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Background and Aims: Riboflavin transporter deficiency (RTD) is a progressive inherited neuropathy of childhood onset, characterised clinically by pontobulbar palsy, sensory ataxia, sensorineural deafness, muscle weakness, optic atrophy and respiratory failure. A robust and responsive functional outcome measure is essential for future clinical trials of disease‐modifying therapies including genetic therapies. The Charcot–Marie–Tooth disease Pediatric Scale (CMTPedS) is a well‐validated outcome measure for CMT and related neuropathies, and might have utility for measuring disease progression in individuals with RTD. However, the CMTPedS requires modifications to account for phenotypic differences between children with CMT and RTD. The aim of this study was to develop a functional outcome measure based on the CMTPedS for specific use in individuals with RTD. Methods: The CMTPedS data collected over the last 10 years in individuals with RTD attending the Peripheral Neuropathy Management Clinic at the Children's Hospital at Westmead (Sydney, Australia) were reviewed to evaluate each item within the CMTPedS. A literature review of articles published until September 2021 for functional outcome measures generated an item pool for pilot testing. The results of this pilot testing, alongside analysis of existing CMTPedS item scores in the RTD cohort, informed the modification of the CMTPedS. Results: CMTPedS data were reviewed for eight individuals over the past 10 years. Two items were identified as requiring modification or removal and additional items of proximal strength and function needed to be considered. Six studies were identified in the literature review, and five items were selected for pilot testing. 'Shoulder internal rotation' and the '30‐s sit to stand test' were added as proximal measures of strength and function. The composite balance item comprising nine tasks in the CMTPedS showed a ceiling effect and was replaced with the single 'Feet apart on a line eyes open' balance item. 'Pinprick sensation' was removed due to a floor effect. Interpretation: This study provides preliminary evidence that the Riboflavin Transporter Deficiency Pediatric Scale (RTDPedS) is a functional outcome measure covering strength, upper and lower limb function, balance and mobility for individuals with RTD to assess disease severity and progression in clinical trials and cohort studies. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored. Methods: In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique. Results: The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load. Conclusions: There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role. [ABSTRACT FROM AUTHOR]

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol‐binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid‐upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron‐containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha‐1‐acid‐glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care‐seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children. Key messages: Anaemia is a public health concern among women and young children due to multiple causes and biological, socioeconomic and ecological risk factors.Anaemia was assessed among women and their young children hospitalised for clinical signs and symptoms suggestive of thiamine deficiency disorders. The risk of anaemia was significantly associated with multiple indicators of micronutrient status and factors related to poverty and health and dietary practices.The present study highlights that anaemia and iron, thiamine, riboflavin and vitamin A deficiencies are highly prevalent in the study population and that multiple strategies are required to prevent anaemia and the other consequences of these micronutrient deficiencies. [ABSTRACT FROM AUTHOR]

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 B6, 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. [ABSTRACT FROM AUTHOR]

Riboflavin deficiency produces severe peripheral neve demyelination in young, rapidly growing chickens. While this naturally-occurring vitamin B2 deficiency can cause a debilitating peripheral neuropathy, and mortality, in poultry flocks, it can also be a useful experimental animal model to study the pathogenesis of reliably reproducible peripheral nerve demyelination. Moreover, restitution of normal riboflavin levels in deficient birds results in brisk remyelination. It is the only acquired, primary, demyelinating tomaculous neuropathy described to date in animals. The only other substance that causes peripheral nerve demyelination similar to avian riboflavin deficiency is tellurium and the pathologic features of the peripheral neuropathy produced by this developmental neurotoxin in weanling rats are also described. [ABSTRACT FROM AUTHOR]

Background and Objectives: Poor nutritional status is a common finding in pulmonary tuberculosis (TB) patients with and without type 2 diabetes mellitus (T2DM), thiamin (VB-1) and riboflavin (VB-2) are coenzymes important for the activation of many enzymes involved in improving nutritional status. We aimed to investigate enzymatic activities and the associations between VB-1 and VB-2, and their relations to nutritional status in TB and TB+T2DM patients.Methods and Study Design: This was a cross-sectional study that prospectively enrolled TB 40 patients with or without T2DM respectively from the Chest Hospital of Qingdao and 76 healthy controls with similar age and gender distributions were recruited from the medical center of the affiliated hospital of Qingdao Medical College. The erythrocyte transketolase activation coefficient (ETKac, for VB-1 deficiency), the glutathione reductase activation coefficient (EGRac, for VB-2 deficiency), and metabolic enzyme activities were analyzed.Results: VB-1 and VB-2 deficiency rates were higher, and enzyme activities were lower in TB and TB+T2DM relative to control group. ETKac and EGRac were negatively correlated with enzyme activities, either with body mass index (BMI), while enzyme activities were positively associated with BMI.Conclusions: VB-1 and VB-2 concentrations were lower in TB patients with or without T2DM relative to controls, with concomitant reductions in the activity levels of key metabolic enzymes. Significant correlations were observed between VB-1 and VB-2 concentrations and the activity of these metabolic enzymes, they all correlated with nutrition status. VB-1 and VB-2 concentrations may thus impact metabolic enzyme activity and thereby influence nutritional status. [ABSTRACT FROM AUTHOR]

Micronutrients are involved in various vital cellular metabolic processes including thyroid hormone metabolism. This study aimed to investigate the correlation between serum levels of micronutrients and their effects on thyroid parameters. The correlation of serum levels of micronutrients and thyroid markers was studied in a group of 387 healthy individuals tested for thyroid markers (T4, T3, FT4, FT3, TSH, anti-TPO, RT3, and anti-Tg) and their micronutrient profile at Vibrant America Clinical Laboratory. The subjects were rationalized into three groups (deficient, normal, or excess levels of micronutrients), and the levels of their thyroid markers were compared. According to our results, deficiency of vitamin B2, B12, and B9 and Vit-D25[OH] (p < 0.05) significantly affected thyroid functioning. Other elemental micronutrients such as calcium, copper, choline, iron, and zinc (p < 0.05) have a significant correlation with serum levels of free T3. Amino acids asparagine (r = 0.1765, p < 0.001) and serine (r = 0.1186, p < 0.05) were found to have a strong positive correlation with TSH. Valine, leucine, and arginine (p < 0.05) also exhibited a significant positive correlation with serum levels of T4 and FT4. No other significant correlations were observed with other micronutrients. Our study suggests strong evidence for the association of the levels of micronutrients with thyroid markers with a special note on the effect of serum levels of certain amino acids. [ABSTRACT FROM AUTHOR]

Purpose: Riboflavin deficiency causes ariboflavinosis, a common nutritional deficiency disease. The purpose of this study is to investigate the effects of riboflavin deficiency on the important internal organs and its potential mechanisms. Methods: Experiment 1, male F344 rats were randomly assigned to R6 (normal riboflavin, 6 mg/kg) and R0 (riboflavin-deficient, 0 mg/kg) groups. Experiment 2 rats were assigned to R6, R0.6 (0.6 mg/kg) and R0.06 (0.06 mg/kg) groups. Experiment 3 rats were assigned to R6 and R0 → R6 (riboflavin replenishment) groups. Bacterial communities were analyzed based on 16S rRNA gene sequencing. Results: Riboflavin deficiency induced ariboflavinosis (R0.06 46.7%; R0 72%) and esophageal epithelial atrophy (R0.06 40%; R0 44%) in rats, while the R6 group did not display symptoms (P < 0.001, respectively). Esophageal epithelial atrophy occurred simultaneously (R0.06 66.7%; R0 63.6%) with ariboflavinosis or appeared alone (R0.06 33.3%; R0 36.4%). Esophagus is the most vulnerable internal organ. Riboflavin deficiency followed by replenishment (R0 → R6) was effective in treating ariboflavinosis (83.3% vs. 0%, P < 0.001) and esophageal epithelial atrophy (66.7% vs. 20%, P = 0.17). Riboflavin deficiency modulated gut microbiota composition. The several key genera (Romboutsia, Turicibacter and Clostridium sensu stricto 1) were strongly correlated with ariboflavinosis and esophageal epithelial atrophy (P < 0.01 or P < 0.05). The potential mechanism is that gut microbiota affects body's xenobiotic biodegradation and metabolism, and genomic instability. Conclusions: Riboflavin deficiency induces ariboflavinosis and esophageal epithelial atrophy by modulating the gut microbiota, and offers new Queryinsight into riboflavin deficiency and esophageal lesions. [ABSTRACT FROM AUTHOR]

Background: Riboflavin is required for erythropoiesis, which is increased in people with hemoglobinopathies due to increased hemolysis and erythrocyte turnover. Dietary intake and status of riboflavin is poor in Cambodia, where hemoglobinopathies are common.Objective: We assessed the association between genetic hemoglobin disorders and riboflavin status in women of reproductive age in Cambodia.Methods: Venous blood samples from 515 Cambodian women of reproductive age, 18-45 y, were analyzed for biomarker status of riboflavin [erythrocyte glutathione reductase activation coefficient (EGRac)], genetic hemoglobin (Hb) disorders, and hematological indices. Linear regression analysis was used to estimate the association between EGRac with Hb, ferritin, and Hb genotypes. EGRac was log transformed in the analyses, and the regression coefficients represent the geometric mean differences.Results: Genetic Hb disorders were present in 57% of the population, with the homozygous hemoglobin E variant (Hb EE) occurring in ∼10% of women (n = 53). Deficient (EGRac ≥1.40) or marginal riboflavin status (EGRac ≥1.30 and <1.40) was observed in 92% (n = 475) of women. The variant Hb EE genotype was associated with 18% (95% CI: 9%, 28%) higher geometric mean EGRac values than the normal Hb AA genotype (P < 0.001).Conclusions: Although riboflavin biomarker deficiency or marginal status is widely prevalent in Cambodian women, lower riboflavin status was observed more frequently in women with the Hb EE genotype than in women with normal Hb AA. The relation between genetic Hb disorders and riboflavin warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01593423 and NCT02481375. [ABSTRACT FROM AUTHOR]

Objectives: Adequate intake of vitamin B complex could be prerequisite to health. However, few studies have been reported on the association of thiamine (vit B1), riboflavin (vit B2) and niacin (vit B3) with periodontal health. This study described the association between periodontal health and dietary vit B1, vit B2 and vit B3 intake in the Korean population. Methods: A total of 12 750 adults aged over 19 years were selected for this study as a sub‐sample of the national data set from Korean National Health and Nutrition Examination Survey (IV and V). Periodontitis and gingivitis were defined as Community Periodontal Index (CPI) scores of 3‐4 and 1‐2, respectively. Information on dietary vit B1, vit B2 and vit B3 intake was from 24‐hour dietary recall method. Multivariable complex logistic regression analyses estimated association between vit B1, vit B2 and vit B3 intakes and periodontal health after adjusting for various potential confounders. Stratified analyses by age, sex, dyslipidemia and total energy intake were also undertaken. Results: The overall estimated prevalence of periodontitis (CPI 3‐4) and gingivitis (CPI 1‐2) was 29.9% and 46.6%, respectively. Our data showed none of the inadequate intake of vit B1, vit B2 and B3 showed significant association with gingivitis after adjusting for potential confounders. Inadequate intake of vit B3 showed higher prevalence odds of periodontitis by 1.25 times (adjusted odds ratio = 1.25, 95% CI = 1.07‐1.46). The association of vit B3 with periodontitis was stronger in females and participants aged 40‐59 years. Conclusions: Inadequate dietary intake of vit B3 was associated with periodontitis. [ABSTRACT FROM AUTHOR]

Lipid metabolism is dependent on riboflavin status. Apolipoprotein B100 plays an important role in lipids transportation. This study was aimed to investigate the effect of riboflavin status on lipid metabolism and explore its association with apolipoprotein B100 synthesis in vivo. Riboflavin deficiency was developed in rats by feeding riboflavin-deficient diets. Compared to the control rats, the mRNA and protein expressions of apolipoprotein B100 were significantly reduced in riboflavin-deficient rats. Endoplasmic reticulum oxidoreductin 1 (ERO1) and protein disulfide isomerase (PDI), two enzymes involved in the oxidative folding of apolipoprotein B100, were also lowered remarkably in expression at protein level. Meanwhile, total cholesterol and triglyceride levels were decreased in the plasma and increased in the liver of riboflavin-deficient rats. The plasma very low-density lipoprotein cholesterol (VLDL-c) and low-density lipoprotein cholesterol (LDL-c) were also reduced in riboflavin-deficient rats. Our findings demonstrate that riboflavin deficiency affects lipid metabolism partly by reducing apolipoprotein B100 synthesis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Metabolic syndrome is a leading global public health concern. Nutritional approaches are important for preventing and managing cardiometabolic risks, including metabolic syndrome. The aim of this study was to examine the potential association between riboflavin intake and cardiometabolic risks according to sex among Koreans.Methods and Study Design: We used data from the Korea National Health and Nutrition Examination Survey 2015-2016, a nationwide cross-sectional survey that assesses the health and nutritional status of the Korean population. A total of 6,062 individuals aged ≥19 years were included. The nutrition survey was performed using 24-h dietary recall.Results: A significant association was observed between low riboflavin intake with only increased HDL-cholesterol (OR 1.362, 95% CI 1.017-1.824, p=0.038) among metabolic syndrome and its components in men, whereas insufficient riboflavin intake was positively associated with hypertension (OR 1.352, 95% CI 1.085-1.685, p=0.007), diabetes (OR 1.493, 95% CI 1.137-1.959, p=0.004) and metabolic syndrome (OR 1.289, 95% CI 1.014-1.640, p=0.038) in women after adjusting for the other covariates. For post-menopausal women, central obesity was also correlated with insufficient riboflavin intake (OR 1.315, 95% CI 1.019-1.696, p=0.035).Conclusions: Insufficient riboflavin intake may contribute to development of cardiometabolic disorder, particularly in women. It was also found that riboflavin may have different influences on its risks in women according to menopausal status. This study highlighted the importance of public policies targeted at these sex-specific groups for reducing cardiometabolic risks. [ABSTRACT FROM AUTHOR]

The article comments on a study on riboflavin deficiency and vitamin B-6 status. It identifies strengths of the study including its use of erythrocyte glutathione reductase activation (EGRac), inclusion of data on dietary intake and riboflavin marker and determination of the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on riboflavin requirements. Also noted is the significance of the study to defining nutrient reference intake.

We discuss the case of a 22-year-old man who presented with paraesthesia, reduced sensation and weakness in his limbs. Examination was in keeping with a myeloneuropathy. Initial investigations including vitamin B12 were unremarkable but magnetic resonance imaging of the spinal cord showed subacute combined degeneration. The patient reported heavy recreational use of nitrous oxide, which can cause functional deficiency of vitamin B12 with neurological sequelae. A diagnosis of functional vitamin B12 deficiency was made and confirmed by an elevated methylmalonic acid level. The patient received intramuscular hydroxocobalamin and made a good recovery following rehabilitation. Nitrous oxide use is prevalent and can have significant health effects. Many adverse effects are mediated through inactivation of vitamin B12 and can be detected by elevated homocysteine and methylmalonic acid levels. Early identification and prompt treatment are important to support neurological recovery. [ABSTRACT FROM AUTHOR]

Background: Riboflavin is an essential component of the human diet and its derivative cofactors play an established role in oxidative metabolism. Riboflavin deficiency has been linked with various human diseases.Objective: The objective of this study was to identify whether riboflavin depletion promotes tumorigenesis.Methods: HEK293T and NIH3T3 cells were cultured in riboflavin-deficient or riboflavin-sufficient medium and passaged every 48 h. Cells were collected every 5 generations and plate colony formation assays were performed to observe cell proliferation. Subcutaneous tumorigenicity assays in NU/NU mice were used to observe tumorigenicity of riboflavin-depleted HEK293T cells. Mechanistically, gene expression profiling and gene ontology analysis were used to identify abnormally expressed genes induced by riboflavin depletion. Western blot analyses, cell cycle analyses, and chromatin immunoprecipitation were used to validate the expression of cell cycle-related genes.Results: Plate colony formation of NIH3T3 and HEK293T cell lines was enhanced >2-fold when cultured in riboflavin-deficient medium for 10-20 generations. Moreover, we observed enhanced subcutaneous tumorigenicity in NU/NU mice following injection of riboflavin-depleted compared with normal HEK293T cells (55.6% compared with 0.0% tumor formation, respectively). Gene expression profiling and gene ontology analysis revealed that riboflavin depletion induced the expression of cell cycle-related genes. Validation experiments also found that riboflavin depletion decreased p21 and p27 protein levels by ∼20%, and increased cell cycle-related and expression-elevated protein in tumor (CREPT) protein expression >2-fold, resulting in cyclin D1 and CDK4 levels being increased ∼1.5-fold, and cell cycle acceleration. We also observed that riboflavin depletion decreased intracellular riboflavin levels by 20% and upregulated expression of riboflavin transporter genes, particularly SLC52A3, and that the changes in CREPT and SLC52A3 correlated with specific epigenetic changes in their promoters in riboflavin-depleted HEK293T cells.Conclusion: Riboflavin depletion contributes to HEK293T and NIH3T3 cell tumorigenesis and may be a risk factor for tumor development. [ABSTRACT FROM AUTHOR]

Hand function is a problem in patients with Charcot‐Marie‐Tooth disease type 1A (CMT1A) and Riboflavin Transporter Deficiency type 2 (RTD2). However, a detailed understanding of upper limb involvement in these conditions is lacking. The aim of this pilot study was to compare hand and upper limb function between children with CMT1A, RTD2 and healthy controls using established and novel outcome measures. Three age‐and sex‐matched groups of four children (5–15 years, 1 male/group) with CMT1A, RTD2, and healthy controls were assessed for function, strength, and sensation. Fatigue and muscle activity of the FDI was also assessed using a submaximal contraction at 40% of the participants' maximal voluntary contraction. Functional measures were most affected in children with RTD2 followed by children with CMT1A, compared to healthy controls. Strength was similarly impaired in CMT1A and RTD2 compared to controls (p < 0.05). Sensation was significantly impaired in RTD2 compared to CMT1A and controls (p = 0.008). While time to fatigue did not differ between groups, a decline in muscle activity while force remained constant showed that controls compensated with other muscles during the fatigue task while children with CMT1A and RTD2 did not have this compensatory ability. Children with CMT1A and RTD2 exhibited marked hand/upper limb impairment. These results suggest the upper limb should be a focus of rehabilitative therapy in affected children using sensitive outcome measures of strength and sensation, as well as functional activities of daily living, which are most relevant to the patient. [ABSTRACT FROM AUTHOR]

Aim of the study:To report a novel mutation in the electron transfer flavoprotein dehydrogenase (ETFDH) gene in an adult patient with late-onset riboflavin-responsive multiple acyl-CoA dehydrogenase deficiency. Materials and methods:The genomic DNAs from a patient whose main clinical presentations are muscles weakness and hypoglycemia was analysed. Results:The patient was identified to carry compound heterozygous mutations in ETFDH gene. Two missense mutations c.814 G > A and c.389 A > T were found. Conclusion:This is the first report of c.814G > A mutation in ETFDH in adult patient with MADD. [ABSTRACT FROM AUTHOR]

In this study, we evaluated the effect of oral administration of riboflavin combined with whole-body ultraviolet A (UVA) irradiation on the biochemical and biomechanical properties of sclera in a guinea pig model to control the progression of myopia. Experimental groups were administered 0.1% riboflavin solution with or without vitamin C by gavage from 3 days before myopic modeling and during the modeling process. Guinea pigs underwent 30 min of whole-body UVA irradiation after each gavage for 2 weeks. For control groups, guinea pigs were administered vitamin C and underwent either whole-body UVA irradiation without 0.1% riboflavin solution or whole-body fluorescent lamp irradiation with or without 0.1% riboflavin solution. Resultantly, myopia models were established with an increased axial length and myopic diopter. Compared with myopic eyes in the control groups, the net increase in axial length, diopter and strain assessment decreased significantly, and the net decrease in sclera thickness, ultimate load, and stress assessment decreased significantly in experimental groups. MMP-2 expression showed a lower net increase, while TIMP-2 expression showed a lower net decrease. In addition, hyperplasia of scleral fibroblasts was more active in myopic eyes of experimental groups. Overall, our results showed that oral administration of riboflavin with whole-body UVA irradiation could increase the strength and stiffness of sclera by altering the biochemical and biomechanical properties, and decreases in axial elongation and myopic diopter are greater in the guinea pig myopic model. [ABSTRACT FROM AUTHOR]

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There has lately been a renewed interest in Riboflavin owing to insight into its recognition as an essential component of cellular biochemistry. The knowledge of the mechanisms and regulation of intestinal absorption of riboflavin and its health implications has significantly been expanded in recent years. The purpose of this review is to provide an overview of the importance of riboflavin, its absorption and metabolism in health and diseased conditions, its deficiency and its association with various health diseases, and metabolic disorders. Efforts have been made to review the available information in literature on the relationship between riboflavin and various clinical abnormalities. The role of riboflavin has also been dealt in the prevention of a wide array of health diseases like migraine, anemia, cancer, hyperglycemia, hypertension, diabetes mellitus, and oxidative stress directly or indirectly. The riboflavin deficiency has profound effect on iron absorption, metabolism of tryptophan, mitochondrial dysfunction, gastrointestinal tract, brain dysfunction, and metabolism of other vitamins as well as is associated with skin disorders. Toxicological and photosensitizing properties of riboflavin make it suitable for biological use, such as virus inactivation, excellent photosensitizer, and promising adjuvant in chemo radiotherapy in cancer treatment. A number of recent studies have indicated and highlighted the cellular processes and biological effects associated with riboflavin supplementation in metabolic diseases. Overall, a deeper understanding of these emerging roles of riboflavin intake is essential to design better therapies for future. [ABSTRACT FROM AUTHOR]

Background: The waterborne diarrheagenic bacterium Vibrio cholerae, cause of the pandemic cholera disease, thrives in a variety of environments ranging from estuarine waters to the human intestinal tract. This species has two ways to obtain the essential micronutrient riboflavin, de novo biosynthesis and environmental uptake through the RibN importer. The way these functions interrelate to fulfill riboflavin needs in different conditions in this species is unknown. Results: This study analyzed the contributions of riboflavin biosynthesis and transport to the culturability of Vibrio cholerae in river and seawater in vitro and in the Caenorhabditis elegans nematode host model. Elimination of the ribD riboflavin biosynthetic gene renders the bacteria riboflavin-auxotrophic, while a ribN mutant strain has no growth defect in minimal media. When growing in river water, deletion of ribD causes an impairment in culturability. In this condition, the ΔribN strain has a defect to compete against a wild type strain but outcompetes the ΔribD strain. The latter effect is inverted by the addition of riboflavin to the water. In contrast, growth in seawater causes a loss in culturability independent of riboflavin biosynthesis or transport. In the C. elegans model, only the ΔribD strain is attenuated. Conclusion: Results indicate that while riboflavin biosynthesis seems to outweigh riboflavin uptake, the latter may still provide a selective advantage to V. cholerae in some environments. [ABSTRACT FROM AUTHOR]

Suboptimal vitamin B2 status is encountered globally. Riboflavin deficiency depresses growth and results in a fatty liver. The underlying mechanisms remain to be established and an overview of molecular alterations is lacking. We investigated hepatic proteome changes induced by riboflavin deficiency to explain its effects on growth and hepatic lipid metabolism. In all, 360 1-d-old Pekin ducks were divided into three groups of 120 birds each, with twelve replicates and ten birds per replicate. For 21 d, the ducks were fed ad libitum a control diet (CAL), a riboflavin-deficient diet (RD) or were pair-fed with the control diet to the mean daily intake of the RD group (CPF). When comparing RD with CAL and CPF, growth depression, liver enlargement, liver lipid accumulation and enhanced liver SFA (C6 : 0, C12 : 0, C16 : 0, C18 : 0) were observed. In RD, thirty-two proteins were enhanced and thirty-one diminished (>1·5-fold) compared with CAL and CPF. Selected proteins were confirmed by Western blotting. The diminished proteins are mainly involved in fatty acid β-oxidation and the mitochondrial electron transport chain (ETC), whereas the enhanced proteins are mainly involved in TAG and cholesterol biosynthesis. RD causes liver lipid accumulation and growth depression probably by impairing fatty acid β-oxidation and ETC. These findings contribute to our understanding of the mechanisms of liver lipid metabolic disorders due to RD. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Riboflavin plays an important role in myelin formation, and its deficiency is implicated as a risk factor for multiple sclerosis. Here, we systematically reviewed the literature concerning the health benefits of riboflavin on MS. The literature recorded within four main databases, including relevant clinical trials, experimental, and case-control studies from 1976 to 2017 were considered. Both human and animal studies were included for review, with no restrictions on age, gender, or ethnicity. Experimental studies demonstrated that riboflavin deficiency triggers neurologic abnormalities related to peripheral neuropathies such as demyelinating neuropathy. Moreover, randomized controlled trials (RCT) and case-control studies in which MS patients received riboflavin supplementation or had higher dietary riboflavin intake showed improvements in neurological motor disability. Riboflavin is a cofactor of xanthine oxidase and its deficiency exacerbates low uric acid caused by high copper levels, leading to myelin degeneration. The vitamin additionally plays a significant role in the normal functioning of glutathione reductase (GR) as an antioxidant enzyme, and conditions of riboflavin deficiency lead to oxidative damage. Riboflavin promotes the gene and protein levels of brain-derived neurotrophic factor (BDNF) in the CNS of an animal model of MS, suggesting that BDNF mediates the beneficial effect of riboflavin on neurological motor disability. Research to date generally supports the role of riboflavin in MS outcomes. However, further observational and interventional studies on human populations are warranted to validate the effects of riboflavin. [ABSTRACT FROM AUTHOR]

Aims Adipose tissue is an endocrine organ important for regulation of such physiological processes as energy metabolism or lipids homeostasis. In an obesity state, it participates in the induction of chronic systemic inflammation accompanied by pro-inflammatory cytokines and fatty acid elevation. For this reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes or hyperlipidemia development. In our previous study, we have shown that riboflavin deficiency induces a pathological pro-inflammatory response of macrophages, the main component of adipose tissue. Therefore, in the current study, we investigated the alteration of the pro-inflammatory activity of adipocytes. Main methods The study was conducted on mouse 3T3 L1 preadipocytes differentiated to adipocyte and culture in the state of riboflavin deficiency (3.1 nM) or control condition (10.4 nM). The cell viability, adiposity and glucose uptake was assessed. Moreover, mRNA expression, as well as crucial pro-inflammatory cytokines (TNFα, IL-6) and adipokines (adiponectin, leptin, resistin) release and NFκB activation, were evaluated. Key findings Results showed that riboflavin deprivation induced a significant elevation in adipocyte lipolysis and enhance obesity-related apoptosis of adipocytes. The generation of reactive oxygen species was enhanced in riboflavin-deficient adipocytes by 43%. Moreover, NFκB phosphorylation and the expression and release of both TNFα, IL-6 as well as leptin were elevated in a deficient group what was accompanied by a reduction of adiponectin level. Conclusion Our study shows that riboflavin deficiency can promote the intensification of pro-inflammatory activity of adipocyte cells, leading consequently to the severity of chronic inflammation that accompanies obesity state. [ABSTRACT FROM AUTHOR]

Background: The one-carbon metabolism pathway is highly dependent on a number of B vitamins in order to provide one-carbon units for purine and thymidylate biosynthesis as well as homocysteine remethylation. Previous studies have examined folate and vitamin B-12 deficiency and their effects on formate metabolism; as of yet, to our knowledge, no studies on the effects of riboflavin deficiency on formate metabolism have been published.Objective: Our objective was to determine the effects of riboflavin deficiency on formate metabolism.Methods: Weanling male rats were randomly assigned either to control, riboflavin-replete (RR) or to experimental, riboflavin-deficient (RD) versions of the AIN-93G diet for 13 d, at which time a constant infusion of [13C]-formate was carried out to ascertain the effects of deficiency on formate production. Gas chromatography-mass spectrometry was used to measure plasma formate concentration and [13C]-formate enrichment. HPLC, LC-mass spectrometry (MS)/MS, and enzymatic assays were used for the measurement of one-carbon precursors and other metabolites.Results: RD rats had significantly lower rates of formate production (15%) as well as significantly reduced hepatic methylenetetrahydrofolate reductase activity (69%) and protein concentration (54%) compared with RR rats. There was no difference in plasma formate concentrations between the groups. Plasma serine, a potential one-carbon precursor, was significantly higher in RD rats (467 ± 73 μM) than in RR rats (368 ± 52 μM).Conclusions: Although deficiencies in folate and vitamin B-12 lead to major changes in plasma formate concentrations, riboflavin deficiency results in no significant difference; this disagrees with the prediction of a published mathematical model. Our observation of a lower rate of formate production is consistent with a role for flavoproteins in this process. [ABSTRACT FROM AUTHOR]

Purpose: To examine the associations between the dietary intakes of certain B-vitamins from different food sources with the relevant plasma status indices in children. Methods: A representative subsample of 600 children aged 9-13 years from the Healthy Growth Study was selected. Dietary intakes of vitamins B, B, B and folate derived from different food sources were estimated. Plasma levels of vitamin B (or riboflavin), methylmalonic acid (MMA) and total homocysteine (tHcy) were also measured. Results: Plasma concentrations of vitamin B below 3 μg/L were found in 22.8 % of the children. Children in the lower quartile of dietary vitamin B intake were found to have the lowest plasma vitamin B levels compared to children in the upper three quartiles (5.06 ± 7.63 vs. 6.48 ± 7.88, 6.34 ± 7.63 and 6.05 ± 4.94 μg/L respectively; P = 0.003). Regarding vitamin B children in the lower quartile of dietary intake had higher mean plasma tHcy levels compared to children in the upper two quartiles, respectively (6.00 ± 1.79 vs. 5.41 ± 1.43 and 5.46 ± 1.64 μmol/L; P = 0.012). Positive linear associations were observed between plasma vitamin B levels and dietary vitamin B derived from milk and fruits ( β = 0.133; P = 0.001 and β = 0.086; P = 0.037). Additionally, nonlinear associations were also observed between plasma vitamin B levels and vitamin B derived from red meat, as well as between tHcy levels and vitamins B and B derived from milk; vitamins B, B and folate derived from cereal products and folate derived from fruits. Conclusion: A considerably high prevalence of poor plasma vitamin B status was observed in children. The intake of milk, fruits and cereals was associated with more favorable tHcy levels, while the intake of milk and fruits with more favorable plasma B2 levels. However, these findings need to be further confirmed from controlled dietary intervention studies examining the modulation of biomarkers of B-vitamins. [ABSTRACT FROM AUTHOR]

Aim: Mutations in the genes encoding the riboflavin transporters RFVT2 and RFVT3 have been identified in Brown-Vialetto-Van Laere syndrome, a neurodegenerative disorder characterized by hearing loss and pontobulbar palsy. Treatment with riboflavin has been shown to benefit individuals with the phenotype of RFVT2 deficiency. Understanding the characteristics of hearing loss in riboflavin transporter deficiency would enable early diagnosis and therapy.Method: We performed hearing assessments in seven children (from four families) with RFVT2 deficiency and reviewed results from previous assessments. Assessments were repeated after 12 months and 24 months of riboflavin therapy and after cochlear implantation in one individual.Results: Hearing loss in these individuals was due to auditory neuropathy spectrum disorder (ANSD). Hearing loss was identified between 3 years and 8 years of age and progressed rapidly. Hearing aids were not beneficial. Riboflavin therapy resulted in improvement of hearing thresholds during the first year of treatment in those with recent-onset hearing loss. Cochlear implantation resulted in a significant improvement in speech perception in one individual.Interpretation: Riboflavin transporter deficiency should be considered in all children presenting with an auditory neuropathy. Speech perception in children with ANSD due to RFVT2 deficiency may be significantly improved by cochlear implantation. [ABSTRACT FROM AUTHOR]

Clinical deficiency of the B-vitamin riboflavin (vitamin B2) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5–13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required. [ABSTRACT FROM PUBLISHER]

B vitamin deficiency is a leading cause of neurological impairment and disability throughout the world. Multiple B vitamin deficiencies often coexist, and thus an understanding of the complex relationships between the different biochemical pathways regulated in the brain by these vitamins may facilitate prompter diagnosis and improved treatment. Particular populations at risk for multiple B vitamin deficiencies include the elderly, people with alcoholism, patients with heart failure, patients with recent obesity surgery, and vegetarians/vegans. Recently, new clinical settings that predispose individuals to B vitamin deficiency have been highlighted. Moreover, other data indicate a possible pathogenetic role of subclinical chronic B vitamin deficiency in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. In light of these findings, this review examines the clinical manifestations of B vitamin deficiency and the effect of B vitamin deficiency on the adult nervous system. The interrelationships of multiple B vitamin deficiencies are emphasized, along with the clinical phenotypes related to B vitamin deficiencies. Recent advances in the clinical determinants and diagnostic clues of B vitamin deficiency, as well as the suggested therapies for B vitamin disorders, are described. [ABSTRACT FROM AUTHOR]

Riboflavin or B2, isolated from a wide variety of animals and plant products is an important vitamin commonly found in the diets of various cultures. This vitamin has been generally known to impart antimicrobial properties when exposed to ultra-violet A irradiation. In the current work, we investigated the possibility of preventing or reducing pathogenic infections using both ultra-violet A assisted and stand-alone riboflavin solutions on selected strains of bacteria. The antimicrobial properties of riboflavin were determined by the effective inhibition of the growth of pathogens through the disc diffusion method. Zones of inhibition studies indicated that riboflavin on its own was found to be quite effective and was able to inhibit the pathogens when diffused at a concentration of 50.0 µL. Stand-alone riboflavin solution successfully inhibitedStaphylococcus aureus, Enterococcus faecalis, Salmonella typhi, andPseudomonas aeruginosawith an inhibition range of (18.7 ± 0.6) mm; (17.7 ± 0.6) mm; (17.3 ± 0.6) mm, and (15.7 ± 0.6) mm, respectively. Intermediate zones of inhibition were observed forEscherichia coliandCandida albicanswith a range of (11.7 ± 0.6) mm and (11.7 ± 0.6) mm, respectively.Klebsiella pneumoniaewas the only resistant pathogen at (7.7 ± 0.6) mm for the riboflavin concentration used in this work. These results may indicate the exciting prospects of the applications of riboflavin as a complementary approach toward inactivation of pathogenic infections. [ABSTRACT FROM PUBLISHER]

This study investigated the effects of riboflavin on intestinal immunity, tight junctions and antioxidant status of young grass carp ( Ctenopharyngodon idella ). Fish were fed diets containing graded levels of riboflavin (0.63–10.04 mg/kg diet) for 8 weeks. The study indicated that riboflavin deficiency decreased lysozyme, acid phosphatase, copper/zinc superoxide dismutase, glutathione reductase and glutathione peroxidase activities, and contents of complement component 3 and reduced glutathione in the intestine of fish ( P < 0.05). Meanwhile, riboflavin deficiency increased reactive oxygen species, malondialdehyde and protein carbonyl contents and catalase activity ( P < 0.05) in the intestine of fish. Furthermore, real-time polymerase chain reaction analysis was used to investigate mRNA expression patterns and found that the mRNA levels of interleukin 10 and transforming growth factor β1, Occludin, zonula occludens 1, Claudin-b and Claudin-c, inhibitor protein κBα, target of rapamycin, ribosomal S6 protein kinase 1 and NF-E2-related factor 2, copper/zinc superoxide dismutase, glutathione peroxidase and glutathione reductase were decreased ( P < 0.05) in the intestine of fish fed riboflavin-deficient diet. Conversely, the mRNA levels of tumor necrosis factor α, interleukin 1β, interleukin 8, nuclear factor kappa B p65, Ikappa B kinase β, Ikappa B kinase γ, Kelch-like-ECH-associated protein 1b, p38 mitogen-activated protein kinase, myosin light chain kinase and Claudin-12 were increased ( P < 0.05) in the intestine of fish fed riboflavin-deficient diet. In conclusion, riboflavin deficiency decreased immunity and structural integrity of fish intestine. The optimum riboflavin level for intestinal acid phosphatase activity of young grass carp was estimated to be 6.65 mg/kg diet. [ABSTRACT FROM AUTHOR]

This study investigated the effects of dietary riboflavin on the growth, gill immunity, tight junction proteins, antioxidant system and related signaling molecules mRNA expression of young grass carp ( Ctenopharyngodon idella ). Fish were fed six diets containing graded levels of riboflavin (0.63–10.04 mg/kg diet) for 8 weeks. The study indicated that riboflavin deficiency decreased lysozyme and acid phosphatase activities, and complement component 3 content in the gills of fish ( P < 0.05). Moreover, riboflavin deficiency caused oxidative damage, which might be partly due to decrease copper, zinc superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase activities and reduced glutathione content in the gills of fish ( P < 0.05). Furthermore, the relative mRNA levels of antimicrobial peptides (liver expressed antimicrobial peptide 2 and Hepcidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor β1), tight junction proteins (Occludin, zonula occludens 1, Claudin-c and Claudin-3), signaling molecules (inhibitor of κBα, target of rapamycin and NF-E2-related factor 2) and antioxidant enzymes (copper, zinc superoxide dismutase and glutathione reductase) were significantly decreased ( P < 0.05) in the gills of fish fed riboflavin-deficient diet. Conversely, the mRNA levels of pro-inflammatory cytokines (tumor necrosis factor α, interleukin 8, interferon γ2, and interleukin 1β), signaling molecules (nuclear factor kappa B p65, IκB kinase β, IκB kinase γ, Kelch-like-ECH-associated protein 1b and myosin light chain kinase) and tight junction protein Claudin-12 were significantly increased ( P < 0.05) in the gills of fish fed riboflavin-deficient diet. In addition, this study indicated for the first time that young fish fed a riboflavin-deficient diet exhibited anorexia and poor growth. In conclusion, riboflavin deficiency decreased growth and gill immunity, impaired gill antioxidant system, as well as regulated mRNA expression of gill tight junction proteins and related signaling molecules of fish. Based on percent weight gain, gill lysozyme activity and reduced glutathione content, the dietary riboflavin requirements for young grass carp (275–722 g) were estimated to be 5.85, 7.39 and 6.34 mg/kg diet, respectively. [ABSTRACT FROM AUTHOR]

Vitamin loss during irradiation has been claimed as a critical area in food irradiation technology, especially that of thiamine (B1), which has been considered as the most sensitive to radiation. Although it has been suggested that no vitamin deficiency could result from consuming irradiated food, a long debate on the loss of vitamins and other nutrients during food irradiation has been maintained by the lack of experimental studies monitoring decomposition rates at different concentrations and doses. Since thiamine, riboflavin, and pyridoxine are labile vitamins, this study has focused on their radiolytic decomposition in dilute aqueous solutions in the presence of air. The decomposition process was followed by HPLC and UV-spectroscopy. The results obtained in aqueous solutions showed a dependence of the decomposition as a nonlinear function of the dose. Of these three compounds, the decomposition was higher for thiamine than for riboflavin and even less in pyridoxine. [ABSTRACT FROM AUTHOR]

Lysine-specific demethylase (LSD) 1 is an FAD-dependent demethylase that catalyzes the removal of methyl groups from lysine-4 in histone H3, thereby mediating gene repression. Here we tested the hypothesis that riboflavin deficiency causes a loss of LSD1 activity in HepG2 human hepatocarcinoma cells, leading to an accumulation of lysine-4-dimethylated histone H3 (H3K4me2) marks in the albumin promoter and aberrant upregulation of albumin expression. Cells were cultured in riboflavin- defined media providing riboflavin at concentrations representing moderately deficient (3.1 nmol/L), sufficient (12.6 nmol/L), and supplemented (301 nmol/L) cells in humans for 7 d. The efficacy of treatment was confirmed by assessing glutathione reductase activity and concentrations of reduced glutathione as markers of riboflavin status. LSD activity was 21 % greater in riboflavin-supplemented cells compared with riboflavin-deficient and -sufficient cells. The loss of LSD activity was associated with a gain in the abundance of H3K4me2 marks in the albumin promoter; the abundance of H3K4me2 marks was ~170% higher in riboflavin-deficient cells compared with sufficient and supplemented cells. The abundance of the repression mark, K9-trimethylated histone H3, was 38% lower in the albumin promoter of riboflavin-deficient cells compared with the other treatment groups. The expression of albumin mRNA was aberrantly increased by 200% in riboflavin-deficient cells compared with sufficient and supplemented cells. In conclusion, riboflavin deficiency impairs gene regulation by epigenetic mechanisms, mediated by a loss of LSD1 activity. [ABSTRACT FROM AUTHOR]

Riboflavin, also known as vitamin B2, is converted by riboflavin kinase (RFK) into flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are essential cofactors of dehydrogenases, reductases, and oxidases including the phagocytic NADPH oxidase 2 (Nox2). Riboflavin deficiency is common in young adults and elderly individuals, who are at the coincidental risk for listeriosis. To address the impact of acute riboflavin deficiency on host defense against Listeria monocytogenes (L.m.), we generated conditional RFK knockout (KO) strains of mice. Phagocyte-specific RFK KO impaired the capability of phagocytes to control intracellular L.m., which corresponded to a greater susceptibility of mice to in vivo challenge with L.m. The oxidative burst of RFK-deficient phagocytes in response to L.m. infection was significantly reduced. Mechanistically, TNF-induced priming of Nox2, which is needed for oxidative burst, was defective in RFK-deficient phagocytes. Lack of riboflavin in wild-type macrophages for only 6 h shut down TNF-induced, RFK-mediated de novo FMN/FAD generation, which was accompanied by diminished ROS production and impaired anti-listerial activity. Vice versa, ROS production by riboflavin-deprived macrophages was rapidly restored by riboflavin supplementation. Our results suggest that acute riboflavin deficiency immediately impairs priming of Nox2, which is of crucial relevance for an effective phagocytic immune response in vivo. [ABSTRACT FROM AUTHOR]

1. Growth and skeletal responses to different dietary concentrations of riboflavin and biotin were compared in turkey poults from hatch to 21 d of age. The birds were fed on a turkey starter diet with different concentrations of supplementary riboflavin (0, 20 and 40 mg/kg) and biotin (0, 0.3 and 0.6 mg/ kg) in a factorial design. 2. Poults fed on diets with no supplementary riboflavin had poor gait scores, decreased times to sit and higher rates of culling compared to poults fed on the control diet (20 mg biotin and 0.3 mg riboflavin/kg diet). Histologically, riboflavin deficiency was associated with a peripheral neuropathy similar to that described previously in chicks and, unexpectedly, in growth plate abnormalities. 3. Tibiae of poults fed on the control diet were larger, more dense, stronger and stiffer than the diets with no supplementary riboflavin. 4. Increasing supplementary biotin in poults fed on diets with no supplementary riboflavin was associated with a decrease in tibia weight, density, strength and stiffness. 5. The results demonstrated that riboflavin deficiency in fast-growing turkey poults was associated with growth retardation, growth plate disturbance and peripheral nerve dysfunction leading to an inability to walk. [ABSTRACT FROM AUTHOR]

Riboflavin deficiency can cause a variety of metabolic problems that lead to skin and mucosal disorders. Limited evidence suggests that high intake of riboflavin may reduce overall risks of cancer. However, association of this deficiency with cervical cancer and precancerous lesions are still not definitively known. In this study, we characterized the relationship between plasma and tissue riboflavin levels and C20orf54 protein expression in patients with cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) as well as the relationship of these levels with human papillomavirus virus 16, 18 (HPV16/18) infections. High-performance liquid chromatography (HPLC) was used to measure blood riboflavin levels in patients with CIN and CSCC, and an enzyme-linked immunosorbent assay (ELISA) was used to determine tissue riboflavin levels in patients with CSCC and matched normal mucous epithelia. The expression of C20orf54 in fresh CSCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry (IHC) with formalin-fixed, paraffin-embedded CIN and CSCC. An HPV genotyping chip was used to analyze HPV infection and typing. The results showed that patients with CIN and CSCC had decreased plasma riboflavin levels as compared with normal controls. There was also significantly decreased riboflavin in tissues from CSCC patients, when compared with normal cervical epithelia. C20orf54 expression were significantly up-regulated in CSCC compared to matched control on both mRNA and protein level. Tissue riboflavin levels were significantly lower in HPV16/18 positive tissue compared with HPV16/18-negative tissue, and an inverse association was found between tissue riboflavin levels and C20orf54 mRNA and protein expression in CSCC. Additionally, C20orf54 was significantly correlated with tumor stages. In conclusion, C20orf54 tend to play a protective role in Uyghur cervical carcinogenesis of which modulating riboflavin absorption, and it is also related with HPV infection. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to prepare riboflavin laurate (RFL) nanosuspensions as an intramuscular injection for long-term riboflavin supplementation. Stable RFL nanosuspensions were obtained by injecting RFL/poloxamer solution in N,N-dimethyl formamide into a trehalose solution. Long soft nanostructures initially appeared and then tube-like rigid nanostructures were obtained after removal of solvents according to the transmission electron microscopic images. The nanosuspensions had narrow size distribution and the mean size was about 300nm. Molecular self-assembly of RFL may drive the formation of nanostructures. RFL formed a monolayer at the air/water interface and poloxamer 188 could insert into the monolayer. The nanosuspensions were intramuscularly injected into rats to provide long-term riboflavin supplementation for more than 30 days in light of body weight, food intake, and urinary riboflavin. The nanosuspensions were also used to resist the riboflavin deficiency induced by methotrexate chemotherapy. RFL nanosuspensions are a promising nanomedicine for long-term riboflavin supplementation. [Copyright &y& Elsevier]

Background: In 2009, a humanitarian response was launched to address a food security and livelihoods crisis in Karamoja, Uganda. During a polio immunization campaign in mid-August 2009, health workers in Nakapiripit District reported a concern about an increase in mouth sores, or angular stomatitis (AS) and gum ulcerations, among children in one village, and an investigation was launched. Objective: This article describes the investigation, lessons learned, and provides guidance for monitoring micronutrient deficiencies among populations receiving food assistance. Design: An investigation into a suspected outbreak of riboflavin (vitamin B2) deficiency was initiated, including a rapid assessment, mass screening, a convenience sample collection of blood specimens (n = 58 symptomatic cases and n = 18 asymptomatic individuals), and analysis of the general food ration (70% ration). Results: Findings showed signs of AS in only 399 (0.2%) of 179,172 screened individuals, including adults and children. Biochemical analysis confirmed riboflavin deficiency in 84.5% of specimens from symptomatic individuals and 94.4% of specimens from asymptomatic individuals. Ration distribution data showed that 55% of distributions provided less than half the riboflavin RDA. Conclusion: Evidence was insufficient to confirm an actual outbreak of riboflavin deficiency, though the present investigation adds further documentation that micronutrient deficiencies continue to persist among populations in emergency settings. This article describes challenges, lessons learned, and guidance for monitoring micronutrient deficiencies among food assistance recipients, including: ongoing nutrition monitoring and surveillance; training and sensitization about micronutrient deficiencies, sensitization of the population about locally-available food, and identifying ways to improve micronutrient interventions. [ABSTRACT FROM AUTHOR]

Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessively inherited disorder of fatty acid metabolism due to ETFA, ETFB or ETFDH mutations. Riboflavin treatment ameliorates symptoms and metabolic profile in ETFDH-related MADD patients. We report on a 20-year-old boy with an 8-year history of progressive difficulty in walking, running and climbing stairs. Muscle biopsy showed a lipid myopathy and the acylcarnitine profile analysis was suggestive of MADD. Nevertheless, no evidence of molecular defects in the ETFA, ETFB and ETFDH exons or intron-exon boundaries was found. Treatment with riboflavin for 1 year resulted in a clear improvement in motor functions. Our report shows that some cases of MADD are not linked to ETFA, ETFB and ETFDH exon or intron-exon boundary changes. They could be due to quite rare promoter or deep intronic mutations or, most likely, to some unknown genetic defect. We therefore suggest to extend in these cases molecular studies to cDNA analysis and indicate the need of extensive pedigree studies to identify other possible disease-related loci. Most important, treatment of these cases with riboflavin can also be effective. Therefore, early diagnosis is essential to achieve the best treatment response. [ABSTRACT FROM AUTHOR]

The first observation of a pigment in milk with yellow-green fluorescence can be traced to the English chemist Alexander Wynter Blyth in 1872, but it was not until the early 1930s that the substance was characterized as riboflavin. Interest in accessory food factors began in the latter half of the 19th century with the discovery of the first vitamin, thiamin. Thiamin was water soluble and given the name vitamin B1. However, researchers realized that there were one or more additional water-soluble factors and these were called the vitamin B-2 complex. The search to identify these accessory food factors in milk, whole wheat, yeast, and liver began in the early 1900s. As there is no classical nutritional disease attributable to riboflavin deficiency, it was the growth-stimulating properties of the food extracts given to young rats that provided the tool with which to investigate and eventually extract riboflavin. Riboflavin was the second vitamin to be isolated and the first from the vitamin B-2 complex; the essential nature of the vitamin as a food constituent for man was shown in 1939. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article discusses a study which assessed the relationship between the dietary intake and blood status of riboflavin and the prevalence of systemic inflammation among depressed and nondepressed nurses. A total of 45 depressed and 53 nondepressed female clinical nurses were studied using Beck Depression Inventory. The study found that marginal riboflavin deficiency was more prevalent in depressed subjects.

Background: Moderate riboflavin deficiency is prevalent in certain population groups in affluent countries, but the functional significance of this deficiency is not clear. Studies have indicated a role for riboflavin in the absorption and use of iron. Objective: We investigated the effect of riboflavin supplementation on hematologic status in a group of moderately riboflavin-deficient women aged 19-25 y in the United Kingdom. Design: One hundred twenty-three women with biochemical evidence of riboflavin deficiency [erythrocyte glutathione reductase activation coefficient (EGRAC) >1.40] were randomly assigned to receive 2 or 4 mg riboflavin or a placebo for 8 wk. Measurements of hematologic status were made pre- and postsupplementation, and dietary intakes were also assessed; iron absorption was measured in a subgroup of women. Results: One hundred nineteen women completed the intervention. The use of a riboflavin supplement for 8 wk elicited a significant improvement in riboflavin status with a dose response (P < 0.0001). For women who received supplemental riboflavin, an increase in hemoglobin status correlated with improved riboflavin status (P < 0.02). Women in the lowest tertile of riboflavin status at baseline (EGRAC >1.65) showed a significantly greater increase in hemoglobin status in response to the supplement than did women in the first and second tertiles (P < 0.01). Dietary iron intake and iron absorption did not change during the study. Conclusions: Moderately poor riboflavin status can affect iron status: the lower the riboflavin status, the greater the hematologic benefits of improving status. The results also suggest that consideration should be given to raising the currently accepted EGRAC threshold for deficiency. This trial was registered at controlled-trials.com as ISRCTN35811298. [ABSTRACT FROM AUTHOR]

Background and Aims: Riboflavin (vitamin B2) is an essential dietary component with a known function in oxidative metabolism. Our previous data using a rat model of riboflavin deficiency suggested that riboflavin also functions as a luminal signaling molecule regulating crypt development and cell turnover. Riboflavin deficiency is prevalent in both high- and low-income countries across the globe. This study aims to establish whether riboflavin deficiency has consequences for gastrointestinal (GI) morphology in adults and what the effects and effectors of any such alteration may be.Methods: Duodenal biopsies and blood samples were collected from a cross-section of gastroscopy patients. Crypt morphology and cell division were studied by immunohistochemistry, and biochemical riboflavin status was determined. Additionally a cell culture model of riboflavin deficiency was developed and analyzed using a combination of flow cytometry, and microarray and clonogenic assays.Result: Duodenal crypts from subjects in the lowest quartile of riboflavin status were significantly shorter (P=0.023), less cellular (P=0.007), and had fewer cell divisions (P=0.034) than the crypts of subjects in the top quartile of riboflavin status. Following riboflavin depletion of colon cells in culture, cell cycle slowed. Microscopy revealed impaired mitosis and accumulation of aneuploid cells. Alterations in gene expression profiles reflected this alteration, with several mitosis-related genes altered, including AspM, cyclin B1, and Birc5 downregulated and Kif23 upregulated. Riboflavin depletion in vitro caused irreversible loss of proliferative potential of cells.Conclusions: Riboflavin depletion in adult humans impairs proliferation and proliferative potential of intestinal cells, which may have implications for gastrointestinal function. [ABSTRACT FROM AUTHOR]