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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 -
Nutrients Sep 2022The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized... (Review)
Review
The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B complex intake. Most studies examined such issues concerning a specific vitamin B or life stage, with the majority reporting the effect of either excess or deficiency. Deep insight into the orchestration of the eight different B vitamins requirements is reviewed across the human life cycle, beginning from fertility and pregnancy and reaching adulthood and senility, emphasizing interactions among them and underlying action mechanisms. The effect of sex is also reviewed for each vitamin at each life stage to highlight the different daily requirements and/or outcomes. Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one's overall health in adolescence and adulthood. A higher intake of B vitamins in the elderly is also associated with preventing some aging problems, especially those related to inflammation. All supplementation should be carefully monitored to avoid toxicity and hypervitaminosis. More research should be invested in studying each vitamin individually concerning nutritional disparities in each life stage, with extensive attention paid to cultural differences and lifestyles.
Topics: Adolescent; Adult; Aged; Child; Female; Folic Acid; Humans; Male; Niacin; Pantothenic Acid; Pregnancy; Pyridoxine; Riboflavin; Sex Characteristics; Thiamine; Vitamin B 12; Vitamin B Complex
PubMed: 36235591
DOI: 10.3390/nu14193940 -
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 -
Cell Reports Apr 2021Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at...
Ablation of Slc22a14 causes male infertility in mice, but the underlying mechanisms remain unknown. Here, we show that SLC22A14 is a riboflavin transporter localized at the inner mitochondrial membrane of the spermatozoa mid-piece and show by genetic, biochemical, multi-omic, and nutritional evidence that riboflavin transport deficiency suppresses the oxidative phosphorylation and reprograms spermatozoa energy metabolism by disrupting flavoenzyme functions. Specifically, we find that fatty acid β-oxidation (FAO) is defective with significantly reduced levels of acyl-carnitines and metabolites from the TCA cycle (the citric acid cycle) but accumulated triglycerides and free fatty acids in Slc22a14 knockout spermatozoa. We demonstrate that Slc22a14-mediated FAO is essential for spermatozoa energy generation and motility. Furthermore, sperm from wild-type mice treated with a riboflavin-deficient diet mimics those in Slc22a14 knockout mice, confirming that an altered riboflavin level causes spermatozoa morphological and bioenergetic defects. Beyond substantially advancing our understanding of spermatozoa energy metabolism, our study provides an attractive target for the development of male contraceptives.
Topics: Animals; Carnitine; Citric Acid Cycle; Diet; Fatty Acids; Female; Fertility; Fertilization in Vitro; Gene Expression; Humans; Infertility, Male; Male; Metabolome; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitochondria; Mitochondrial Membranes; Models, Molecular; Organic Cation Transport Proteins; Oxidative Phosphorylation; Riboflavin; Sperm Motility; Spermatozoa
PubMed: 33882315
DOI: 10.1016/j.celrep.2021.109025 -
Annual Review of Nutrition Aug 2023Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant... (Review)
Review
Riboflavin, in its cofactor forms flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), plays fundamental roles in energy metabolism, cellular antioxidant potential, and metabolic interactions with other micronutrients, including iron, vitamin B, and folate. Severe riboflavin deficiency, largely confined to low-income countries, clinically manifests as cheilosis, angular stomatitis, glossitis, seborrheic dermatitis, and severe anemia with erythroid hypoplasia. Subclinical deficiency may be much more widespread, including in high-income countries, but typically goes undetected because riboflavin biomarkers are rarely measured in human studies. There are adverse health consequences of low and deficient riboflavin status throughout the life cycle, including anemia and hypertension, that could contribute substantially to the global burden of disease. This review considers the available evidence on causes, detection, and consequences of riboflavin deficiency, ranging from clinical deficiency signs to manifestations associated with less severe deficiency, and the related research, public health, and policy priorities.
Topics: Humans; Riboflavin Deficiency; Riboflavin; Causality; Antioxidants; Bone Marrow Failure Disorders; Disease Progression; Lip Diseases
PubMed: 37603429
DOI: 10.1146/annurev-nutr-061121-084407 -
Frontiers in Immunology 2023Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell... (Review)
Review
Mucosal associated invariant T (MAIT) cells are innate-like T lymphocytes, strikingly enriched at mucosal surfaces and characterized by a semi-invariant αβ T cell receptor (TCR) recognizing microbial derived intermediates of riboflavin synthesis presented by the MHC-Ib molecule MR1. At barrier sites MAIT cells occupy a prime position for interaction with commensal microorganisms, comprising the microbiota. The microbiota is a rich source of riboflavin derived antigens required in early life to promote intra-thymic MAIT cell development and sustain a life-long population of tissue resident cells. A symbiotic relationship is thought to be maintained in health whereby microbes promote maturation and homeostasis, and in turn MAIT cells can engage a TCR-dependent "tissue repair" program in the presence of commensal organisms conducive to sustaining barrier function and integrity of the microbial community. MAIT cell activation can be induced in a MR1-TCR dependent manner or through MR1-TCR independent mechanisms pro-inflammatory cytokines interleukin (IL)-12/-15/-18 and type I interferon. MAIT cells provide immunity against bacterial, fungal and viral pathogens. However, MAIT cells may have deleterious effects through insufficient or exacerbated effector activity and have been implicated in autoimmune, inflammatory and allergic conditions in which microbial dysbiosis is a shared feature. In this review we summarize the current knowledge on the role of the microbiota in the development and maintenance of circulating and tissue resident MAIT cells. We also explore how microbial dysbiosis, alongside changes in intestinal permeability and imbalance between pro- and anti-inflammatory components of the immune response are together involved in the potential pathogenicity of MAIT cells. Whilst there have been significant improvements in our understanding of how the microbiota shapes MAIT cell function, human data are relatively lacking, and it remains unknown if MAIT cells can conversely influence the composition of the microbiota. We speculate whether, in a human population, differences in microbiomes might account for the heterogeneity observed in MAIT cell frequency across mucosal sites or between individuals, and response to therapies targeting T cells. Moreover, we speculate whether manipulation of the microbiota, or harnessing MAIT cell ligands within the gut or disease-specific sites could offer novel therapeutic strategies.
Topics: Humans; Mucosal-Associated Invariant T Cells; Histocompatibility Antigens Class I; Dysbiosis; Minor Histocompatibility Antigens; Receptors, Antigen, T-Cell; Riboflavin; Microbiota
PubMed: 36911683
DOI: 10.3389/fimmu.2023.1127588 -
Asia-Pacific Journal of Ophthalmology... Sep 2022Keratoconus is a progressive corneal thinning disorder that can lead to vision loss. In the last 2 decades, corneal crosslinking (CXL) has emerged as an effective method... (Review)
Review
Keratoconus is a progressive corneal thinning disorder that can lead to vision loss. In the last 2 decades, corneal crosslinking (CXL) has emerged as an effective method to halt the progression of keratoconus and reduce the number of patients requiring keratoplasty. The procedure has been adopted globally and has evolved to become a part of combination treatments to regularize the cornea and improve visual outcomes. CXL has even been extrapolated in managing other ocular pathologies such as progressive myopia, infectious keratitis, and bullous keratopathy. This review aims to summarize the current role of CXL in keratoconus and its alternative uses, and provide insights into future developments in this fast-developing field.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 36094381
DOI: 10.1097/APO.0000000000000557 -
The Ocular Surface Oct 2023Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia... (Review)
Review
Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia and Keratoconus. Some effects of the procedure such as induced mechanical stiffening, corneal flattening, and cellular toxicity are well-known, but others remain more controversial. Authors report a variety of contradictory effects, and provide evidence based on individual results and observations. A full understanding of the effects of and mechanisms behind this procedure are essential to predicting its outcome. A growing interest in modifications to the standard UVA CXL protocol, such as transepithelial or accelerated UVA CXL, makes analyzing the literature as a whole more urgent. This review presents an analysis of both the agreed-upon and contradictory results reported and the various methods used to obtain them.
Topics: Humans; Cornea; Ultraviolet Rays; Collagen; Riboflavin; Keratoconus; Cross-Linking Reagents; Photosensitizing Agents; Corneal Stroma
PubMed: 37683969
DOI: 10.1016/j.jtos.2023.09.003 -
The American Journal of Clinical... Feb 2023Thiamine and riboflavin deficiencies exist to varying degrees worldwide, especially in developing countries. Evidence regarding the association between thiamine and... (Clinical Trial)
Clinical Trial
BACKGROUND
Thiamine and riboflavin deficiencies exist to varying degrees worldwide, especially in developing countries. Evidence regarding the association between thiamine and riboflavin intake and gestational diabetes mellitus (GDM) is scarce.
OBJECTIVES
We aimed to evaluate the association of thiamine and riboflavin intake during pregnancy, including dietary source and supplementation, with GDM risk in a prospective cohort study.
METHODS
We included 3036 pregnant women (923 in the first trimester and 2113 in the second trimester) from the Tongji Birth Cohort. A validated semi-quantitative food frequency questionnaire and a lifestyle questionnaire were used to assess thiamine and riboflavin intake from dietary source and supplementation, respectively. GDM was diagnosed using the 75 g 2-h oral glucose tolerance test at 24-28 weeks of gestation. A modified Poisson regression or logistic regression model was used to evaluate the association between thiamine and riboflavin intake and GDM risk.
RESULTS
Dietary intake of thiamine and riboflavin was at low levels during pregnancy. In the fully adjusted model, compared with participants in quartile 1 (Q1), those who had more total thiamine and riboflavin intake had a lower risk of GDM during the first trimester [thiamine: Q2: RR: 0.58 (95% CI: 0.34, 0.98); Q3: RR: 0.45 (95% CI: 0.24, 0.84); Q4: RR: 0.35 (95% CI: 0.17, 0.72), P for trend = 0.002; riboflavin: Q2: RR: 0.63 (95% CI: 0.37, 1.09); Q3: RR: 0.45 (95% CI: 0.24, 0.87); Q4: RR: 0.39 (95% CI: 0.19, 0.79), P for trend = 0.006]. This association was also observed during the second trimester. Similar results were observed for the association between thiamine and riboflavin supplement use but not dietary intake and GDM risk.
CONCLUSIONS
Higher intake of thiamine and riboflavin during pregnancy is associated with a lower incidence of GDM. This trial was registered at http://www.chictr.org.cn as ChiCTR1800016908.
Topics: Female; Humans; Pregnancy; Diabetes, Gestational; Logistic Models; Prospective Studies; Riboflavin; Risk Factors; Thiamine
PubMed: 36811572
DOI: 10.1016/j.ajcnut.2022.11.014 -
Virulence Dec 2021To resolve the growing problem of drug resistance in the treatment of bacterial and fungal pathogens, specific cellular targets and pathways can be used as targets for... (Review)
Review
To resolve the growing problem of drug resistance in the treatment of bacterial and fungal pathogens, specific cellular targets and pathways can be used as targets for new antimicrobial agents. Endogenous riboflavin biosynthesis is a conserved pathway that exists in most bacteria and fungi. In this review, the roles of endogenous and exogenous riboflavin in infectious disease as well as several antibacterial agents, which act as analogues of the riboflavin biosynthesis pathway, are summarized. In addition, the effects of exogenous riboflavin on immune cells, cytokines, and heat shock proteins are described. Moreover, the immune response of endogenous riboflavin metabolites in infectious diseases, recognized by MHC-related protein-1, and then presented to mucosal associated invariant T cells, is highlighted. This information will provide a strategy to identify novel drug targets as well as highlight the possible clinical use of riboflavin.
Topics: Anti-Infective Agents; Cytokines; Heat-Shock Proteins; Riboflavin
PubMed: 34490839
DOI: 10.1080/21505594.2021.1963909