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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 -
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 -
International Journal of Molecular... Nov 2023Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion... (Review)
Review
Many inherited metabolic disorders (IMDs), including disorders of amino acid, fatty acid, and carbohydrate metabolism, are treated with a dietary reduction or exclusion of certain macronutrients, putting one at risk of a reduced intake of micronutrients. In this review, we aim to provide available evidence on the most common micronutrient deficits related to specific dietary approaches and on the management of their deficiency, in the meanwhile discussing the main critical points of each nutritional supplementation. The emerging concepts are that a great heterogeneity in clinical practice exists, as well as no univocal evidence on the most common micronutrient abnormalities. In phenylketonuria, for example, micronutrients are recommended to be supplemented through protein substitutes; however, not all formulas are equally supplemented and some of them are not added with micronutrients. Data on pyridoxine and riboflavin status in these patients are particularly scarce. In long-chain fatty acid oxidation disorders, no specific recommendations on micronutrient supplementation are available. Regarding carbohydrate metabolism disorders, the difficult-to-ascertain sugar content in supplementation formulas is still a matter of concern. A ketogenic diet may predispose one to both oligoelement deficits and their overload, and therefore deserves specific formulations. In conclusion, our overview points out the lack of unanimous approaches to micronutrient deficiencies, the need for specific formulations for IMDs, and the necessity of high-quality studies, particularly for some under-investigated deficits.
Topics: Humans; Diet; Dietary Supplements; Micronutrients; Trace Elements; Metabolic Diseases; Fatty Acids
PubMed: 38069347
DOI: 10.3390/ijms242317024 -
PLoS Medicine Dec 2023Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from... (Randomized Controlled Trial)
Randomized Controlled Trial
Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial.
BACKGROUND
Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from preconception through early and late pregnancy and postpartum have been inferred from cross-sectional data, but longitudinal data on vitamin status from preconception throughout pregnancy and postdelivery are sparse. As such, the influence of vitamin supplementation on vitamin status during pregnancy remains uncertain. This study presents one prespecified outcome from the randomized controlled NiPPeR trial, aiming to identify longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determine the influence of vitamin supplementation.
METHODS AND FINDINGS
In the NiPPeR trial, 1,729 women (from the United Kingdom, Singapore, and New Zealand) aged 18 to 38 years and planning conception were randomized to receive a standard vitamin supplement (control; n = 859) or an enhanced vitamin supplement (intervention; n = 870) starting in preconception and continued throughout pregnancy, with blinding of participants and research staff. Supplement components common to both treatment groups included folic acid, β-carotene, iron, calcium, and iodine; components additionally included in the intervention group were riboflavin, vitamins B6, B12, and D (in amounts available in over-the-counter supplements), myo-inositol, probiotics, and zinc. The primary outcome of the study was glucose tolerance at 28 weeks' gestation, measured by oral glucose tolerance test. The secondary outcome reported in this study was the reduction in maternal micronutrient insufficiency in riboflavin, vitamin B6, vitamin B12, and vitamin D, before and during pregnancy. We measured maternal plasma concentrations of B-vitamins, vitamin D, and markers of insufficiency/deficiency (homocysteine, hydroxykynurenine-ratio, methylmalonic acid) at recruitment, 1 month after commencing intervention preconception, in early pregnancy (7 to 11 weeks' gestation) and late pregnancy (around 28 weeks' gestation), and postdelivery (6 months after supplement discontinuation). We derived standard deviation scores (SDS) to characterize longitudinal changes among participants in the control group and measured differences between the 2 groups. At recruitment, the proportion of patients with marginal or low plasma status was 29.2% for folate (<13.6 nmol/L), 7.5% and 82.0% for riboflavin (<5 nmol/L and ≤26.5 nmol/L, respectively), 9.1% for vitamin B12 (<221 pmol/L), and 48.7% for vitamin D (<50 nmol/L); these proportions were balanced between the groups. Over 90% of all participants had low or marginal status for one or more of these vitamins at recruitment. Among participants in the control group, plasma concentrations of riboflavin declined through early and late pregnancy, whereas concentrations of 25-hydroxyvitamin D were unchanged in early pregnancy, and concentrations of vitamin B6 and B12 declined throughout pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation. In the control group, 54.2% of participants developed low late-pregnancy vitamin B6 concentrations (pyridoxal 5-phosphate <20 nmol/L). After 1 month of supplementation, plasma concentrations of supplement components were substantially higher among participants in the intervention group than those in the control group: riboflavin by 0.77 SDS (95% CI 0.68 to 0.87, p < 0.0001), vitamin B6 by 1.07 SDS (0.99 to 1.14, p < 0.0001), vitamin B12 by 0.55 SDS (0.46 to 0.64, p < 0.0001), and vitamin D by 0.51 SDS (0.43 to 0.60, p < 0.0001), with higher levels in the intervention group maintained during pregnancy. Markers of vitamin insufficiency/deficiency were reduced in the intervention group, and the proportion of participants with vitamin D insufficiency (<50 nmol/L) during late pregnancy was lower in the intervention group (35.1% versus 8.5%; p < 0.0001). Plasma vitamin B12 remained higher in the intervention group than in the control group 6 months postdelivery (by 0.30 SDS (0.14, 0.46), p = 0.0003). The main limitation is that generalizability to the global population is limited by the high-resource settings and the lack of African and Amerindian women in particular.
CONCLUSIONS
Over 90% of the trial participants had marginal or low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactational period.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02509988; U1111-1171-8056.
Topics: Female; Humans; Pregnancy; Cross-Sectional Studies; Dietary Supplements; Folic Acid; Pregnancy Outcome; Riboflavin; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamin D; Adolescent; Young Adult; Adult
PubMed: 38051700
DOI: 10.1371/journal.pmed.1004260 -
Journal of the Neurological Sciences Jan 2024There are scarce reports of riboflavin-responsive lipid storage myopathy in elderly patients with onset in their sixties. We describe three elderly patients with...
There are scarce reports of riboflavin-responsive lipid storage myopathy in elderly patients with onset in their sixties. We describe three elderly patients with riboflavin-responsive lipid-storage myopathy. All three patients (aged 67-71 years on first examination) had subacute onset of neck extensors and proximal limb weakness progressing to inability to rise from a sitting position or to walk. Muscle biopsies showed vacuoles with lipid content, mainly in type 1 fibers. Genetic analysis failed to identify any pathogenic variant in one patient, identified a heterozygous variant of uncertain significance c.812 A > G; p.Tyr271Cys in the ETFDH gene in the second patient, and revealed a heterozygote likely pathogenic variant c.1286-2 A > C in the ETFDH gene predicted to cause abnormal splicing in the third patient. All patients responded to treatment with riboflavin and carnitine, and regained normal strength. This report emphasizes the importance of muscle biopsy in revealing treatable lipid storage myopathy in elderly patients with progressive myopathy of unidentifiable cause.
Topics: Humans; Aged; Muscle, Skeletal; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Oxidoreductases Acting on CH-NH Group Donors; Muscular Diseases; Riboflavin; Lipids; Lipid Metabolism, Inborn Errors; Muscular Dystrophies
PubMed: 38043332
DOI: 10.1016/j.jns.2023.122808 -
Journal of the Neurological Sciences Dec 2023
PubMed: 38040566
DOI: 10.1016/j.jns.2023.122809 -
BMJ (Clinical Research Ed.) Nov 2023
Topics: Humans; Vitamin B 12; Vitamin B 12 Deficiency; Vitamins
PubMed: 37984968
DOI: 10.1136/bmj-2022-071725 -
Toxicology in Vitro : An International... Feb 2024Riboflavin (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...
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 (LD: 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.
Topics: Animals; Antioxidants; Oncorhynchus mykiss; Flavin Mononucleotide; Riboflavin; DNA Damage; Gene Expression
PubMed: 37944868
DOI: 10.1016/j.tiv.2023.105730 -
Maternal & Child Nutrition Jan 2024Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and...
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.
Topics: Adult; Female; Humans; Male; Pregnancy; Young Adult; Anemia; Anemia, Iron-Deficiency; Ferritins; Hemoglobins; Laos; Prevalence; Risk Factors; Thiamine Deficiency
PubMed: 37803889
DOI: 10.1111/mcn.13565 -
The Journal of Nutritional Biochemistry Dec 2023Insufficient 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...
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.
Topics: Rats; Animals; Bone Density; Core Binding Factor Alpha 1 Subunit; Osteocalcin; Signal Transduction; Riboflavin Deficiency; Alkaline Phosphatase; Calcium; Bone Morphogenetic Protein 2; Osteoblasts; p38 Mitogen-Activated Protein Kinases; Riboflavin; Cell Differentiation
PubMed: 37788723
DOI: 10.1016/j.jnutbio.2023.109453