Riboflavin Deficiency Research Articles

VITAMIN B2 AND ITS STATUS IN VEGETARIANS AND VEGANS

The main goal of this review was to briefly highlight the key points of today’s knowledge about the role and metabolism of vitamin B2 as well as to compare its status in vegans, vegetarians, and omnivores according to present data. Biologically active forms of water-soluble vitamin B2 (riboflavin) are represented by flavin mononucleotide (FMN) and flavin adenine diphosphate (FAD), which are coenzymes in the reactions of the electron transport chain and the pyruvate dehydrogenase complex. Riboflavin is also involved in the metabolism of fatty acids, the synthesis of cholesterol and steroid hormones. Riboflavin also participates in the folate cycle. Vitamin B2 is crucial for the metabolism of other vitamins. FMN is necessary for the for-mation of the active form of vitamin B6, while FAD is necessary for the synthesis of niacin. Severe clinical insufficiency of vitamin B2 is not common. Besides insufficient riboflavin consumption, hypothyroidism can also be a cause of vitamin B2 deficiency as thyroxine regulates the conversion of ribo-flavin to its active forms  FMN and FAD. Lack of riboflavin can cause tissue damage; especially of the epithelial, reproductive, and nervous system. The variety of its manifestations is related to the fact that riboflavin deficiency also disrupts the metabolism of vitamins B6, or PP. Similarly, riboflavin deficiency can also disrupt the folate cycle, increasing the level of homocysteine which damages vascular intima and leads to endothelial dysfunction and atherosclerosis as a result. Rapid urinary excretion of riboflavin makes it safe even if taken in a high dose, changing the urine colour into bright-yellow. This safety of riboflavin makes it unharmful to be used as an oral tracer for monitoring compliance in clinical research. Ultra-high doses of ribo-flavin (more than 400 mg/day) can cause diarrhoea or polyuria. The content of vitamin B2 in animal-derived products is higher than in plant-based ones. This also determines its lower intake in vegans and vegetarians compared to omnivores. While there is a shred of evidence that plant-based diets in-crease the production of bioavailable riboflavin by the gut microbiota, this does not appear to be sufficient to completely compensate for the vegetari-ans’/vegans’ reduced dietary intake of vitamin B2, as most of the researches point the fact that vegans and vegetarians are more prone to lack vita-min B2 than omnivores. At the same time, it should be noted that there exists no universally adopted optimal method for assessing the status of vit-amin B2 in the body. Further research and standardization of methods may ease to assess the prevalence and risks of riboflavin deficiency in various dietary groups

Molecular genetic analysis of candidate genes for glutaric aciduria type II in a cohort of patients from Queensland, Australia

Glutaric aciduria type II (GAII) is a heterogeneous genetic disorder affecting mitochondrial fatty acid, amino acid and choline oxidation. Clinical manifestations vary across the lifespan and onset may occur at any time from the early neonatal period to advanced adulthood. Historically, some patients, in particular those with late onset disease, have experienced significant benefit from riboflavin supplementation. GAII has been considered an autosomal recessive condition caused by pathogenic variants in the gene encoding electron-transfer flavoprotein ubiquinone-oxidoreductase (ETFDH) or in the genes encoding electron-transfer flavoprotein subunits A and B (ETFA and ETFB respectively). Variants in genes involved in riboflavin metabolism have also been reported. However, in some patients, molecular analysis has failed to reveal diagnostic molecular results. In this study, we report the outcome of molecular analysis in 28 Australian patients across the lifespan, 10 paediatric and 18 adult, who had a diagnosis of glutaric aciduria type II based on both clinical and biochemical parameters. Whole genome sequencing was performed on 26 of the patients and two neonatal onset patients had targeted sequencing of candidate genes. The two patients who had targeted sequencing had biallelic pathogenic variants (in ETFA and ETFDH). None of the 26 patients whose whole genome was sequenced had biallelic variants in any of the primary candidate genes. Interestingly, nine of these patients (34.6%) had a monoallelic pathogenic or likely pathogenic variant in a single primary candidate gene and one patient (3.9%) had a monoallelic pathogenic or likely pathogenic variant in two separate genes within the same pathway. The frequencies of the damaging variants within ETFDH and FAD transporter gene SLC25A32 were significantly higher than expected when compared to the corresponding allele frequencies in the general population. The remaining 16 patients (61.5%) had no pathogenic or likely pathogenic variants in the candidate genes. Ten (56%) of the 18 adult patients were taking the selective serotonin reuptake inhibitor antidepressant sertraline, which has been shown to produce a GAII phenotype, and another two adults (11%) were taking a serotonin-norepinephrine reuptake inhibitor antidepressant, venlafaxine or duloxetine, which have a mechanism of action overlapping that of sertraline. Riboflavin deficiency can also mimic both the clinical and biochemical phenotype of GAII. Several patients on these antidepressants showed an initial response to riboflavin but then that response waned. These results suggest that the GAII phenotype can result from a complex interaction between monoallelic variants and the cellular environment. Whole genome or targeted gene panel analysis may not provide a clear molecular diagnosis.

Effects of deficiency or supplementation of riboflavin on energy metabolism: a systematic review with preclinical studies.

Riboflavin (vitamin B2) is a water-soluble micronutrient considered to be a precursor of the nucleotides flavin adenine dinucleotide and flavin mononucleotide. This vitamin makes up mitochondrial complexes and participates as an enzymatic cofactor in several mechanisms associated with energy metabolism. This systematic review collected and discussed the most relevant results on the role of riboflavin in the energy metabolism of lipids, proteins, and carbohydrates. A systematic search was carried out in the PubMed-Medline, Scopus, Embase, and Web of Science databases using the PICOS (Population, Intervention, Comparison, Outcome, Study design) strategy. The screening of studies went through 2 stages following predefined eligibility criteria. The information extracted covered reference details, study design, population characteristics, experimental model, treatment parameters and dosage, route of administration, duration of treatment, and results found. The risk of bias was assessed using the SYRCLE Risk of Bias (RoB) tool for in vivo studies and the QUIN tool adapted for in vitro studies, utilizing 10 domains, including selection bias, performance bias, detection bias, attrition bias, reporting bias, and other biases, to evaluate the methodological quality of the included studies. This review concludes that riboflavin regulates energy metabolism by activating primary metabolic pathways and is involved in energy balance homeostasis.

Abstract 1252 Synthesis and Characterization of Novel Chemical Analogues to Detect Riboflavin (B2) Deficiency

Abstract 1252 Synthesis and Characterization of Novel Chemical Analogues to Detect Riboflavin (B2) Deficiency

Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease

BackgroundNon-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.MethodsIn 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.ResultsThe 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.ConclusionsThere is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.

B2 or Not B2: A Systematic Literature Review on Migraine Headaches and Riboflavin Deficiency

ObjectiveTo assess the prevalence of riboflavin deficiency in patients with migraines or headaches.MethodsSystematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.ResultsTwo articles met the inclusion and exclusion criteria, and neither of these discussed riboflavin deficiency prevalence in those patients who suffer from migraines.ConclusionThe prevalence of riboflavin deficiency in migraineurs and in headache patients is unknown.

Riboflavin bio-enrichment of soy beverage by selected roseoflavin-resistant and engineered lactic acid bacteria

Some lactic acid bacteria (LAB) have the ability to synthesize riboflavin, a trait linked to the presence of ribG, ribB, ribA and ribH genes located in the rib operon. Previous screening of riboflavin producers identified several LAB strains belonging to different species with this ability, but none of them surpassed 0.25 mg/L production of the vitamin. In this study, we explored two strategies to obtain riboflavin-overproducing strains: by roseoflavin selection of mutants, and by the transformation of selected strains with plasmids pNZ:TuR.rib or pNZ:TuB.rib containing the genes ribG, ribB, ribA and ribH from Lactococcus cremoris MG1363. The resulting riboflavin-overproducing strains were able to produce yields between 0.5 and 6 mg/L in culture media and several of them were selected for the fermentation of soy beverages. Riboflavin in bio-enriched soy beverages was evaluated by direct fluorescence measurement and high-performance liquid chromatography-fluorescence analysis. Soy beverages fermented with the recombinant strains Lactococcus cremoris ESI 277 pNZ:TuB.rib and Lactococcus lactis INIA 12 pNZ:TuR.rib showed the highest riboflavin yields (>5 mg/L) after 24 h fermentation. On the other hand, roseoflavin-resistant mutant Limosilactobacillus fermentum INIA P143R2 was able to enrich fermented soy beverages with 1.5 mg/L riboflavin. Riboflavin-overproducing LAB strains constitute a good option for riboflavin enrichment of soy beverages by fermentation and the commercialization of such beverages could be very useful to prevent riboflavin deficiency.

Impacts of high-dose riboflavin on cytotoxicity, antioxidant, growth, reproductive gene expressions, and genotoxicity in the rainbow trout gonadal cells

Riboflavin (vitamin B2 found in food) is a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which study as coenzymes for a variety of cellular processes including biosynthesis, homocysteine metabolism, detoxification, and various oxidation and reduction reactions. Although studies on the symptoms resulting from riboflavin deficiency are intense, studies on the effects of high doses of riboflavin are almost absent. This report aimed to examine the actions of riboflavin on cell viability, the transcriptional expressions of antioxidant enzyme (gsr and gpx1a), growth (gh1, igf1, and igf2), the reproductive (bol) genes and DNA damage in the rainbow trout gonad cells (RTG-2) for 48 h. All concentrations of riboflavin (3.125, 6.25, 12.5, 25, 50, and 100 μM) significantly reduced the RTG-2 cell viability. Riboflavin (LD50: 12.5 μM) significantly downregulated the transcriptional expressions of gpx1a, igf1, and bol genes, while it non-significantly upregulated or downregulated the transcriptional expression of gsr, igf2, and gh1 genes in the RTG-2 cells in comparison to the control group for 48 h. The comet assay demonstrated that riboflavin significantly raised tail DNA% >10% DMSO (positive control). Based on the outcomes, high doses of riboflavin exhibit the potential to have a role in cellular mechanisms, including especially reproduction, DNA damage, and cell death.

Riboflavin deficiency reduces bone mineral density in rats by compromising osteoblast function

Insufficient riboflavin intake has been associated with poor bone health. This study aimed to investigate the effect of riboflavin deficiency on bone health in vivo and in vitro. Riboflavin deficiency was successfully developed in rats and osteoblasts. The results indicated that bone mineral density, serum bone alkaline phosphatase, bone phosphorus, and bone calcium were significantly decreased while serum ionized calcium and osteocalcin were significantly increased in the riboflavin-deficient rats. Riboflavin deficiency also induced the reduction of Runx2, Osterix, and BMP-2/Smad1/5/9 cascade in the femur. These results were further verified in cellular experiments. Our findings demonstrated that alkaline phosphatase activities and calcified nodules were significantly decreased while intracellular osteocalcin and pro-collagen I c-terminal propeptide were significantly increased in the riboflavin-deficient osteoblasts. Additionally, the protein expression of Osterix, Runx2, and BMP-2/Smad1/5/9 cascade were significantly decreased while the protein expression of p-p38 MAPK were significantly increased in the riboflavin-deficient cells compared to the control cells. Blockage of p38 MAPK signaling pathway with SB203580 reversed these effects in riboflavin-deficient osteoblastic cells. Our data suggest that riboflavin deficiency causes osteoblast malfunction and retards bone matrix mineralization via p38 MAPK/BMP-2/Smad1/5/9 signaling pathway.

Improving Anemia Assessment in Clinical and Public Health Settings

We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the “ecology of anemia,” which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

A metal-complex based chemosensor for the detection of riboflavin and folate

The vitamins of riboflavin and folate are necessary nutrients for maintaining the proper functioning of human body. Riboflavin and folate deficiency will cause nerve damage, leading to peripheral neuritis, depression, tongue inflammation and other diseases. The sensitive detection of riboflavin and folate keeps its significance for patients and food quality control. In this study, a quinoline-pyridine-combined chemosensor (HQ-TPE) modified by tetraphenylethene was developed. After chelating Cd2+, the chemosensor exhibited high selectivity and sensitivity for riboflavin and folate. Moreover, it can discriminate the two different vitamins through different fluorescent responses, which should arise from the different intermolecular π-π interactions between the sensor HQ-TPE and the analyte upon coordination of riboflavin or folate with Cd2+. More importantly, the chemosensor could be used in visual semi-quantitative determination of riboflavin and folate in real samples (milk and lettuce). Therefore, the sensor presented here will not only be a powerful tool for the detection of riboflavin and folate, but also provides a new template for the design of metal complex as fluorescent sensor.

A Missense Variant in AIFM1 Caused Mitochondrial Dysfunction and Intolerance to Riboflavin Deficiency.

AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have been associated with multiple clinical phenotypes, but the effectiveness of riboflavin treatment remains controversial. Furthermore, few studies explored the reasons underlying this controversy. We reported a 7-year-old boy with ataxia, sensorimotor neuropathy and muscle weakness. Genetic and histopathological analyses were conducted, along with assessments of mitochondrial function and apoptosis level induced by staurosporine. Riboflavin deficiency and supplementation experiments were performed using fibroblasts. A missense c.1019T > C (p. Met340Thr) variant of AIFM1 was detected in the proband, which caused reduced expression of AIFM1 protein and mitochondrial dysfunction as evidenced by downregulation of mitochondrial complex subunits, respiratory deficiency and collapse of ΔΨm. The proportion of apoptotic cells in mutant fibroblasts was lower than controls after induction of apoptosis. Riboflavin deficiency resulted in decreased AIFM1 protein levels, while supplementation with high concentrations of riboflavin partially increased AIFM1 protein levels in variant fibroblasts. In addition, mitochondrial respiratory function of mutant fibroblasts was partly improved after riboflavin supplementation. Our study elucidated the pathogenicity of the AIFM1 c.1019T > C variant and revealed mutant fibroblasts was intolerant to riboflavin deficiency. Riboflavin supplementation is helpful in maintaining the level of AIFM1 protein and mitochondrial respiratory function. Early riboflavin treatment may serve as a valuable attempt for patients with AIFM1 variant.

Causes and Clinical Sequelae of Riboflavin Deficiency.

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.

A Case Report of Riboflavin Treatment and Cochlear Implants in a 4-Year-Old Girl with Progressive Hearing Loss and Delayed Speech Development: Brown-Vialetto-Van Laere Syndrome.

BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a motor neuron disorder of childhood, which can be associated with sensorineural deafness. This report describes a 4-year-old Polish girl with progressive hearing loss and delayed speech development diagnosed with Brown-Vialetto-Van Laere syndrome who was treated with riboflavin (vitamin B2) and cochlear implants. CASE REPORT The case report concerns a girl from Poland who, at the age of 2 years 10 months, developed progressive atypical neurological symptoms of unknown etiology: ataxia of the upper and lower limbs, gait abnormalities, generalized muscle weakness, visual and hearing problems, and regression of speech development. A karyotype study (whole-exome sequencing) revealed alterations within SLC52A2, leading to the diagnosis of Brown-Vialetto-Van Laere syndrome and initiation of high-dose riboflavin treatment. As a 4-year-old child, she presented to the Institute of Physiology and Pathology of Hearing-World Hearing Center in Poland with progressive hearing loss and speech regression. Hearing tests revealed bilateral profound sensorineural hearing loss with auditory neuropathy. Surgical treatment was applied in the form of bilateral cochlear implantation. CONCLUSIONS This report shows the importance of genetic testing in infants who present with atypical symptoms or signs. In this case, the diagnosis of Brown-Vialetto-Van Laere syndrome resulted in timely correction of the genetic riboflavin (vitamin B2) deficiency and improved hearing following the use of cochlear implants.

Premature farrowing and stillbirths in two organic sow farms due to riboflavin deficiency

BackgroundRiboflavin deficiency can lead to premature farrowing, stillborn piglets, weak-born piglets and neonatal death. Riboflavin (vitamin B2) is considered essential for reproductive function. The longer the period on riboflavin-deficient diets, the more severe the clinical signs become. Litter size as well as body size of piglets can also be considered risk factors that may contribute to the problem.Case presentationThis case report involved two organic farms of 320 (farm A) and 250 sows (farm B). Between 2019 and 2020, premature farrowing with weak-born or stillborn piglets and severe intra-litter mortality, ranging from 60 to 100% were observed. Investigations for infectious causes of reproductive disease, drinking water quality and general feed composition were performed, but showed no significant results. Feed composition was subsequently evaluated more in detail. Riboflavin levels were very low specifically 1.25 mg/kg of diet (3.75 mg/kg of diet is the NRC minimum recommended level). Riboflavin as a vitamin complex supplement (B complex) was administered to sows one month before the farrowing date and this led to a rapid improvement of the problem such that no stillbirth or intra-litter mortality was observed.ConclusionsThe clinical presentation, the low riboflavin levels in the feed below the recommended levels for gestating sows and the effectiveness of the riboflavin supplementation, led to an ex juvantibus diagnosis of this deficiency condition. This case report highlights that riboflavin deficiency during gestation should be considered in case of premature parturition and stillborn litters.

Effect of riboflavin deficiency on intestinal morphology, jejunum mucosa proteomics, and cecal microbiota of Pekin ducks.

This study was to determine the effects of riboflavin deficiency (RD) on intestinal development, jejunum mucosa proteome, cecal short-chain fatty acids (SCFA) profiling, and cecal microbial diversity and community of starter Pekin ducks. Male white Pekin ducks (1d old, n=240) were allocated into 2 groups, with 12 replicates and 10 birds per replicate in each group. For 21d, all ducks had ad libitum access to either an RD or a riboflavin adequate (control, CON) diet, formulated by supplementing a basal diet with 0 or 10mg riboflavin per kg of diet, respectively. Compared to the CON group, growth retardation, high mortality, and poor riboflavin status were observed in the RD group. Furthermore, RD reduced the villus height and the ratio of villus height to crypt depth of jejunum and ileum (P<0.05), indicating morphological alterations of the small intestine. In addition, dietary RD enhanced relative cecum weight and decreased cecal SCFA concentrations (P<0.05), including propionate, isobutyrate, butyrate, and isovalerate. The jejunum mucosa proteomics showed that 208 proteins were upregulated and 229 proteins were downregulated in the RD group compared to those in the CON group. Among these, RD mainly suppressed intestinal absorption and energy generation processes such as glycolysis and gluconeogenesis, fatty acid beta oxidation, tricarboxylic acid cycle, and oxidative phosphorylation, leading to impaired ATP generation. In addition, RD decreased the community richness and diversity of the bacterial community in the cecum of ducks. Specifically, RD reduced the abundance of butyrate-producing bacteria in the cecum (P<0.05), such as Eubacterium coprostanoligenes, Prevotella and Faecalibacterium. Dietary RD resulted in growth depression and intestinal hypofunction of Pekin ducks, which could be associated with impaired intestinal absorption and energy generation processes in intestinal mucosa, as well as gut microbiota dysbiosis. These findings contribute to our understanding of the mechanisms of intestinal hypofunction due to RD.

Avian riboflavin deficiency causes reliably reproducible peripheral nerve demyelination and, with vitamin supplementation, rapid remyelination.

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.

Hepatic CCAAT/Enhancer Binding Protein (C/EBP-α and C/EBP-β) Expression Changes with Riboflavin Deficiency, Diet Restriction and Starvation in Rats , ,

To study the role of nuclear regulatory proteins in mediating dietary effects, hepatic CCAAT/enhancer binding protein (C/EBP), mRNA and transcription rate were measured for C/EBP-alpha and C/EBP-beta in nutritional states that profoundly alter energy metabolism and growth. Weanling male Sprague-Dawley rats were fed riboflavin-sufficient (R+) or deficient (R-) diets for 4 wk. A diet-restricted, pair-fed (RP) group was maintained concurrently, because riboflavin-deficient rats voluntarily decrease food consumption by approximately 50% compared with controls. Half of each group was deprived of food for 48 h. The 4-wk treatment altered hepatic levels of both proteins (P < 0.05). C/EBP-alpha protein levels were increased -twofold by diet restriction. C/ EBP-beta protein levels were increased nearly threefold by riboflavin deficiency. Starvation had no significant effect on the expression of either protein. We investigated the mechanism responsible for increased protein by measuring steady-state mRNA levels and transcription rates for C/EBP-alpha and C/EBP-beta. In both isoforms, increases in mRNA were parallel to increases in transcription rates. The nutrient-induced changes in protein, mRNA and transcription rates could not be attributed only to alterations in serum glucagon or insulin concentrations. We conclude that 1) C/EBP-alpha and C/EBP-beta expression responds to diet but may involve different dietary signals for diet restriction vs. riboflavin deficiency; 2) the dietary regulation of C/EBP-alpha and C/EBP-beta expression seems to be controlled in part at the level of gene transcription; and 3) C/EBP-alpha and C/EBP-beta nuclear proteins, by virtue of their increased quantities, may participate in regulating altered energy metabolism and growth by influencing hepatic transcription of key metabolic enzymes.

Twin Premature Infants With Riboflavin and Biotin Deficiency Presenting With Refractory Lactic Acidosis, Rash, and Multiorgan Failure During Prolonged Parenteral Nutrition.

We are reporting monochorionic, diamniotic twin premature infants born at 25 weeks and 6 days gestation with riboflavin (vitamin B2) and biotin (vitamin B7) deficiency, while on prolonged total parenteral nutrition (TPN) during vitamin shortage. They presented initially with skin rash, lactic acidosis, and thrombocytopenia. Both twins progressed to severe respiratory failure, severe lactic acidosis, with refractory vasodilatory shock, pancytopenia, ischemic bowel injury, acute kidney injury, liver injury, and capillary leak syndrome leading to death of twin A. The surviving twin B was diagnosed with riboflavin and biotin deficiency that presented with abnormal metabolic work up suggestive of maple syrup urine disease, glutaric acidemia type 2, and X-linked adrenoleukodystrophy. Twin B was started on riboflavin and biotin supplementation at 41 days of life, with rapid improvement in clinical findings and laboratory abnormalities within days of starting biotin and riboflavin supplementation. He was discharged home in stable condition at 49 weeks of postmenstrual age.

Riboflavin deficiency is associated with an increased risk of hypertension in pregnancy

Riboflavin deficiency is associated with an increased risk of hypertension in pregnancy