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Deficiency of this vitamin is not rare and can cause hair loss, dry flaky skin, rashes and fatigue. Those with a poor diet, alcoholism or long term antibiotic use are at risk of deficiency.
Biotin-binding immunoglobulin (BBI) was recently identified in human serum and has been suggested to have a significant association with allergic and autoimmune disorders. Attempts were made to evaluate the clinical significance of BBI in autoimmune thyroid disorders. Prevalence of BBI was significantly higher in Graves' disease (47%) than in Hashimoto's disease (8%) and healthy controls (10%). The BBI consisted of heterogeneous subtypes with respect to binding of several immunoglobulin classes. Sera in Graves' disease showed predominantly IgG-binding BBI, whereas healthy subjects had IgM-binding BBI. Thyroid stimulating hormone receptor antibody (TRAb) level was significantly higher in the BBI non-detected group than in the detected group. There was no significant relationship between BBI prevalence and thyroid hormone concentrations, anti-thyroglobulin antibody (TGAb) or anti-thyroid microsomal antibody (McAb) titers. In addition, biotin levels in peripheral blood and red blood cells and biotinidase activity did not differ in the BBI detected and non-detected groups. The present results suggest that BBI is associated with autoimmune dysfunction in Graves' disease.
This article reviews current knowledge concerning the dermatologic manifestations of biotin deficiency. Biotin is a water-soluble vitamin that acts as an essential cofactor for four carboxylases, each of which catalyzes an essential step in intermediary metabolism. For example, acetyl-CoA carboxylase catalyzes the rate-limiting step in fatty acid elongation. In infants, children, and adults, deficiency of biotin causes alopecia and a characteristic scaly, erythematous dermatitis distributed around body orifices. The rash closely resembles that of zinc deficiency. Candida albicans often can be cultured from the skin lesions. Biotinidase deficiency, an inborn error, causes biotin deficiency, probably as a consequence of unpaired intestinal absorption, cellular salvage, and renal reclamation of biotin; biotinidase deficiency causes dermatologic manifestations similar to biotin deficiency. There is evidence that impaired fatty acid metabolism secondary to reduced activities of the biotin-dependent carboxylases (especially acetyl-CoA carboxylase) plays an etiologic role in the dermatologic manifestations of biotin deficiency. Candida infections secondary to impaired immune function might also contribute to the dermatitis of biotin deficiency.
Biotin deficiency is known to affect immune function in both humans and experimental animals. In this study, we determined the effect of biotin deficiency on 4-wk-old Balb/cAnN mice during 20 wk of experimentation. The growth rate of mice slowed significantly during the first 6 wk of consumption of a diet designed to induce biotin deficiency; thereafter, from weeks 7 to 20 there was progressive weight loss in the mice receiving the biotin-deficient diet. In the livers of biotin-deficient mice, the specific activities of two biotin-dependent enzymes--pyruvate carboxylase and propionyl-CoA carboxylase--decreased by as much as 75% and 80%, respectively, and in spleen lymphocytes the specific activities of these two enzymes decreased by 63% and 75%, respectively. With respect to the effects of biotin deficiency on the immune system, we observed statistically significant changes in both the absolute number of spleen cells and in the proportions of spleen cells carrying different phenotypic markers: after 16 wk the percentage of cells expressing surface immunoglobulin (sIg) decreased from 47% (control and supplemented) to 27% (deficient) and CD3+ cells increased from 42% (control and supplemented) to 54% (deficient). The mitogen-induced proliferation of spleen cells from deficient mice was lower than that of spleen cells from the control mice. These findings suggest that biotin could have an important role in lymphocyte maturation and responsiveness to stimulation, and consequently in the capacity of the immune system to respond to an antigenic challenge.
The effects of biotin and protein-calorie deficiency on metabolism of liver phospholipids in rats were determined. Weanling male Long-Evans rats were fed ad libitum a biotin-deficient (0.4 micrograms biotin/g diet) or a biotin-adequate (2.4 micrograms biotin/g diet) diet for 49 days. A pair-fed group was fed biotin-adequate diet but restricted to the amount consumed by biotin-deficient rats. The effects of these diets on food intake, weight gain, biotin content of serum and fatty acid composition of liver phospholipid were determined. Growth and food intake were significantly depressed in biotin-deficient and pair-fed rats. Biotin concentration in serum was significantly reduced in biotin-deficient and in pair-fed rats. Biotin deficiency caused significantly increased concentrations of 15:0, 17:0 and total odd-chain fatty acids in liver phospholipids. Combined biotin and protein-calorie deficiency and protein-calorie deficiency alone caused significantly increased concentrations of 18:2 omega 6 in liver phospholipids. Biotin deficiency caused significant reduction in liver phospholipid 20:3 omega 6. Reduced arachidonic acid (20:4 omega 6) level was due to combined biotin protein-calorie deficiency. Protein-calorie deficiency alone was primarily responsible for reduced levels of 22:5 omega 6. Biotin deficiency alone caused significant increases in liver phospholipids 18:3 omega 3 and 22:6 omega 3.
We have studied testicular function in the biotin-deficient rat biochemically and morphologically. Serum testosterone and luteinizing hormone (LH) levels were decreased significantly in the deficient rats. Administration of biotin or gonadotropins to the deficient rats reversed this decrease in serum testosterone. There was no difference in the serum cholesterol level between the control and biotin-deficient rats. A significant degree of sloughing of seminiferous tubule germinal epithelium was noticed in the biotin-deficient rat testes. Biotin treatment of biotin-deficient rats reversed this condition whereas testosterone treatment was without any effect. The development and maintenance of morphological and functional integrity of the seminiferous tubules appears to require a biotin-mediated step in addition to testosterone.
Biotin-deficient conditions are frequently associated with epileptic disorders. Biotin deficiency may be caused by long-term treatment with anticonvulsants or excessive ingestion of avidin. Absence of biotinidase activity can also lead to biotin deficiency, and is characterized by developmental delay as well as neurological and dermatological abnormalities. Because seizures are one of the most frequent signs of the latter, biotin-deficient conditions could conceivably facilitate convulsive disorders. To test this hypothesis, we investigated the occurrence of a latent kindling hyperexcitability in biotin-deprived rats. In these animals, duration of after-discharge on the first stimulation was longer at threshold amplitude, kindling development through its early stages was accelerated and duration of the forelimb clonus of fully kindled seizures was increased. Biotin deprivation in mixed cerebellar granule cell-astrocyte cultures also produced a tetrodotoxin-sensitive delayed loss of the glutamatergic neuronal population. The data thus support a facilitatory role for biotin-deficient conditions in convulsive disorders.
Lewis rats were maintained on diets which provided either an adequate or deficient concentration of biotin. Biotin deficiency produced a marked reduction in thymus size and cellularity, a depressed immune response to sheep erythrocytes and prevented the development of experimental allergic encephalomyelitis following immunization with guinea pig myelin basic protein. Total T cells, T-helper and T-suppressor cells were quantitatively the same in the spleens of rats fed biotin-adequate or deficient diets. By using an adoptive lymphocyte transfer procedure, it was determined that the afferent immune response to myelin basic protein was impaired in biotin deficiency. These results indicate that experimentally induced autoimmune disease is susceptible to the nutritional influence of dietary biotin.
The structure of the hoof epidermis is the link between nutrition and horn quality. The aim of this study was to demonstrate the relationship of single structures in the process of keratinization and cornification of bovine hoof epidermis to certain nutritional factors such as lipids, minerals and vitamins. Furthermore, we wanted to show the structural changes in the dyskeratotic epidermis caused by an insufficient supply of keratinizing epidermal cells. For our study we used samples of hoof epidermis from 25 dual-purpose dairy cattle, with ages ranging between 2.5 and 4 years. We also obtained a complete set of hooves from a biotin-deficient calf. All samples were investigated by light and transmission electron microscopy, using routine methods as well as histochemical and enzyme-histochemical techniques. We focused on epidermal structures that have a major influence on horn quality and are known to be related to single nutritional factors. The strength of the keratin filament bundles is determined by their cross-linking via sulphur-containing amino acids. Essential fatty acids are required for the synthesis of an intercellular cementing substance connecting the horn cells and establishing a permeability barrier in the stratum corneum. Minerals, in particular calcium, are essential for activation of enzymes that are a prerequisite for physiological keratinization and cornification. Furthermore, vitamins such as biotin are essential in the metabolism of the keratinizing epidermal cells.
Supplemental biotin for swine. III. Influence of supplementation to corn- and wheat-based diets on the incidence and severity of toe lesions, hair and skin characteristics and structural soundness of sows housed in confinement during four parities.
The influence of supplementing 0 (NB) or 440 (SB) micrograms biotin/kg to corn- or wheat-based diets on toe lesions, hair characteristics and structural soundness in 116 crossbred female swine was studied from selection (100 kg) until completion of four parities. Gilts that had been previously fed corn-soybean meal diets with 0 or 220 micrograms supplemental biotin/kg diet during growth and development, remained on either the biotin unsupplemented or supplemented diet. Females were housed in buildings containing partially slatted and solid concrete floors. Toe, hair and soundness evaluations were made at a mean age of 240, 521, 732, 916 and 1,090 d. Type of grain fed did not influence (P greater than .10) any response criteria evaluated. Six types of toe lesions were observed across all dietary treatments and varied in severity from minor to very severe. The percentage of females with heel cracks, heel-horn junction cracks and side-wall horn cracks was reduced (P less than .01) when females were fed SB diets. Females fed SB diets had fewer (P less than .001) total lesions, heel cracks, heel-horn junction cracks, side-wall horn cracks and white-line horn cracks (P less than .03) compared with females consuming NB diets. In general, biotin supplementation was more effective in reducing the number and percentage of toe lesions in multiparous sows compared with gilts and primiparous sows. Biotin supplementation increased (P less than .001) the number of hairs/cm2 skin and improved (P less than .001) hair scores. Histological evaluation and soundness scores were not affected (P greater than .10) by level of biotin fed.(ABSTRACT TRUNCATED AT 250 WORDS)
1. Exogenous oestrogen administration to immature male and female chickens significantly increased plasma biotin and significantly reduced liver biotin concentrations. 2. The elevation in plasma biotin concentrations was dose dependent and maximum values were observed 48 hr after a single injection of oestrogen. 3. A second oestrogen injection significantly increased plasma biotin concentrations compared with values obtained after the initial injection given 10 days previously. 4. Plasma biotin concentrations were significantly increased in female, but not male, birds approaching sexual maturity. This increase coincided with the time of the known surge in endogenous oestrogen production by the developing ovary.
Single biotin doses (600 micrograms and 900 micrograms) orally administered to male and female volunteers were very rapidly eliminated from plasma after absorption leading to a remarkable increase of urinary excretion. A prolonged enhancement of plasma levels occurred only after continuous supplementation with 300 micrograms biotin/day for 1 week and following 900 micrograms biotin/day for another week. From the diurnal turnover of the plasma level after oral stimulation with 600 micrograms biotin some biokinetic indices, such as the constants of invasion and elimination rate as well as the elimination half life time were determined. The median of the invasion constant was calculated to 2.068 h-1, that one of elimination constant to 0.3867 h-1 suggesting no indication of diminished body stores. The elimination half life time of the administered biotin dose from plasma amounted to 1 hour, 50 minutes.
Mol Cell Endocrinol1985 Apr;40(1):79-86
Estrogen induction of biotin-binding protein in immature chicks: kinetics, hormonal specificity and modulation.
Murty CV, Adiga PR
Employing a specific radioimmunoassay for quantification, the kinetics of estrogen-induced elevation in the plasma concentration of biotin-binding protein (BBP) in immature male chicks was investigated. A single injection of the steroid hormone enhanced the plasma BBP content several-fold at 6 h, reaching peak levels around 48 h and declining thereafter. A 2-fold amplification of the response was evident during secondary stimulation with the hormone. The magnitude of the response was hormonal dose-dependent while the initial lag phase and the time of peak protein accumulation were unaltered within the hormonal doses tested. The circulatory half-life of the specific protein in normal and estrogenized birds was 10 h. Hyperthyroidism markedly decreased the hormonal response while the opposite effect was seen during hypothyroidism. The antiestrogens E- and Z-clomiphene citrate effectively blocked the protein induction whereas progesterone, either alone or in combination with estrogen, was ineffective in modulating the induction. Cycloheximide administration drastically inhibited the inductive response. The above observations clearly suggest that the genes corresponding to the two isofunctional proteins of chicken egg, viz. BBP and avidin, are differentially regulated.
New insight into the causes of immunodeficiency disorders.
J Am Acad Dermatol, 11(4 Pt 1):653-60 1984 Oct
The ability to define subpopulations of immunologically competent lymphocytes has permitted an enhanced understanding of the interaction between functionally distinct components of the immune system. T cells can provide help in antibody formation or they may suppress antibody production. Abnormal immunoregulatory mechanisms have been demonstrated in the hyperimmunoglobulin E-recurrent infection syndrome. This disorder is associated with a marked elevation of IgE and specific elevations of IgE antibodies directed toward staphylococcal antigens. Abnormal T cell regulation of immune responses has been demonstrated. Graft-versus-host disease (GVHD) occurs in an immunodeficient patient who has received an infusion of immunocompetent cells. The diagnosis of graft-versus-host (GVH) reaction may be complicated by the protean manifestations of the disorder. The acute form, consisting of a maculopapular rash, fever, and diarrhea, may be confused with acute infection or drug reaction. Chronic GVHD has been incorrectly diagnosed as histiocytosis X, acrodermatitis enteropathica, or scleroderma. Utilizing chromosome markers and/or identification of histocompatibility antigens, the presence of circulating lymphocytes from donor immunocompetent cells (blood transfusion, maternal source) can be documented. The development of sensitive technics for identifying cells can establish a precise diagnosis. Certain immunodeficiency disorders can be identified by biochemical means. Biotin-dependent multiple carboxylase enzyme deficiency is associated with a chronic dermatitis, alopecia, ataxia, and secondary infection of the skin with Candida. The disorder responds promptly to the administration of biotin with correction of dermatologic, neurologic, and immunologic abnormalities.
Relationships between biotin and thymus morphology, and thymic and plasma peptides controlling DNA transcription.
Moretti P, Petrelli C, Petrelli F, Gabrielli MG, Palatroni P
Department of Cellular biology, University of Camerino, Italy.
Biotin-deficient rats show a slower growth rate and thymus involution. The amount of the thymic peptides controlling DNA template, based on thymus weight, is higher in deficient than control rats. No significant difference was noticed in the content of active peptides when evaluated for the rat. This observation suggests that involution of the thymus does not involve those cells which produce active peptides. Inhibition of RNA synthesis is the same for peptides extracted from normal and from biotin-deficient rat thymus. The amount of plasma peptides controlling DNA template per milliliter of plasma is higher and inhibition of activity on RNA synthesis is lower in deficient as compared to control rats. These effects are reversible following biotin administration.
Acta Vitaminol Enzymol1985;7(3-4):199-206
Relationships between biotin and DNA contents and DNA turnover in lymphoid organs: thymus, lymph nodes and spleen.
Petrelli F, Moretti P, Sciarresi P, Dahir AM
Biotin-deficient rats show a slower growth rate and a reduction in thymus, intestinal lymph nodes and spleen weight. The effect is reversible. Biotin administration to normal rats (1 mg/rat/day) causes an increase in intestinal lymph nodes and spleen, while there is no effect on body and thymus weight. The amount of thymus and spleen DNA is lower for deficient than control rats. No difference was noticed between the levels of DNA from normal control and biotin-deficient rat lymph nodes, and between the levels of DNA from normal rats treated and untreated with biotin. The time-course of the specific radioactivity of DNA and the DNA turnover shows that biotin increases both the incorporation of labelling in DNA and DNA turnover rate.
Arch Int Physiol Biochim1980 May;88(2):163-8
Behaviour in biotin-deficient rats of thymic peptides controlling DNA transcription.
Petrelli F, Moretti P, Paparelli M, Guglielmi L, Barra D
Biotin-deficient rats show a slowing down of the growth and an involution of the thymus. The amount of the thymic peptides controlling DNA template, if referred to the thymus weight is higher in deficient than in control rats; no significant difference is noticed among the contents of the active peptides when evaluated per rat. The inhibiting activity on RNA synthesis is the same for the peptides extracted from normal and from biotin-deficient rat thymus.
Med Hypotheses1999 May;52(5):401-6
High-dose biotin, an inducer of glucokinase expression, may synergize with chromium picolinate to enable a definitive nutritional therapy for type II diabetes.
NutriGuard Research, Encinitas, CA 92024, USA.
Glucokinase (GK), expressed in hepatocyte and pancreatic beta cells, has a central regulatory role in glucose metabolism. Efficient GK activity is required for normal glucose-stimulated insulin secretion, postprandial hepatic glucose uptake, and the appropriate suppression of hepatic glucose output and gluconeogenesis by elevated plasma glucose. Hepatic GK activity is subnormal in diabetes, and GK may also be decreased in the beta cells of type II diabetics. In supraphysiological concentrations, biotin promotes the transcription and translation of the GK gene in hepatocytes; this effect appears to be mediated by activation of soluble guanylate cyclase. More recent evidence indicates that biotin likewise increases GK activity in islet cells. On the other hand, high-dose biotin suppresses hepatocyte transcription of phosphoenolpyruvate carboxykinase, the rate-limiting enzyme for gluconeogenesis. Administration of high-dose biotin has improved glycemic control in several diabetic animals models, and a recent Japanese clinical study concludes that biotin (3 mg t.i.d. orally) can substantially lower fasting glucose in type II diabetics, without side-effects. The recently demonstrated utility of chromium picolinate in type II diabetes appears to reflect improved peripheral insulin sensitivity--a parameter which is unlikely to be directly influenced by biotin. Thus, the joint administration of supranutritional doses of biotin and chromium picolinate is likely to combat insulin resistance, improve beta-cell function, enhance postprandial glucose uptake by both liver and skeletal muscle, and inhibit excessive hepatic glucose production. Conceivably, this safe, convenient, nutritional regimen will constitute a definitive therapy for many type II diabetics, and may likewise be useful in the prevention and management of gestational diabetes. Biotin should also aid glycemic control in type I patients.
Wallace JC, Jitrapakdee S, Chapman-Smith A
Department of Biochemistry, University of Adelaide, Australia. firstname.lastname@example.org
Pyruvate carboxylase [EC 184.108.40.206] is a member of the family of biotin-dependent carboxylases and is found widely among eukaryotic tissues and in many prokaryotic species. It catalyses the ATP-dependent carboxylation of pyruvate to form oxaloacetate which may be utilised in the synthesis of glucose, fat, some amino acids or their derivatives and several neurotransmitters. Diabetes and hyperthyroidism increase the level of expression of pyruvate carboxylase in the long term, while its activity in the short term is controlled by the intramitochondrial concentrations of acetyl-CoA and pyruvate. Many details of this enzyme's regulation are yet to be described in molecular terms. However, progress towards this goal and towards understanding the relationship of pyruvate carboxylase structure to its catalytic reaction mechanism, has been enormously enhanced recently by the cloning and sequencing of genes and cDNAs encoding the approximately 130 kDa subunit of this homotetramer. Defects in the expression or biotinylation of pyruvate carboxylase in humans almost invariably results in early death or at best a severely debilitating psychomotor retardation, clearly reflecting the vital role it plays in intermediary metabolism in many tissues including the brain.