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Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role in transcriptional repression of genes and genome stability. Biotin deficiency may be caused by insufficient dietary uptake of biotin, drug-vitamin interactions and, perhaps, by increased biotin catabolism during pregnancy and in smokers. Biotin deficiency can also be precipitated by decreased activities of the following proteins that play critical roles in biotin homeostasis: the vitamin transporters sodium-dependent multivitamin transporter and monocarboxylate transporter 1, which mediate biotin transport in the intestine, liver and peripheral tissues, and renal reabsorption; holocarboxylase synthetase, which mediates the binding of biotin to carboxylases and histones; and biotinidase, which plays a central role in the intestinal absorption of biotin, the transport of biotin in plasma and the regulation of histone biotinylation. Symptoms of biotin deficiency include seizures, hypotonia, ataxia, dermatitis, hair loss, mental retardation, ketolactic acidosis, organic aciduria and also fetal malformations. This review focuses on the deficiencies of both biotin and biotinidase, and the medical management of such cases.
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... It is also said to prevent breakage of hair and improve hair elasticity. 39 However, current evidence of the utility of biotin as a hair and nail supplement for normal individuals is limited. Its utility has been demonstrated in pregnancy, malnutrition and to treat biotinidase deficiency in children (Table 2). ...
... Can be low, but supplements do not help 39,51 Level 4 ...
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Background While a plethora of literature continues to be published on the role of nutritional agents both in lay press and indexed journals, the data is not on a firm footing and leaves the dermatologist in a quandry and the patient confused. The various agents include vitamins, minerals, amino acids, antioxidants, diets & gluten. A proper knowledge of the role of nutritional supplements in dermatological diseases can be a useful tool in advising the patients and in certain cases ameliorating the disorder. Patients/Methods Literature review of last 15 years was made using the terms “diet in dermatology,” “nutrition and skin,” “nutritional supplements in dermatology,” “nutritional agents and acne,” “nutritional agents and alopecia,” and “nutritional agents and psoriasis.” Results While there are multiple publications on the use of nutritional supplements for amelioration of skin diseases, most of them are based on either associations or in vitro studies, but very few transcend the rigors of a clinical trial or the holey grail of a double-blinded randomized controlled trial. There seem to be some evidence in acne, psoriasis, telogen effluvium, urticaria & vitiligo. Coeliac disease and dermatitis herpetiformis have a strong link with diet. Rosacea has a strong link with certain foods, but the other disorders like melasma, aphthous stomatitis do not have any scientifically validated association with diet. Conclusions Our updated review examines the role of nutritional supplements and antioxidants in various dermatological disorders. We have found that there are varying levels of evidence with notable associations of low glycemic diet & acne, fish oil & weight loss with psoriasis, fish oils & probiotics with atopic dermatitis & vitamins & botanical extracts with vitiligo. The evidence for diet and nutrition in bullous disorders and photoageing is scarce. The role of low histamine diet in urticaria is useful in select cases of episodic urticaria. Rosacea is triggered by hot and spicy food . Apart from gluten and Dermatitis Herpetiformis, no diet can be considered disease modifying in our reveiw. The lack of comparison of nutritional or dietary modiffication with conventional validated agents, makes the data difficult to translate in real world patient management.
... Untreated patients suffer mainly from severe neurological symptoms such as hypotonia, seizures, ataxia, developmental delay, sensorineural deafness, and optic nerve atrophy [4,5]. Alopecia and skin rash (though not specific) are also frequently observed [4][5][6]. Treatment of BD consists of regular oral supplementation of biotin in pharmacological doses [7]. ...
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Biotinidase deficiency (BD) is a rare autosomal recessive metabolic disease. Previously the disease was identified only by clinical signs and symptoms, and since recently, it has been included in newborn screening programs (NBS) worldwide, though not commonly. In Europe, BD prevalence varies highly among different countries, e.g., from 1:7 116 in Turkey to 1:75 842 in Switzerland. This paper aimed to present the molecular spectrum of BD (profound and partial forms) in Polish patients diagnosed within the national NBS of 1,071,463 newborns. The initial suspicion of BD was based on an abnormal biotinidase activity result determined in a dry blood spot (DBS) by colorimetric and by fluorimetric methods while biochemical verification was determined by serum biotinidase activity (as quantitative analysis). The final diagnosis of BD was established by serum enzyme activity and the BTD gene direct sequencing. The obtained results allowed for the estimation of disease prevalence (1:66,966 births, while 1:178,577 for profound and 1:107,146 for partial forms), and gave novel data on the molecular etiology of BD.
... An increase was noted in the serum level of biotinidase in the MgB-supplement groups. Biotinidase is an essential enzyme in biotin synthesis and helps transfer biotin to the peripheral tissues [14,53]. Additionally, the serum levels of arginine, biotin, Mg, Si, and Zn were found to have increased in all study groups. ...
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The purpose of this study was to examine the effects of a combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on hair and nail growth in an animal model. Twenty-eight female Sprague–Dawley rats (8 weeks old) were randomized into one of the following groups: (i) group (control), shaved; (ii) group (ASI), shaved + ASI (4.14 mg/rat/day); (iii) group (ASI + MgB I), shaved + ASI (4.14 mg/rat/day) + MgB (48.7 μg/rat/day); and (iv) group (ASI + MgB II), shaved + ASI (4.14 mg/rat/day) + MgB (325 μg/rat/day). On day 42, compared with the control group, while hair density (p < 0.05, p < 0.01, and p < 0.0001, respectively) and anagen ratio (p < 0.01, p < 0.01, and p < 0.001) increased in the ASI, ASI + MgB I, and ASI + MgB II groups, telogen ratio decreased (p < 0.01, p < 0.01, and p < 0.001, respectively). In the molecular analysis, VEGF, HGF, and KGF-2 increased in the ASI (p < 0.01, p < 0.01, and p < 0.05, respectively), ASI + MgB I (p < 0.0001 for all), and ASI + MgB II (p < 0.0001 for all) groups when compared to the control group. FGF-2 (p < 0.01) and IGF-1 (p < 0.001) were found to be increased in the ASI + MgB I and ASI + MgB II groups. SIRT-1 and β-catenin increased in the ASI (p < 0.05 and p < 0.01), ASI + MgB I (p < 0.001 for both), and ASI + MgB II (p < 0.0001 for both) groups. Wnt-1 increased in the ASI + MgB I (p < 0.001) and ASI + MgB II (p < 0.0001) groups. In conclusion, the combination of ASI and MgB could promote hair growth by regulating IGF-1, FGF, KGF, HGF, VEGF, SIRT-1, Wnt, and β-catenin signal pathways. It was also established that ASI did not affect nail growth, whereas the MgB combination was effective using a higher dose of biotin.
... Despite the prevailing assumption that biotin deficiency is rare, there is mounting evidence indicating the existence of several physiological and pharmacological states in which biotin status is compromised. Other than primary causes, such as neonatal biotinidase deficiency or inborn errors of biotin metabolism, biotin deficiency has been associated with such diverse factors as protein-energy malnutrition, long-term parenteral nutrition, anticonvulsant therapy, pregnancy, alcoholism, smoking, and aging [48][49][50][51][52][53][54][55][56][57]. ...
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Background: Biotin, a water-soluble B vitamin, has demonstrable anti-inflammatory properties. A biotin-deficient diet induced a colitis-like phenotype in mice, alleviable by biotin substitution. Mice with dextran sulfate sodium (DSS)-induced colitis showed biotin deficiency and diminished levels of sodium-dependent multivitamin transporter, a protein involved in biotin absorption. Biotin substitution induced remission by reducing activation of NF-κB, a transcription factor involved in intestinal permeability and inflammatory bowel disease (IBD). We investigated for the first time a possible clinical role of biotin status in IBD. Methods: In a comparative, retrospective, cross-sectional study, serum samples of 138 patients with IBD (67 female; 72 Crohn's disease (CD), 66 ulcerative colitis (UC)) aged 18-65 years and with a mean age (±SD) of 42.5 ± 14.3 years as well as 80 healthy blood donors (40 female; 40.0 ± 10.0 years; range 20-60 years) were analyzed. Inflammation was defined as hsCRP ≥5 mg/L, and to determine biotin status, serum 3-hydroxyisovaleryl carnitine (3HIVc) levels were measured by LC-MS/MS. Results: A total of 138 patients with IBD (67f; 72CD/66 UC; 42.5 ± 14.3 years) were enrolled: 83/138 had inflammation. Mean serum 3HIVc levels were significantly higher in IBD patients but unaffected by inflammation. Biotin deficiency (95th percentile of controls: >30 nmol/L 3HIVc) was significantly more common in IBD patients versus controls. Conclusion: High serum 3HIVc levels and biotin deficiency were associated with IBD but not inflammatory activity or disease type. Our findings suggest biotin may play a role as cause or effect in IBD pathogenesis. Routine assessment and supplementation of biotin may ameliorate IBD and support intestinal integrity.
... The Vitamin B7 (biotin)recommended doses is2-10 mg/day, PO [130]. Biotin, a waterdissolved nutrient, acts as an essential coenzyme for five carboxylases involved in the digestion of carbohydrates, synthesis of fatty acids, and gluconeogenesis [139]. An open-label trial investigated the effects of a 12-month combined regimen including 25 mcg/day of biotin,CoQ10, carnitine, vitamin C, vitamin K1, riboflavin, thiamine, niacin, pyridoxine, pantothenic acid, cyanocobalamin, and folic acid in twelve MD patients. ...
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Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS)syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.
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– Background: The aim of this study is to define the interference of biotin in several endocrine, tumor marker, and vitamin assays performed by an electrochemiluminescence method, trying to determinate the critical level that causes biotin interference. – Material and methods: Working biotin solutions were prepared in phosphate-buffered saline (PBS) at different concentrations (10000, 7500, 5000, 2500, 1250, 625, and 312.5 ng/mL), which were spiked on the samples to obtain final concentrations ten-fold lower. Each serum biotin dilution was tested in triplicate, using at least two levels of analytes. Determinations of several endocrine, vitamins, tumor and bone markers were carried-out with eletrochemilumenescent immunoassays on the cobas e801 and cobas e411. Comparison between the results obtained by analyzing the biotin-spiked samples and the reference PBS-spiked samples was performed using Microsoft Excel. The relative bias with the interfering-free specimen was calculated for each biotin concentration. Interference was considered significant when the relative bias exceeded 10%. Glick´s interferographs were performed plotting the percentage of change vs. biotin concentration. – Results: Analyte concentrations were spuriously decreased in 12 sandwich immunoassays and falsely increased in 11 competitive immunoassays. However thyrotropin and CA 15.3 antigen were not significantly affected. – Conclusions: Except CA 15.3 and TSH, the methods tested were susceptible to biotin interference. Falsely low values occurred in sandwich assays and high bias in competitive assays. Clinicians and laboratorians should be aware of the medical importance of biotin interference as a cause of misdiagnosis and incorrect treatment.
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Previous studies indicated that in pancreatic islets the amount of glucose-derived pyruvate that enters mitochondrial metabolism via carboxylation is approximately equal to that entering via decarboxylation and that both carboxylation and decarboxylation are correlated with capacitation of glucose metabolism and insulin release. The relatively high rate of carboxylation is consistent with the current study's finding that pyruvate carboxylase is as abundant in pancreatic islets as it is in liver and kidney. Since islets do not contain phosphoenolpyruvate carboxykinase and, therefore, cannot carry out glyconeogenesis from pyruvate, the carboxylase might be present in the islet to participate in novel anaplerotic reactions. This idea was first explored by incubating mitochondria from various tissues with pyruvate. Mitochondria from tissues, such as pancreatic islets, liver, and kidney, in which pyruvate carboxylase is abundant, exported a large amount of malate and little or no citrate, isocitrate, and aspartate to the medium. The amount of malate within the mitochondria was <1% that in the medium. When pancreatic islet mitochondria were incubated with [1-¹⁴C]pyruvate, radioactive carbon appeared in the medium primarily in malate. Very little radioactivity appeared in amino acids, and little or no radioactivity appeared in citrate and isocitrate. Carbon 1 of pyruvate can be incorporated into malate and other citric acid cycle intermediates only via carboxylation, as this carbon would be lost via decarboxylation when pyruvate enters the citric acid cycle as acetyl-CoA via the pyruvate dehydrogenase reaction. The amount of malate formed equaled the ¹⁴CO2 formed and the radioactivity from C-1 of pyruvate recovered in malate slightly exceeded the formation of ¹⁴CO2 in agreement with our previous studies that reported a high rate of carboxylation of pyruvate in intact islets. When intact pancreatic islets were incubated with methyl [U-¹⁴C]succinate as a mitochondrial source of four-carbon dicarboxylic acids, radioactivity appeared in pyruvate and lactate. Taken together with previous studies, the current results suggest that during glucose-induced insulin secretion there is a shuttle operating across the mitochondrial membrane in which glucose-derived pyruvate is taken up by mitochondria and carboxylated to oxaloacetate by pyruvate carboxylase. The oxaloacetate is converted to malate which exits the mitochondrion, where, in the cytosol, it is decarboxylated to pyruvate in the reaction catalyzed by malic enzyme. This pyruvate re-enters mitochondrial pools. Such a cycle produces NADPH in the cytosol. Since it is a cycle, this shuttle can produce far more NADPH than the pentose phosphate pathway, which is known to be a very minor route of glucose metabolism in the islet. If it is accepted that this shuttle is active in the insulin cell, this implicates NADPH regeneration in insulin secretion.
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From 1989 to 2001, 1 336 145 newborns were screened for biotinidase deficiency in Hungary. Fifty‐eight children with the disorder were identified as enzyme‐deficient. We have characterized the clinical and biochemical features and mutations of 20 of these children. Eleven children had profound biotinidase deficiency, 7 had partial biotinidase deficiency, and 2 were found to be heterozygous for profound deficiency by mutation analysis. Seventeen different mutations were identified in this population including seven novel mutations. Six of these new mutations are missense, 245C>A, 334G>A, 652G>C, 832C>G, 1253G>C, 1511T>A, and one is a unique allelic double mutation [212T>C;236G>A]. Of five Romanian Gypsies, four were homozygous for the 1595C>T mutation and one was heterozygous for this mutation. Most of the children with profound deficiency have been asymptomatic on therapy; however, four exhibited minimal brain abnormalities, motor delay and abnormal blood chemistries. Compliance with therapy must be questioned in these cases. Of clinical importance, all of the children with partial deficiency exhibited mild symptoms at the time of diagnosis, at several weeks to months of age. These symptoms resolved following biotin therapy. This is in contrast to the experience in the United States, where the children with partial deficiency have been asymptomatic at the time of diagnosis. This finding further indicates that children with partial deficiency should be treated. The incidence of biotinidase deficiency in Hungary is more than twice that observed in a worldwide survey. These results indicate that newborn screening in Hungary is effective and warranted.
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Background: Marginal biotin deficiency may be a human teratogen. A biotin status indicator that is not dependent on renal function may be useful in studies of biotin status during pregnancy. A previous study of experimental biotin deficiency suggested that propionyl-coenzyme A carboxylase (PCC) activity in peripheral blood lymphocytes (PBLs) is a sensitive indicator of biotin status. Objective: We examined the utility of measuring PCC activity and the activation of PCC by biotin in detecting marginal biotin deficiency. Design: Marginal biotin deficiency was induced in 7 adults (3 women) by egg-white feeding for 28 d. Blood and urine were obtained on days 0, 14, and 28 (depletion phase) and 44 and 65 (repletion phase). PBLs were incubated with (activated) or without (control) biotin before PCC assay. The activation coefficient of PCC is the ratio of PCC activity in activated PBLs to that in control PBLs. The significance of differences for all measurements was tested by repeated-measures analysis of variance with Fisher’s post hoc test and Bonferroni correction. Results: Changes in the urinary excretion of biotin and of 3-hydroxyisovaleric acid confirmed that marginal biotin deficiency was successfully induced. By day 14, PCC activity had decreased (P < 0.0001) to below the lower limit of normal in all subjects. By day 28, the activation coefficient of PCC had increased significantly (P = 0.003) and was above the upper limit of normal in 6 of 7 subjects. Conclusion: PCC activity is the most sensitive indicator of biotin status tested to date. In future pregnancy studies, the use of lymphocyte PCC activity data should prove valuable in the assessment of biotin status.
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Recent studies of biotin status during pregnancy provide evidence that a marginal degree of biotin develops in a substantial proportion of women during normal pregnancy. Several lines of evidence suggest that, although the degree of biotin deficiency is not severe enough to produce the classic cutaneous and behavioral manifestations of biotin deficiency, the deficiency is severe enough to produce metabolic derangements in women and that characteristic fetal malformations occur at a high rate in some mammals. Moreover, our analysis of data from a published multivitamin supplementation study provide significant albeit indirect evidence that the marginal degree of biotin deficiency that occurs spontaneously in normal human gestation is teratogenic. Investigation of potential mechanisms provides evidence that biotin transport by the human placenta is weak. Further, proliferating cells accumulate biotin at a rate five times faster than quiescent cells; this observation suggests that there is an increased biotin requirement associated with cell proliferation. Perhaps this requirement arises from the need to synthesize additional biotin-dependent holocarboxylases or provide additional biotin as a substrate for biotinylation of cellular histones. Reduced activity of the biotin-dependent enzymes acetyl-CoA carboxylase and propionyl-CoA carboxylase can cause alterations of lipid metabolism and might theoretically lead to alterations of polyunsaturated fatty acid and prostaglandin metabolism that derange normal skeletal development.