A preclinical study to determine the anti-epileptic effect of biotin on maximal electroshock (MES) and pentylenetetrazole (PTZ) models in albino rats.

OBJECTIVES: Vitamin B7(biotin) is not synthesized in our body and is retrieved from some food products like eggs, liver, pork and leafy vegetables and as well as microbes of gut. Deficiency of biotin majorly leads to loss of hair, rashes over skin, lethargy and seizures. It is noted that biotin is an anti-oxidant and negates free radical effects. Biotin is also involved in carbon dioxide metabolism and it might alter seizure threshold. Studies also suggest its effect on lipid metabolism as well. So, the primary objective of this study was to assess the efficacy of biotin in maximal electric shock (MES) induced generalized tonic-clonic seizures (GTCS) and pentylenetetrazole (PTZ) induced absence seizures. The secondary objective is to study the effect of combined treatment of biotin and sodium valproate on seizures as well as plasma lipid profile in rats. METHODS: In our study 30 albino Wistar rats each were used in MES and PTZ model respectively. 30 rats were divided equally into following groups: I - distilled water (negative control) II - distilled water (positive control) III - sodium valproate (300 mg/kg) IV - biotin (10 mg/kg/day) V - biotin (10 mg/kg) + sodium valproate (150 mg/kg). RESULTS: We observed that the tonic hind limb extension was significantly reduced in the treatment group in MES model. Nitric oxide levels were also seen raised in combination group in MES model and all the treated groups in PTZ model. Biotin treated group showed increased high-density lipoproteins and reduced low density lipoproteins and triglycerides. CONCLUSIONS: Biotin had an additive effect to sodium valproate in both the models of epilepsy in rats. Further, it was also able to counteract hyperlipidemia cause by sodium valproate.

Co-cultures of Propionibacterium freudenreichii and Bacillus amyloliquefaciens cooperatively upgrade sunflower seed milk to high levels of vitamin B12 and multiple co-benefits.

BACKGROUND: Sunflower seeds (Helianthus annuus) display an attractive source for the rapidly increasing market of plant-based human nutrition. Of particular interest are press cakes of the seeds, cheap residuals from sunflower oil manufacturing that offer attractive sustainability and economic benefits. Admittedly, sunflower seed milk, derived therefrom, suffers from limited nutritional value, undesired flavor, and the presence of indigestible sugars. Of specific relevance is the absence of vitamin B12. This vitamin is required for development and function of the central nervous system, healthy red blood cell formation, and DNA synthesis, and displays the most important micronutrient for vegans to be aware of. Here we evaluated the power of microbes to enrich sunflower seed milk nutritionally as well as in flavor. RESULTS: Propionibacterium freudenreichii NCC 1177 showed highest vitamin B12 production in sunflower seed milk out of a range of food-grade propionibacteria. Its growth and B12 production capacity, however, were limited by a lack of accessible carbon sources and stimulants of B12 biosynthesis in the plant milk. This was overcome by co-cultivation with Bacillus amyloliquefaciens NCC 156, which supplied lactate, amino acids, and vitamin B7 for growth of NCC 1177 plus vitamins B2 and B3, potentially supporting vitamin B12 production by the Propionibacterium. After several rounds of optimization, co-fermentation of ultra-high-temperature pre-treated sunflower seed milk by the two microbes, enabled the production of 17 µg (100 g)-1 vitamin B12 within four days without any further supplementation. The fermented milk further revealed significantly enriched levels of L-lysine, the most limiting essential amino acid, vitamin B3, vitamin B6, improved protein quality and flavor, and largely eliminated indigestible sugars. CONCLUSION: The fermented sunflower seed milk, obtained by using two food-grade microbes without further supplementation, displays an attractive, clean-label product with a high level of vitamin B12 and multiple co-benefits. The secret of the successfully upgraded plant milk lies in the multifunctional cooperation of the two microbes, which were combined, based on their genetic potential and metabolic signatures found in mono-culture fermentations. This design by knowledge approach appears valuable for future development of plant-based milk products.

The Effectiveness of Biotin (Vitamin B7) Added to the Diet in Improving the Efficiency of Productivity, and Some Physiological Traits for Broiler Chickens (Ross-308) Exposed to Oxidative Stress.

Biotin (B7) acts as an antioxidant, as it inhibits the effect of many free radicals that are naturally formed within the organism's body. This study aimed to determine the effect of adding different concentrations of biotin to the diet of broilers exposed to oxidative stress in improving productive and physiological performance. 180 unsexed Ross-308 one-day age chicks of broiler chickens were used, and they were reared together until 7 days. Then the chicks were randomly distributed into 5 treatments; each treatment included 3 replicates, 12 chicks for each replicate. Oxidative stress was induced by adding 0.5% H2O2 to drinking water. The first treatment, T1 (control), was free from adding B7 or H2O2, and the second treatment (T2): was a positive control treatment free from adding vitamin B7 + water added to it H2O2 at an average of 0.5%. The third treatment (T3): adding 550 micrograms of B7/kg of feed + water added H2O2 at an average of 0.5%. Fourth treatment (T4): 650 micrograms/kg vitamin B7 + water with 0.5% H2O2 added on average. Fifth treatment (T5): 750 micrograms of vitamin B7/kg of feed + 0.5% H2O2 added to the water. The results of adding vitamin B7 to the diet of T4 and T5 birds exposed to oxidative stress showed a significant increase (P<0.05) in the average live body weight, total weight gain and cumulative feed consumption average, and the best cumulative feed conversion ratio for treated birds (T3, T4, T5). In comparison to the other therapies, all additional vitamin B7 treatments demonstrated a significant decrease (P<0.05) in the concentrations of glucose, cholesterol, triglycerides, as well as Malondialdehyde (MDA), and low-density lipoproteins (LDL) and a significant increase (P<0.05) in the concentrations of high-density lipoproteins (HDL) and total protein. The concentration of glutathione peroxidase (GSH-Px) was significantly elevated (P<0.05) in the serum of T5-treated birds compared to all other treatments. We conclude that adding vitamin B7 in different concentrations improved the productivity and some physiological traits of broilers exposed to the induced oxidative stress compared with the negative and positive control treatments.

Association between Serum Biotin Levels and Cedar Pollinosis in Japanese Schoolchildren.

Biotin is a water-soluble B complex vitamin and coenzyme of five types of carboxylase and plays crucial roles in fatty acid, glucose, and amino acid metabolism. Nutritional biotin deficiency and defective enzymes essential for biotin metabolism cause inflammatory diseases such as eczema-like dermatitis and Crohn's disease; however, little is known about the pathophysiological roles of biotin. This study investigated the relationship between biotin metabolism and human allergic sensitization and diseases by measuring serum levels of biotin, total immunoglobulin E (IgE) and allergen-specific IgEs in more than 400 Japanese schoolchildren aged 6 to 12. The prevalence of allergic diseases, and environmental and life-style factors were also examined by a questionnaire. Like total IgE, serum biotin levels of children showed a log-normal distribution. Meanwhile, Spearman's rank correlation analysis showed weak but significant positive associations between serum biotin levels and total IgE (rho=0.147, p=0.0029) as well as allergen-specific IgEs against egg whites (rho=0.215, p=0.00013), cedar pollen (rho=0.176, p=0.00036), and cat dander (rho=0.130, p=0.0085). Furthermore, mean serum biotin levels in children with cedar pollinosis, but not with other allergic diseases such as asthma and allergic rhinitis, were significantly higher than in those without (p=0.0015). These results suggest a correlation between serum biotin levels and the development of cedar pollinosis. Further prospective studies are needed to evaluate the causal relationship between biotin metabolism and cedar pollen sensitization and pollinosis development.

Engineering oxygen-independent biotin biosynthesis in Saccharomyces cerevisiae.

An oxygen requirement for de novo biotin synthesis in Saccharomyces cerevisiae precludes the application of biotin-prototrophic strains in anoxic processes that use biotin-free media. To overcome this issue, this study explores introduction of the oxygen-independent Escherichia coli biotin-biosynthesis pathway in S. cerevisiae. Implementation of this pathway required expression of seven E. coli genes involved in fatty-acid synthesis and three E. coli genes essential for the formation of a pimelate thioester, key precursor of biotin synthesis. A yeast strain expressing these genes readily grew in biotin-free medium, irrespective of the presence of oxygen. However, the engineered strain exhibited specific growth rates 25% lower in biotin-free media than in biotin-supplemented media. Following adaptive laboratory evolution in anoxic cultures, evolved cell lines that no longer showed this growth difference in controlled bioreactors, were characterized by genome sequencing and proteome analyses. The evolved isolates exhibited a whole-genome duplication accompanied with an alteration in the relative gene dosages of biosynthetic pathway genes. These alterations resulted in a reduced abundance of the enzymes catalyzing the first three steps of the E. coli biotin pathway. The evolved pathway configuration was reverse engineered in the diploid industrial S. cerevisiae strain Ethanol Red. The resulting strain grew at nearly the same rate in biotin-supplemented and biotin-free media non-controlled batches performed in an anaerobic chamber. This study established an unique genetic engineering strategy to enable biotin-independent anoxic growth of S. cerevisiae and demonstrated its portability in industrial strain backgrounds.

Biotin Deficiency in Telogen Effluvium: Fact or Fiction?

BACKGROUND: Biotin is popular in hair loss treatment supplements, although the frequency of its deficiency in patients with hair loss has not been established. OBJECTIVES: This work sought to assess the serum levels of biotin in patients with telogen effluvium. METHODS: This case-control study included 60 patients with telogen effluvium and 20 control subjects. Subjects who were on biotin therapy three months prior to the study and those reporting other causes of hair loss were excluded. The scalp of each patient was clinically and dermoscopically examined. Serum biotin levels were measured using enzyme-linked immunosorbent assay kits. RESULTS: Serum levels of biotin were optimal in patients and control groups with no significant difference between the groups. Insignificantly lower biotin levels in elderly patients, smokers, athletes, those with a history of recurrent infections, and women who were pregnant and/or lactating were observed. There was also an insignificant positive correlation between the serum level of biotin and patient age and an insignificant negative correlation between disease duration and patient body mass index. Serum biotin has a weak specificity and sensitivity in differentiating between cases and control subjects or between acute and chronic telogen effluvium. CONCLUSION: There was no significant difference in serum biotin levels between cases and controls or between those with acute or chronic telogen effluvium.

Exploiting the Diversity of Saccharomycotina Yeasts To Engineer Biotin-Independent Growth of Saccharomyces cerevisiae.

Biotin, an important cofactor for carboxylases, is essential for all kingdoms of life. Since native biotin synthesis does not always suffice for fast growth and product formation, microbial cultivation in research and industry often requires supplementation of biotin. De novo biotin biosynthesis in yeasts is not fully understood, which hinders attempts to optimize the pathway in these industrially relevant microorganisms. Previous work based on laboratory evolution of Saccharomyces cerevisiae for biotin prototrophy identified Bio1, whose catalytic function remains unresolved, as a bottleneck in biotin synthesis. This study aimed at eliminating this bottleneck in the S. cerevisiae laboratory strain CEN.PK113-7D. A screening of 35 Saccharomycotina yeasts identified six species that grew fast without biotin supplementation. Overexpression of the S. cerevisiaeBIO1 (ScBIO1) ortholog isolated from one of these biotin prototrophs, Cyberlindnera fabianii, enabled fast growth of strain CEN.PK113-7D in biotin-free medium. Similar results were obtained by single overexpression of C. fabianii BIO1 (CfBIO1) in other laboratory and industrial S. cerevisiae strains. However, biotin prototrophy was restricted to aerobic conditions, probably reflecting the involvement of oxygen in the reaction catalyzed by the putative oxidoreductase CfBio1. In aerobic cultures on biotin-free medium, S. cerevisiae strains expressing CfBio1 showed a decreased susceptibility to contamination by biotin-auxotrophic S. cerevisiae This study illustrates how the vast Saccharomycotina genomic resources may be used to improve physiological characteristics of industrially relevant S. cerevisiaeIMPORTANCE The reported metabolic engineering strategy to enable optimal growth in the absence of biotin is of direct relevance for large-scale industrial applications of S. cerevisiae Important benefits of biotin prototrophy include cost reduction during the preparation of chemically defined industrial growth media as well as a lower susceptibility of biotin-prototrophic strains to contamination by auxotrophic microorganisms. The observed oxygen dependency of biotin synthesis by the engineered strains is relevant for further studies on the elucidation of fungal biotin biosynthesis pathways.

Clinically Significant Lab Errors due to Vitamin B7 (Biotin) Supplementation: A Case Report Following a Recent FDA Warning.

A 67-year-old female with a past medical history of multiple endocrine issues presented for follow-up subsequent to abnormal routine blood testing results. These included low thyroid stimulating hormone (TSH), low parathyroid hormone (PTH), and mildly elevated calcium levels. The presence of hypercalcemia and accompanying low PTH raised the concern for malignancy, while the depressed TSH indicated hyperthyroidism. Review of the patient's medications revealed daily supplementation with 5 mg of vitamin B7 (biotin). The biotin was discontinued after suspecting the supplement was interfering with the patient's lab values. The labs were repeated one month later. The results showed normalized TSH, PTH, and calcium levels. The increasingly wide-spread use of biotin supplementation and the use of biotin as a component in many of the most common clinical assays has led to a trend of lab errors due to biotin interference. While some physicians are aware of the possibility of skewed results, steps need to be taken to prevent misdiagnosis. This includes ensuring that information about this issue is more widely disseminated, accurately accounting for a patient's supplement use, reconciling proper clinical correlation with lab results, and promptly reporting when biotin is determined to be the cause of otherwise unexplained lab errors.

Effect of biotin supplementation on milk yield of Girolando cows reared in a tropical climate.

The objective of this study was to evaluate the effect of biotin supplementation on milk yield and the reproductive efficiency in Girolando cows. The study was conducted on a dairy farm located in central Brazil, between April 2012 and December 2016. Thirty-six Girolando cows in their first lactation were used. The cows were distributed in two treatment groups, each with equivalent weight distributions. Control treatment (CT) cows (n = 18) received a diet without any supplemental biotin, whereas biotin treatment (BT) cows (n = 18) received a diet supplemented with 20 mg/day of biotin during lactation. Biotin supplementation caused a significant increase (p = 0.001) in milk yield in the second lactation, and a trend (p = 0.09) toward higher average production during the three lactations was evaluated. There was no statistically significant difference between the treatments in terms of reproductive efficiency. In conclusion, biotin supplementation (20 mg/day) during lactation for Girolando cows reared in a tropical climate is able to increase milk yield, but does not improve reproductive efficiency.