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  • 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, 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 (μg)/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. Yet, it is not known if marginal biotin deficiency during pregnancy increases the risk for congenital anomalies in humans. (More information)
  • Biotin is used in the treatment of biotin-thiamin responsive basal ganglia disease, an inherited disorder of thiamin transport. (More information)
  • Recent randomized controlled trials have not found high-dose biotin supplementation to be beneficial in the treatment of multiple sclerosis. Yet, results of animal studies and meta-analyses of human clinical trials are promising. (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)
  • Use of high-dose biotin supplements can result in aberrant results of laboratory tests that utilize the very high affinity biotin-streptavidin (avidin) interaction. (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 non-protein cofactors are termed “prosthetic groups” and are common in water-soluble vitamins. The covalent attachment of biotin to the apocarboxylase (i.e., the carboxylase protein without the biotin prosthetic group and is catalytically inactive) is catalyzed by the enzyme, holocarboxylase synthetase (HCS). The term “biotinylation” refers to the covalent addition of biotin to any molecule, including the 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 histone that 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).

Figure 1a. 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.

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 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; however, the two enzymes have different roles in metabolism and different intracellular locations. ACC1 is located in the cytosol, and the malonyl CoA generated by ACC1 is a rate-limiting substrate for the synthesis of fatty acids (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 located on the outer mitochondrial membrane, and the malonyl CoA generated via ACC2 inhibits CPT1, an enzyme that regulates malonyl-CoA entry into the inner mitochondria, thereby regulating fatty acid oxidation (Figure 3). ACC2 is especially abundant in skeletal muscle and heart (4).

Biotin Figure 2. 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.

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. 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.

Methylcrotonyl-CoA carboxylase catalyzes an essential step in the catabolism of leucine, an essential branched-chain amino acid. This 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) and the side chain of cholesterol (Figure 4a) and of the amino acids methionine and threonine (Figure 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). The H1 linker histone 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 for DNA replication and transcription. Chemical modifications of DNA and histones affect the folding of chromatin, increasing or reducing DNA accessibility to factors involved in replication and transcription. DNA methylation and 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 modifications of histone tails (“marks”), including acetylation, methylation, phosphorylation, ubiquitination, SUMOylation, ADP-ribosylation, carbonylation, deimination, hydroxylation, and biotinylation, have various 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. H4 biotinylation appears to be enriched in transposable elements known as long terminal repeats (3). These biotinylation marks also 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 down regulates hSMVT synthesis and reduces biotin uptake. Conversely, in biotin-deficient cells, biotinylation marks in the SLC5A6 promoter are removed increasing gene expression and enabling the synthesis of hSMVT and uptake of biotin (7).


Although clinically 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 avidin; this antimicrobial protein binds biotin with an affinity and specificity that is almost unique as a reversible binding. Because native avidin is resistant to mammalian and microbial digestion, avidin prevents biotin absorption. Cooking egg white denatures avidin, rendering it susceptible to digestion and therefore unable to block 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) that result in functional biotin deficiency often have similar physical findings, 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 for histone biotinylation; hence, the maternal 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). Moreover, certain types of liver disease may decrease biotinidase activity and theoretically increase the requirement for biotin. For example, 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. Additionally, 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

Biotinidase deficiency is an autosomal recessive inherited disorder that is often detected upon newborn screening for metabolic disorders, although late-onset forms have been recently described (15-17). Biotinidase deficiency leads to secondary biotin deficiency in several ways. Intestinal absorption is decreased because deficient biotinidase impairs release of biotin from dietary protein (18). Further, recycling of intracellular 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 responds to supplemental biotin. Oral supplementation with as much as 5 to 20 milligrams (mg) of biotin daily is sometimes required (19, 20), although smaller doses may be sufficient, especially later in childhood (reviewed in 20, 21). Prognosis is characteristically good when biotin therapy is introduced in infancy or early childhood and reliably continued for life (10).

Holocarboxylase synthetase deficiency

Holocarboxylase synthetase 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). Holocarboxylase synthetase deficiency responds to supplementation with pharmacologic doses of biotin in some cases but not others. The prognosis of holocarboxylase synthetase is usually, but not always, good if biotin therapy is introduced early (even antenatally) and continued for life (10, 22).

Biotin transport deficiency

There has been one case report of a child with biotin transport deficiency who responded to high-dose biotin supplementation (23). Of note, the presence of a defective human sodium-dependent multivitamin transporter (hSMVT) was ruled out as a cause of biotin transport deficiency.

Markers of biotin status

Four measures of marginal biotin deficiency have been validated as indicators of biotin status: and (1) reduced levels of holo-methylcrotonyl-CoA carboxylase and holo-propionyl-CoA carboxylase in lymphocytes, the most reliable indicators of biotin status (24); (2) reduced propionyl-CoA carboxylase activity in peripheral blood lymphocytes (5); (3) high urinary excretion of an organic acid, 3-hydroxyisovaleric acid, and its derivative, 3-hydroxyisovaleryl carnitine, both of which reflect decreased activity of biotin-dependent methylcrotonyl-CoA carboxylase; (4) reduced urinary excretion of biotin and some of its catabolites. These markers have been only validated in men and nonpregnant women, and they may not accurately reflect biotin status in pregnant or breast-feeding women (12, 25).

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 of the National Academy of Medicine set recommendations for an Adequate Intake (AI; Table 1). The AI for adults (30 μg/day) was extrapolated from the AI for infants exclusively fed human milk and probably overestimates the dietary requirement for biotin for most adults. Dietary intakes of generally healthy adults have been estimated to be 40 to 60 micrograms (μg) of biotin daily (1). The requirement for biotin in pregnancy may be increased (26).

Table 1. Adequate Intake (AI) for Biotin Life Stage Age Males (μg/day) Females (μg/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 (27, 28). In a randomized, single-blinded intervention study in 26 pregnant women, supplementation with 300 μg/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 (29). A small cross-sectional study in 22 pregnant women reported an incidence of low lymphocyte propionyl-CoA carboxylase activity greater than 80% (13). Although these levels of biotin deficiency are 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 (30). 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).

Analogous to pregnant women who 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 μg/day of biotin, and no toxicity has ever been reported at this level of intake (see Safety).

Disease Treatment

Biotin-thiamin-responsive basal ganglia disease

Biotin-thiamin-responsive basal ganglia disease (also called biotin-responsive basal ganglia disease, thiamin transporter-2 deficiency, and thiamin metabolism dysfunction syndrome-2) is caused by an autosomal recessive mutation in the SLC19A3 gene that codes for thiamin transporter-2 (THTR-2). The disease usually presents around 3 to 10 years of age (31), but an early infantile form of the disease exists with onset as early as one month of age (32). Clinical features include subacute encephalopathy (confusion, drowsiness, 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 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 diagnosis and immediate treatment with biotin and thiamin led to positive outcomes (33). Although the specific mechanism for therapeutic effects of biotin in biotin-thiamin-responsive basal ganglia disease remains unknown, lifelong high-dose supplementation with a combination of biotin and thiamin is the recommended treatment (31). Early diagnosis and treatment is important to ensure a better prognosis (32, 34).

Multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive damage to the myelin sheath surrounding nerve fibers (axons) and neuronal loss in the brain and spinal cord of affected individuals in anatomic locations that vary widely among affected individuals producing variable signs and symptoms. 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 (35). Given its role in energy production by intermediary metabolism and fatty acid oxidation and in fatty acid synthesis (required for myelin formation) (see Function), high-dose biotin supplementation it has been hypothesized that to exert beneficial effects that would limit or reverse MS-associated functional impairments (35).

The mechanism of action of high-dose biotin has been investigated in a genetic mouse model of chronic axon injury caused by oxidative damage and bioenergetic failure. High-dose biotin restored redox homeostasis, mitochondria biogenesis, and ATP levels, and reversed axonal death and locomotor impairment. Dysregulation of the transcriptional program for lipid synthesis and degradation in the spinal cord was also normalized, possibly as the result of hyperactivation of a nutrient/energy/redox sensor that controls protein synthesis restoring lipid homeostasis.

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 five (out of five) 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 (36). Additionally, a multicenter, randomized, placebo-controlled trial in 154 subjects with progressive MS reported that 13 out of 103 patients supplemented with high-dose, pharmaceutical-grade biotin (300 mg/day) for 12 months achieved MS-related disability reversal — assessed by improved EDSS or 25-foot walk time (37). In comparison, none of the 51 patients randomized to the placebo group showed significant clinical improvements (37). However, when this regimen of high-dose biotin supplementation was examined in a larger, international cohort of patients with progressive MS (326 patients receiving biotin and 316 patients receiving placebo), no benefits on EDSS or walk time were seen after 12 months (38). Moreover, a randomized, double-blind, placebo-controlled trial in 93 MS patients with chronic visual loss found that 300 mg/day of pharmaceutical-grade biotin for six months did not improve visual acuity, but an interesting trend favoring the biotin group was observed in the subgroup of patients with progressive optic neuritis (39). Moreover, a meta-analysis of three randomized controlled trials (2 on disability; 3 on adverse effects), involving 889 individuals diagnosed with MS (the preponderance of participants [830] had progressive MS while only 59 had remitting relapsing MS) was conducted (40). Pooling results of two trials found no benefit of high-dose biotin on MS-related disability, but there was significant heterogeneity between the trials. When the subgroup progressive MS was analyzed separately, a moderate certainty of evidence suggested a potential benefit in favor of high-dose biotin for the 25-foot minute walk time (40). On balance, studies remain inconclusive but promising.

Diabetes mellitus

Overt biotin deficiency has been shown to impair glucose utilization in mice (41) 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 control subjects without the disease; an inverse relationship between fasting blood glucose and biotin concentrations was observed as well (42). 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 45% decrease in mean fasting blood glucose concentrations (42). Yet, another small study in 10 patients with type 2 diabetes and 7 controls without diabetes found no effect of biotin supplementation (15 mg/day) for 28 days on fasting blood glucose concentrations in either group (43). A more recent double-blind, placebo-controlled study by the same research group showed that the same biotin regimen lowered plasma triglyceride concentrations in patients with hypertriglyceridemia — independent of whether they had type 2 diabetes (44). 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 (45-48). For information on chromium supplementation as a monotherapy for type 2 diabetes, see the article on Chromium.

Potential mechanisms for the glucose and lipid effects have been suggested. As a cofactor of carboxylases required for fatty acid synthesis, biotin may increase the utilization of glucose for fat synthesis. Also, biotin stimulates glucokinase, a liver enzyme that increases synthesis of glycogen, the storage form of glucose. Biotin also triggers the secretion of insulin in the pancreas of rats and improves glucose homeostasis (50). Yet, reduced activity of ACC1 and ACC2 would be expected to reduce fatty acid synthesis and increase fatty acid oxidation, respectively. Hence, whether pharmacologic doses of biotin benefits the management of hyperglycemia in patients with impaired glucose tolerance remains unclear. Moreover, whether supplemental biotin lowers the risk of cardiovascular complications in patients with diabetes by reducing serum triglycerides and LDL-cholesterol remains to be proven (44-46).

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 (50-52). Three uncontrolled trials examining the effects of biotin supplementation (2.5 mg/day for several months) in women with brittle fingernails have been published (53-55). 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 (53, 54). 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 (55). 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 (56). Although preliminary evidence suggests that supplemental biotin may help strengthen fragile nails (reviewed in 57), 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 has been associated with alopecia reversal in children treated with the anticonvulsant valproic acid (see Drug interactions), as well as with hair regrowth or normal hair growth in some children with inborn errors of biotin metabolism or other genetic disorders (i.e., uncombable hair syndrome) (reviewed in 58). Yet, while 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 (59, 60). Randomized, placebo-controlled trials in healthy individuals would be needed to evaluate this claim.


Food sources

Biotin is found in many foods, either as the free (i.e., unbound) 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 (μg) 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. (61) employed a high-performance liquid chromatography method rather than bioassays (62) and reported relatively different biotin content for some selected foods. Table 2 lists some food sources of biotin, along with their content in μg.

Table 2. Some Food Sources of Biotin (61, 62) Food Serving Biotin (μg) 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 (63). 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 (64), 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 (many containing 5,000 μg [5 mg] of biotin) and is often included in B-complex and multivitamin-mineral supplements. Several multivitamin supplements contain 30 μg of biotin, although the amount varies by product (65).



Biotin is not known to be toxic. In people without disorders of biotin metabolism, doses of up to 5 mg/day (5,000 μg) for two years were not associated with adverse effects (66). 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 (36, 67). 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 (68). Because reports of adverse events were lacking when the Dietary Reference Intakes (DRIs) for biotin were established in 1998, the Food and Nutrition Board 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) (69, 70). Biotin also shares the hSMVT with lipoic acid (71). Pharmacologic (very high) 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 (72).

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, Phenytek), and carbamazepine (Carbatrol, Epitol, Equetro, Tegretol), include inhibition of biotin intestinal absorption and renal reabsorption, as well as increased biotin catabolism (73). Use of the anticonvulsant valproic acid in children has resulted in hair loss reversed by biotin supplementation (74-77). 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 (73).

Interference with lab assays

In 2017, the US Food and Drug Administration (FDA) released a safety communication regarding high-dose biotin supplementation and its potential interference with streptavidin (avidin)-biotin immunoassays, including assays of thyroid hormones, reproductive hormones, and the cardiac protein, troponin. Such interference can cause aberrant results — either falsely high or falsely low depending on the method of the particular assay — and potential misdiagnosis of disease (78-81). An updated FDA communication in 2019 focused on biotin interference in certain lab assays of troponin that have not addressed the concern of falsely low blood concentrations (82). Troponin in blood is a marker of cardiac damage and often used in the clinical diagnosis of a myocardial infarction (heart attack). When blood work is planned, patients should routinely inform their health care provider concerning supplementation of biotin at doses substantially greater than those in usual diets or in routine daily multivitamins.

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 National Academy of Medicine, which is 30 micrograms (μg) 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 μg/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 μg 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

Updated in July 2022 by: Victoria J. Drake, Ph.D. Linus Pauling Institute Oregon State University

Reviewed in March 2023 by: Donald Mock, M.D., Ph.D. Professor Emeritus Departments of Biochemistry and Molecular Biology and Pediatrics University of Arkansas for Medical Sciences

Copyright 2000-2023 Linus Pauling Institute


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