• Water-soluble biotin is an essential cofactor to enzymes in intermediary metabolism and a key regulator of gene expression. (More information)
  • Both parenteral nutrition devoid of biotin and prolonged consumption of raw egg white have been associated with symptoms of frank biotin deficiency, including hair loss, dermatitis, and skin rash, ataxia, seizures, and other neurologic dysfunctions. (More information)
  • Biotinidase deficiency is a rare hereditary disorder that impairs biotin absorption and recycling, resulting in secondary biotin deficiency. (More information)
  • The recommended adequate intake (AI) of biotin is set at 30 micrograms (mcg)/day in adults. Biotin requirements are likely increased during pregnancy and breast-feeding. (More information)
  • Animal studies have shown that biotin sufficiency is essential for normal fetal development. Whether marginal biotin deficiency during pregnancy increases the risk for congenital anomalies in humans is currently an area of concern and investigation. (More information)
  • Biotin is used in the treatment of an inherited disorder of thiamin transport, called biotin-responsive basal ganglia disease, and is currently being tested in trials to limit or reverse functional disabilities in individuals with multiple sclerosis. (More information)
  • Definitive evidence that establishes whether biotin supplementation improves glucose and lipid homeostasis in individuals with type 2 diabetes mellitus is currently lacking, but suggestive observations have been published. (More information)
  • Biotin cannot be synthesized by mammalian cells and must be obtained from exogenous sources. Biotin is widely found in food, and good dietary sources include egg yolk, liver, whole-grain cereal, and some vegetables. (More information)
  • Long-term anticonvulsant (anti-seizure) therapy may increase the dietary requirement for biotin because anticonvulsants can interfere with the intestinal absorption and renal re-absorption of biotin and likely also increase degradation of biotin to inactive metabolites. (More information)

Biotin is a water-soluble vitamin that is generally classified as a B-complex vitamin. After its initial discovery in 1927, 40 years of additional research was required to unequivocally establish biotin as a vitamin (1). Biotin is required by all organisms but can be synthesized by some strains of bacteria, yeast, mold, algae, and some plant species (2).



Biotin functions as a covalently bound cofactor required for the biological activity of the five known mammalian biotin-dependent carboxylases  (see below). Such a non-protein cofactor is known as a "prosthetic group." The covalent attachment of biotin to the apocarboxylase (i.e., catalytically inactive carboxylase) is catalyzed by the enzyme, holocarboxylase synthetase (HCS). The term "biotinylation" refers to the covalent addition of biotin to any molecules, including apocarboxylases and histones. HCS catalyzes the post-translational biotinylation of the epsilon amino group of a lysine residue at the active site of each apocarboxylase, converting the inactive apocarboxylase into a fully active holocarboxylase (Figure 1a). Particular lysine residues within the N-terminal tail of specific histones, which help package DNA in eukaryotic nuclei, can also be biotinylated (3). Biotinidase is the enzyme that catalyzes the release of biotin from biotinylated histones and from the peptide products of holocarboxylase breakdown (Figure 1b).

Biotin Figure 1a. Biotinylation of Carboxylases. Holocarboxylase synthetase catalyzes the transfer of biotin to a specific lysine residue at the active site of apocarboxylase, converting the enzyme to a fully active holocarboxylase. Five mammalian carboxylases are known to require biotin for their biological activity: acetyl-CoA carboxylases 1 and 2, pyruvate-CoA carboxylase, propionyl-CoA carboxylase, and methylcrotonyl-CoA carboxylase. ATP, adenosine triphosphate; CoA, coenzyme A; PPi, pyrophosphate.

Biotin Figure 1b. Biotin Recycling. The biotinylation of apocarboxylase is catalyzed by holocarboxylase synthetase, while the enzyme biotinidase catalyzes the removal of biotin from the peptide products of carboxylase breakdown.

Enzyme cofactor

Five mammalian carboxylases that catalyze essential metabolic reactions:

• Both acetyl-Coenzyme A (CoA) carboxylase 1 (ACC1) and acetyl-CoA carboxylase 2 (ACC2) catalyze the conversion of acetyl-CoA to malonyl-CoA using bicarbonate and ATP; malonyl CoA generated via ACC1 is a rate-limiting substrate for the synthesis of fatty acids in the cytosol, and malonyl CoA generated via ACC2 inhibits CPT1, an outer mitochondrial membrane enzyme important in fatty acid oxidation (Figure 2). ACC1 is found in all tissues and is particularly active in lipogenic tissues (i.e., liver, white adipose tissue, and mammary gland), heart, and pancreatic islets. ACC2 is especially abundant in skeletal muscle and heart (4).

Biotin Figure 2. Acetyl-CoA Carboxylase 1 and Acetyl-CoA Carboxylase 2. In the cytosol of liver cells, fatty acids are converted to acyl-CoA, and glucose undergoes glycolysis that produces pyruvate. Acyl-CoA is shuttled into the mitochondria via CPT1-mediated transport and undergoes β-oxidation that generates acetyl-CoA. In addition, pyruvate is converted to acetyl-CoA in the mitochondria, and acetyl-CoA is condensed with oxaloacetate to form citrate. The latter can be exported to the cytosol and cleaved to oxaloacetate and acetyl-CoA. Acetyl-CoA is used to generate malonyl-CoA in a reaction catalyzed by biotin-containing acetyl-CoA carboxylase 1 (ACC1) in the presence of ATP and bicarbonate. Malonyl-CoA is an essential substrate for the biosynthesis of fatty acids and subsequent triglycerides, phospholipids, and lipoproteins. Malonyl-CoA is also a regulator of fatty acid β-oxidation. Indeed, malonyl-CoA generated from acetyl-CoA by another biotin-containing enzyme, acetyl-CoA carboxylase 2 (ACC2), localized at the outer mitochondrial membrane, has been shown to downregulate fatty acid β-oxidation in the mitochondria by inhibiting CPT1. ACC1, acetyl-coenzyme A carboxylase 1; ACC2, acetyl-coenzyme A carboxylase 2; CoA, coenzyme A; CPT1, carnitine/palmitoyl-transferase 1.

Pyruvate carboxylase is a critical enzyme in gluconeogenesis — the formation of glucose from sources other than carbohydrates, such as pyruvate, lactate, glycerol, and the glucogenic amino acids. Pyruvate carboxylase catalyzes the ATP-dependent incorporation of bicarbonate into pyruvate, producing oxaloacetate; hence, pyruvate carboxylase is anaplerotic for the citric acid cycle (Figure 3). Oxaloacetate can then be converted to phosphoenolpyruvate and eventually to glucose.

Biotin Figure 3. Pyruvate Carboxylase and Acetyl-CoA Carboxylase 1. Biotin-containing pyruvate carboxylase supplies the citric acid cycle with oxaloacetate by catalyzing the conversion of pyruvate to oxaloacetate using bicarbonate and ATP. In the liver, oxaloacetate can be used as a precursor for gluconeogenesis. It is first converted to phosphoenolpyruvate (PEP) by PEP carboxykinase and then to glucose via the reverse pathway of glycolysis. In the citric acid cycle, oxaloacetate can also be condensed with acetyl-CoA to produce citrate, which can be exported from the mitochondria. In the liver, adipose tissue, and skeletal muscle, citrate is cleaved to oxaloacetate and acetyl-CoA in the cytosol. Acetyl-CoA is converted to malonyl-CoA by another biotin-containing enzyme, acetyl-CoA carboxylase 1. Malonyl-CoA is then used by fatty acid synthase 1 to generate long-chain fatty acids. CoA, coenzyme A.

Methylcrotonyl-CoA carboxylase catalyzes an essential step in the catabolism of leucine, an essential branched-chain amino acid. This biotin-containing enzyme catalyzes the production of 3-methylglutaconyl-CoA from methylcrotonyl-CoA (Figure 4a).

Propionyl-CoA carboxylase produces D-malonylmalonyl-CoA from propionyl-CoA, a by-product in the β-oxidation of fatty acids with an odd number of carbon atoms (Figure 4a). The conversion of propionyl-CoA to D-malonylmalonyl-CoA is also required in the catabolic pathways of two branched-chain amino acids (isoleucine and valine), methionine, threonine, and the side chain of cholesterol (Figure 4a and 4b).

Biotin Figure 4a. Biotin-containing Carboxylases in the Metabolism of BCAAs, Odd Chain Fatty Acids, and Cholesterol. Two biotin-containing enzymes, namely propionyl-CoA carboxylase and methylcrotonyl-CoA carboxylase, are required in the metabolism of branched chain amino acids (leucine, valine, and isoleucine), the oxidation of odd chain fatty acids, and the degradation of cholesterol side chain. The metabolic pathways generate acetyl-CoA and succinyl-CoA, which then enter the citric acid cycle. BCAAs, branched chain amino acids; CoA, coenzyme A.

Biotin Figure 4b. Biotin-containing Propionyl-CoA Carboxylase in the Metabolism of Methionine and Threonine. Propionyl-CoA carboxylase converts propionyl-CoA to D-malonylmalonyl-CoA in the metabolism of methionine and threonine. CoA, coenzyme A; SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine.

Regulation of chromatin structure and gene expression

In eukaryotic nuclei, DNA is packaged into compact structures to form nucleosomes — fundamental units of chromatin. Each nucleosome is composed of 147 base pairs of DNA wrapped around eight histones (paired histones: H2A, H2B, H3, and H4). Another histone, called H1 linker, is located at the outer surface of each nucleosome and serves as an anchor to fix the DNA around the histone core. The compact packaging of chromatin must be relaxed from time to time to allow biological processes, such as DNA replication and transcription to occur. Chemical modifications of DNA and histones affect the folding of chromatin, increasing or reducing DNA accessibility to factors involved in the above-mentioned processes. Together with DNA methylation, a number of chemical modifications within the N-terminal tail of core histones modify their electric charge and structure, thereby changing chromatin conformation and transcriptional activity of genes.

The various modifications of histone tails, including acetylation, methylation, phosphorylation, ubiquitination, SUMOylation, ADP-ribosylation, carbonylation, deimination, hydroxylation, and biotinylation, have different regulatory functions. Several sites of biotinylation have been identified in histones H2A, H3, and H4 (5). Amongst them, histone H4 biotinylation at lysine (K) 12 (noted H4K12bio) appears to be enriched in heterochromatin, a tightly condensed chromatin associated with repeat regions in (peri)centromeres and telomeres, and with transposable elements known as long terminal repeats (3). In addition, biotinylation marks co-localize with well-known gene repression marks like methylated lysine 9 in histone H3 (H3K9me) in transcriptionally competent chromatin (6). For example, H4K12bio can be found at the promoter of the gene SLC5A6 that codes for the transporter mediating biotin uptake into cells, the human sodium-dependent multivitamin transporter (hSMVT). When biotin is abundant, HCS can biotinylate histones H4 in the SLC5A6 promoter, which halts hSMVT synthesis and reduces biotin uptake. Conversely, in biotin-deficient cells, biotinylation marks in the SLC5A6 promoter are removed such that gene expression can occur, enabling the synthesis of hSMVT and subsequently increasing the uptake of biotin (7).


Although overt biotin deficiency is very rare, the human requirement for dietary biotin has been demonstrated in three different situations: prolonged intravenous feeding (parenteral) without biotin supplementation, infants fed an elemental formula devoid of biotin, and consumption of raw egg white for a prolonged period (many weeks to years) (8). Raw egg white contains an antimicrobial protein known as avidin that can bind biotin and prevent its absorption. Cooking egg white denatures avidin, rendering it susceptible to digestion and therefore unable to prevent the absorption of dietary biotin (5).

Signs and symptoms of biotin deficiency

Signs of overt biotin deficiency include hair loss (alopecia) and a scaly red rash around the eyes, nose, mouth, and genital area. Neurologic symptoms in adults have included depression, lethargy, hallucinations, numbness and tingling of the extremities, ataxia, and seizures. The characteristic facial rash, together with unusual facial fat distribution, has been termed the "biotin deficient facies" by some investigators (1). Individuals with hereditary disorders of biotin metabolism (see Inborn metabolic disorders) resulting in functional biotin deficiency often have similar physical findings, as well as seizures and evidence of impaired immune system function and increased susceptibility to bacterial and fungal infections (9, 10).

Risk factors for biotin deficiency

Aside from prolonged consumption of raw egg white or total intravenous nutritional support lacking biotin, other conditions may increase the risk of biotin depletion. Smoking has been associated with increased biotin catabolism (11). The rapidly dividing cells of the developing fetus require biotin for synthesis of essential carboxylases and histone biotinylation; hence, the biotin requirement is likely increased during pregnancy. Research suggests that a substantial number of women develop marginal or subclinical biotin deficiency during normal pregnancy (see also Disease Prevention) (8, 12, 13). Additionally, certain types of liver disease may decrease biotinidase activity and theoretically increase the requirement for biotin. A 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 (14). However, this study did not provide evidence of biotin deficiency. Further, anticonvulsant medications, used to prevent seizures in individuals with epilepsy, increase the risk of biotin depletion (for more information on biotin and anticonvulsants, see Drug interactions).

Inborn metabolic disorders

Biotinidase deficiency

There are several ways in which the hereditary disorder, biotinidase deficiency, leads to secondary biotin deficiency. Intestinal absorption is decreased because a lack of biotinidase prevents the release of biotin from dietary protein (15). Recycling of one's own biotin bound to carboxylases and histones is also impaired, and urinary loss of biocytin (N-biotinyl-lysine) and biotin is increased (see Figure 1 above) (5). Biotinidase deficiency uniformly responds to supplemental biotin. Oral supplementation with as much as 5 to 10 milligrams (mg) of biotin daily is sometimes required, although smaller doses are often sufficient (reviewed in 16).

Holocarboxylase synthetase (HCS) deficiency

Some forms of HCS deficiency respond to supplementation with pharmacologic doses of biotin. HCS deficiency results in decreased formation of all holocarboxylases at physiological blood biotin concentrations; thus, high-dose biotin supplementation (10-80 mg of biotin daily) is required (10).

The prognosis of these two disorders is usually good if biotin therapy is introduced early (infancy or childhood) and continued for life (10).

Biotin transport deficiency

There has been one case report of a child with biotin transport deficiency who responded to high-dose biotin supplementation (17). Of note, the presence of a defective human sodium-dependent multivitamin transporter (hSMVT) was ruled out as a cause of biotin transport deficiency.

Phenylketonuria (PKU)

Abnormally elevated concentrations of the amino acid, phenylalanine, in the blood of PKU-affected individuals may inhibit the activity of biotinidase. Schulpis et al. speculated that the seborrheic dermatitis associated with low biotinidase activity in these patients would resolve upon compliance with a special low-protein diet but not with biotin supplementation (18).

Markers of biotin status

Four measures of marginal biotin deficiency have been validated as indicators of biotin status: (1) reduced urinary excretion of biotin and some of its catabolites; (2) high urinary excretion of an organic acid, 3-hydroxyisovaleric acid, and its derivative, carnityl-3-hydroxyisovaleric acid, both of which reflect decreased activity of biotin-dependent methylcrotonyl-CoA carboxylase; (3) reduced propionyl-CoA carboxylase activity in peripheral blood lymphocytes (5); and (4) reduced levels of holo-methylcrotonyl-CoA carboxylase and holo-propionyl-CoA carboxylase in lymphocytes — the most reliable indicators of biotin status (19). These markers have been only validated in men and nonpregnant women, and they may not accurately reflect biotin status in pregnant and breast-feeding women (12).

The Adequate Intake (AI)

Sufficient scientific evidence is lacking to estimate the dietary requirement for biotin; thus, no Recommended Dietary Allowance (RDA) for biotin has been established. Instead, the Food and Nutrition Board (FNB) of the Institute of Medicine (IOM) set recommendations for an Adequate Intake (AI; Table 1). The AI for adults (30 micrograms [mcg]/day) was extrapolated from the AI for infants exclusively fed human milk and is expected to overestimate the dietary requirement for biotin in adults. Dietary intakes of generally healthy adults have been estimated to be 40-60 mcg/day of biotin (1). The requirement for biotin in pregnancy may be increased (20).

Table 1. Adequate Intake (AI) for Biotin
Life Stage Age Males (mcg/day) Females (mcg/day)
Infants 0-6 months 5 5
Infants 7-12 months 6 6
Children 1-3 years 8 8
Children 4-8 years 12 12
Children 9-13 years 20 20
Adolescents 14-18 years 25 25
Adults 19 years and older 30 30
Pregnancy all ages - 30
Breast-feeding all ages - 35

Disease Prevention

Congenital anomalies

Current research indicates that at least one-third of women develop marginal biotin deficiency during pregnancy (8). Small observational studies in pregnant women have reported an abnormally high urinary excretion of 3-hydroxyisovaleric acid in both early and late pregnancy, suggesting decreased activity of biotin-dependent methylcrotonyl-CoA carboxylase (21, 22). In a randomized, single-blinded intervention study in 26 pregnant women, supplementation with 300 mcg/day of biotin for two weeks limited the excretion of 3-hydroxyisovaleric acid compared to placebo, confirming that increased 3-hydroxyisovaleric acid excretion indeed reflected marginal biotin deficiency in pregnancy (23). A small cross-sectional study in 22 pregnant women reported an incidence of low lymphocyte propionyl-CoA carboxylase activity (another marker of biotin deficiency) greater than 80% (13). Although the level of biotin deficiency is not associated with overt signs of deficiency in pregnant women, such observations are sources of concern because subclinical biotin deficiency has been shown to cause cleft palate and limb hypoplasia in several animal species (reviewed in 13). In addition, biotin depletion has been found to suppress the expression of biotin-dependent carboxylases, remove biotin marks from histones, and decrease the proliferation in human embryonic palatal mesenchymal cells in culture (24). Impaired carboxylase activity may result in alterations in lipid metabolism, which have been linked to cleft palate and skeletal abnormalities in animals. Further, biotin deficiency leading to reduced histone biotinylation at specific genomic loci may increase genomic instability and result in chromosome anomalies and fetal malformations (13).

While pregnant women are advised to consume supplemental folic acid prior to and during pregnancy to prevent neural tube defects (see Folate), it would also be prudent to ensure adequate biotin intake throughout pregnancy. The current AI for pregnant women is 30 mcg/day of biotin, and no toxicity has ever been reported at this level of intake (see Safety).

Disease Treatment

Biotin-responsive basal ganglia disease

Biotin-responsive basal ganglia disease, also called thiamin metabolism dysfunction syndrome-2, is caused by mutations in the gene coding for thiamin transporter-2 (THTR-2). The clinical features appear around three to four years of age and include sub-acute encephalopathy (confusion, drowsiness, and altered level of consciousness), ataxia, and seizures. A retrospective study of 18 affected individuals from the same family or the same tribe in Saudi Arabia was recently conducted. The data showed that biotin monotherapy (5-10 mg/kg/day) efficiently abolished the clinical manifestations of the disease, although one-third of the patients suffered from recurrent acute crises. Often associated with poor outcomes, acute crises were not observed after thiamin supplementation started (300-400 mg/day) and during a five-year follow-up period. Early diagnostic and immediate treatment with biotin and thiamin led to positive outcomes (25). The mechanism for the beneficial effect of biotin supplementation has yet to be elucidated.

Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive damages to the myelin sheath surrounding nerve fibers (axons) and neuronal loss in the brain and spinal cord of affected individuals. The progression of neurologic disabilities in MS patients is often assessed by the Expanded Disability Status Scale (EDSS) with scores from 1 to 10, from minimal signs of motor dysfunction (score of 1) to death by MS (score of 10). ATP deficiency due to mitochondrial dysfunction and increased oxidative stress may be partly responsible for the progressive degeneration of neurons in MS (26). Given its role in intermediary metabolism and fatty acid synthesis (required for myelin formation) (see Function), it has been hypothesized that biotin might exert beneficial effects that would limit or reverse MS-associated functional impairments (26).

A nonrandomized, uncontrolled pilot study in 23 patients with progressive MS found high doses of biotin (100-600 mg/day) to be associated with sustained clinical improvements in 5 (out of 5) patients with progressive visual loss and 16 (out of 18) patients with partial paralysis of the limbs after a mean three months following treatment onset (27). In addition, the preliminary results from a multicenter, randomized, placebo-controlled trial in 154 subjects with progressive MS indicated that 13 out of 103 patients randomized to receive daily oral biotin (300 mg) for 48 weeks achieved a composite functional endpoint that included a decrease in EDSS scores. In comparison, none of the 51 patients randomized to the placebo group showed significant clinical improvements (28). Two ongoing trials are evaluating the effect of high-dose biotin supplementation in the treatment of MS (see trials NCT02220933 and NCT02220244 at

Diabetes mellitus

Overt biotin deficiency has been shown to impair glucose utilization in mice (29) and cause fatal hypoglycemia in chickens. Overt biotin deficiency likely also causes abnormalities in glucose regulation in humans (see Function). One early human study reported lower serum biotin concentrations in 43 patients with type 2 diabetes mellitus compared to 64 non-diabetic control subjects, as well as an inverse relationship between fasting blood glucose and biotin concentrations (30). In a small, randomized, placebo-controlled intervention study in 28 patients with type 2 diabetes, daily supplementation with 9 milligrams (mg) of biotin for one month resulted in a mean 45% decrease in fasting blood glucose concentrations (30). Yet, another small study in 10 patients with type 2 diabetes and 7 nondiabetic controls found no effect of biotin supplementation (15 mg/day) for 28 days on fasting blood glucose concentrations in either group (31). A more recent double-blind, placebo-controlled study by the same research group showed that the same biotin regimen lowered plasma triglyceride concentrations in both diabetic and nondiabetic patients with hypertriglyceridemia (32). In this study, biotin administration did not affect blood glucose concentrations in either patient group. Additionally, a few studies have shown that co-supplementation with biotin and chromium picolinate may be a beneficial adjunct therapy in patients with type 2 diabetes (33-36). However, administration of chromium picolinate alone has been shown to improve glycemic control in diabetic subjects (see the article on Chromium) (37).

As a cofactor of carboxylases required for fatty acid synthesis, biotin may increase the utilization of glucose for fat synthesis. Biotin has been found to stimulate glucokinase, a liver enzyme that increases synthesis of glycogen, the storage form of glucose. Biotin also appeared to trigger the secretion of insulin in the pancreas of rats and improve glucose homeostasis (38). Yet, reduced activity of ACC1 and ACC2 would be expected to reduce fatty acid synthesis and increase fatty acid oxidation, respectively. Not surprisingly, it is currently unclear whether pharmacologic doses of biotin could benefit the management of hyperglycemia in patients with impaired glucose tolerance. Moreover, whether supplemental biotin lowers the risk of cardiovascular complications in diabetic patients by reducing serum triglycerides and LDL-cholesterol remains to be proven (32-34).

Brittle fingernails (onychorrhexis)

The finding that biotin supplements were effective in treating hoof abnormalities in hoofed animals suggested that biotin might also be helpful in strengthening brittle fingernails in humans (39-41). Three uncontrolled trials examining the effects of biotin supplementation (2.5 mg/day for several months) in women with brittle fingernails have been published (42-44). 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 (42, 43). One trial that used scanning electron microscopy to assess fingernail brittleness reported less fingernail splitting and a 25% increase in the thickness of the nail plate in patients supplemented with biotin for 6 to 15 months (44). Biotin supplementation (5 mg/day) was also found to be effective in controlling unruly hair and splitting nails in two toddlers with inherited uncombable hair syndrome (45). Although preliminary evidence suggests that supplemental biotin may help strengthen fragile nails, larger placebo-controlled trials are needed to assess the efficacy of high-dose biotin supplementation for the treatment of brittle fingernails.

Hair loss (alopecia)

Biotin administration was found to reverse alopecia in children treated with the anticonvulsant, valproic acid (see Drug interactions). Yet, 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 (46).


Food sources

Biotin is found in many foods, either as the free form that is directly taken up by enterocytes or as biotin bound to dietary proteins. Egg yolk, liver, and yeast are rich sources of biotin. Estimates of average daily intakes of biotin from small studies ranged between 40 and 60 micrograms (mcg) per day in adults (1). However, US national nutritional surveys have not yet been able to estimate biotin intake due to the scarcity and unreliability of data regarding biotin content of food. Food composition tables for biotin are incomplete such that dietary intakes cannot be reliably estimated in humans. A study by Staggs et al. (47) employed a high-performance liquid chromatography method rather than bioassays (48) and reported relatively different biotin content for some selected foods. Table 2 lists some food sources of biotin, along with their content in mcg.

Table 2. Some Food Sources of Biotin (47, 48)
Food Serving Biotin (mcg)
Yeast 1 packet (7 grams) 1.4-14
Bread, whole-wheat 1 slice 0.02-6
Egg, cooked 1 large 13-25
Cheese, cheddar 1 ounce 0.4-2
Liver, cooked 3 ounces* 27-35
Pork, cooked 3 ounces* 2-4
Salmon, cooked 3 ounces* 4-5
Avocado 1 whole 2-6
Raspberries 1 cup 0.2-2
Cauliflower, raw 1 cup 0.2-4
*A three-ounce serving of meat is about the size of a deck of cards.

Bacterial synthesis

A majority of bacteria that normally colonize the small and large intestine (colon) synthesize biotin (49). Whether the biotin is released and absorbed by humans in meaningful amounts remains unknown. The uptake of free biotin into intestinal cells via the human sodium-dependent multivitamin transporter (hSMVT) has been identified in cultured cells derived from the lining of the small intestine and colon (50), suggesting that humans may be able to absorb biotin produced by enteric bacteria — a phenomenon documented in swine.


Biotin is available as a single-nutrient supplement in various doses and is often included in B-complex and multivitamin-mineral (MVM) supplements. Many MVM supplements contain 30 mcg of biotin (51).



Biotin is not known to be toxic. In people without disorders of biotin metabolism, doses of up to 5 mg/day for two years were not associated with adverse effects (52). Oral biotin supplementation has been well tolerated in doses up to 200 mg/day (nearly 7,000 times the AI) in people with hereditary disorders of biotin metabolism (1). Daily supplementation with a highly concentrated formulation of biotin (100-600 mg) for several months was also found to be well tolerated in individuals with progressive multiple sclerosis (27, 28). 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 (vitamin B5) for two months (53). Because reports of adverse events were lacking when the Dietary Reference Intakes (DRI) for biotin were established in 1998, the Institute of Medicine did not establish a tolerable upper intake level (UL) for biotin (1).

Nutrient interactions

Large doses of pantothenic acid (vitamin B5) have the potential to compete with biotin for intestinal and cellular uptake by the human sodium-dependent multivitamin transporter (hSMVT) (54, 55). Biotin also shares the hSMVT with α-lipoic acid (56). Pharmacologic (very high) doses of α-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 (57).

Drug interactions

Individuals on long-term anticonvulsant (anti-seizure) therapy reportedly have reduced blood biotin concentrations, as well as an increased urinary excretion of organic acids (e.g., 3-hydroxyisovaleric acid) that indicate decreased carboxylase activity (see Markers of biotin status) (5). Potential mechanisms of biotin depletion by the anticonvulsants, primidone (Mysoline), phenytoin (Dilantin), and carbamazepine (Carbatrol, Tegretol), include inhibition of biotin intestinal absorption and renal reabsorption, as well as increased biotin catabolism (51). Use of the anticonvulsant valproic acid in children has resulted in hair loss reversed by biotin supplementation (58-61). Long-term treatment with antibacterial sulfonamide (sulfa) drugs or other antibiotics may decrease bacterial synthesis of biotin. Yet, given that the extent to which bacterial synthesis contributes to biotin intake in humans is not known, effects of antimicrobial drugs on biotin nutritional status remain uncertain (51).

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 made by the Institute of Medicine, which is 30 micrograms (mcg) of biotin per 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-mineral supplement will generally provide an intake of at least 30 mcg/day of biotin.

Older adults (>50 years)

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

Authors and Reviewers

Originally written in 2000 by: 
Jane Higdon, Ph.D. 
Linus Pauling Institute 
Oregon State University

Updated in June 2004 by: 
Jane Higdon, Ph.D. 
Linus Pauling Institute 
Oregon State University

Updated in August 2008 by: 
Victoria J. Drake, Ph.D. 
Linus Pauling Institute 
Oregon State University

Updated in July 2015 by:
Barbara Delage, Ph.D.
Linus Pauling Institute
Oregon State University

Reviewed in September 2015 by: 
Donald Mock, M.D., Ph.D. 
Departments of Biochemistry and Molecular Biology and Pediatrics 
University of Arkansas for Medical Sciences

Copyright 2000-2015  Linus Pauling Institute


1.  Food and Nutrition Board, Institute of Medicine. Biotin. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, D.C.: National Academy Press; 1998:374-389.  (National Academy Press)

2.  Mock DM. Biotin. Handbook of vitamins. 4th ed. Boca Raton, FL: CRC Press; 2007:361-383.

3.  Zempleni J, Teixeira DC, Kuroishi T, Cordonier EL, Baier S. Biotin requirements for DNA damage prevention. Mutat Res. 2012;733(1-2):58-60.  (PubMed)

4.  Saggerson D. Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr. 2008;28:253-272.  (PubMed)

5.  Zempleni J, Wijeratne SSK, Kuroishi T. Biotin. In: Erdman JWJ, Macdonald IA, Zeisel SH, eds. Present Knowledge in Nutrition. 10th ed.: John Wiley & Sons, Inc.; 2012:359-374.

6.  Zempleni J, Li Y, Xue J, Cordonier EL. The role of holocarboxylase synthetase in genome stability is mediated partly by epigenomic synergies between methylation and biotinylation events. Epigenetics. 2011;6(7):892-894.  (PubMed)

7.  Zempleni J, Gralla M, Camporeale G, Hassan YI. Sodium-dependent multivitamin transporter gene is regulated at the chromatin level by histone biotinylation in human Jurkat lymphoblastoma cells. J Nutr. 2009;139(1):163-166.  (PubMed)

8.  Mock DM. Biotin. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern Nutrition in Health and Disease. 11th ed.: Lippincott Williams & Wilkins; 2014:390-398.

9.  Baumgartner ER, Suormala T. Inherited defects of biotin metabolism. Biofactors. 1999;10(2-3):287-290.  (PubMed)

10.  Elrefai S, Wolf B. Disorders of biotin metabolism. In: Rosenberg RN, Pascual JM, eds. Rosenberg's Molecular and Genetic basis of Neurological and Psychiatric Disease. 5th ed. United States of America: Elsevier; 2015:531-539.

11.  Sealey WM, Teague AM, Stratton SL, Mock DM. Smoking accelerates biotin catabolism in women. Am J Clin Nutr. 2004;80(4):932-935.  (PubMed)

12.  Perry CA, West AA, Gayle A, et al. Pregnancy and lactation alter biomarkers of biotin metabolism in women consuming a controlled diet. J Nutr. 2014;144(12):1977-1984.  (PubMed)

13.  Mock DM. Marginal biotin deficiency is common in normal human pregnancy and is highly teratogenic in mice. J Nutr. 2009;139(1):154-157.  (PubMed)

14.  Pabuccuoglu A, Aydogdu S, Bas M. Serum biotinidase activity in children with chronic liver disease and its clinical significance. J Pediatr Gastroenterol Nutr. 2002;34(1):59-62.  (PubMed)

15.  Zempleni J, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. 2008;3(6):715-724.  (PubMed)

16.  Wolf B. Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have." Genet Med. 2012;14(6):565-575.  (PubMed)

17.  Mardach R, Zempleni J, Wolf B, et al. Biotin dependency due to a defect in biotin transport. J Clin Invest. 2002;109(12):1617-1623.  (PubMed)

18.  Schulpis KH, Nyalala JO, Papakonstantinou ED, et al. Biotin recycling impairment in phenylketonuric children with seborrheic dermatitis. Int J Dermatol. 1998;37(12):918-921.  (PubMed)

19.  Eng WK, Giraud D, Schlegel VL, Wang D, Lee BH, Zempleni J. Identification and assessment of markers of biotin status in healthy adults. Br J Nutr. 2013;110(2):321-329.  (PubMed)

20.  Mock DM. Adequate intake of biotin in pregnancy: why bother? J Nutr. 2014;144(12):1885-1886.  (PubMed)

21.  Mock DM, Stadler DD. Conflicting indicators of biotin status from a cross-sectional study of normal pregnancy. J Am Coll Nutr. 1997;16(3):252-257.  (PubMed)

22.  Mock DM, Stadler DD, Stratton SL, Mock NI. Biotin status assessed longitudinally in pregnant women. J Nutr. 1997;127(5):710-716.  (PubMed)

23.  Mock DM, Quirk JG, Mock NI. Marginal biotin deficiency during normal pregnancy. Am J Clin Nutr. 2002;75(2):295-299.  (PubMed)

24.  Takechi R, Taniguchi A, Ebara S, Fukui T, Watanabe T. Biotin deficiency affects the proliferation of human embryonic palatal mesenchymal cells in culture. J Nutr. 2008;138(4):680-684.  (PubMed)

25.  Alfadhel M, Almuntashri M, Jadah RH, et al. Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases. Orphanet J Rare Dis. 2013;8:83.  (PubMed)

26.  Sedel F, Bernard D, Mock DM, Tourbah A. Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis. Neuropharmacology. 2015.  (PubMed)

27.  Sedel F, Papeix C, Bellanger A, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study. Mult Scler Relat Disord. 2015;4(2):159-169.  (PubMed)

28.  Tourbah A LFC, Edan G, Clanet M, Papeix C, Vukusic S, et al. Effect of MD1003 (high doses of biotin) in progressive multiple sclerosis: results of a pivotal phase III randomized double blind placebo controlled study. Paper presented at: American Association of Neurological Surgeons (AANS) Annual Scientific Meeting 2015; Washington, D.C. Available at: Accessed 9/17/15.

29.  Larrieta E, Vega-Monroy ML, Vital P, et al. Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis. J Nutr Biochem. 2012;23(4):392-399.  (PubMed)

30.  Maebashi M, Makino Y, Furukawa Y, Ohinata K, Kimura S, Sato T. Therapeutic evaluation of the effect of biotin on hyperglycemia in pateints with non-insulin dependent diabetes mellitus. J Clin Biochem Nutr. 1993;14:211-218.

31.  Baez-Saldana A, Zendejas-Ruiz I, Revilla-Monsalve C, et al. Effects of biotin on pyruvate carboxylase, acetyl-CoA carboxylase, propionyl-CoA carboxylase, and markers for glucose and lipid homeostasis in type 2 diabetic patients and nondiabetic subjects. Am J Clin Nutr. 2004;79(2):238-243.  (PubMed)

32.  Revilla-Monsalve C, Zendejas-Ruiz I, Islas-Andrade S, et al. Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia. Biomed Pharmacother. 2006;60(4):182-185.  (PubMed)

33.  Geohas J, Daly A, Juturu V, Finch M, Komorowski JR. Chromium picolinate and biotin combination reduces atherogenic index of plasma in patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized clinical trial. Am J Med Sci. 2007;333(3):145-153.  (PubMed)

34.  Albarracin C, Fuqua B, Geohas J, Juturu V, Finch MR, Komorowski JR. Combination of chromium and biotin improves coronary risk factors in hypercholesterolemic type 2 diabetes mellitus: a placebo-controlled, double-blind randomized clinical trial. J Cardiometab Syndr. 2007;2(2):91-97.  (PubMed)

35.  Singer GM, Geohas J. The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther. 2006;8(6):636-643.  (PubMed)

36.  Albarracin CA, Fuqua BC, Evans JL, Goldfine ID. Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev. 2008;24(1):41-51.  (PubMed)

37.  Suksomboon N, Poolsup N, Yuwanakorn A. Systematic review and meta-analysis of the efficacy and safety of chromium supplementation in diabetes. J Clin Pharm Ther. 2014;39(3):292-306.  (PubMed)

38.  Lazo de la Vega-Monroy ML, Larrieta E, German MS, Baez-Saldana A, Fernandez-Mejia C. Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and beta-cell proportion. J Nutr Biochem. 2013;24(1):169-177.  (PubMed)

39.  Randhawa SS, Dua K, Randhawa CS, Randhawa SS, Munshi SK. Effect of biotin supplementation on hoof health and ceramide composition in dairy cattle. Vet Res Commun. 2008;32(8):599-608.  (PubMed)

40.  Reilly JD, Cottrell DF, Martin RJ, Cuddeford DJ. Effect of supplementary dietary biotin on hoof growth and hoof growth rate in ponies: a controlled trial. Equine Vet J Suppl. 1998(26):51-57.  (PubMed)

41.  Zenker W, Josseck H, Geyer H. Histological and physical assessment of poor hoof horn quality in Lipizzaner horses and a therapeutic trial with biotin and a placebo. Equine Vet J. 1995;27(3):183-191.  (PubMed)

42.  Romero-Navarro G, Cabrera-Valladares G, German MS, et al. Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats. Endocrinology. 1999;140(10):4595-4600.  (PubMed)

43.  Floersheim GL. [Treatment of brittle fingernails with biotin]. Z Hautkr. 1989;64(1):41-48.  (PubMed)

44.  Hochman LG, Scher RK, Meyerson MS. Brittle nails: response to daily biotin supplementation. Cutis. 1993;51(4):303-305.  (PubMed)

45.  Boccaletti V, Zendri E, Giordano G, Gnetti L, De Panfilis G. Familial Uncombable Hair Syndrome: Ultrastructural Hair Study and Response to Biotin. Pediatr Dermatol. 2007;24(3):E14-16.  (PubMed)

46.  Famenini S, Goh C. Evidence for supplemental treatments in androgenetic alopecia. J Drugs Dermatol. 2014;13(7):809-812.  (PubMed)

47.  Staggs CG, Sealey WM, McCabe BJ, Teague AM, Mock DM. Determination of the biotin content of select foods using accurate and sensitive HPLC/avidin binding. J Food Compost Anal. 2004;17(6):767-776.  (PubMed)

48.  Briggs DR, Wahlqvist ML. Food facts: the complete no-fads-plain-facts guide to healthy eating. Victoria, Australia: Penguin Books; 1988.

49.  Magnusdottir S, Ravcheev D, de Crecy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015;6:148.  (PubMed)

50.  Said HM. Cell and molecular aspects of human intestinal biotin absorption. J Nutr. 2009;139(1):158-162.  (PubMed)

51.  Natural-Medicines. Biotin/Drug interactions. 2014 ed.; 2014

52.  Koutsikos D, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic peripheral neuropathy. Biomed Pharmacother. 1990;44(10):511-514.  (PubMed)

53.  Debourdeau PM, Djezzar S, Estival JL, Zammit CM, Richard RC, Castot AC. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother. 2001;35(4):424-426.  (PubMed)

54.  Chirapu SR, Rotter CJ, Miller EL, Varma MV, Dow RL, Finn MG. High specificity in response of the sodium-dependent multivitamin transporter to derivatives of pantothenic acid. Curr Top Med Chem. 2013;13(7):837-842.  (PubMed)

55.  Said HM, Ortiz A, McCloud E, Dyer D, Moyer MP, Rubin S. Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. Am J Physiol. 1998;275(5 Pt 1):C1365-1371.  (PubMed)

56.  Prasad PD, Wang H, Kekuda R, et al. Cloning and functional expression of a cDNA encoding a mammalian sodium-dependent vitamin transporter mediating the uptake of pantothenate, biotin, and lipoate. J Biol Chem. 1998;273(13):7501-7506.  (PubMed)

57.  Zempleni J, Trusty TA, Mock DM. Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. J Nutr. 1997;127(9):1776-1781.  (PubMed)

58.  Castro-Gago M, Gomez-Lado C, Eiris-Punal J, Diaz-Mayo I, Castineiras-Ramos DE. Serum biotinidase activity in children treated with valproic acid and carbamazepine. J Child Neurol. 2010;25(1):32-35.  (PubMed)

59.  Castro-Gago M, Perez-Gay L, Gomez-Lado C, Castineiras-Ramos DE, Otero-Martinez S, Rodriguez-Segade S. The influence of valproic acid and carbamazepine treatment on serum biotin and zinc levels and on biotinidase activity. J Child Neurol. 2011;26(12):1522-1524.  (PubMed)

60.  Schulpis KH, Karikas GA, Tjamouranis J, Regoutas S, Tsakiris S. Low serum biotinidase activity in children with valproic acid monotherapy. Epilepsia. 2001;42(10):1359-1362.  (PubMed)

61.  Yilmaz Y, Tasdemir HA, Paksu MS. The influence of valproic acid treatment on hair and serum zinc levels and serum biotinidase activity. Eur J Paediatr Neurol. 2009;13(5):439-443.  (PubMed)