Biotin

Biotin is a water-soluble vitamin, generally classified as a B-complex vitamin. After the initial discovery of biotin, nearly forty years of research were required to establish it as a vitamin. Biotin is required by all organisms but can only be synthesized by bacteria, yeasts, molds, algae, and some plant species.

Function

In its physiologically active form biotin is attached at the active site of four important enzymes, known as carboxylases. Each carboxylase catalyzes an essential metabolic reaction.

Enzyme cofactor

Acetyl-CoA carboxylase catalyzes the binding of bicarbonate to acetyl-CoA to form malonyl-CoA. Malonyl-CoA is required for the synthesis of fatty acids.

Pyruvate carboxylase is a critical enzyme in gluconeogenesis, the formation of glucose from sources other than carbohydrates, for example, amino acids and fats.

Methylcrotonyl-CoA carboxylase catalyzes an essential step in the metabolism of leucine, an indispensable (essential) amino acid.

Propionyl-CoA carboxylase catalyzes essential steps in the metabolism of amino acids, cholesterol, and odd chain fatty acids (fatty acids with an odd number of carbon molecules).

Histone biotinylation

Histones are proteins that bind to DNA and package it into compact structures to form chromosomes. The compact packaging of DNA must be relaxed somewhat for DNA replication and transcription to occur. Modification of histones through the attachment of acetyl or methyl groups (acetylation or methylation) has been shown to affect the structure of histones, thereby affecting replication and transcription of DNA. The attachment of biotin to another molecule, such as a protein, is known as "biotinylation".  The enzyme biotinidase has recently been shown to catalyze the biotinylation of histones, suggesting that biotin may play a role in DNA replication and transcription.

Deficiency

Although biotin deficiency is very rare, the human requirement for dietary biotin has been demonstrated in two different situations: prolonged intravenous feeding without biotin supplementation and consumption of raw egg white for a prolonged period (many weeks to years). Avidin is a protein found in egg white, which binds biotin and prevents its absorption. Cooking egg white denatures avidin, rendering it susceptible to digestion, and unable to prevent the absorption of dietary biotin.

Symptoms

Symptoms of overt biotin deficiency include hair loss and a scaly red rash around the eyes, nose, mouth, and genital area. Neurologic symptoms in adults have included depression, lethargy, hallucination, and numbness and tingling of the extremities. The characteristic facial rash, together with an unusual facial fat distribution, have been termed the "biotin deficient face" by some experts. Individuals with hereditary disorders of biotin metabolism resulting in functional biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.

Predisposing conditions

Two hereditary disorders, biotinidase deficiency and holocarboxylase synthetase (HCS) deficiency, result in an increased biotin requirement. Biotinidase is an enzyme that catalyzes the release of biotin from small proteins and the amino acid, lysine, thereby recycling biotin. There are several ways in which biotinidase deficiency leads to biotin deficiency. Intestinal absorption is decreased because a lack of biotinidase inhibits the release of biotin from dietary protein. Recycling of one's own biotin bound to protein is impaired, and urinary loss of biotin is increased because the kidneys appear to excrete biotin that is not bound to biotinidase more rapidly. Biotinidase deficiency sometimes requires supplementation of as much as 5 to 10 milligrams (mg) of oral biotin/day, though smaller doses are often sufficient. HCS is an enzyme that catalyzes the attachment of biotin to all four carboxylase enzymes (see Function). HCS deficiency results in decreased formation of all carboxylases at normal blood levels of biotin, and requires high-dose supplementation of 40 to 100 mg of biotin/day. In general, the prognosis of both disorders is good if biotin therapy is introduced early (infancy or childhood) and continued for life.

Aside from prolonged consumption of raw egg white or intravenous feedings lacking biotin, other conditions may increase the risk of biotin depletion. The rapidly dividing cells of the developing fetus require biotin for DNA replication and synthesis of essential carboxylases, thereby increasing the biotin requirement in pregnancy. Recent research suggests that a substantial number of women develop marginal or subclinical biotin deficiency during normal pregnancy. Some types of liver disease may also increase the requirement for biotin. A recent study of 62 children with chronic liver disease and 27 healthy controls found serum biotinidase activity to be abnormally low in those with severely impaired liver function due to cirrhosis (10). Anticonvulsant medications, used to prevent seizures in individuals with epilepsy, increase the risk of biotin depletion. See Safety for more information on biotin and anticonvulsants.

Disease Prevention

Birth defects

Recent research indicates that biotin is broken down more rapidly during pregnancy and that biotin nutritional status declines during the course of pregnancy. In 6 out of 13 women studied biotin excretion dropped below the normal range during late pregnancy, suggesting that their biotin status was abnormally low. Approximately half of pregnant women have abnormally high excretion of a metabolite (3-hydroxyisovaleric acid) thought to reflect decreased activity of a biotin-dependent enzyme. A recent study of 26 pregnant women found that biotin supplementation decreased the excretion of this metabolite compared to placebo, suggesting that marginal biotin deficiency is relatively common in pregnancy. Although the level of biotin depletion was not severe enough to cause symptoms, it was reason for concern because subclinical biotin deficiency has been shown to cause birth defects in several animal species. There exists no direct evidence that marginal biotin deficiency causes birth defects in humans. However, the potential risk for biotin depletion makes it prudent to ensure adequate biotin intake throughout pregnancy.  Since pregnant women are advised to consume supplemental folic acid prior to and during pregnancy (see Folic Acid) to prevent neural tube defects, it would be easy to consume supplemental biotin (at least 30 mcg/day) in the form of a multivitamin that also contains at least 400 mcg of folic acid.

Disease Treatment

Diabetes mellitus

It has been known for many years that overt biotin deficiency results in impaired utilization of glucose. Blood biotin levels were significantly lower in 43 patients with non-insulin dependent diabetes mellitus (NIDDM) than in non-diabetic control subjects, and lower fasting blood glucose levels were associated with higher blood biotin levels. After one month of biotin supplementation (9 mg/day) fasting blood glucose levels decreased by an average of 45%. Reductions in blood glucose levels were also found in 7 insulin-dependent diabetics after 1 week of supplementation with 16 mg of biotin daily. Several mechanisms could explain the glucose-lowering effect of biotin. As a cofactor of enzymes required for fatty acid synthesis, biotin may increase the utilization of glucose to synthesize fats. Biotin has been found to stimulate glucokinase, an enzyme in the liver, resulting in increased synthesis of glycogen, the storage form of glucose. Biotin has also been found to stimulate the secretion of insulin in the pancreas of rats, which also has the effect of lowering blood glucose. An effect on cellular glucose (GLUT) transporters is also currently under investigation. Presently, studies of the effect of supplemental biotin on blood glucose levels in humans are extremely limited, but they highlight the need for further research.

Brittle fingernails

The finding that biotin supplements were effective in treating hoof abnormalities in horses and swine led to speculation that biotin supplements might also be helpful in strengthening brittle fingernails in humans. Three uncontrolled trials examining the effects of biotin supplementation (2.5 mg/day for up to six months) in women with brittle fingernails have been published. In two of the trials, subjective evidence of clinical improvement was reported in 67-91% of the participants available for follow-up at the end of the treatment period. One trial that used scanning electron microscopy to assess fingernail thickness and splitting found that fingernail thickness increased by 25% and splitting decreased after biotin supplementation. Although the results of these small uncontrolled trials suggest that biotin supplements may be helpful in strengthening brittle nails, larger placebo-controlled trials are needed to assess the efficacy of high-dose biotin supplementation for the treatment of brittle fingernails.

Hair loss

Although hair loss is a symptom of severe biotin deficiency (see Deficiency), there are no published scientific studies that support the claim that high-dose biotin supplements are effective in preventing or treating hair loss in men or women.

Safety

Toxicity

Biotin is not known to be toxic. Oral biotin supplementation has been well-tolerated in doses up to 200 mg/day in people with hereditary disorders of biotin metabolism. In people without disorders of biotin metabolism, doses of up to 5 mg/day for two years were not associated with adverse effects. However, there is one case report of life-threatening eosinophilic pleuropericardial effusion in an elderly woman who took a combination of 10 mg/day of biotin and 300 mg/day of pantothenic acid for two months. Due to the lack of reports of adverse effects when the Dietary Reference Intakes (DRI) were established for biotin in 1998, the Institute of Medicine did not establish a tolerable upper level of intake (UL) for biotin. Note: 1 mg = 1,000 mcg.

Drug interactions

Individuals on long-term anticonvulsant (anti-seizure) therapy have been found to have reduced levels of biotin in their blood, and urinary excretion of organic acids consistent with decreased carboxylase activity. The anticonvulsants, primidone and carbamazepine, inhibit biotin absorption in the small intestine. Phenobarbital, phentyoin, and carbamazepine appear to increase urinary excretion of biotin. Use of the anti-convulsant, valproic acid, has been associated with decreased biotinidase activity in children. Long-term treatment with sulfa drugs or other antibiotics may decrease bacterial synthesis of biotin, potentially increasing the requirement for dietary biotin. Large doses of the nutrient, pantothenic acid, have the potential to compete with biotin for intestinal and cellular uptake due to their similar structures. Very high (pharmacologic) doses of lipoic acid have been found to decrease the activity of biotin-dependent carboxylases in rats, but such an effect has not been demonstrated in humans.

Linus Pauling Institute Recommendation

Little is known regarding the amount of dietary biotin required to promote optimal health or prevent chronic disease. The Linus Pauling Institute supports the recommendation by the Food and Nutrition Board of 30 micrograms (mcg) of biotin/day for adults. A varied diet should provide enough biotin for most people.  However, following the Linus Pauling Institute recommendation to take a daily multivitamin/multimineral supplement will generally provide an intake of at least 30 mcg of biotin/day.

Older adults (65 years and older)

Presently, there is no indication that older adults have an increased requirement for biotin. If dietary biotin intake is not sufficient, a daily multivitamin/multimineral supplement will generally provide an intake of at least 30 mcg of biotin/day.

Reference: http://lpi.oregonstate.edu/infocenter/vitamins/biotin/