Biotin Abstracts 2

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Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.
            (Albarracin et al., 2008) Download
BACKGROUND:  Chromium and biotin play essential roles in regulating carbohydrate metabolism. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the combination of chromium picolinate and biotin on glycaemic control. METHODS:  Four hundred and forty-seven subjects with poorly controlled type 2 diabetes (HbA(1c) > or = 7.0%) were enrolled and received either chromium picolinate (600 microg Cr(+3)) with biotin (2 mg), or matching placebo, for 90 days in combination with stable oral anti-diabetic agents (OADs). Major endpoints were reductions in HbA(1c), fasting glucose, and lipids. Safety and tolerability were assessed. RESULTS:  Change in HbA(1c) was significantly different between treatment groups (p = 0.03). HbA(1c) in the chromium picolinate/biotin group decreased 0.54%. The decrease in HbA(1c) was most pronounced in chromium picolinate/biotin subjects whose baseline HbA(1c) > or = 10%, and highly significant when compared with placebo (-1.76% vs - 0.68%; p = 0.005). Fasting glucose levels were reduced in the entire chromium picolinate/biotin group versus placebo (-9.8 mg/dL vs 0.7 mg/dL; p = 0.02). Reductions in fasting glucose were also most marked in those subjects whose baseline HbA(1c) > or = 10.0%, and significant when compared to placebo (-35.8 mg/dL vs. 16.2 mg/dL; p = 0.01). Treatment was well tolerated with no adverse effects dissimilar from placebo. CONCLUSIONS:  These results suggest that the chromium picolinate/biotin combination, administered as an adjuvant to current prescription anti-diabetic medication, can improve glycaemic control in overweight to obese individuals with type 2 diabetes; especially those patients with poor glycaemic control on oral therapy.

Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process.
            (Ghosal et al., 2014) Download
Biotin is essential for the normal function of pancreatic beta cells. These cells obtain biotin from their surroundings via transport across their cell membrane. Little is known about the uptake mechanism involved, how it is regulated, and how it is affected by internal and external factors. We addressed these issues using the mouse-derived pancreatic beta-TC-6 cells and freshly isolated mouse and human primary pancreatic beta cells as models. The results showed biotin uptake by pancreatic beta-TC-6 cells occurs via a Na(+)-dependent, carrier-mediated process, that is sensitive to desthiobiotin, as well as to pantothenic acid and lipoate; the process is also saturable as a function of concentration (apparent Km = 22.24 ± 5.5 μM). These cells express the sodium-dependent multivitamin transporter (SMVT), whose knockdown (with doxycycline-inducible shRNA) led to a sever inhibition in biotin uptake. Similarly, uptake of biotin by mouse and human primary pancreatic islets is Na(+)-dependent and carrier-mediated, and both cell types express SMVT. Biotin uptake by pancreatic beta-TC-6 cells is also adaptively regulated (via transcriptional mechanism) by extracellular substrate level. Chronic treatment of pancreatic beta-TC-6 cells with bacterial lipopolysaccharides (LPS) leads to inhibition in biotin uptake. This inhibition is mediated via a Toll-Like receptor 4-mediated process and involves a decrease in membrane expression of SMVT. These findings show, for the first time, that pancreatic beta cells/islets take up biotin via a specific and regulated carrier-mediated process, and that the process is sensitive to the effect of LPS.

Regulation of immunological and inflammatory functions by biotin.
            (Kuroishi, 2015) Download
Biotin is a water-soluble B-complex vitamin and is well-known as a co-factor for 5 indispensable carboxylases. Holocarboxylase synthetase (HLCS) catalyzes the biotinylation of carboxylases and other proteins, whereas biotinidase catalyzes the release of biotin from biotinylated peptides. Previous studies have reported that nutritional biotin deficiency and genetic defects in either HLCS or biotinidase induces cutaneous inflammation and immunological disorders. Since biotin-dependent carboxylases involve various cellular metabolic pathways including gluconeogenesis, fatty acid synthesis, and the metabolism of branched-chain amino acids and odd-chain fatty acids, metabolic abnormalities may play important roles in immunological and inflammatory disorders caused by biotin deficiency. Transcriptional factors, including NF-κB and Sp1/3, are also affected by the status of biotin, indicating that biotin regulates immunological and inflammatory functions independently of biotin-dependent carboxylases. An in-vivo analysis with a murine model revealed the therapeutic effects of biotin supplementation on metal allergies. The novel roles of biotinylated proteins and their related enzymes have recently been reported. Non-carboxylase biotinylated proteins induce chemokine production. HLCS is a nuclear protein involved in epigenetic and chromatin regulation. In this review, comprehensive knowledge on the regulation of immunological and inflammatory functions by biotin and its potential as a therapeutic agent is discussed.


 

Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis.
            (Larrieta et al., 2012) Download
Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on glucose metabolism, we presently analyzed the effect of biotin deprivation on glucose homeostasis and on pancreatic islet morphology. Three-week-old male BALB/cAnN Hsd mice were fed a biotin-deficient or a biotin-control diet (0 or 7.2 μmol of free biotin/kg diet, respectively) over a period of 8 weeks. We found that biotin deprivation caused reduced concentrations of blood glucose and serum insulin concentrations, but increased plasma glucagon levels. Biotin-deficient mice also presented impaired glucose and insulin tolerance tests, indicating defects in insulin sensitivity. Altered insulin signaling was linked to a decrease in phosphorylated Akt/PKB but induced no change in insulin receptor abundance. Islet morphology studies revealed disruption of islet architecture due to biotin deficiency, and an increase in the number of α-cells in the islet core. Morphometric analyses found increased islet size, number of islets and glucagon-positive area, but a decreased insulin-positive area, in the biotin-deficient group. Glucagon secretion and gene expression increased in islets isolated from biotin-deficient mice. Our results suggest that biotin deficiency promotes hyperglycemic mechanisms such as increased glucagon concentration and decreased insulin secretion and sensitivity to compensate for reduced blood glucose concentrations. Variations in glucose homeostasis may participate in the changes observed in pancreatic islets.

Pyridoxal-5'-phosphate-dependent enzymes involved in biotin biosynthesis: structure, reaction mechanism and inhibition.
            (Mann and Ploux, 2011) Download
The four last steps of biotin biosynthesis, starting from pimeloyl-CoA, are conserved among all the biotin-producing microorganisms. Two enzymes of this pathway, the 8-amino-7-oxononanoate synthase (AONS) and the 7,8-diaminopelargonic acid aminotransferase (DAPA AT) are dependent on pyridoxal-5'-phosphate (PLP). This review summarizes our current understanding of the structure, reaction mechanism and inhibition on these two interesting enzymes. Mechanistic studies as well as the determination of the crystal structure of AONS have revealed a complex mechanism involving an acylation with inversion of configuration and a decarboxylation with retention of configuration. This reaction mechanism is shared by the homologous 5-aminolevulinate synthase and serine palmitoyltransferase. While the reaction catalyzed by DAPA AT is a classical PLP-dependent transamination, the inactivation of this enzyme by amiclenomycin, a natural antibiotic that is active against Mycobacterium tuberculosis, involves the irreversible formation of an adduct between PLP and amiclenomycin. Mechanistic and structural studies allowed the complete description of this unique inactivation mechanism. Several potent inhibitors of these two PLP-dependent enzymes have been prepared and might be useful as starting points for the design of herbicides or antibiotics. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology.

Generalized seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients.
            (Messaritakis et al., 1975) Download
Twenty-five infants with generalized seborrhoeic dermatitis have been studied with reference to the provision of optimum treatment. Leucocyte counts and chest x-ray examination are recommended in every case. Irrespective of clinical findings, antibiotics should be given to patients with overt bacterial infection and those with leucocytosis, shift to the left, and toxic granulation. One group of infants was treated with vitamin B complex plus biotin given slowly intravenously over 24 hours; a second group was given only biotin intravenously over 2-3 hours; and a third group only biotin over 1-2 minutes. A fourth group was treated with both biotin and antibiotics for confirmed or suspected superimposed bacterial infection. The results were excellent in all groups. Skin lesions improved within 4-8 days and cleared completely within 15-30 days. Intravenous administration of biotin is recommended as less painful and less dangerous than multiple intramuscular injections.

Biotin ameliorates muscle cramps of hemodialysis patients: a prospective trial.
            (Oguma et al., 2012) Download
Patients with renal failure undergoing hemodialysis often have muscle cramps during and after the dialysis therapy. Muscle cramps are defined as the sudden onset of a prolonged involuntary muscle contraction accompanied with severe pain, resulting in early termination of a HD session and inadequate dialysis. The etiology of the cramps is unknown and effective anti-cramp medicine is not available. We have hypothesized that water-soluble vitamins are deficient in HD patients. Accordingly, we administrated biotin to 14 patients who had frequent muscle cramps during HD sessions. Oral administration of 1 mg/day biotin promptly reduced the onset and the severity of cramps in 12 patients both during and after HD. Then, the plasma biotin levels were measured by an enzyme-linked immunosorbent assay method (ELISA) in HD patients, including 14 patients with cramps and 13 patients without cramps, and 11 healthy volunteers. Plasma biotin levels were elevated in 27 HD patients at baseline compared with healthy volunteers [451 (377 - 649) vs. 224 (148 - 308) ng/l, median (lower-upper quartiles); p < 0.0001]. Unexpectedly, among the 14 cramp patients, the biotin levels were significantly higher in biotin-ineffective 7 patients than biotin-effective 7 patients [1,064 (710 - 1,187) vs. 445 (359 - 476) ng/l; p < 0.001]. Thus, the biotins measured by ELISA may consist of not only intact biotin but also its metabolites that do not function as a vitamin. In conclusion, biotin administration is one choice to relieve HD patients from muscle cramps regardless of their elevated plasma biotin levels.

 

Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia.
            (Revilla-Monsalve et al., 2006) Download
Biotin is a water-soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism. Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects. Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days. Plasma samples obtained at baseline and after treatment were analyzed for total triglyceride, cholesterol, very low density lipoprotein (VLDL), glucose and insulin. We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group. Biotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects. We conclude that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia.

High doses of biotin in chronic progressive multiple sclerosis: a pilot study.
            (Sedel et al., 2015a) Download
BACKGROUND:  No drug has been found to have any impact on progressive multiple sclerosis (MS). Biotin is a vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially rate-limiting enzyme in myelin synthesis. OBJECTIVES:  The aim of this pilot study is to assess the clinical efficacy and safety of high doses of biotin in patients suffering from progressive MS. STUDY DESIGN:  Uncontrolled, non-blinded proof of concept study METHODS:  23 consecutive patients with primary and secondary progressive MS originated from three different French MS reference centers were treated with high doses of biotin (100-300mg/day) from 2 to 36 months (mean=9.2 months). Judgement criteria varied according to clinical presentations and included quantitative and qualitative measures. RESULTS:  In four patients with prominent visual impairment related to optic nerve injury, visual acuity improved significantly. Visual evoked potentials in two patients exhibited progressive reappearance of P100 waves, with normalization of latencies in one case. Proton magnetic resonance spectroscopy (H-MRS) in one case showed a progressive normalization of the Choline/Creatine ratio. One patient with left homonymous hemianopia kept on improving from 2 to 16 months following treatment׳s onset. Sixteen patients out of 18 (89%) with prominent spinal cord involvement were considered as improved as confirmed by blinded review of videotaped clinical examination in 9 cases. In all cases improvement was delayed from 2 to 8 months following treatment׳s onset. CONCLUSIONS:  These preliminary data suggest that high doses of biotin might have an impact on disability and progression in progressive MS. Two double-blind placebo-controlled trials are on going.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.
            (Sedel et al., 2015b) Download
Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production.


 

The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial.
            (Singer and Geohas, 2006) Download
BACKGROUND:  Preclinical studies have shown that the combination of chromium picolinate and biotin significantly enhances glucose uptake in skeletal muscle cells and enhances glucose disposal. The present pilot study was conducted to determine if supplementation with chromium picolinate and biotin can improve glycemic control in patients with type 2 diabetes mellitus with suboptimal glycemic control despite use of oral antihyperglycemic agents. METHODS:  Forty-three subjects with impaired glycemic control (2-h glucose >200 mg/dL; glycated hemoglobin >or=7%), despite treatments with oral antihyperglycemic agents, were randomized to receive 600 microg of chromium as chromium picolinate and biotin (2 mg/day) (Diachrome(, Nutrition 21, Inc., Purchase, NY) in addition to their prestudy oral antihyperglycemic agent therapy. Measurements of glycemic control and blood lipids were taken at baseline and after 4 weeks. RESULTS:  After 4 weeks, there was a significantly greater reduction in the total area under the curve for glucose during the 2-h oral glucose tolerance test for the treatment group (mean change -9.7%) compared with the placebo group (mean change +5.1%, P < 0.03). Significantly greater reductions were also seen in fructosamine (P < 0.03), triglycerides (P < 0.02), and triglycerides/ high-density lipoprotein cholesterol ratio (P < 0.05) in the treatment group. No significant adverse events were attributed to chromium picolinate and biotin supplementation. CONCLUSIONS:  This pilot study demonstrates that supplementation with a combination of chromium picolinate and biotin in poorly controlled patients with diabetes receiving antidiabetic therapy improved glucose management and several lipid measurements. Chromium picolinate/ biotin supplementation may represent an effective adjunctive nutritional therapy to people with poorly controlled diabetes with the potential for improving lipid metabolism.

Serum Biotin Levels in Women Complaining of Hair Loss.
            (Trüeb, 2016) Download
Biotin is a coenzyme for carboxylase enzymes that assist various metabolic reactions involved in fatty acid synthesis, branched-chain amino acid catabolism, and gluconeogenesis important for maintenance of healthy skin and hair. Due to its availability, affordability, and effective marketing for this purpose, biotin is a popular nutritional supplement for treatment of hair loss. However, there are little data on the frequency of biotin deficiency in patients complaining of hair loss and on the value of oral biotin for treatment of hair loss that is not due to an inborn error of biotin metabolism or deficiency. The aim of this study was to determine the frequency and significance of biotin deficiency in women complaining of hair loss. Biotin deficiency was found in 38% of women complaining of hair loss. Of those showing diffuse telogen effluvium in trichograms (24%), 35% had evidence of associated seborrheic-like dermatitis. About 11% of patients with biotin deficiency had a positive personal history for risk factors for biotin deficiency. The custom of treating women complaining of hair loss in an indiscriminate manner with oral biotin supplementation is to be rejected, unless biotin deficiency and its significance for the complaint of hair loss in an individual has been demonstrated on the basis of a careful patient history, clinical examination, determination of serum biotin levels, and exclusion of alternative factors responsible for hair loss.

 


References

Albarracin, CA, et al. (2008), ‘Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes.’, Diabetes Metab Res Rev, 24 (1), 41-51. PubMed: 17506119
Ghosal, A, TV Sekar, and HM Said (2014), ‘Biotin uptake by mouse and human pancreatic beta cells/islets: a regulated, lipopolysaccharide-sensitive carrier-mediated process.’, Am J Physiol Gastrointest Liver Physiol, 307 (3), G365-73. PubMed: 24904078
Kuroishi, T (2015), ‘Regulation of immunological and inflammatory functions by biotin.’, Can J Physiol Pharmacol, 93 (12), 1091-96. PubMed: 26168302
Larrieta, E, et al. (2012), ‘Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis.’, J Nutr Biochem, 23 (4), 392-99. PubMed: 21596550
Mann, S and O Ploux (2011), ‘Pyridoxal-5’-phosphate-dependent enzymes involved in biotin biosynthesis: structure, reaction mechanism and inhibition.’, Biochim Biophys Acta, 1814 (11), 1459-66. PubMed: 21182990
Messaritakis, J, et al. (1975), ‘Generalized seborrhoeic dermatitis. Clinical and therapeutic data of 25 patients.’, Arch Dis Child, 50 (11), 871-74. PubMed: 129036
Oguma, S, et al. (2012), ‘Biotin ameliorates muscle cramps of hemodialysis patients: a prospective trial.’, Tohoku J Exp Med, 227 (3), 217-23. PubMed: 22791079
Revilla-Monsalve, C, et al. (2006), ‘Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in nondiabetic subjects with hypertriglyceridemia.’, Biomed Pharmacother, 60 (4), 182-85. PubMed: 16677798
Sedel, F, et al. (2015a), ‘High doses of biotin in chronic progressive multiple sclerosis: a pilot study.’, Mult Scler Relat Disord, 4 (2), 159-69. PubMed: 25787192
Sedel, F, et al. (2015b), ‘Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.’, Neuropharmacology, PubMed: 26327679
Singer, GM and J Geohas (2006), ‘The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial.’, Diabetes Technol Ther, 8 (6), 636-43. PubMed: 17109595
Trüeb, RM (2016), ‘Serum Biotin Levels in Women Complaining of Hair Loss.’, Int J Trichology, 8 (2), 73-77. PubMed: 27601860