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Nutrition & Metabolism Jan 2024Non-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...
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.
PubMed: 38169398
DOI: 10.1186/s12986-023-00775-8 -
Orphanet Journal of Rare Diseases Jan 2024Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the...
BACKGROUND
Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population.
METHODS
Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations.
RESULTS
Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067-0.00084%.
CONCLUSIONS
This study reveals the first extensive genotype-phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population.
Topics: Humans; Child, Preschool; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Mutation; South Africa; Genotype; Riboflavin; Guanine Nucleotide Exchange Factors; Death Domain Receptor Signaling Adaptor Proteins
PubMed: 38221620
DOI: 10.1186/s13023-023-03014-8 -
International Journal of Food... Feb 2024Some 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....
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.
Topics: Lactobacillales; Soy Milk; Riboflavin; Fermentation; Lactococcus lactis
PubMed: 38150774
DOI: 10.1016/j.ijfoodmicro.2023.110547 -
Frontiers in Nutrition 2023The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the...
BACKGROUND
The maternal diet greatly influences the nutritional composition of human milk. With the rise of vegan diets by lactating mothers, there are concerns about the nutritional adequacy of their milk. Two important nutrients, vitamin B2 and carnitine, are mostly ingested via animal products.
OBJECTIVE
We investigated the influence of a vegan diet on the vitamin B2 and carnitine concentrations in milk and serum of lactating women.
METHODS
In this case-control study, 25 lactating mothers following an exclusive vegan diet were comparted to 25 healthy lactating mothers with an omnivorous diet without use of supplements. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry were used to measure vitamin B2 and carnitine concentrations, respectively. A linear regression model was used to determine differences in human milk and serum concentrations between study groups.
RESULTS
Vitamin B2 concentrations in human milk and serum did not differ between study groups. While the human milk free carnitine (C) and acetyl carnitine (C) concentrations did not differ between study groups, serum carnitine concentrations were lower in participants following a vegan diet than in omnivorous women ( < 0.0001).
CONCLUSION
A maternal vegan diet did not affect human milk concentration of vitamin B2 and carnitine. Breastfed infants of mothers following an exclusive vegan diet therefore are likely not at increased risk of developing a vitamin B2 or carnitine deficiency.
PubMed: 37599690
DOI: 10.3389/fnut.2023.1107768 -
The Journal of Nutrition Dec 2023We 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...
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 B, 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.
Topics: Humans; Public Health; Anemia; Iron; Iron Deficiencies; Inflammation; Anemia, Iron-Deficiency
PubMed: 37778891
DOI: 10.1016/j.tjnut.2023.05.032 -
The American Journal of Case Reports Oct 2023BACKGROUND Brown-Vialetto-Van Laere (BVVL) syndrome is a rare autosomal recessive disorder caused by mutations in intestinal riboflavin transporter genes, resulting in a...
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.
Topics: Female; Infant; Humans; Child, Preschool; Cochlear Implantation; Cochlear Implants; Speech; Hearing Loss, Sensorineural; Bulbar Palsy, Progressive; Riboflavin; Deafness
PubMed: 37786244
DOI: 10.12659/AJCR.940439 -
Plant Physiology and Biochemistry : PPB May 2024Riboflavins are secreted under iron deficiency as a part of the iron acquisition Strategy I, mainly when the external pH is acidic. In plants growing under Fe-deficiency...
Riboflavins are secreted under iron deficiency as a part of the iron acquisition Strategy I, mainly when the external pH is acidic. In plants growing under Fe-deficiency and alkaline conditions, riboflavins have been reported to accumulate inside the roots, with very low or negligible secretion. However, the fact that riboflavins may undergo hydrolysis under alkaline conditions has been so far disregarded. In this paper, we report the presence of riboflavin derivatives and products of their alkaline hydrolysis (lumichrome, lumiflavin and carboxymethylflavin) in nutrient solutions of Cucumis sativus plants grown under different iron regimes (soluble Fe-EDDHA in the nutrient solution, total absence of iron in the nutrient solution, or two different doses of FeSO supplied as a foliar spray), either cultivated in slightly acidic (pH 6) or alkaline (pH 8.8, 10 mM bicarbonate) nutrient solutions. The results show that root synthesis and exudation of riboflavins is controlled by shoot iron status, and that exuded riboflavins undergo hydrolysis, especially at alkaline pH, with lumichrome being the main product of hydrolysis.
Topics: Plant Roots; Hydrolysis; Cucumis sativus; Iron Deficiencies; Riboflavin; Hydrogen-Ion Concentration; Stress, Physiological; Iron; Plant Exudates
PubMed: 38569423
DOI: 10.1016/j.plaphy.2024.108573 -
Genes & Diseases Jul 2024
PubMed: 38515939
DOI: 10.1016/j.gendis.2023.06.038 -
Frontiers in Pediatrics 2024Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter...
BACKGROUND
Brown-Vialetto-Van Laere (BVVL) syndrome is an extremely rare autosomal recessive progressive motoneuron disease that is caused by a defect in the riboflavin transporter genes SLC52A2 and SLC52A3. BVVL syndrome has a variable age of presentation, and it is characterized by progressive auditory neuropathy, bulbar palsy, stridor, muscle weakness, and respiratory compromise secondary to diaphragmatic and vocal cord paralysis. BVVL syndrome has a poor prognosis in the absence of treatment, including morbidity with quadriparesis and sensorineural hearing loss, with mortality in the younger age group. Early administration of riboflavin is associated with prolonged survival, low morbidity, and reversal of some clinical manifestations.
CASE PRESENTATION
We describe an 18-month-old male infant with progressive pontobulbar palsy, loss of developmental milestones, and a clinical picture suggestive of chronic inflammatory demyelinating neuropathy. A nerve conduction study revealed axonal neuropathy, while molecular analysis revealed a homozygous mutation in one of the riboflavin transporter genes, SLC52A3, confirming BVVL syndrome. The patient needed long-term respiratory support and a gastrostomy tube to support feeding. With high-dose riboflavin supplementation, he experienced moderate recovery of motor function.
CONCLUSION
This report highlights the importance of considering BVVL syndrome in any patient who presents with the clinical phenotype of pontobulbar palsy and peripheral axonal neuropathy, as early riboflavin treatment may improve or halt disease progression, thus reducing the associated mortality and morbidity.
PubMed: 38745833
DOI: 10.3389/fped.2024.1377515 -
Frontiers in Pediatrics 2024Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure...
INTRODUCTION
Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important.
CASE PRESENTATION
A 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment.
CONCLUSION
RTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.
PubMed: 38694724
DOI: 10.3389/fped.2024.1391245