting infants and children, and usually have serious consequences. Some involve mutations in genes encoding the three proteins involved in biotin homeostasis. Defects in these cause multiple carboxylase deficiencies. Biotinidase deficiency occurs at a frequency of 1 in 60,000 live births, compromising the ability to release biotin from dietary proteins and recycle it from endogenous biotinylated proteins. They show the neurological and dermatological symptoms of biotin deficiency, with onset in the first year of life (sometimes within weeks). They also experience additional signs, including hearing loss and optic atrophy, which has been interpreted as suggestive of other, still-unidentified functions of biotinidase. This can lead to irreversible neurologic damage, but can be prevented by life-long high doses (5–20 mg/day) of biotin.
The frequency of marginal biotin status (deficiency without clinical manifestation) is not known, but the incidence of low circulating biotin levels has been found to be substantially greater among alcoholics than the general population. Relatively low levels of biotin (vs. healthy controls) have also been reported in the plasma or urine of patients with partial gastrectomy or other causes of achlorhydria, burn patients, epileptics, elderly individuals, and athletes. Because animal products figure prominently as dietary sources of biotin, it has been suggested that vegetarians may be at risk for deficiency. Studies have failed to support that hypothesis; in fact, both plasma and urinary biotin levels of strict vegetarians (vegans) and lacto-ovovegetarians have been found to exceed those of persons eating mixed diets, indicating that the biotin status of the former groups was not impaired relative to the latter group.
Because biotin is required in several aspects of intermediary metabolism, deficient individuals show abnormal metabolic profiles. One of the first indicators of biotin deficiency in humans is an increase in circulating concentrations of 3-hydroxyisovaleryl carnitine. Studies with validated biomarkers of biotin status indicate that subclinical biotin deficiency may be common in pregnancy – perhaps as frequent as one-third of pregnancies (8). The increased urinary excretion of 3-hydroxyisovaleric acid, which can occur late in pregnancy, has been found to respond to biotin supplementation. This finding suggests that pregnant women may experience marginal biotin deficiency due to increased catabolism of the vitamin.
The toxicity of biotin appears to be very low. No cases have been reported of adverse reactions by humans to high levels (doses as high as 200 mg orally or 20 mg intravenously) of the vitamin, as are used in treating seborrheic dermatitis in infants., biotin excess appears to provide effective therapy to reduce the diabetic state, lowering postprandial glucose and improving glucose tolerance.
SOURCES OF BIOTIN
Biotin is widely distributed in foods and feedstuffs, but mostly in very low concentrations. Only a couple of foods (royal jelly and brewers’ yeast) contain biotin in large amounts. Milk, liver, egg (egg yolk), and a few vegetables are the most important natural sources of the vitamin in human nutrition. The biotin contents of foods can be highly variable; for the cereal grains at least it is influenced by such factors as plant variety, season, and yield (9). Biotin is found in human milk; it occurs almost exclusively as free biotin in the skim fraction. Most foods contain the vitamin as free biotin and as biocytin – i.e., biotin bound to protein residues.
Biotin is unstable to oxidizing conditions and therefore is destroyed by heat, especially under conditions that support simultaneous lipid peroxidation. For this reason, such processing techniques as canning, heat curing, and solvent extraction can result in substantial losses of biotin. These losses can be reduced by the use of a food-grade antioxidant (e.g., vitamin C, vitamin E).
In general, less than one-half of the biotin present in feedstuffs is biologically available. Although all of the biotin in corn is available, only 20–30% of that in most other grains, and none in wheat, is available. Biotin in meat products also tends to be very low. Differences in biotin bioavailability appear to be due to differential susceptibilities to digestion of the various biotin–protein linkages in which the vitamin occurs in foods and feedstuffs. Biotin from purified preparations, such as are used in dietary supplements, should be well utilized.
In humans it has been found that total faecal excretion of biotin exceeds the amount consumed in the diet. This is due to the biosynthesis of significant amounts of biotin by the microflora of the colon (10). In the digestion of food proteins, protein-bound biotin is released by the hydrolytic action of the intestinal enzymes to yield biocytin, from which free biotin is liberated by the action of biotinidase.
Biotin uptake is inhibited by pantothenic acid, lipoic acid, certain anticonvulsant drugs, and ethanol (11). Suboptimal sodium-dependent multivitamin transporter (SMVT) expression is thought to underly the low biotin absorption observed in alcoholics, pregnant women, and patients with inflammatory bowel disease, seborrheic dermatitis, or on anti-convulsants or long-term parenteral nutrition (12,13).
Appreciable storage of the vitamin appears to occur in the liver. Hepatic stores, however, appear to be poorly mobilized during biotin deprivation, and thus do not show the reductions measurable in plasma under such conditions.
BIOTIN IN HEALTH AND DISEASE
It has been suggested that marginal biotin status may be teratogenic. Because humans appear to have relatively poor transport of biotin across the placenta, it has been suggested that human foetuses may be predisposed to biotin deficiency when maternal intakes of the vitamin are marginal (14).
Sudden Infant Death Syndrome (SIDS)
It has been suggested that marginal biotin status may play a role in the etiology of SIDS, which occurs in human infants at two to four months of age. Studies have shown that infants who died of SIDS had significantly lower hepatic concentrations of biotin than did those who died of unrelated causes (15).
A number of reports have shown a beneficial effect of biotin treatment in seborrheic dermatitis. Skin lesions have also been reported in children and adults receiving long term parenteral nutrition without biotin. When on treatment with biotin, or on switching to a multivitamin containing biotin, skin lesions healed and hair began to regrow in all patients (16-18).
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Keywords-biotin; pregnancy; Skin