Summary of Biotin
Primary Information, Benefits, Effects, and Important Facts
Biotin is an essential vitamin that has been grouped with the B-complex vitamins since it was discovered, in yeast alongside other B vitamins. Although it is technically known as vitamin B7, this designation is not too common as it is usually simply referred to as biotin.
It was initially found to be a component of nails, skin, and hair to a relatively high degree. Biotin has been seen as the go-to vitamin for beauty ever since one pilot study in women with brittle nails showed supplementation to be beneficial. It is currently being marketed for improving nail, skin, and hair aesthetics. These claims, however, were not followed up scientifically so there is not much evidence to support biotin's role here. It can plausibly have these actions mechanistically, but there is simply not much evidence that can be used as support.
Beyond that, biotin's general role as an enzymatic cofactor has also led to some research suggesting it may interact with glucose metabolism in the human body. As a general statement it seems that in rodents with a higher circulating biotin level in their blood, the amount of insulin released in response to a glucose test is higher, leading to less elevation of glucose over time. This rodent evidence also suggests that the higher glucose is not met with higher insulin resistance suggesting a potentially beneficial role.
Not too much evidence has been conducted in humans in regard to diabetes, with one study finding that intramuscular biotin was able to attenuate symptoms of neuropathy in three diabetic subjects.
Overall, aside from instances where biotin may be deficient (alcoholism, some epileptic drug therapies, and overconsumption of raw egg whites) the supplement does not have any solid evidence for benefits and may have a role as a beauty supplement pending better evidence.
How to Take Biotin
Recommended dosage, active amounts, other details
The only known supplemental dose of biotin that has been tested orally in humans, for the purposes of enhancing the quality of brittle nails, is 2.5mg taken once daily over six months.
This dose appears relatively safe although it is much higher than the recommended daily intake (RDI) of biotin which ranges from 25-30mcg (youth) upwards to 100mcg (adults). The biotin dose found in many multivitamins (30mcg or 0.03mg) seems more than sufficient.
Human Effect Matrix
The Human Effect Matrix looks at human studies (it excludes animal and in vitro studies) to tell you what effects biotin has on your body, and how strong these effects are.
|Grade||Level of Evidence [show legend]|
|Robust research conducted with repeated double-blind clinical trials|
|Multiple studies where at least two are double-blind and placebo controlled|
|Single double-blind study or multiple cohort studies|
|Uncontrolled or observational studies only|
Level of Evidence
? The amount of high quality evidence. The mo re evidence, the more we can trust the results.
Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
|Blood Glucose||-||- See study|
|Insulin||-||- See study|
|Total Cholesterol||-||- See study|
|Triglycerides||-||- See 2 studies|
|Weight||-||- See study|
|vLDL-C||-||- See study|
|Nail Quality||-||- See study|
Scientific Research on Biotin
Click on any below to expand the corresponding section. Click on to collapse it.
Biotin is an essential vitamin officially designated Vitamin B7 but also historically given the name Vitamin H (not commonly used anymore, but named after the German word for skin, 'haut'). Biotin was initially discovered alongside other B-vitamins from yeast with a collection of heat-stable B-vitamins (biotin, Vitamin B3, and pantothenic acid) but given vitamin status later due to biotin deficiency not being as prevalent as that of thiamin (beriberi) or niacin (pellagra) at the time. It was named biotin as it was believed to be a component of the 'Bios' factor.
Biotin is stored in the body via biotinylation, an ATP-dependent process where biotin is first converted to an intermediate (biotinyl-5'-AMP) for subsequent attachment to lysine residues of proteins (as biotin, releasing the AMP). The enzyme that mediates biotin attachment to enzymes is known as holocarboxylase synthetase, (also known as biotin protein ligase) and encoded by a single gene.
Biotinylation underlies the role of biotin as a vitamin, where particular proteins require biotin binding for proper function. Examples of biotin-dependent proteins are members of the biotin carboxylase and decarboxylase family which includes the enzymes acetyl-CoA carboxylase (ACC), propionyl-CoA carboxylase (PCC), and pyruvate carboxylase (PC). As a general statement, biotin-dependent enzymes tend to be important in pathways related to gluconeogenesis, fatty acid synthesis, and branched chain amino acids catabolism. Carboxylase enzyme reactions occur via a two-step mechanism, where bicarbonate is initially used for the ATP-dependent conversion of biotin to carboxybiotin. The newly formed CO2 group from carboxybiotin is then transfered to the target protein (comprehensive review here).
Biotin can be covalently attached to other proteins in a process known as biotinylation, a requirement for the function of certain enzymes. This underlies the role of biotin as a vitamin, where it supports biotinylation of biotin-dependent enzymes, many of which are essential for metabolic function.
Biotinylated proteins can also function as a resevoir for extra biotin, which is liberated from proteins it is stored on via biotinidase, which exists in the cell's microsomes and mitochondria. A major storage protein for biotin is the protein known as acetyl CoA carboxylase. Biotinidase also has the function of transferring biotin to histones which is thought to explain the presence of biotin in nuclei (presence of the biotinidase in the nucleus is controversial.)
Currently, the biotinylated proteins biotinylated 3-methylcrotonyl-CoA carboxylase (holo-MCC) and propionyl-CoA carboxylase (holo-PCC) have been suggested to be reliable biomarkers of biotin deficiency.
Both a decrease in biotin in the urine and an increase in urinary 3-hydroxyisovaleric acid (3HIA) have been suggested to indicate biotin deficiency, but while the former may not have good predictive power the latter may also cause some false positives.
Although low-cost and reliable ways to assess biotin deficiency are currently lacking, biotinylated proteins are being examined as possible biomarkers for deficiency. 3-hydroxyisovaleric acid concentrations in urine seem to be the most well-studied biomarker, however its predictive power has been called into question.
Biotin deficiencies are relatively rare, being observed in some youth (as seborrheic dermatitis) when maternal breast milk is low in biotin or in subjects with a genetic biotinidase deficiency who cannot recycle biotin. Both of these conditions can be treated with supplemental biotin, although genetic biotinidase deficiencies require timely intervention and lifetime supplementation to avoid severe neurological disorders. The disorder also requires lifetime biotin supplementation at 5-20mg daily due to drastically reduced biotin retention. Biotinidase deficiency has been reported to have a prevalence of 1 in 112,271 (profound deficiency of less than 10% biotinidase activity) and 1 in 129,282 for partial deficiency (10-30% biotinidase deficiency). If left untreated severe neurological symptoms develop, including seizures, ataxia, and mental retardation.
Biotin deficiencies are relatively rare, thought to be limited to a genetic lack of the biotinidase enzyme or due to a lack of biotin in breast milk fed to infants. Both of these instances can be treated with the addition of supplemental biotin to the diet, although biotinidase deficiency requires quick intervention in infanthood.
Biotin deficiency has also been induced in rodents by adding raw egg whites to the diet which contain the protein avidin that binds and sequesters biotin with high affinity, preventing its utilization. Avidin does appear to affect humans after oral ingestion, where subsequent biotin deficiencies can be treated with supplemental biotin. This can be avoided by cooking egg whites before consumption, which denatures avidin preventing it from binding to biotin. Cooking egg yolks is also advisable; while they do not contain signficant amounts of avidin, they do contain other biotin-binding proteins.
Consumption of large amounts of raw egg whites can cause biotin deficiencies due to the presence of the antinutrient avidin, which binds and sequesters biotin, preventing its utilization as a nutrient. While this can be overcome by superloading biotin, it is best to limit consumption of raw egg whites, or cook them before consumption to eliminate avidin binding.
Biotin has been noted to have a plasma membrane-associated receptor in liver cells with EC50 values for saturation ranging between 1-10nM. The function this receptor is not well-understood in humans, but a few vitamins including biotin (as well as folate and B12) initiate endocytosis in plant cells and biotinylation of proteins has been found to allow larger molecules to enter the cell without harming the membrane. It is thought that biotin may have a transportation role for other molecules. This has been noted in cancer cells expressing the biotin receptor, which allowed more of a conjugated polymer to enter the cell compared to the polymer alone.
Since the biotinidase enzyme exists in the blood where it can bind biotin at an affinity (KD values of 3nM and 59nM) similar to the receptor EC50 values and possesses transferase properties, it is plausible that biotin has a role in helping bigger molecules enter the cell.
Biotin appears to have a receptor that responds to it on the plasma membrane (so far detected in liver cells). While its practical function is unknown, it seems to be able to facilitate endocytosis (a transportation process for bringing in larger molecules like glucose or some drugs) and thus may be involved in trafficking larger molecules across the cell membrane.
Biotin is absorbed from the intestines via a sodium-dependent transporter known as the sodium-dependent multivitamin transporter (SMVT), which also mediates uptake of Vitamin B5 and alpha-lipoic acid. The SMVT is expressed on the apical membrane of the intestines (allowing transport from the lumen of the intestines up into intestinal cells) and is present in the small intestine showing higher density in the jejunem relative to the ileum. It is also present in the colon to facilitate uptake of the biotin produced by intestinal bacteria and possesses an affinity of around 3.2+/-0.7µM.
The regulation of this transporter seems responsive to the environment as while it can increase during the aging process and during periods of biotin deficiency it can be reduced by alcohol consumption.
While the SMVT mediates most biotin uptake at concentrations of biotin found in the human diet (nanomolar concentrations) at higher concentrations biotin is absorbed from the intestines via a mechanism independent of the SMVT. This latter process is not dependent on sodium or inhibited by chronic alcohol consumption and may involve passive diffusion. There is a high affinity receptor for biotin on mononuclear cells and keratinocytes which likely does not exist in intestinal cells.
Biotin can be absorbed in various parts of the intestines by the transporter known as the sodium-dependent multivitamin transporter (SMVT) at levels seen with dietary intake. At high biotin concentrations SMVT becomes saturated, and biotin is taken up via passive diffusion.
When tested in humans, topical application of an ointment containing biotin (7g of ointment with 0.3% biotin) was able to increase the amount of serum biotin in both healthy subjects (21%) and subjects with atopic dermatitis (81.7%). The difference in increases between healthy and dermatitis subjects can explained by lower baseline biotin levels in subjects with dermatitis, as both groups ended up with approximately 50nM biotin in serum after treatment.
Biotin applied to the skin appears to increase the amount of biotin detectable in the blood.
In the blood, biotin can be present in free form, or bound to proteins in a covalent or non-covalent manner. Up to 81% of biotin in transport has been suggested to be free, although this particular study used an avidin binding assay that assumed whatever bound to avidin was biotin. Avidin binding assays were later found to detect molecules other than biotin, where molecules such as bisnorbiotin (BNB) and biotin sulfoxide (BSO) readily bound to avidin  and are known to be endogenous metabolites in humans. One study measuring biotin in cerebrospinal fluid noted that biotin did indeed account for less than half of the avidin binding assay (at 42+/-16%, with equal amounts binding to BSO and 8+/-14% bound to BNB).
Protein-bound biotin is thought to account for 7% (reversibly bound) and 11% (covalently) but these measurements occur after the avidin binding assay (by measuring what is left).
Biotin is known to exist in the blood in both a free form as well as being bound to proteins. The protein biotinidase is a possible biotin carrier-protein in the blood.
Supplementation of 900mcg biotin appears to be sufficient to increase circulating biotin concentrations in otherwise healthy adults without a deficiency.
There appears to be a transporter on peripheral blood mononuclear cells and keratinocytes designated a high-affinity Na-K-ATPase dependent biotin transporter, as it can take up biotin at a concentration of as little as 0.1nM and saturated at a Kt of 2.6+/-0.1nM.
Expression of the biotin transporters (either the sodium-dependent multivitamin transporter (SMVT) or the high-affinity transporter) have been noted in keratinocytes, cardiomyocytes, renal cells, microvessels in brain tissue, the liver (known to be the SMVT) and the placenta.
Biotin status has been noted to be lower in epileptics undergoing treatment with some anticonvulsants (primidone, carbamazepine, phenytoin, phenobarbital; not valproate sodium) while epileptics not undergoing treatment appear to have normal biotin levels.
Carbamazepine and valproic acid have been found to not influence serum biotinidase levels or biotin in children (duplication in Pubmed), although there were a few instances of valproic acid-induced hair loss treatable with biotin.
In rats, biotin supplementation in water (approximately 2mg biotin per rat) has been shown to have a modest suppressive effect on circulating vLDL relative to control mice, although it should be noted that biotin deficiency in this model decreased vLDL to a greater extent than control or biotin-supplemented rats. Biotin supplementation in mice has been shown to decrease serum triglycerides by 35%, which was associated with the suppression of lipogenic genes including SREBP1-c. It was later noted that in mice given the same dose of biotin (97.7mg/kg of the diet, or 56-fold higher than normal dietary concentrations) that the reductions in both serum (36%) and liver (37%) triglycerides occurred alongside a 40% increase in AMPKα phosphorylation and increased cGMP concentrations.
In regard to acetyl-CoA carboxylase 1, there has either been a reduction reported or no changes in expression with increased phosphorylation (resulting in less activity), both of which would lead to less malonyl-CoA available for fatty acid synthesis.
Biotin may be able to increase the activity of AMPK in the liver secondary to cGMP, which seems to result in a reduction of serum triglycerides and vLDL.
Biotin supplementation at 900mcg in otherwise healthy men and women has been noted to reduce circulating triglycerides while improvements in lipids have also been noted in subjects with medical conditions given 5mg (atherosclerotic subjects) or 15mg (type II diabetic subjects) of biotin daily. 15mg biotin daily also has been shown to reduce triglycerides and vLDL in both diabetic and nondiabetic subjects without any changes in total cholesterol or insulin sensitivity.
Glucokinase (GK) is an enzyme which mediates the first step of glucose utilization in a cell (phosphorylation into glucose-6-phosphate). Its activity is reduced by 40-45% in the liver of biotin-deficient rats. GK activity also is generally reduced in both fasting and diabetic rodents, although lower GK activities persist in nonfasting biotin-deficient rats.
GK can be restored to normal levels with insulin treatment (even without fixing the biotin deficiency) and administration of biotin to fasted rats restored GK activity even in the absence of biotin deficiency. In diabetic rats, biotin administration (1,250µg/kg bodyweight injections) restored GK activity with equal efficacy to insulin, although the effects of biotin and insulin were not additive. Biotin was only effective at increasing GK activity shortly after diabetes induction, however.
Biotin at a concentration of 1µM in the culture medium of hepatocytes has been noted to induce cGMP production and increase GK activity. Increased GK activity was thought to be mediated by cGMP, as N-acetylglucosamine (an inhibitor of GK only in the absence of cGMP) failed to prevent the increase in hexose utilization from biotin. This increase in GK activity was dependent on insulin and was not additive with both glucose and 8-bromo-cGMP (a hydrolysis-resistant cGMP analog). It is thought that biotin induces GK enzyme expression in a similar manner to biotin-mediated insulin receptor expression in vitro, which is also driven by cGMP. (It should be noted that biotin-mediated increases in insulin receptor expression have have not been observed in vivo, however.)
Glucokinase, a pivotal enzyme in utilizing glucose, appears to be depressed in instances of biotin deficiency, diabetes, and during fasting. In all instances biotin can restore glucokinase activity via a cGMP-mediated mechanism.
In mice given sufficient biotin to increase serum biotin 10-fold to 590nM (approximately 50µM/kg bodyweight), insulin secretion in response to a fasted oral glucose tolerance test significantly increased and pancreatic islet secretion also increased (69% at 5.6mM glucose). Biotin supplementation also was associated with a 70% increase glucokinase (GK) gene expression and a doubling of Ins2gene expression without affecting GLUT2 or insulin receptor levels. The average islet size appears to increase by around 75% in biotin-treated mice due to an increase in alpha and beta-cells and when tested in vitro the increase in GK expression was confirmed to be secondary to cGMP and protein kinase G (PKG) and dependent on insulin.
One mouse study found that while insulin sensitivity does not appear to be affected by biotin supplementation, insulin release upon glucose feeding was improved. However, in a rat model of diabetes, insulin sensitivity was improved when the rats were given water with with 3.3 mg/L biotin for 8 weeks. This seemed to be due to an increase in glucose transporter type 4 (GLUT4) expression in the muscles.
One preliminary study using high-dose biotin (10mg intramuscularly thrice a week over six weeks, later maintained on 5mg biotin daily orally) in three diabetic subjects with neuropathy on insulin therapy appeared to improve symptoms of neuropathy and reduced paresthesias after one year, with muscular function not being fully recovered. As low biotin concentrations exist in subjects who report neuropathy (such as epileptics undergoing therapy and alcoholics) it is thought to have a causative role, possibly related to known alterations in pyruvate metabolism and the biotin-dependent enzyme pyruvate carboxylase during neuropathies.
The acetyl CoA carboxylase (ACC) enzymes catalyzes the conversion of acetyl CoA into malonyl CoA which is an inhibitor of fatty acid oxidation and substrate of lipogenesis (by being added to fatty acids to elongate their chains), but the enzyme itself is also a storage form of biotin. Biotin stores seem to increase in adipose (but not liver or muscle) during aging in the mouse in a manner inversely related to SIRT1 activity which inactivates ACC via deacetylation. Reduced ACC content in adipose is associated with less lipogenesis from non-lipid sources (mice) while increased dietary biotin (approximately 2.5mg/kg in the mouse) increases adipose biotin and ACC stores.
Biotin seems to be an inhibitor of SIRT1 activity by blocking the deacetylase function of this enzyme (IC50 of approximately 200μM) whereas the metabolite biotinyl-5'-AMP was equipotent with nicotinamide (500μM) and a direct inhibitor of the NAD+ binding pocket.
One study in mice with lifetime biotin supplementation (estimated 2.5mg/kg) found a decrease in lipolysis rate of adipose when compared to genetically similar mice (high SIRT1 activity) without biotin, with similar effects also noted in skeletal muscle.
A study in mice demonstrated that chronic, high-level biotin supplementation decreases insulin sensitivity and lipolysis by reducing the activity of the deacetylase enzyme, SIRT1. Although the reciprocal relationship between SIRT1 and biotin levels is an important factor for energy homeostasis, relevance of this work to humans is not yet clear, where biotin requirements and equivalent typical daily intakes are much lower.
Biotin was first known to have a role in skin health since biotin deficiency leads to complications with the skin, primarily seen as scaly and red (erythematous) dermatitis. It is known to readily pass through the skin membrane to a greater degree in damaged skin (assessed by its usage as a tracer molecule in vitro) and can increase serum biotin when applied to the skin.
A high-affinity biotin transporter appears to exist in keratinocytes which can uptake biotin at low nanomolar concentrations while at high concentrations of biotin (10mM) approximately 8% appears to be taken up by nonsaturatable means (possibly diffusion). This transporter which has affinity for biotin (Ki of 10.7+/-0.9µM) also seems to also have affinity for Vitamin B5 (pantothenate at 1.2+/-0.3µM), desthiobiotin (15.2+/-2.5µM), and both oxidized (4.6+/-0.6µM) and reduced (11.4+/-0.9µM) forms of Alpha-lipoic acid, although low concentrations of these other molecules (20nM) do not interfere with the absorption of low concentrations of biotin (1nM).
There is a transporter in keratinocytes (outer layer skin cells) which is highly specific for biotin at low concentrations which also might have affinity for Vitamin B5 and ALA at higher concentrations.
One preliminary study has noted that, in four subjects being given chemotherapy (gefitinib or erlotinib) known to induce skin rashes, administration of biotin reduced the severity of the rash.
The induction of biotin deficiency (via avidin), amongst other side effects, is known to cause alopecia in the rat and humans with biotinidase deficiency, both of which are treatable with biotin supplementation to alleviate the deficiency.
The antiepileptic drug valproic acid has been noted to induce hair loss in some rats (6.6-26.6%) in a dose-dependent manner, which is thought to be related to reductions in biotinidase activity. Notably, hair loss was reduced in valproic acid-treated rats that also received biotin supplementation (0.6mg and 6mg/kg performing equally).  Such a reduction of biotinidase does not seem to reliably occur in humans given these antiepileptic drugs (some positive and null results, with one showing variance between subjects) but hair loss seems to be an infrequent side effect with valproic acid that is responsive to 10mg biotin supplementation. Although valproic acid does not appear to be a direct inhibitor of biotinidase, it is known to influence other enzymes that use biotin as a cofactor (3-methylcrotonyl-CoA carboxylase).
In instances that biotin deficiency occurs, of which there are numerous possible causes (genetic deficiency of biotinidase, avidin consumption, and as a possible side-effect of pharmaceuticals), administration of biotin appears to be able to restore hair loss that occurs with biotin deficiency.
Biotin was initially investigated for nail health due to studies conducted in horses where some pathological hoof changes could be normalized by biotin administration. Moreover, biotin deficiencies have also been shown to coincide with changes to the nails of swine.
One study in women who had brittle nails or splitting of the nails (onychoschizia) noted that oral supplementation of biotin at 2.5mg over the course of at least six months increased nail thickness by 25% (reaching normal/healthy control values). About half the group with brittle nails (4 of 8 subjects) also experienced reductions in nail splitting. All nails from biotin-treated individuals showed some improvement when assessed by electron microscopy.
One study has found biotin supplementation to be effective when taken by women with brittle and splitting nails.
Due to similarities in structure between Alpha-lipoic acid (ALA) and biotin, ALA has been examined as a possible inhibitor of biotin-dependent enzyme activity. A study in rats found that intraperitoneal administration of ALA suppressed the catalytic activity of biotin-dependent enzymes. Both low (4.3μmol/kg) and high doses (15.6μmol/kg) of ALA for 28 days were able to lower the catalytic activity of the enzymes pyruvate carboxylase (28% and 35% at respective low and high doses) and β-methylcrotonyl-CoA carboxylase (36% and 29% at respective low and high doses) in a manner that was negated by also administering 2μmol/kg biotin for the same time period. Propionyl-CoA carboxylase and cytosolic acetyl-CoA carboxylase activites were not affected. No overt symptoms of biotin deficiency or organ harm were found in this study.
Lipoic acid and biotin (along with Vitamin B5) are also known to share the same intestinal transporter, the sodium-dependent multivitamin transporter.
Alpha-lipoic acid (ALA) appears to reduce the activity of some biotin-dependent enzymes in the liver according to one study. This occured in a manner that was reversible with biotin supplementation. ALA-induced suppression of biotin-dependent enzyme function did not appear to cause overt physiological dysfunction, however, so the practical implications of this work as they relate to ALA and biotin supplementation are not clear.
Alcohol is able to inhibit transportation of biotin across the intestinal wall when biotin is at a physiological concentrations (0.01-0.3µM). The transport was reduced to 38-76% control values at 2% alcohol, but there was no efffect on transport at higher concentrations of biotin (100µM) and at low biotin concentrations alcohol was more effective at inhibiting absorption at 5% than at lower levels, with minimal (10%) inhibitory actions at 0.5% alcohol. Acetaldehyde (a metabolite of alcohol) also has inhibitory effects on biotin transport, and its effect is explained by potent inhibition of carrier-mediated biotin absorption (which occurs at low levels of biotin) but not passive diffusion of biotin.
The transporter that mediates biotin uptake, the sodium-dependent multivitamin transporter (SMVT) from the SLC5A6 gene is known to be expressed in the small intestines and colon and its concentration is reduced in response to alcohol feeding to rats.
Alcohol reduces biotin absorption rates, with more potency the higher the alcohol concentration and the lower the biotin concentration, due to reducing the amount of transporters available to take biotin up into the body. This process may not affect superloading biotin, since at that dose biotin has another way of entering the body: passive diffusion.
- Chapman-Smith A1, Cronan JE Jr. Molecular biology of biotin attachment to proteins. J Nutr. (1999)
- Lanska DJ. The discovery of niacin, biotin, and pantothenic acid. Ann Nutr Metab. (2012)
- Chapman-Smith A1, Cronan JE Jr. The enzymatic biotinylation of proteins: a post-translational modification of exceptional specificity. Trends Biochem Sci. (1999)
- Tong L. Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci. (2013)
- Knowles JR. The mechanism of biotin-dependent enzymes. Annu Rev Biochem. (1989)
- Tong L1, Harwood HJ Jr. Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. J Cell Biochem. (2006)
- Huang CS1, et al. Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. Nature. (2010)
- Xiang S1, Tong L. Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction. Nat Struct Mol Biol. (2008)
- Depeint F1, et al. Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism. Chem Biol Interact. (2006)
- Hymes J1, Wolf B. Human biotinidase isn't just for recycling biotin. J Nutr. (1999)
- Pispa J. Animal biotinidase. Ann Med Exp Biol Fenn. (1965)
- Shriver BJ1, Roman-Shriver C, Allred JB. Depletion and repletion of biotinyl enzymes in liver of biotin-deficient rats: evidence of a biotin storage system. J Nutr. (1993)
- Hymes J1, Fleischhauer K, Wolf B. Biotinylation of histones by human serum biotinidase: assessment of biotinyl-transferase activity in sera from normal individuals and children with biotinidase deficiency. Biochem Mol Med. (1995)
- Kuroishi T1, et al. Biotinylation is a natural, albeit rare, modification of human histones. Mol Genet Metab. (2011)
- Healy S1, et al. Nonenzymatic biotinylation of histone H2A. Protein Sci. (2009)
- Eng WK1, et al. Identification and assessment of markers of biotin status in healthy adults. Br J Nutr. (2013)
- Mock NI1, et al. Increased urinary excretion of 3-hydroxyisovaleric acid and decreased urinary excretion of biotin are sensitive early indicators of decreased biotin status in experimental biotin deficiency. Am J Clin Nutr. (1997)
- Mock DM1. Biotin status: which are valid indicators and how do we know. J Nutr. (1999)
- Mock DM1, et al. Indicators of marginal biotin deficiency and repletion in humans: validation of 3-hydroxyisovaleric acid excretion and a leucine challenge. Am J Clin Nutr. (2002)
- Nisenson A. Seborrheic dermatitis of infants: treatment with biotin injections for the nursing mother. Pediatrics. (1969)
- Wolf B. Biotinidase deficiency: "if you have to have an inherited metabolic disease, this is the one to have". Genet Med. (2012)
- Cowan TM1, Blitzer MG, Wolf B; Working Group of the American College of Medical Genetics Laboratory Quality Assurance Committee. Technical standards and guidelines for the diagnosis of biotinidase deficiency. Genet Med. (2010)
- Wolf B. Worldwide survey of neonatal screening for biotinidase deficiency. J Inherit Metab Dis. (1991)
- Kresge N, Simoni RD, Hill RL. The Discovery of Avidin by Esmond E. Snell. J Biol Chem. (2004)
- Sydenstricker VP, et al. OBSERVATIONS ON THE "EGG WHITE INJURY" IN MAN AND ITS CURE WITH A BIOTIN CONCENTRATE. JAMA. (1942)
- Baugh CM, Malone JH, Butterworth CE Jr. Human biotin deficiency. A case history of biotin deficiency induced by raw egg consumption in a cirrhotic patient. Am J Clin Nutr. (1968)
- WEI RD, WRIGHT LD. HEAT STABILITY OF AVIDIN AND AVIDIN-BIOTIN COMPLEX AND INFLUENCE OF IONIC STRENGTH ON AFFINITY OF AVIDIN FOR BIOTIN. Proc Soc Exp Biol Med. (1964)
- Murthy CV, Adiga PR. Purification of biotin-binding protein from chicken egg yolk and comparison with avidin. Biochim Biophys Acta. (1984)
- White HB 3rd, et al. Biotin-binding protein from chicken egg yolk. Assay and relationship to egg-white avidin. Biochem J. (1976)
- Vesely DL, Kemp SF, Elders MJ. Isolation of a biotin receptor from hepatic plasma membranes. Biochem Biophys Res Commun. (1987)
- Leamon CP1, Low PS. Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis. Proc Natl Acad Sci U S A. (1991)
- Wuerges J1, Geremia S, Randaccio L. Structural study on ligand specificity of human vitamin B12 transporters. Biochem J. (2007)
- Horn MA1, Heinstein PF, Low PS. Biotin-mediated delivery of exogenous macromolecules into soybean cells. Plant Physiol. (1990)
- Russell-Jones G1, et al. Vitamin-mediated targeting as a potential mechanism to increase drug uptake by tumours. J Inorg Biochem. (2004)
- Yellepeddi VK1, Kumar A, Palakurthi S. Biotinylated poly(amido)amine (PAMAM) dendrimers as carriers for drug delivery to ovarian cancer cells in vitro. Anticancer Res. (2009)
- Chauhan J, Dakshinamurti K. Role of human serum biotinidase as biotin-binding protein. Biochem J. (1988)
- Said HM1, Redha R, Nylander W. A carrier-mediated, Na+ gradient-dependent transport for biotin in human intestinal brush-border membrane vesicles. Am J Physiol. (1987)
- Said HM1, Redha R. Biotin transport in rat intestinal brush-border membrane vesicles. Biochim Biophys Acta. (1988)
- Said HM1, Derweesh I. Carrier-mediated mechanism for biotin transport in rabbit intestine: studies with brush-border membrane vesicles. Am J Physiol. (1991)
- Balamurugan K1, Ortiz A, Said HM. Biotin uptake by human intestinal and liver epithelial cells: role of the SMVT system. Am J Physiol Gastrointest Liver Physiol. (2003)
- Prasad PD1, 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)
- Subramanian VS1, et al. Membrane targeting and intracellular trafficking of the human sodium-dependent multivitamin transporter in polarized epithelial cells. Am J Physiol Cell Physiol. (2009)
- Subramanya SB1, et al. Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms. Am J Physiol Gastrointest Liver Physiol. (2011)
- Branner GR1, Roth-Maier DA. Influence of pre-, pro-, and synbiotics on the intestinal availability of different B-vitamins. Arch Anim Nutr. (2006)
- Wang H1, et al. Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. J Biol Chem. (1999)
- Said HM1, Horne DW, Mock DM. Effect of aging on intestinal biotin transport in the rat. Exp Gerontol. (1990)
- Said HM1, Mock DM, Collins JC. Regulation of intestinal biotin transport in the rat: effect of biotin deficiency and supplementation. Am J Physiol. (1989)
- León-Del-Río A1, Hol-Soto-Borja D, Velázquez A. Studies on the mechanism of biotin uptake by brush-border membrane vesicles of hamster enterocytes. Arch Med Res. (1993)
- Zempleni J1, Mock DM. Uptake and metabolism of biotin by human peripheral blood mononuclear cells. Am J Physiol. (1998)
- Grafe F1, et al. Transport of biotin in human keratinocytes. J Invest Dermatol. (2003)
- Makino Y1, et al. Percutaneous absorption of biotin in healthy subjects and in atopic dermatitis patients. J Nutr Sci Vitaminol (Tokyo). (1999)
- Gilby ED, Taylor KJ. Ultrasound monitoring of hepatic metastases during chemotherapy. Br Med J. (1975)
- Mock DM1, Lankford GL, Mock NI. Biotin accounts for only half of the total avidin-binding substances in human serum. J Nutr. (1995)
- Mock DM1, Lankford GL, Cazin J Jr. Biotin and biotin analogs in human urine: biotin accounts for only half of the total. J Nutr. (1993)
- Zempleni J1, McCormick DB, Mock DM. Identification of biotin sulfone, bisnorbiotin methyl ketone, and tetranorbiotin-l-sulfoxide in human urine. Am J Clin Nutr. (1997)
- Bogusiewicz A1, et al. Biotin accounts for less than half of all biotin and biotin metabolites in the cerebrospinal fluid of children. Am J Clin Nutr. (2008)
- Marshall MW, et al. Effects of biotin on lipids and other constituents of plasma of healthy men and women. Artery. (1980)
- Beinlich CJ1, et al. Myocardial metabolism of pantothenic acid in chronically diabetic rats. J Mol Cell Cardiol. (1990)
- Baur B1, Wick H, Baumgartner ER. Na(+)-dependent biotin transport into brush-border membrane vesicles from rat kidney. Am J Physiol. (1990)
- Baur B1, Baumgartner ER. Biotin and biocytin uptake into cultured primary calf brain microvessel endothelial cells of the blood-brain barrier. Brain Res. (2000)
- Said HM1, et al. Transport of biotin in basolateral membrane vesicles of rat liver. Am J Physiol. (1990)
- Grassl SM. Human placental brush-border membrane Na(+)-biotin cotransport. J Biol Chem. (1992)
- Prasad PD1, et al. Molecular and functional characterization of the intestinal Na+-dependent multivitamin transporter. Arch Biochem Biophys. (1999)
- Krause KH, et al. Biotin status of epileptics. Ann N Y Acad Sci. (1985)
- Castro-Gago M1, et al. Serum biotinidase activity in children treated with valproic acid and carbamazepine. J Child Neurol. (2010)
- Castro-Gago M1, et al. The influence of valproic acid and carbamazepine treatment on serum biotin and zinc levels and on biotinidase activity. J Child Neurol. (2011)
- Suchy SF, Wolf B. Effect of biotin deficiency and supplementation on lipid metabolism in rats: cholesterol and lipoproteins. Am J Clin Nutr. (1986)
- Larrieta E1, et al. Pharmacological concentrations of biotin reduce serum triglycerides and the expression of lipogenic genes. Eur J Pharmacol. (2010)
- Aguilera-Méndez A1, Fernández-Mejía C. The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation. Biofactors. (2012)
- Ha J1, et al. Critical phosphorylation sites for acetyl-CoA carboxylase activity. J Biol Chem. (1994)
- Dokusova OK, Krivoruchenko IV. The effect of biotin on the level of cholesterol in the blood of patients with atherosclerosis and essential hyperlipidemia. Kardiologiia. (1972)
- Revilla-Monsalve C1, et al. Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia. Biomed Pharmacother. (2006)
- Sarabu R1, Grimsby J. Targeting glucokinase activation for the treatment of type 2 diabetes--a status review. Curr Opin Drug Discov Devel. (2005)
- Dakshinamurti K, Cheah-Tan C. Liver glucokinase of the biotin deficient rat. Can J Biochem. (1968)
- Dakshinamurti K, Tarrago-Litvak L, Hong HC. Biotin and glucose metabolism. Can J Biochem. (1970)
- Spence JT, Koudelka AP. Effects of biotin upon the intracellular level of cGMP and the activity of glucokinase in cultured rat hepatocytes. J Biol Chem. (1984)
- Agius L. Control of glucokinase translocation in rat hepatocytes by sorbitol and the cytosolic redox state. Biochem J. (1994)
- Davagnino J, Ureta T. The identification of extrahepatic "glucokinase" as N-acetylglucosamine kinase. J Biol Chem. (1980)
- Spence JT, Pitot HC. Induction of lipogenic enzymes in primary cultures of rat hepatocytes. Relationship between lipogenesis and carbohydrate metabolism. Eur J Biochem. (1982)
- Chauhan J1, Dakshinamurti K. Transcriptional regulation of the glucokinase gene by biotin in starved rats. J Biol Chem. (1991)
- Dakshinamurti K, Cheah-Tan C. Biotin-mediated synthesis of hepatic glucokinase in the rat. Arch Biochem Biophys. (1968)
- Vilches-Flores A1, et al. Biotin increases glucokinase expression via soluble guanylate cyclase/protein kinase G, adenosine triphosphate production and autocrine action of insulin in pancreatic rat islets. J Nutr Biochem. (2010)
- De La Vega LA1, Stockert RJ. Regulation of the insulin and asialoglycoprotein receptors via cGMP-dependent protein kinase. Am J Physiol Cell Physiol. (2000)
- Lazo de la Vega-Monroy ML1, et al. Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and beta-cell proportion. J Nutr Biochem. (2013)
- Sasaki Y, et al. Administration of biotin prevents the development of insulin resistance in the skeletal muscles of Otsuka Long-Evans Tokushima Fatty rats. Food Funct. (2012)
- Koutsikos D1, Agroyannis B, Tzanatos-Exarchou H. Biotin for diabetic peripheral neuropathy. Biomed Pharmacother. (1990)
- Krause KH, Berlit P, Bonjour JP. Impaired biotin status in anticonvulsant therapy. Ann Neurol. (1982)
- Bonjour JP. Vitamins and alcoholism. V. Riboflavin, VI. Niacin, VII. Pantothenic acid, and VIII. Biotin. Int J Vitam Nutr Res. (1980)
- THOMPSON RH, BUTTERFIELD WJ, FRY IK. Pyruvate metabolism in diabetic neuropathy. Proc R Soc Med. (1960)
- Xu C1, et al. Selective overexpression of human SIRT1 in adipose tissue enhances energy homeostasis and prevents the deterioration of insulin sensitivity with ageing in mice. Am J Transl Res. (2013)
- Law IK1, et al. Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti-aging and metabolic effects of sirtuins. Proteomics. (2009)
- Mao J1, et al. aP2-Cre-mediated inactivation of acetyl-CoA carboxylase 1 causes growth retardation and reduced lipid accumulation in adipose tissues. Proc Natl Acad Sci U S A. (2009)
- Fukuwatari T1, Wada H, Shibata K. Age-related alterations of B-group vitamin contents in urine, blood and liver from rats. J Nutr Sci Vitaminol (Tokyo). (2008)
- Mock DM1. Skin manifestations of biotin deficiency. Semin Dermatol. (1991)
- Gschwandtner M1, et al. Histamine suppresses epidermal keratinocyte differentiation and impairs skin barrier function in a human skin model. Allergy. (2013)
- Ogawa Y1, et al. Prospective study of biotin treatment in patients with erythema due to gefitinib or erlotinib. Gan To Kagaku Ryoho. (2014)
- Zempleni J1, Hassan YI, Wijeratne SS. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab. (2008)
- Korkmazer N1, et al. Serum and liver tissue biotinidase enzyme activity in rats which were administrated to valproic acid. Brain Dev. (2006)
- Arslan M1, et al. The effects of biotin supplementation on serum and liver tissue biotinidase enzyme activity and alopecia in rats which were administrated to valproic acid. Brain Dev. (2009)
- Schulpis KH1, et al. Low serum biotinidase activity in children with valproic acid monotherapy. Epilepsia. (2001)
- Luís PB1, et al. Inhibition of 3-methylcrotonyl-CoA carboxylase explains the increased excretion of 3-hydroxyisovaleric acid in valproate-treated patients. J Inherit Metab Dis. (2012)
- Comben N, Clark RJ, Sutherland DJ. Clinical observations on the response of equine hoof defects to dietary supplementation with biotin. Vet Rec. (1984)
- CUNHA TJ, LINDLEY DC, ENSMINGER ME. Biotin deficiency syndrome in pigs fed desicated egg white. J Anim Sci. (1946)
- Colombo VE, et al. Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy. J Am Acad Dermatol. (1990)
- Hale G, Wallis NG, Perham RN. Interaction of avidin with the lipoyl domains in the pyruvate dehydrogenase multienzyme complex: three-dimensional location and similarity to biotinyl domains in carboxylases. Proc Biol Sci. (1992)
- Zempleni J, Trusty TA, Mock DM. Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. J Nutr. (1997)
- Said HM1, et al. Chronic ethanol feeding and acute ethanol exposure in vitro: effect on intestinal transport of biotin. Am J Clin Nutr. (1990)
- FENNELLY J, et al. PERIPHERAL NEUROPATHY OF THE ALCOHOLIC: I, AETIOLOGICAL ROLE OF ANEURIN AND OTHER B-COMPLEX VITAMINS. Br Med J. (1964)