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International Journal of Molecular... Jan 2020Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical... (Review)
Review
Riboflavin (RF) is a water-soluble member of the B-vitamin family. Sufficient dietary and supplemental RF intake appears to have a protective effect on various medical conditions such as sepsis, ischemia etc., while it also contributes to the reduction in the risk of some forms of cancer in humans. These biological effects of RF have been widely studied for their anti-oxidant, anti-aging, anti-inflammatory, anti-nociceptive and anti-cancer properties. Moreover, the combination of RF and other compounds or drugs can have a wide variety of effects and protective properties, and diminish the toxic effect of drugs in several treatments. Research has been done in order to review the latest findings about the link between RF and different clinical aberrations. Since further studies have been published in this field, it is appropriate to consider a re-evaluation of the importance of RF in terms of its beneficial properties.
Topics: Animals; Dietary Supplements; Drug Interactions; Functional Food; Humans; Riboflavin; Vitamin B Complex
PubMed: 32023913
DOI: 10.3390/ijms21030950 -
Advanced Science (Weinheim,... Apr 2023Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2)...
Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates cognitive impairment via anti-oxidative stress and anti-inflammation properties; however, the underlying mechanisms linking riboflavin metabolism and microglial function in cognitive impairment remain unclear. Here, it is demonstrated that riboflavin kinase (RFK), a critical enzyme in riboflavin metabolism, is specifically expressed in microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression via regulation of lysine-specific methyltransferase 2B (KMT2B). FMN supplementation attenuated the pro-inflammatory TNFR1/NF-κB signaling pathway, and this effect is abolished by KMT2B overexpression. To improve the limited anti-inflammatory efficiency of free FMN, a biomimetic microglial nanoparticle strategy (designated as MNPs@FMN) is established, which penetrated the blood brain barrier with enhanced microglial-targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide-induced inflammatory mouse model and in a 5xFAD mouse model of Alzheimer's disease. Taken together, biomimetic microglial delivery of FMN may serve as a potential therapeutic approach for inflammation-dependent cognitive decline.
Topics: Mice; Animals; Microglia; Neuroinflammatory Diseases; Biomimetics; Riboflavin; Cognitive Dysfunction
PubMed: 36799538
DOI: 10.1002/advs.202300180 -
Cornea Oct 2022When treating corneal ectasias, successful corneal cross-linking (CXL) requires three factors: riboflavin saturation of the corneal stroma, ultraviolet (UV) light, and...
When treating corneal ectasias, successful corneal cross-linking (CXL) requires three factors: riboflavin saturation of the corneal stroma, ultraviolet (UV) light, and oxygen. Riboflavin is too large to pass through epithelial tight junctions, so traditionally epithelial debridement is performed before riboflavin is applied making this approach an epithelium-off (epi-off) technique. However, this can result in pain as the epithelium regrows, corneal haze, and an increased infection risk postoperatively, which needs careful management with pharmacotherapy. Epithelium-on (epi-on) CXL should reduce the extent of these issues. Riboflavin can be passed through the epithelium into the stroma either by iontophoresis or with penetration enhancers, however this alone results in suboptimal cross-linking effects, as the epithelium not only absorbs around 20% of incoming UV energy, it also acts as a barrier to oxygen diffusion into the stroma. While it is simple to adjust the UV fluence delivered to the stroma to compensate for the energy lost in the epithelium, compensating for the lack of stromal oxygen is less simple. Several approaches (including oxygen goggles) have been taken to achieve this. However, adding iontophoresis and supplemental oxygen through goggles in the operating theater adds complexities that could be engineered out. Accordingly, the technique has advanced in the laboratory to a point where penetration enhancers, optimized UV irradiation profiles, and atmospheric oxygen can now provide epi-on CXL with the same corneal strengthening efficacy as epi-off CXL, suggesting simple, effective epi-on CXL could soon be in clinical use.
Topics: Cross-Linking Reagents; Humans; Keratoconus; Oxygen; Photosensitizing Agents; Riboflavin
PubMed: 36107842
DOI: 10.1097/ICO.0000000000003075 -
Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis.Nutritional Neuroscience Sep 2022Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Migraine is a common disease worldwide and migraine prevention is primarily currently based on pharmaceuticals. The mechanism of Vitamin B2 may positively contribute to migraine. This systematic review and meta-analysis aimed to evaluate the impact of Vitamin B2 supplementation on the days, duration, frequency, and pain score of the migraine attack.
METHODS
: The PRISMA guideline was used for the studying process. Five electronic databases, PubMed, Embase, Cochrane, CINAHL, and CEPS were searched from 1990 to March 2019. The search terms were Vitamin B2, migraine, and prophylactic. A meta-analysis was performed using Comprehensive Meta-Analysis (CMA) version.
RESULTS
: Nine articles were included in systemic review and finally meta-analysis. Eight randomized controlled trials and one controlled clinical trial with 673 subjects were analyzed using meta-analysis. Vitamin B2 supplementation significantly decreased migraine days (= .005, = 89%), duration (= .003, = 0), frequency (= .001, = 65%), and pain score (= .015, = 84%).
CONCLUSIONS
A pooled analysis of available randomized controlled clinical trials demonstrated that Vitamin B2 400 mg/day for three months supplementation had significant effect on days, duration, frequency, and pain score of migraine attacks.
Topics: Dietary Supplements; Humans; Migraine Disorders; Pain; Randomized Controlled Trials as Topic; Riboflavin
PubMed: 33779525
DOI: 10.1080/1028415X.2021.1904542 -
Clinical Drug Investigation Jun 2021Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD)... (Review)
Review
Riboflavin is classified as one of the water-soluble B vitamins. It is part of the functional group of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) cofactors and is required for numerous flavoprotein-catalysed reactions. Riboflavin has important antioxidant properties, essential for correct cell functioning. It is required for the conversion of oxidised glutathione to the reduced form and for the mitochondrial respiratory chain as complexes I and II contain flavoprotein reductases and electron transferring flavoproteins. Riboflavin deficiency has been demonstrated to impair the oxidative state of the body, especially in relation to lipid peroxidation status, in both animal and human studies. In the nervous system, riboflavin is essential for the synthesis of myelin and its deficiency can determine the disruption of myelin lamellae. The inherited condition of restricted riboflavin absorption and utilisation, reported in about 10-15% of world population, warrants further investigation in relation to its association with the main neurodegenerative diseases. Several successful trials testing riboflavin for migraine prevention were performed, and this drug is currently classified as a Level B medication for migraine according to the American Academy of Neurology evidence-based rating, with evidence supporting its efficacy. Brown-Vialetto-Van Laere syndrome and Fazio-Londe diseases are now renamed as "riboflavin transporter deficiency" because these are autosomal recessive diseases caused by mutations of SLC52A2 and SLC52A3 genes that encode riboflavin transporters. High doses of riboflavin represent the mainstay of the therapy of these diseases and high doses of riboflavin should be rapidly started as soon as the diagnosis is suspected and continued lifelong. Remarkably, some mitochondrial diseases respond to supplementation with riboflavin. These include multiple acyl-CoA-dehydrogenase deficiency (which is caused by ETFDH gene mutations in the majority of the cases, or mutations in the ETFA and ETFB genes in a minority), mutations of ACAD9 gene, mutations of AIFM1 gene, mutations of the NDUFV1 and NDUFV2 genes. Therapeutic riboflavin administration has been tried in other neurological diseases, including stroke, multiple sclerosis, Friedreich's ataxia and Parkinson's disease. Unfortunately, the design of these clinical trials was not uniform, not allowing to accurately assess the real effects of this molecule on the disease course. In this review we analyse the properties of riboflavin and its possible effects on the pathogenesis of different neurological diseases, and we will review the current indications of this vitamin as a therapeutic intervention in neurology.
Topics: Animals; Bulbar Palsy, Progressive; Electron-Transferring Flavoproteins; Hearing Loss, Sensorineural; Humans; Membrane Transport Proteins; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Mutation; Nervous System Diseases; Riboflavin
PubMed: 33886098
DOI: 10.1007/s40261-021-01038-1 -
Journal Francais D'ophtalmologie Dec 2020Since two decades, corneal crosslinking (CXL) has been proposed as the sole therapeutic option to halt progression of keratoconus or other ectatic diseases. CXL aims at... (Review)
Review
Since two decades, corneal crosslinking (CXL) has been proposed as the sole therapeutic option to halt progression of keratoconus or other ectatic diseases. CXL aims at stiffening the cornea using a combination of ultraviolet-A light and a chromophore (vitamin B2, riboflavin), and has been proposed in various indications, from progressive ectatic diseases to corneal infection. Despite being in clinical use for many years, many controversies and discrepancies exist towards CXL procedure and its exact role is still under debate. We report an up-to-date review of the state of the art of CXL and describe the basic principles, the different existing CXL techniques reporting basic and clinical evidence, as well as the new perspectives and the possible future developments of the procedure.
Topics: Collagen; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays; Ultraviolet Therapy
PubMed: 32972759
DOI: 10.1016/j.jfo.2020.07.002 -
Archives of Biochemistry and Biophysics Oct 2023The rapid resistance of pathogens to antibiotics has emerged as a major threat to global health. Identification of new antibiotic targets is thus needed for developing... (Review)
Review
The rapid resistance of pathogens to antibiotics has emerged as a major threat to global health. Identification of new antibiotic targets is thus needed for developing alternative drugs. Genes encoding enzymes involved in the biosynthesis of riboflavin and flavin cofactors (FMN/FAD) are attractive targets because these enzymatic reactions are necessary for most bacteria to synthesize flavin cofactors for use in their central metabolic reactions. Moreover, humans lack most of these enzymes because we uptake riboflavin from our diet. This review discusses the current knowledge of enzymes involved in bacterial biosynthesis of riboflavin and other flavin cofactors, as well as the functions of the FMN riboswitch. Here, we highlight recent progress in the structural and mechanistic characterization, and inhibition of GTP cyclohydrolase II (GCH II), lumazine synthase (LS), riboflavin synthase (RFS), FAD synthetase (FADS), and FMN riboswitch, which have been identified as plausible antibiotic targets. As the structures and functions of these enzymes and regulatory systems are not completely understood, they are attractive as subjects for future in-depth biochemical and biophysical analysis.
Topics: Humans; Anti-Bacterial Agents; Flavin Mononucleotide; Riboswitch; Riboflavin; Flavin-Adenine Dinucleotide
PubMed: 37739114
DOI: 10.1016/j.abb.2023.109762 -
Journal of Inherited Metabolic Disease Jul 2019Riboflavin (vitamin B2), a water-soluble vitamin, is an essential nutrient in higher organisms as it is not endogenously synthesised, with requirements being met... (Review)
Review
Riboflavin (vitamin B2), a water-soluble vitamin, is an essential nutrient in higher organisms as it is not endogenously synthesised, with requirements being met principally by dietary intake. Tissue-specific transporter proteins direct riboflavin to the intracellular machinery responsible for the biosynthesis of the flavocoenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). These flavocoenzymes play a vital role in ensuring the functionality of a multitude of flavoproteins involved in bioenergetics, redox homeostasis, DNA repair, chromatin remodelling, protein folding, apoptosis, and other physiologically relevant processes. Hence, it is not surprising that the impairment of flavin homeostasis in humans may lead to multisystem dysfunction including neuromuscular disorders, anaemia, abnormal fetal development, and cardiovascular disease. In this review, we provide an overview of riboflavin absorption, transport, and metabolism. We then focus on the clinical and biochemical features associated with biallelic FLAD1 mutations leading to FAD synthase deficiency, the only known primary defect in flavocoenzyme synthesis, in addition to providing an overview of clinical disorders associated with nutritional deficiency of riboflavin and primary defects of riboflavin transport. Finally, we give a brief overview of disorders of the cellular flavoproteome. Because riboflavin therapy may be beneficial in a number of primary or secondary disorders of the cellular flavoproteome, early recognition and prompt management of these disorders is imperative.
Topics: Animals; Biological Transport; Flavin-Adenine Dinucleotide; Homeostasis; Humans; Membrane Transport Proteins; Metabolic Networks and Pathways; Nucleotidyltransferases; Riboflavin
PubMed: 30680745
DOI: 10.1002/jimd.12058 -
Practical Neurology Mar 2024Strachan's syndrome comprises a triad of optic, auditory and painful sensory peripheral neuropathy. It has been recognised since the late 19th century and is presumed to... (Review)
Review
Strachan's syndrome comprises a triad of optic, auditory and painful sensory peripheral neuropathy. It has been recognised since the late 19th century and is presumed to result from nutritional deficiency. Patients present acute or subacutely after a period of systemic illness, weight loss or, most commonly, dietary restriction, especially veganism, which can cause riboflavin (vitamin B) and vitamin B deficiencies. The syndrome is more common in people who are black British and often of Jamaican descent. We describe the clinical phenotype using a typical case example, review other endemic nutritional peripheral neuropathies and discuss the potential benefit of riboflavin as a treatment.
Topics: Humans; Peripheral Nervous System Diseases; Riboflavin Deficiency; Optic Nerve Diseases; Riboflavin; Vitamins; Vitamin B 12 Deficiency
PubMed: 38290841
DOI: 10.1136/pn-2023-003822 -
Current Eye Research Feb 2023Corneal Crosslinking (CXL) strengthens the keratoconus cornea and prevents further disease progression. Modified crosslinking protocols and different riboflavin...
PURPOSE
Corneal Crosslinking (CXL) strengthens the keratoconus cornea and prevents further disease progression. Modified crosslinking protocols and different riboflavin solutions have been proposed to optimize the procedure and improve treatment success.
METHODS
PubMed research of relevant publications and report of own experiences with different CXL protocols.
RESULTS
Accelerated CXL shows comparable efficiency with shorter surgery time and similar complication rates. Customized CXL provides improved results with faster epithelial healing. CXL in a hyperoxic environment seems to be a safe and effective transepithelial alternative with presumably less complications and fewer side effects. Thin corneas (<400 µm) can be treated safely by corneal swelling using hypoosmolar riboflavin solutions and reducing the applied UV-energy. The combination of CXL with photorefractive keratectomy (PRK) can be considered in patients with contact lens intolerance improving visual acuity, however, with increased risk of visual loss compared to CXL alone. Two-Photon (2Ph) CXL is a promising new technology enabling three-dimensional CXL.
DISCUSSION
Recently developed CXL protocols offer advantages over the standard "Dresden-protocol" and should be considered in patients with progressive keratectasia.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Refraction, Ocular; Corneal Topography; Cornea; Riboflavin; Keratoconus; Cross-Linking Reagents; Ultraviolet Rays
PubMed: 36458595
DOI: 10.1080/02713683.2022.2146725