Riboflavin Deficiency Research Articles

Pregnancy thiamine and riboflavin intake and the risk of gestational diabetes mellitus: A prospective cohort study

BackgroundThiamine 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. ObjectivesWe 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. MethodsWe 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. ResultsDietary 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. ConclusionsHigher 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.

Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18–102 years

The generation of the active form of vitamin B-6, pyridoxal 5'-phosphate (PLP), in tissues is dependent upon riboflavin as flavin mononucleotide, but whether this interaction is important for maintaining vitamin B-6 status is unclear. To investigate vitamin B-6 and riboflavin status, their metabolic interaction, and relationship with methylenetetrahydrofolate reductase (MTHFR) genotype in adulthood. Data from 5612 adults aged 18-102 y were drawn from the Irish National Adult Nutrition Survey (NANS; population-based sample) and the Trinity-Ulster Department of Agriculture (TUDA) and Genovit cohorts (volunteer samples). Plasma PLP and erythrocyte glutathione reductase activation coefficient (EGRac), as a functional indicator of riboflavin, were determined. Older (≥65 y) compared with younger (<65 y) adults had significantly lower PLP concentrations (P<0.001). A stepwise decrease in plasma PLP was observed across riboflavin categories, from optimal (EGRac ≤1.26), to suboptimal (EGRac: 1.27-1.39), to deficient (EGRac ≥1.40) status, an effect most pronounced in older adults (mean±SEM: 76.4±0.9 vs 65.0±1.1 vs 55.4±1.2nmol/L; P<0.001). In individuals with the variant MTHFR 677TT genotype combined with riboflavin deficiency, compared with non-TT (CC/CT) genotype participants with sufficient riboflavin, we observed PLP concentrations of 52.1±2.9 compared with 76.8±0.7nmol/L (P<0.001). In participants with available dietary data (i.e., NANS cohort, n = 936), PLP was associated with vitamin B-6 intake (nonstandardized regression coefficient β: 2.49; 95% CI 1.75, 3.24; P<0.001), supplement use (β: 81.72; 95% CI: 66.01, 97.43; P<0.001), fortified food (β: 12.49; 95% CI: 2.08, 22.91; P=0.019), and EGRac (β: -65.81; 95% CI: -99.08, -32.54; P<0.001), along with BMI (β: -1.81; 95% CI: -3.31, -0.30; P=0.019). These results are consistent with the known metabolic dependency of PLP on flavin mononucleotide (FMN) and suggest that riboflavin may be the limiting nutrient for maintaining vitamin B-6 status, particularly in individuals with the MTHFR 677TT genotype. Randomized trials are necessary to investigate the PLP response to riboflavin intervention within the dietary range. The TUDA study and the NANS are registered at www.ClinicalTrials.gov as NCT02664584 (27 January 2016) and NCT03374748 (15 December 2017), respectively.Clinical Trial Registry details: Trinity-Ulster-Department of Agriculture (TUDA) study, ClinicalTrials.gov no. NCT02664584 (January 27th 2016); National Adult Nutrition Survey (NANS), ClinicalTrials.gov no. NCT03374748 (December 15th 2017).

Riboflavin deficiency due to vitamin shortage in neonates with parenteral nutrition dependence

Riboflavin deficiency due to vitamin shortage in neonates with parenteral nutrition dependence

Riboflavin (Vitamin B2) Deficiency Induces Apoptosis Mediated by Endoplasmic Reticulum Stress and the CHOP Pathway in HepG2 Cells.

Riboflavin is an essential micronutrient and a precursor of flavin mononucleotide and flavin adenine dinucleotide for maintaining cell homeostasis. Riboflavin deficiency (RD) induces cell apoptosis. Endoplasmic reticulum (ER) stress is considered to induce apoptosis, and C/EBP homologous protein (CHOP) is a key pathway involved in this process. However, whether RD-induced apoptosis is mediated by ER stress and the CHOP pathway remains unclear and needs further investigation. Therefore, the current study presents the effect of RD on ER stress and apoptosis in the human hepatoma cell line (HepG2). Firstly, cells were cultured in a RD medium (4.55 nM riboflavin) and a control (CON) medium (1005 nM riboflavin). We conducted an observation of cell microstructure characterization and determining apoptosis. Subsequently, 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, was used in HepG2 cells to investigate the role of ER stress in RD-induced apoptosis. Finally, CHOP siRNA was transfected into HepG2 cells to validate whether RD triggered ER stress-mediated apoptosis by the CHOP pathway. The results show that RD inhibited cell proliferation and caused ER stress, as well as increased the expression of ER stress markers (CHOP, 78 kDa glucose-regulated protein, activating transcription factor 6) (p < 0.05). Furthermore, RD increased the cell apoptosis rate, enhanced the expression of proapoptotic markers (B-cell lymphoma 2-associated X, Caspase 3), and decreased the expression of the antiapoptotic marker (B-cell lymphoma 2) (p < 0.05). The 4-PBA treatment and CHOP knockdown markedly alleviated RD-induced cell apoptosis. These results demonstrate that RD induces cell apoptosis by triggering ER stress and the CHOP pathway.

The Neuroprotective Role of Retbindin, a Metabolic Regulator in the Neural Retina.

Dysregulation of retinal metabolism is emerging as one of the major reasons for many inherited retinal diseases (IRDs), a leading cause of blindness worldwide. Thus, the identification of a common regulator that can preserve or revert the metabolic ecosystem to homeostasis is a key step in developing a treatment for different forms of IRDs. Riboflavin (RF) and its derivatives (flavins), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are essential cofactors for a wide range of cellular metabolic processes; hence, they are particularly critical in highly metabolically active tissues such as the retina. Patients with RF deficiency (ariboflavinosis) often display poor photosensitivity resulting in impaired low-light vision. We have identified a novel retina-specific RF binding protein called retbindin (Rtbdn), which plays a key role in retaining flavin levels in the neural retina. This role is mediated by its specific localization at the interface between the neural retina and retinal pigment epithelium (RPE), which is essential for metabolite and nutrient exchange. As a consequence of this vital function, Rtbdn’s role in flavin utilization and metabolism in retinal degeneration is discussed. The principal findings are that Rtbdn helps maintain high levels of retinal flavins, and its ablation leads to an early-onset retinal metabolic dysregulation, followed by progressive degeneration of rod and cone photoreceptors. Lack of Rtbdn reduces flavin levels, forcing the neural retina to repurpose glucose to reduce the production of free radicals during ATP production. This leads to metabolic breakdown followed by retinal degeneration. Assessment of the role of Rtbdn in several preclinical retinal disease models revealed upregulation of its levels by several folds prior to and during the degenerative process. Ablation of Rtbdn in these models accelerated the rate of retinal degeneration. In agreement with these in vivo studies, we have also demonstrated that Rtbdn protects immortalized cone photoreceptor cells (661W cells) from light damage in vitro. This indicates that Rtbdn plays a neuroprotective role during retinal degeneration. Herein, we discussed the specific function of Rtbdn and its neuroprotective role in retinal metabolic homeostasis and its role in maintaining retinal health.

Riboflavin deficiency leads to irreversible cellular changes in the RPE and disrupts retinal function through alterations in cellular metabolic homeostasis

Ariboflavinosis is a pathological condition occurring as a result of riboflavin deficiency. This condition is treatable if detected early enough, but it lacks timely diagnosis. Critical symptoms of ariboflavinosis include neurological and visual manifestations, yet the effects of flavin deficiency on the retina are not well investigated. Here, using a diet induced mouse model of riboflavin deficiency, we provide the first evidence of how retinal function and metabolism are closely intertwined with riboflavin homeostasis. We find that diet induced riboflavin deficiency causes severe decreases in retinal function accompanied by structural changes in the neural retina and retinal pigment epithelium (RPE). This is preceded by increased signs of cellular oxidative stress and metabolic disorder, in particular dysregulation in lipid metabolism, which is essential for both photoreceptors and the RPE. Though many of these deleterious phenotypes can be ameliorated by riboflavin supplementation, our data suggests that some patients may continue to suffer from multiple pathologies at later ages. These studies provide an essential cellular and mechanistic foundation linking defects in cellular flavin levels with the manifestation of functional deficiencies in the visual system and paves the way for a more in-depth understanding of the cellular consequences of ariboflavinosis.

No Association Between Riboflavin and Choline Status in a Sample of Canadian and Malaysian Women of Reproductive Age

ObjectivesRiboflavin and choline are essential nutrients that are metabolically inter-related and play major roles in one-carbon metabolism. Betaine can donate a methyl group to homocysteine, forming dimethylglycine (DMG) and methionine in the liver and kidney. Betaine is synthesized from choline in two irreversible reactions, the first of which is catalyzed by flavin adenine dinucleotide (FAD), a cofactor formed from riboflavin. In animal models, riboflavin status has been shown to influence choline and its metabolites betaine and DMG but there are no human studies. Here we examine whether riboflavin status modifies plasma choline, betaine, and DMG concentrations in healthy women (19–45 y).MethodsFasting blood was collected from 206 Canadian and 210 Malaysian women between 2015 and 2016. Riboflavin status was assessed using a functional biomarker, erythrocyte glutathione reductase activity coefficient (EGRac). Plasma choline, betaine, and DMG were determined by LCLC MS/MS. Plasma folate and vitamin B12 were determined using the microbiological method and an immune assay, respectively. General linear models were used to assess the independent relationship between EGRac and each of the choline metabolites with adjustment for potential confounders.Results71% of Malaysian women had EGRac ≥1.40 compared to 40% of Canadian women. Betaine, DMG, and vitamin B12 concentrations were significantly higher among Malaysian women compared to Canadian women (40.6 vs. 37.0 mmol/L, 2.7 vs. 2.4 mmol/L and 360 vs. 307 pmol/L, respectively). There were no significant associations between EGRac or riboflavin deficiency (defined as EGRac ≥1.40) and choline or its’ metabolites after adjustments for age, ethnicity, body mass index, plasma folate, and vitamin B12. In the adjusted models, plasma choline was positively associated with vitamin B12 concentrations (B = 0.002, 95% CI: 0.000, 0.003) and plasma betaine was positively associated with plasma folate (B = 0.18, 95%CI: 0.07, 0.29) and vitamin B12 (B = 0.011, 95%CI: 0.002, 0.020).ConclusionsOverall, riboflavin status was not associated with choline and its metabolites in Canadian and Malaysian women.Funding SourcesDairy Farmers of Canada, Saudi Arabian Cultural Bureau in Canada, and BC Children's Hospital Research Institute.

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial

PurposeTo assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children.MethodsChildren (n = 1704) aged 6–23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 μg folic acid, and 0.9 μg vitamin B12 along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline.ResultsThere was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015).ConclusionsCompared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B12 status in young Laotian children.Trial registrationThe trial was registered at www.clinicaltrials.gov (NCT02428647) on April 29 2015.

Effect of riboflavin on intestinal development and intestinal epithelial cell function of weaned piglets.

Riboflavin is a water-soluble vitamin involved in the metabolism of protein, fats and carbohydrates as a coenzyme. Pigs, mainly weaned piglets, are prone to riboflavin deficiency. Therefore, this study devoted to explore the effects of riboflavin on intestinal development and function of weaned piglets. A total of 21 piglets, weaned at day 21 of age, were randomly divided into three treatments. The experiment lasted 28 days. The three treatment groups were administered with 0 mg/kg (L_VB2), 3.5 mg/kg (M_VB2) and 17.5 (H_VB2) mg/kg riboflavin by addition into the dry matter basal diets of each group. During the 28-day trial, the feed conversion ratio of the M_VB2 group was lowest (p < 0.05). Duodenum villus height (VH) and the ratio of VH to crypt depth (VH:CD) in L_VB2 group was significantly lower compared with that in M_VB2 group and H_VB2 group (p < 0.05). In the L_VB2 group the number of Ki67 cells in the crypts of the duodenum was increased significantly (p < 0.05). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis using transcriptomic data showed that pathways related to apoptosis were significantly enriched in the L_VB2 group (p < 0.01). In addition, pathways related to inflammatory factors were significantly enriched in the H_VB2 group. The total antioxidant capacity (p < 0.05) and glutathione peroxidase (GSH-PX) activity (p < 0.05) of the L_VB2 group were lowest. In summary, riboflavin levels may regulate the intestinal morphology of piglet duodenum by affecting the renewal and differentiation of intestinal epithelial cells.

Riboflavin deficiency

This datasheet on riboflavin deficiency covers Identity, Distribution, Hosts/Species Affected, Diagnosis.

Effects of riboflavin supplementation level on health, performance, and fertility of organic broiler parent stock and their chicks

Data from breeder hens and chicks are particularly critical for the development of vitamin B2 recommendations for organic poultry. To test safe thresholds of supplementation, 100 breeder hens (Hubbard JA 57 K) and ten cockerels were allocated to ten housing groups, with each receiving supplementation of either 4.0 (treatment CON) or 2.5 mg (treatment RED) riboflavin per kg feed. After 15 weeks of experimental feeding, 256 eggs were incubated. From the hatched chicks (Hubbard S757), 192 were allocated to four treatments based on their parents’ treatment (CON- or RED-) and on their own supplementation of either 4.0 (-CON) or 2.5 mg (-RED) riboflavin per kg feed. Two groups of each combination (CON-CON, CON-RED, RED-CON, RED-RED), each with 24 chicks of both sexes, were fattened for nine weeks and slaughtered. Analysis of total riboflavin (sum of native concentrations and supplements) in the parent’s feeds revealed an average, over the 15 weeks, of 7.8 and 5.8 mg per kg feed for CON and RED, respectively. Body weight, plumage integrity, gait appearance, footpad, claw and keel bone integrity, lesion scores, laying performance, and egg mass were found to be of similarly high levels for all hens without any treatment effects. Performance traits of the hens in both treatments reached the specifications of the producer for this genotype. Yolk and albumen riboflavin concentrations were not affected although yolk colour in the RED treatment group became darker. Fertility was not affected, and hatchability was 100 per cent. Total riboflavin concentrations in the broiler diets were on average, over 9 weeks, 8.2 and 6.1 mg/kg for CON and RED, respectively. In chicks, RED treatment of their parents led to significant depressions of feed intake and growth. The RED treatment of the chicks themselves also impaired growth. Growth rates of the CON-CON treatment were in line with the specifications of the producer for this genotype. Plumage scores, footpad integrity and walking appearance of the broilers, and dressing percentage of the carcasses were not affected by treatment. The RED treatment of chicks caused lower spleen and heart weights, while pancreas and liver weights, and liver riboflavin concentrations were not affected. In conclusion, supplementation of 4.0 mg/kg to organic diets did not evoke any health or performance problems for breeder hens or broiler chicks, while a supplementation level of 2.5 mg per kg feed led to reduced weight gains, although without any other riboflavin deficiency symptoms.

WHITE AND LESION-MIMIC LEAF1, encoding a lumazine synthase, affects reactive oxygen species balance and chloroplast development in rice.

The riboflavin derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are essential cofactors for enzymes in multiple cellular processes. Characterizing mutants with impaired riboflavin metabolism can help clarify the role of riboflavin in plant development. Here, we characterized a rice (Oryza sativa) white and lesion-mimic (wll1) mutant, which displays a lesion-mimic phenotype with white leaves, chlorophyll loss, chloroplast defects, excess reactive oxygen species (ROS) accumulation, decreased photosystem protein levels, changes in expression of chloroplast development and photosynthesis genes, and cell death. Map-based cloning and complementation test revealed that WLL1 encodes lumazine synthase, which participates in riboflavin biosynthesis. Indeed, the wll1 mutant showed riboflavin deficiency, and application of FAD rescued the wll1 phenotype. In addition, transcriptome analysis showed that cytokinin metabolism was significantly affected in wll1 mutant, which had increased cytokinin and δ-aminolevulinic acid contents. Furthermore, WLL1 and riboflavin synthase (RS) formed a complex, and the rs mutant had a similar phenotype to the wll1 mutant. Taken together, our findings revealed that WLL1 and RS play pivotal roles in riboflavin biosynthesis, which is necessary for ROS balance and chloroplast development in rice.

Efficiency of an organic farming compatible yeast product to ensure the Riboflavin-supply of organically raised B.U.T. 6 turkey poults – Effects on animal performance and health

Abstract With new European Union regulations and a change from synthetic production to GMO-based riboflavin manufacturing in the riboflavin producing industry, a gap in the riboflavin supply in organic monogastric nutrition emerged. This study investigates the efficacy of an organic farming compatible yeast product to ensure the riboflavin supply of male B.U.T. 6 turkey poults up to 28 days of age. The riboflavin recommendations of the NRC ( 1994) and GfE ( 1999) also seem to be outdated and have been replaced by new recommendations of the industry. To prove the efficacy of EcoVit R and to validate the recommendations of NRC and GfE, 576 one-day old male B.U.T. 6 turkeys were raised for 28 days at two locations under similar conditions. At both locations 24 pens with 12 turkeys were set up and 12 dietary treatments were created. The two amino acid concentrations HIGH (5.50Â g met/kg feed-mixture) and LOW (4.90Â g met/kg feed-mixture) included six riboflavin levels (HIGH.1 to HIGH.6 and LOW.1 to LOW.6), each, with decreasing riboflavin content from 7.50Â mg/kg feed-mixture (HIGH.1) to 2.30Â mg/kg feed-mixture (HIGH.6 and LOW.6). Individual body weights were taken at d 14 and 28 and feed consumption was recorded every week. In comparison to the LOW groups, HIGH groups showed higher feed consumption, final body weight and daily weight gain (PÂ <Â 0.05). Only riboflavin groups HIGH.6 and LOW.6 exhibited typical riboflavin deficiency symptoms and had lower performance, relating to feed consumption, final body weight and daily weight gain (PÂ <Â 0.05). No significant differences between the other riboflavin groups (HIGH.1 to HIGH.5 and LOW.1 to LOW.5) were found. The new riboflavin rich yeast product meets the requirements of turkey poults, without negative effects. The recommendation of 4.00Â mg/kg feed of the NRC ( 1994) and GfE ( 1999) can be confirmed, under limitations of this study.

Effects of riboflavin deficiency on the lipid metabolism of duck breeders and duck embryos

This study aimed to evaluate the effects of dietary riboflavin deficiency (RD) on the lipid metabolism of duck breeders and duck embryos. A total of 40 female 40-wk-old white Pekin duck breeders were randomly divided into 2 groups, received either RD diet (1.48 mg riboflavin/kg) or control diet (16.48 mg riboflavin/kg, CON) for 14 wk. Each group consisted of 20 duck breeders (10 replicates per group, 2 birds per replicate), and all experiment birds were single-caged. At the end of the experiment, reproductive performance, hepatic riboflavin, hepatic flavin mononucleotide (FMN), hepatic flavin adenine dinucleotide (FAD), hepatic morphology, hepatic lipid contents, and hepatic protein expression of duck breeders and duck embryos were measured. The results showed that the RD had no effect on egg production and egg fertility but reduced egg hatchability, duck embryo weight, hepatic riboflavin, FMN, and FAD status compared to results obtained in the CON group (all P < 0.05). Livers from RD ducks presented enlarged lipid droplets, excessive accumulation of total lipids, triglycerides, and free fatty acids (all P < 0.05). In addition to excessive lipids accumulation, medium-chain specific acyl-CoA dehydrogenase expression was downregulated (P < 0.05), and short-chain specific acyl-CoA dehydrogenase expression was upregulated in maternal and embryonic livers (P < 0.05). RD did not affect maternal hepatic acyl-CoA dehydrogenase family member 9 (ACAD9) expression, but duck embryonic hepatic ACAD9 expression was reduced in the RD group (P < 0.05). Collectively, dietary RD conditioned lower egg hatchability and inhibited the development of duck embryos. Increased accumulation of lipids, both maternal and embryo, was impaired due to the reduced flavin protein expression, which caused inhibition of hepatic lipids utilization. These findings suggest that abnormal duck embryonic growth and low hatchability caused by RD might be associated with disorders of lipid metabolism in maternal as well as embryos.

Riboflavin fortification of rice endosperm by metabolic engineering

Riboflavin (vitamin B2 ) is an essential nutrient for human health and body development. Riboflavin deficiency may increase the risk of some diseases (Thakur et al., 2017). Humans must regularly consume a sufficient amount of riboflavin, as this vitamin cannot be stored in the body. Data from the 2010-2012 China National Nutrition and Health Surveillance indicated that the riboflavin dietary intake of 85.9% of 14- to 17-year-old Chinese participants was below the estimated average requirement (Wang et al., 2017).

Probiotic Potential of a Novel Vitamin B2-Overproducing Lactobacillus plantarum Strain, HY7715, Isolated from Kimchi

Vitamin B2, also known as riboflavin, is essential for maintaining human health. The purpose of this study was to isolate novel lactic acid bacteria that overproduce vitamin B2 and to validate their potential as probiotics. In this study, Lactobacillus plantarum HY7715 (HY7715) was selected among lactic acid bacteria isolated from Kimchi. HY7715 showed a very high riboflavin-producing ability compared to the control strain due to the high expression of ribA, ribB, ribC, ribH, and ribG genes. HY7715 produced 34.5 ± 2.41 mg/L of riboflavin for 24 h without consuming riboflavin in the medium under optimal growth conditions. It was able to produce riboflavin in an in vitro model of the intestinal environment. In addition, when riboflavin deficiency was induced in mice through nutritional restriction, higher levels of riboflavin were detected in plasma and urine in the HY7715 administration group than in the control group. HY7715 showed high survival rate in simulated gastrointestinal conditions and had antibiotic resistance below the cutoff MIC value suggested by the European Food Safety Authority; moreover, it did not cause hemolysis. In conclusion, HY7715 could be considered a beneficial probiotic strain for human and animal applications, suggesting that it could be a new alternative to address riboflavin deficiency.

Riboflavin in Neurological Diseases: A Narrative 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.

Dietary Riboflavin Intake and Riboflavin Status in Young Adult Women Living in Metro Vancouver, Canada.

ABSTRACTBackgroundNutrition surveys suggest that <10% of Canadian adults have inadequate riboflavin intakes. However, biochemical riboflavin deficiency [erythrocyte glutathione reductase activity coefficient (EGRac) ≥1.40] has been reported in 41% of young adult women living in Metro Vancouver. Canadian Chinese ethnicity comprise >25% of Vancouver's population and are postulated to have poorer riboflavin status than those of European ethnicity because they could be less likely to consume dairy products and fortified wheat.ObjectivesThe objectives of this study were to determine dietary riboflavin intake and food sources, and to assess the association between riboflavin intake and status in young women of European (n = 107) and Chinese (n = 91) ethnicities living in Metro Vancouver, Canada.MethodsThis was a cross-sectional study conducted in women (aged 19–45 y). Women were healthy, not pregnant or breastfeeding, of European or Chinese ethnicities, and not taking riboflavin-containing supplements for the past 4 mo. Dietary riboflavin intake was assessed using the past-year Diet History Questionnaire II, and riboflavin status (EGRac) was measured in fasting venous blood samples.ResultsOnly 7% of participants had dietary riboflavin intakes below the Estimated Average Requirement (0.9 mg/d), but 40% of women had biochemical riboflavin deficiency (EGRac ≥1.40). Although more Canadian women of European ethnicity than Chinese ethnicity had biochemical riboflavin deficiency (46% and 34%; P < 0.001), median dietary riboflavin intake did not differ (1.73 and 1.82 mg/d; P = 0.587). Dairy products and vegetables contributed the most to riboflavin intake. Energy-adjusted dietary riboflavin intake was inversely associated with EGRac (B = −0.04, 95% CI: −0.07, −0.01). However, after further adjustment the relation was not significant.ConclusionsOverall, women of reproductive age living in Metro Vancouver, Canada, had a low prevalence of inadequate dietary riboflavin intake despite the high prevalence of apparent biochemical riboflavin deficiency.

Functional Study of the Human Riboflavin Transporter 2 Using Proteoliposomes System.

Riboflavin is essential for cell viability. The biologically active forms of riboflavin, FMN and FAD, participate in many biochemical redox reactions including the metabolism of carbohydrates, amino acids, and lipids. Differently from bacteria, fungi, and plants which synthesize riboflavin, higher organisms have lost the ability to synthesize the vitamin and must absorb it from food and intestinal microflora production. The riboflavin flux through cell membranes occurs via specific transporters belonging to the SLC52 family. Three members of this family have been identified so far which show poor homology with the riboflavin transporters of Saccharomyces cerevisiae or bacteria. Alterations of RFVTs are causative of severe diseases. Indeed, under pathological stress, humans are susceptible of developing riboflavin deficiency. Such a deficiency in pregnancy induces fetus abnormalities, and has been indicated as a risk factor for anemia, cancer, cardiovascular diseases, and neurodegeneration. Moreover, inherited diseases are also of interest; the most well-described is the Brown-Vialetto-van Laere syndrome, a rare neurological disorder characterized by infancy onset sensorineural deafness and pontobulbar palsy. Numerous polymorphisms of Slc52a2 and Slc52a3 genes associated with this syndrome have been discovered. In spite of their important metabolic role and their relevance to human health, the riboflavin transporters are still poorly characterized. Bacterial overexpression, purification, and protein reconstitution in liposomes represent an up-to-date methodology for obtaining functional data information. The methodology for reconstituting the RFVT2 into proteoliposomes and performing transport assay is described. These methods will be suitable for investigating the functional defects of the variants of RFVTs associated with human pathologies.

Demand-oriented riboflavin supply of organic broiler using a feed material from fermentation of Ashbya gossypii

Alternatives to riboflavin (vitamin B2) production by recombinant microorganisms are needed in organic poultry production, but are cost-intensive, so that a demand-oriented riboflavin supply is necessary. Details on the riboflavin requirements of organic poultry are not available. A feed material with high native riboflavin content from fermentation of the filamentous fungus Ashbya gossypii was studied. Two runs with 800 Ranger Gold™ broilers each (40 pens with 20 animals) were conducted. The fattening period was divided into starter (S), grower (G) and finisher (F) stage. In the first run, a basal diet without riboflavin supplementation (NATIVE; 3.27, 3.50 and 3.16 mg riboflavin/kg DM in S, G and F) was compared to diets with supplementation at low (LOW; 5.30, 4.85 and 5.19 mg/kg in S, G and F), medium (MEDIUM; 7.56, 6.88 and 7.56 mg/kg in S, G and F) and high (HIGH; 10.38, 9.14 and 9.93 mg/kg in S, G and F) dosage. In the second run, different combinations of low and medium riboflavin supplementation were used in S, G and F diets: S-LOW (4.50 mg riboflavin/kg DM), G-MEDIUM (6.66 mg/kg), F-MEDIUM (5.71 mg/kg) (Treatment A), S-LOW (4.50 mg riboflavin/kg DM); G-LOW (4.92 mg/kg), F-LOW (4.01 mg/kg) (Treatment B); S-MEDIUM (6.37 mg/kg), G-MEDIUM (7.37 mg/kg), F-MEDIUM (5.07 mg/kg) (Treatment C); S-MEDIUM (6.37 mg/kg), G-LOW (5.28 mg/kg), F-LOW (4.22 mg/kg) (Treatment D). Body weight, feed and water consumption were recorded weekly, health and welfare indicators were scored bi-weekly. Slaughter traits were assessed for five males and females per pen. In the first run, NATIVE animals showed symptoms of riboflavin deficiency and lower live weights in the second week of age. Riboflavin contents of this group were increased to avoid further deficiency and recovery was observed. Feed conversion was better in HIGH (2.07) compared with NATIVE and LOW (2.11). At slaughter, treatments differed neither for foot pad dermatitis nor plumage cleanliness. In the second run, daily weight gains did not differ between treatments in any of the weeks. Feed conversion ranged between 1.99 and 2.04. Riboflavin deficiency was not observed in the second run, while treatment D showed superior economic efficiency. In conclusion, native contents of feed components (3.27 mg/kg DM) were not sufficient to meet the riboflavin demand and a total content of 4.50 mg/kg DM was identified as safe lower threshold. The levels rather according to commercial recommendations were not additionally beneficial to performance and health.