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Journal of Bone and Mineral Research :... Dec 2022Folate, vitamins B12, B6, and riboflavin are required for one-carbon metabolism and may affect bone health, but no previous randomized trial has investigated all four... (Randomized Controlled Trial)
Randomized Controlled Trial
Folate, vitamins B12, B6, and riboflavin are required for one-carbon metabolism and may affect bone health, but no previous randomized trial has investigated all four nutrients in this context. We investigated the effect of low-dose B-vitamins for 2 years on bone mineral density (BMD) in a dual-centered, 2-year randomized controlled trial (RCT) in adults aged ≥50 years. Eligible participants not consuming B-vitamin supplements or fortified foods >4 times weekly were randomized to receive daily either combined folic acid (200 μg), vitamin B12 (10 μg), vitamin B6 (10 mg), and riboflavin (5 mg), or "active" placebo, whereby both the intervention and placebo groups received vitamin D (10 μg). BMD was assessed before and after intervention using dual-energy X-ray absorptiometry (DXA) scanning of the total hip, femoral neck, and lumbar spine (L1 to L4). Of 205 eligible participants randomized, 167 completed the trial in full. B-vitamin intervention resulted in increases in serum folate (p < 0.001), serum B12 (p < 0.001), and plasma pyridoxal-5-phosphate (p < 0.001) and decreases in functional biomarkers of B-vitamin status, erythrocyte glutathione reductase activation coefficient (p < 0.001), serum methylmalonic acid (MMA; p < 0.001), and serum total homocysteine (p < 0.001). B-vitamin intervention had no overall effect on BMD, which declined in both treatment groups by approximately 1% (ranging from -0.7% to -1.4%). However, in participants with lower baseline B12 status (serum B12 <246 pmol/L or MMA ≥0.22 μmol/L), B-vitamin intervention reduced the 2-year BMD decline versus placebo: adjusted mean (95% confidence interval [CI]) change of -0.003 (-0.008, 0.002) versus -0.015 (-0.021, -0.010) g/cm at the total hip and -0.004 (-0.010, 0.001) versus -0.013 (-0.018, -0.007) g/cm at the femoral neck. In conclusion, the findings indicate that although low-dose B-vitamin intervention for 2 years had no overall effect on BMD, improving B-vitamin status appears to have specific benefits for bone health in adults with lower B12 status. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Adult; Humans; Bone Density; Dietary Supplements; Folic Acid; Lumbar Vertebrae; Riboflavin; Vitamin B 12; Vitamin B Complex
PubMed: 36128889
DOI: 10.1002/jbmr.4709 -
Journal of Cataract and Refractive... Aug 2021Corneal crosslinking is a U.S. Food and Drug Administration--approved therapy to stiffen the cornea and prevent progression of corneal ectasia in patients with...
Corneal crosslinking is a U.S. Food and Drug Administration--approved therapy to stiffen the cornea and prevent progression of corneal ectasia in patients with keratoconus. The standard procedure involves removal of the corneal epithelium (epithelial-off) prior to treatment. Variations to the standard procedure include accelerated crosslinking and transepithelial procedures. This study reviewed what is known regarding the risk for infection after epithelial-off crosslinking, the spectrum of pathogens, and clinical outcomes. 26 publications were identified. All eyes were fit with a bandage contact lens postoperatively. Available data indicate that the overall frequency of infectious keratitis after epithelium-off crosslinking is low. Bacterial infections are the most common, with a mean time of presentation of 4.8 days postoperatively. The use of steroids and bandage contact lenses in the immediate postoperative period and/or a history of atopic or herpetic disease were associated with infection. These patients require intense postoperative care with prophylactic antiviral therapy when appropriate.
Topics: Collagen; Cornea; Cross-Linking Reagents; Humans; Keratitis; Keratoconus; Photosensitizing Agents; Riboflavin
PubMed: 33769765
DOI: 10.1097/j.jcrs.0000000000000620 -
Nutrients Aug 2020Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity,... (Review)
Review
Nutritional optic neuropathy is a cause of bilateral, symmetrical, and progressive visual impairment with loss of central visual acuity and contrast sensitivity, dyschromatopsia, and a central or centrocecal scotoma. The clinical features are not pathognomonic, since hereditary and toxic forms share similar signs and symptoms. It is becoming increasingly common due to the widespread of bariatric surgery and strict vegetarian or vegan diets, so even the scientific interest has recently increased. In particular, recent studies have focused on possible pathogenetic mechanisms, and on novel diagnostic and therapeutic strategies in order to prevent the onset, make a prompt diagnosis and an accurate nutritional supplementation, and to avoid irreversible optic nerve atrophy. Nowadays, there is clear evidence of the role of cobalamin, folic acid, thiamine, and copper, whereas further studies are needed to define the role of niacin, riboflavin, and pyridoxine. This review aims to summarize the etiology, diagnosis, and treatment of nutritional optic neuropathy, and it is addressed not only to ophthalmologists, but to all physicians who could come in contact with a patient with a possible nutritional optic neuropathy, being a fundamental multidisciplinary approach.
Topics: Copper; Folic Acid; Humans; Niacin; Optic Neuritis; Pyridoxine; Riboflavin; Thiamine; Vision Disorders; Visual Acuity; Vitamin B 12
PubMed: 32878163
DOI: 10.3390/nu12092653 -
Tropical Medicine & International... Apr 2023Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Arboviruses are emerging as a relevant threat to transfusion safety. Pathogen inactivation methods (PIMs) may reduce the risk of transmission through transfusion, as long as they meet minimum standards for effectiveness. This study aims to assess the log reduction of viral load achieved with different PIMs, according to the blood product they are used on and the arbovirus targeted.
METHODS
Systematic literature review and meta-analysis. Searches were conducted in MEDLINE and Embase. The study protocol was registered in PROSPERO CRD42022312061. We selected records reporting the log reduction of viral load achieved with the main PIMs (amotosalen + UVA light [INTERCEPT], riboflavin + UV light [Mirasol], methylene blue + visible light/UVC light [THERAFLEX], solvent detergent, amustaline [INTERCEPT] and PEN110 [Inactine]), applied to any blood product (plasma, platelets, red blood cells or whole blood) and for any arbovirus. The log reduction of viral loads was assessed by obtaining the mean log reduction factor (LRF). We compared and classified the LRF of different techniques using statistical methods.
RESULTS
We included 59 publications reporting LRF results in 17 arboviruses. For 13 arboviruses, including Chikungunya virus, Dengue virus, West Nile virus and Zika virus, at least one of the methods achieves adequate or optimal log reduction of viral load-mean LRF ≥4. The LRF achieved with riboflavin + UV light is inferior to the rest of the techniques, both overall and specifically for plasma, platelets preserved in platelet additive solution (PAS)/plasma, and red blood cells/whole blood. The LRF achieved using Mirasol is also lower for inactivating Chikungunya virus, Dengue virus and Zika virus. For West Nile virus, we found no significant differences. In plasma, the method that achieves the highest LRF is solvent/detergent; in platelets, THERAFLEX and INTERCEPT; and in red blood cells/whole blood, PEN110 (Inactine).
CONCLUSION
Not all PIMs achieve the same LRF, nor is this equivalent between the different arboviruses or blood products. Overall, the LRFs achieved using riboflavin + UV light (Mirasol) are inferior to those achieved with the rest of the PIMs. Regarding the others, LRFs vary by arbovirus and blood product. In light of the threat of different arboviruses, blood establishments should have already validated PIMs and be logistically prepared to implement these techniques quickly.
Topics: Humans; Arboviruses; Detergents; Polyamines; Zika Virus; Riboflavin; Zika Virus Infection
PubMed: 36806816
DOI: 10.1111/tmi.13863 -
Poultry Science Apr 2021In a companion study, we found that inclusion of different doses of riboflavin affected growth performance of Ross 708 male broilers' responses to coccidial challenge...
In a companion study, we found that inclusion of different doses of riboflavin affected growth performance of Ross 708 male broilers' responses to coccidial challenge (by 5 Eimeria spp on day 14 of age) and dietary Bacillus subtilis (B. subtilis) supplementation. The current study was conducted to further test whether supplementation of B. subtilis and riboflavin will reduce negative impact and inflammation caused by Eimeria spp proliferation and help proper function of internal organs. A total of 1,248 Ross × Ross 708 male broiler chicks were randomly placed in 96 floor pens (8 blocks, 12 treatments). Treatments were arranged in a 3 (riboflavin) × 2 (B. subtilis) × 2 (Coccidial challenge) factorial arrangement in a randomized complete block design. Coccidial challenge reduced the weight of sampled birds on day 27 and day 36 and increased the relative weights of the internal organs of proventriculus, duodenum, jejunum, ileum, and spleen to BW on day 27, which may be because of inflammation caused by proliferation of Eimeria spp. The increased relative weights of duodenum, jejunum, ileum, and spleen on coccidial challenged birds were lost on day 36. Correlation analysis also indicated that the jejunum weight was positively related to villus height, Eimeria acervulina, and Eimeria maxima on day 27 but was not on day 36. The loss of the positive relationships may be because of recovery of the birds from coccidiosis on day 36. Even though the coccidial challenge and riboflavin interactively affected feed conversion ratio and BW gain and supplementation of dietary B. subtilis reduced mortality from day 35 to 42 in the companion study, the same response of internal organs was not observed in the current study. Coccidial challenge compromised development of internal organs of Ross 708 male broilers at an early age, but the negative effects subsided with age of birds rather than supplementation of riboflavin and B. subtilis at current tested levels under our experimental set up.
Topics: Animal Feed; Animals; Bacillus subtilis; Chickens; Coccidiosis; Diet; Dietary Supplements; Male; Poultry Diseases; Riboflavin
PubMed: 33588345
DOI: 10.1016/j.psj.2020.12.070 -
Scientific Reports Nov 2022Tartrazine is a synthetic yellowish dye considered one of the most common food colorants. Extensive usage of tartrazine in humans led to harmful health impacts. To...
Tartrazine is a synthetic yellowish dye considered one of the most common food colorants. Extensive usage of tartrazine in humans led to harmful health impacts. To investigate the impact of tartrazine administration on the cerebellum and to assess the potential role of riboflavin co-administration in the adult male albino rat. Four groups of adult albino rats were included in this study. Group I was supplied with distilled water. Group II was supplied tartrazine orally at a dose of 7.5 mg/kg BW dissolved in distilled water. Group III was supplied with tartrazine at the same previously mentioned dose and riboflavin orally at a dose of 25 mg/kg BW dissolved in distilled water. Group IV was supplied with riboflavin at the same previously mentioned dose. The study was conducted for 30 days then rats were sacrificed, weighted and the cerebella extracted and handled for light, ultrastructural and immunohistochemical evaluation. It was found with tartrazine treatment focal areas of Purkinje cell loss leaving empty spaces, a broad spread of neuronal affection to the degree of the disappearance of some of the granular cells, reduced the thickness of the molecular and granular layers, and strong positive GFAP immunoreactions. With riboflavin coadministration restored continuous Purkinje layer with normal appeared Purkinje cells, but some cells were still shrunken and vacuolated as well as the molecular and granular cell layers appeared normal. Tartrazine had deleterious effects on the cerebellar cytoarchitecture, and riboflavin co-administration alleviated these neurotoxic effects.
Topics: Male; Rats; Cerebellar Cortex; Food Coloring Agents; Riboflavin; Tartrazine; Animals
PubMed: 36369258
DOI: 10.1038/s41598-022-23894-3 -
Proceedings of the National Academy of... Nov 2021Heme, a porphyrin ring complexed with iron, is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains...
Heme, a porphyrin ring complexed with iron, is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains of life, and is thus considered essential for respiring organisms. Several microbial groups are known to lack the de novo heme biosynthetic pathway and therefore require exogenous heme from the environment. These heme auxotroph groups are largely limited to pathogens, symbionts, or microorganisms living in nutrient-replete conditions, whereas the complete absence of heme biosynthesis is extremely rare in free-living organisms. Here, we show that the acI lineage, a predominant and ubiquitous free-living bacterial group in freshwater habitats, is auxotrophic for heme, based on the experimental or genomic evidence. We found that two recently cultivated acI isolates require exogenous heme for their growth. One of the cultured acI isolates also exhibited auxotrophy for riboflavin. According to whole-genome analyses, all ( = 20) isolated acI strains lacked essential enzymes necessary for heme biosynthesis, indicating that heme auxotrophy is a conserved trait in this lineage. Analyses of >24,000 representative genomes for species clusters of the Genome Taxonomy Database revealed that heme auxotrophy is widespread across abundant but not-yet-cultivated microbial groups, including , (SAR406), (OM1), and Marine groups IIb and III of Our findings indicate that heme auxotrophy is a more common phenomenon than previously thought, and may lead to use of heme as a growth factor to increase the cultured microbial diversity.
Topics: Archaea; Bacteria; Biodiversity; Biosynthetic Pathways; Ecosystem; Fresh Water; Genome, Bacterial; Heme; Riboflavin
PubMed: 34785591
DOI: 10.1073/pnas.2102750118 -
Molecular Medicine (Cambridge, Mass.) Oct 2023High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue.
METHODS
Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab.
RESULTS
Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01).
CONCLUSION
FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.
Topics: Humans; Vitamin B Complex; Thiamine; Fatigue Syndrome, Chronic; Riboflavin; Inflammatory Bowel Diseases
PubMed: 37880581
DOI: 10.1186/s10020-023-00741-3 -
Proceedings of the National Academy of... Nov 2022Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic (EHEC) colonizes and causes diseases. Sensing environmental signals to...
Riboflavin is produced by most commensal bacteria in the human colon, where enterohemorrhagic (EHEC) colonizes and causes diseases. Sensing environmental signals to site-specifically express the type-III secretion system (T3SS), which injects effectors into host cells leading to intestinal colonization and disease, is key to the pathogenesis of EHEC. Here, we reveal that EHEC O157:H7, a dominant EHEC serotype frequently associated with severe diseases, acquired a previously uncharacterized two-component regulatory system , which senses microbiota-produced riboflavin to directly activate the expression of LEE genes encoding the T3SS in the colon. is present in O157:H7 and O145:H28 but absent from other EHEC serotypes. The binding site of RbfR through which it regulates LEE gene expression was identified and is conserved in all EHEC serotypes and , a surrogate for EHEC in mice. Introducing into enabled bacteria to sense microbiota-produced riboflavin in the mouse colon to increase the expression of LEE genes, causing increased disease severity in mice. Phylogenic analysis showed that the O55:H7 ancestor of O157:H7 obtained which has been kept in O157:H7 since then. Thus, acquiring represents an essential step in the evolution of the highly pathogenic O157:H7. The expression of LEE genes and cell attachment ability of other EHEC serotypes in the presence of riboflavin significantly increased when was introduced into them, indicating that those serotypes are ready to use RbfSR to increase their pathogenicity. This may present a potential public health issue as horizontal gene transfer is frequent in enteric bacteria.
Topics: Animals; Humans; Mice; Enterohemorrhagic Escherichia coli; Escherichia coli O157; Microbiota; Riboflavin; Virulence; Intestines
PubMed: 36409903
DOI: 10.1073/pnas.2212436119 -
Accounts of Chemical Research Sep 2021Over the past decade, we have contributed to the chemistry of microbial natural products and synthetic ligands, related to riboflavin and uracils, that modulate immune...
Over the past decade, we have contributed to the chemistry of microbial natural products and synthetic ligands, related to riboflavin and uracils, that modulate immune cells called mucosal associated invariant T cells (MAIT cells). These highly abundant T lymphocytes were only discovered in 2003 and have become recognized for their importance in mammalian immunology. Unlike other T cells, MAIT cells are not activated by peptide or lipid antigens. In collaboration with immunology and structural biology research groups, we discovered that they are instead activated by unstable nitrogen-containing heterocycles synthesized by bacteria. The most potent naturally occurring activating compound (antigen) is -(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU). This compound is an imine (Schiff base) formed through condensation between an intermediate in the biosynthesis of riboflavin (vitamin B2) and a metabolic byproduct of mammalian and microbial glycolysis. Although it is very unstable in water due to intramolecular ring closure or hydrolysis, we were able to develop a non-enzymatic synthesis that yields a pure kinetically stable compound in a nonaqueous solvent. This compound has revolutionized the study of MAIT cell immunology due to its potent activation (EC = 2 pM) of MAIT cells and its development into immunological reagents for detecting and characterizing MAIT cells in tissues. MAIT cells are now linked to key physiological processes and disease, including antibacterial defense, tissue repair, regulation of graft--host disease, gastritis, inflammatory bowel diseases, and cancer. 5-OP-RU activates MAIT cells and, like a vaccine, has been shown to protect mice from bacterial infections and cancers. Mechanistic studies on the binding of 5-OP-RU to its dual protein targets, the major histocompatibility complex class I related protein (MR1) and the MAIT cell receptor (MAIT TCR), have involved synthetic chemistry, 2D H NMR spectroscopy, mass spectrometry, computer modeling and molecular dynamics simulations, biochemical, cellular, and immunological assays, and protein structural biology. These combined studies have revealed structural influences for 5-OP-RU in solution on protein binding and antigen presentation and potency; informed the development of potent (EC = 2 nM) and water stable analogues; led to fluorescent analogues for detecting and tracking binding proteins in and on cells; and enabled discovery of drugs and drug-like molecules that bind MR1 and modulate MAIT cell function. MAIT cells offer new opportunities for chemical synthesis to enhance the stability, potency, selectivity, and bioavailability of small molecule ligands for MR1 or MAIT TCR proteins, and to contribute to the understanding of T cell immunity and the development of prospective new immunomodulating medicines.
Topics: Animals; Antigens; Folic Acid; Humans; Molecular Structure; Mucosal-Associated Invariant T Cells; Protein Folding; Riboflavin; Structure-Activity Relationship
PubMed: 34415738
DOI: 10.1021/acs.accounts.1c00359