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What is Biotin?
Biotin, also known as vitamin B7 or vitamin H, is a water-soluble vitamin that plays a crucial role in various metabolic processes in both prokaryotic and eukaryotic organisms. It is an essential nutrient that must be obtained from the diet in humans and other animals, as they lack the ability to synthesize it de novo. Other names include: Biotina, Biotine, Biotine-D, Coenzyme R, D-Biotin, Vitamin B7, Vitamin H, Vitamine B7, Vitamine H, W Factor, Cis-hexahydro-2-oxo-1H-thieno[3,4-d]-imidazole-4-valeric Acid.
Biotin as a Coenzyme
Biotin functions primarily as a coenzyme for five carboxylases in humans, which are involved in critical metabolic pathways such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism1 2. These biotin-dependent carboxylases catalyze key reactions by transferring a carboxyl group between donor and acceptor molecules during carboxylation reactions2.
Biotin in Gene Regulation
Beyond its role as a coenzyme, biotin also influences gene regulation. It is covalently attached to distinct lysine residues in histones, affecting chromatin structure and mediating gene regulation1. Recent studies have shown that biotin can regulate the expression of holocarboxylase synthetase and mitochondrial carboxylases, indicating its broader role in genetic expression9.
Biotin Metabolism and Homeostasis
Biotin metabolism involves several key proteins, including holocarboxylase synthetase, biotinidase, and biotin transporters such as SMVT and MCT1, which are crucial for maintaining biotin homeostasis1. Inadequate biotin intake can lead to various health issues, including potential birth defects and neurological disorders1 2.
Biotin Biosynthesis in Microorganisms
While humans and animals must obtain biotin from their diet, many microorganisms, plants, and fungi can synthesize biotin de novo. This biosynthetic pathway is absent in mammals, making it an attractive target for antibiotic discovery, particularly against pathogens like Mycobacterium tuberculosis3 5. The biotin synthetic pathway is divided into early and late segments, with recent discoveries elucidating new bacterial pimelate synthesis pathways3.
Biotin in Biotechnology
Biotin is widely used in food, feed, and cosmetic products, creating a significant market demand. However, the chemical synthesis of biotin is environmentally burdensome, leading to efforts in developing biotin-overproducing microbes through biotechnological techniques6 7. Advances in metabolic engineering have enabled efficient microbial production of biotin, offering a sustainable alternative to chemical synthesis7.
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Uses of Biotin
Nail Health Improvement
Oral biotin supplementation has shown promising results in improving the firmness, hardness, and thickness of brittle nails, as well as in treating conditions like triangular worn down nails, trachyonychia, and habit tic nail deformity1.
Metabolic Regulation
Biotin acts as a coenzyme for carboxylases involved in key metabolic pathways such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism, thereby playing a vital role in maintaining metabolic homeostasis2 5 7.
Biotin supplementation has been found to significantly reduce plasma triacylglycerol and VLDL concentrations in both type 2 diabetic and nondiabetic subjects, suggesting its potential use in treating hypertriglyceridemia4 6 8.
Gene Expression and Enzyme Regulation
Biotin regulates gene expression beyond its role as a prosthetic group of carboxylases, influencing genes critical for intermediary metabolism, which may help in managing conditions like hyperglycemia and hyperlipidemia2 5 6 9.
It also affects the expression of holocarboxylase synthetase and mitochondrial carboxylases, indicating its role in modulating genetic expression related to its function as a cofactor9.
Biochemical Tool
Biotin is widely used in bioconjugation techniques to label proteins and DNA. The development of biotin redox-activated chemical tagging (BioReACT) has expanded its utility, enabling stable and predictable chemical conjugation to biomolecules3.
Potential in Antibiotic Development
Biotin biosynthesis is essential for the survival and virulence of Mycobacterium tuberculosis, making it a novel target for antibiotic development. Inhibiting biotin synthesis could lead to new treatments for tuberculosis10.
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Adverse Effects of Biotin
Interference with Diagnostic Tests
Biotin can cause falsely abnormal results in endocrine function tests, such as 25-hydroxyvitamin D and intact parathyroid hormone, particularly in patients with end-stage renal disease1.
Impact on Reproductive Health
High doses of biotin can impair testis morphology and sperm quality, including reduced sperm motility and altered sperm morphology, without affecting sperm count or testosterone levels4.
Growth and Development Issues
Excessive biotin administration in young rats led to decreased food intake and body weight gain, suggesting a need to establish a tolerable upper intake level for biotin7.
Acute high doses of biotin during pregnancy in rats inhibited fetal and placental growth and, in some cases, caused resorption of fetuses and placentae10.
Neurological Effects
In patients with progressive multiple sclerosis, high doses of biotin were well tolerated but did not show long-term benefits. Some patients experienced worsening symptoms, potentially due to increased metabolic demands on the injured central nervous system8.
Metabolic Effects
While biotin supplementation can decrease fasting blood glucose, total cholesterol, and triglycerides in patients with type 2 diabetes mellitus, its effects on other metabolic markers like insulin and glycated hemoglobin are inconclusive2.
Biotin supplementation in malnourished children showed variable effects on lymphocyte carboxylase activities, indicating that biotin deficiency might be rate-limiting in their nutritional homeostasis9.
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How has Biotin Improved Patient Outcomes?
Multiple Sclerosis (MS)
- Limited Efficacy in Progressive MS: High-dose biotin (MD1003) did not significantly improve disability or walking speed in patients with progressive MS, and it also posed risks of inaccurate laboratory results1 6 10.
- Potential Benefits in Subsets: Some studies indicated that a subset of patients with progressive MS experienced disability reversal and improved clinical impressions with high-dose biotin7 9.
- Visual Function: High-dose biotin showed no significant improvement in visual acuity in MS patients with chronic visual loss, although there was a non-significant trend favoring biotin in patients with progressive optic neuropathy6.
- Mechanistic Insights: High-dose biotin may restore redox balance, energy, and lipid homeostasis, and improve axonal health in models of neurodegenerative diseases, suggesting potential underlying mechanisms for observed clinical benefits4.
Type 2 Diabetes Mellitus (T2DM)
- Glycemic Control: Biotin supplementation significantly decreased fasting blood glucose levels in patients with T2DM2 8.
- Lipid Profile: Biotin also reduced total cholesterol and triglyceride levels in T2DM patients, although its impact on other lipid parameters like LDL-C and HDL-C was inconclusive2.
- Insulin Levels: There was no significant effect of biotin on insulin levels in T2DM patients2 8.
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Biotin Mechanisms of Action
Role as a Cofactor for Carboxylases
Biotin acts as a prosthetic group for biotin-dependent carboxylases, facilitating carboxyl transfer reactions essential for gluconeogenesis, fatty acid synthesis, and amino acid catabolism1 2 4 7.
It is involved in the carboxylation of acetyl-CoA and other substrates, which is critical for fatty acid synthesis and other metabolic pathways2 4 7.
Gene Expression Regulation
Biotin regulates the expression of genes involved in intermediary metabolism, including those that influence glucose and lipid homeostasis1 5 8 9.
It increases the expression of glucokinase in pancreatic islets via soluble guanylate cyclase and protein kinase G pathways, leading to enhanced ATP production and insulin secretion7.
Biotin deficiency affects the mRNA levels of holocarboxylase synthetase and mitochondrial carboxylases, indicating its role in modulating genetic expression5.
Neurological and Metabolic Benefits
High-dose biotin has been shown to restore redox balance, energy, and lipid homeostasis, and improve axonal health in models of neurodegenerative diseases3.
It normalizes hyperactivation of mTORC1 signaling, thereby restoring lipid homeostasis in neurological conditions3.
Structural and Mechanistic Insights
Crystallographic studies reveal that biotin’s ureido moiety interacts with ions and polar molecules, facilitating its role in carboxyl transfer reactions6.
The carboxylation of biotin and its subsequent interactions with non-polar molecules are crucial for its function in enzymatic reactions6 8.
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Common Complaints Associated with Biotin Use
Hair Loss and Biotin Deficiency
A significant percentage of women complaining of hair loss were found to have biotin deficiency. However, the cause of hair loss in these cases was often multifactorial, including conditions like seborrheic dermatitis and the use of certain medications1 3.
Clinical Manifestations of Biotin Deficiency
Severe biotin deficiency can lead to dramatic clinical symptoms such as skin eruptions, alopecia, metabolic acidosis, and neurological issues. These symptoms are more commonly seen in genetically determined disorders like multiple carboxylase deficiency2.
Lack of Evidence for Biotin Efficacy in Healthy Individuals
There is a lack of evidence supporting the efficacy of biotin supplementation in healthy individuals without a diagnosed biotin deficiency. Most improvements in hair and nail growth have been observed in patients with established biotin deficiency3.
Immunoassay Interference
High doses of biotin can interfere with immunoassays, leading to falsely abnormal results in various blood tests, including thyroid function tests. This can result in misdiagnosis and inappropriate treatment if not recognized4.
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