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Showing papers on "B vitamins published in 2019"


Journal ArticleDOI
TL;DR: The composition and function of the intestinal microbiota may affect host B vitamin usage and, by extension, host immunity, and the immunological functions of B vitamins and their metabolism by intestinal bacteria with respect to the control of host immunity are reviewed.
Abstract: Vitamins are micronutrients that have physiological effects on various biological responses, including host immunity. Therefore, vitamin deficiency leads to increased risk of developing infectious, allergic, and inflammatory diseases. Since B vitamins are synthesized by plants, yeasts, and bacteria, but not by mammals, mammals must acquire B vitamins from dietary or microbial sources, such as the intestinal microbiota. Similarly, some intestinal bacteria are unable to synthesize B vitamins and must acquire them from the host diet or from other intestinal bacteria for their growth and survival. This suggests that the composition and function of the intestinal microbiota may affect host B vitamin usage and, by extension, host immunity. Here, we review the immunological functions of B vitamins and their metabolism by intestinal bacteria with respect to the control of host immunity.

288 citations


Journal ArticleDOI
TL;DR: The mechanisms of action of the dietary components of the Mediterranean diet are reviewed in prevention of cardiovascular disease, stroke, age-associated cognitive decline and Alzheimer disease, and the important dietary role of cereal grains in Prevention of coronary disease and stroke is reviewed.

186 citations


Journal ArticleDOI
TL;DR: Improved knowledge of how exposure-induced change in DNAm impacts health, both acutely and chronically, may enable preventative and remedial strategies to reduce morbidity in polluted environments.
Abstract: Air pollution exposure is estimated to contribute to approximately seven million early deaths every year worldwide and more than 3% of disability-adjusted life years lost. Air pollution has numerous harmful effects on health and contributes to the development and morbidity of cardiovascular disease, metabolic disorders, and a number of lung pathologies, including asthma and chronic obstructive pulmonary disease (COPD). Emerging data indicate that air pollution exposure modulates the epigenetic mark, DNA methylation (DNAm), and that these changes might in turn influence inflammation, disease development, and exacerbation risk. Several traffic-related air pollution (TRAP) components, including particulate matter (PM), black carbon (BC), ozone (O3), nitrogen oxides (NOx), and polyaromatic hydrocarbons (PAHs), have been associated with changes in DNAm; typically lowering DNAm after exposure. Effects of air pollution on DNAm have been observed across the human lifespan, but it is not yet clear whether early life developmental sensitivity or the accumulation of exposures have the most significant effects on health. Air pollution exposure-associated DNAm patterns are often correlated with long-term negative respiratory health outcomes, including the development of lung diseases, a focus in this review. Recently, interventions such as exercise and B vitamins have been proposed to reduce the impact of air pollution on DNAm and health. Ultimately, improved knowledge of how exposure-induced change in DNAm impacts health, both acutely and chronically, may enable preventative and remedial strategies to reduce morbidity in polluted environments.

166 citations


Journal ArticleDOI
TL;DR: Symbiotic microalgae–bacteria consortia could be utilized to improve microalgal biomass production and to enrich the biomass with valuable chemical and energy compounds and the suitable control of such biological interactions betweenmicroalgae and bacteria will help to improve the microAlgae‐based biomass and biofuel production in the future.
Abstract: Photosynthetic microalgae can capture solar energy and convert it to bioenergy and biochemical products In nature or industrial processes, microalgae live together with bacterial communities and may maintain symbiotic relationships In general interactions, microalgae exude dissolved organic carbon that becomes available to bacteria In return, the bacteria remineralize sulphur, nitrogen and phosphorous to support the further growth of microalgae In specific interactions, heterotrophic bacteria supply B vitamins as organic cofactors or produce siderophores to bind iron, which could be utilized by microalgae, while the algae supply fixed carbon to the bacteria in return In this review, we focus on mutualistic relationship between microalgae and bacteria, summarizing recent studies on the mechanisms involved in microalgae-bacteria symbiosis Symbiotic bacteria on promoting microalgal growth are described and the relevance of microalgae-bacteria interactions for biofuel production processes is discussed Symbiotic microalgae-bacteria consortia could be utilized to improve microalgal biomass production and to enrich the biomass with valuable chemical and energy compounds The suitable control of such biological interactions between microalgae and bacteria will help to improve the microalgae-based biomass and biofuel production in the future

151 citations


Journal ArticleDOI
TL;DR: The possible role of HHcy in neurodegenerative disease and stroke is reviewed to understand its pathogenesis and whether patients should be routinely screened for homocysteine.
Abstract: Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke. The aim of our research is to review the possible role of HHcy in neurodegenerative disease and stroke and to understand its pathogenesis.

141 citations


Journal ArticleDOI
TL;DR: This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS.
Abstract: Recent evidence suggests that immunotherapy efficacy in melanoma is modulated by gut microbiota. Few studies have examined this phenomenon in humans, and none have incorporated metatranscriptomics, important for determining expression of metagenomic functions in the microbial community. In melanoma patients undergoing immunotherapy, gut microbiome was characterized in pre-treatment stool using 16S rRNA gene and shotgun metagenome sequencing (n = 27). Transcriptional expression of metagenomic pathways was confirmed with metatranscriptome sequencing in a subset of 17. We examined associations of taxa and metagenomic pathways with progression-free survival (PFS) using 500 × 10-fold cross-validated elastic-net penalized Cox regression. Higher microbial community richness was associated with longer PFS in 16S and shotgun data (p < 0.05). Clustering based on overall microbiome composition divided patients into three groups with differing PFS; the low-risk group had 99% lower risk of progression than the high-risk group at any time during follow-up (p = 0.002). Among the species selected in regression, abundance of Bacteroides ovatus, Bacteroides dorei, Bacteroides massiliensis, Ruminococcus gnavus, and Blautia producta were related to shorter PFS, and Faecalibacterium prausnitzii, Coprococcus eutactus, Prevotella stercorea, Streptococcus sanguinis, Streptococcus anginosus, and Lachnospiraceae bacterium 3 1 46FAA to longer PFS. Metagenomic functions related to PFS that had correlated metatranscriptomic expression included risk-associated pathways of l-rhamnose degradation, guanosine nucleotide biosynthesis, and B vitamin biosynthesis. This work adds to the growing evidence that gut microbiota are related to immunotherapy outcomes, and identifies, for the first time, transcriptionally expressed metagenomic pathways related to PFS. Further research is warranted on microbial therapeutic targets to improve immunotherapy outcomes.

112 citations


Journal ArticleDOI
TL;DR: The current state of development and challenges for fermentative processes for the B vitamin group are reviewed.

91 citations


Journal ArticleDOI
TL;DR: This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples.
Abstract: The human gut microbiome harbors a diverse array of metabolic pathways contributing to its development and homeostasis via a complex web of diet-dependent metabolic interactions within the microbial community and host. Genomics-based reconstruction and predictive modeling of these interactions would provide a framework for diagnostics and treatment of dysbiosis-related syndromes via rational selection of therapeutic prebiotics and dietary nutrients. Of particular interest are micronutrients, such as B-group vitamins, precursors of indispensable metabolic cofactors, that are produced de novo by some gut bacteria (prototrophs) but must be provided exogenously in the diet for many other bacterial species (auxotrophs) as well as for the mammalian host. Cross-feeding of B vitamins between prototrophic and auxotrophic species is expected to strongly contribute to the homeostasis of microbial communities in the distal gut given the efficient absorption of dietary vitamins in the upper gastrointestinal tract. To confidently estimate the balance of microbiome micronutrient biosynthetic capabilities and requirements using available genomic data, we have performed a subsystems-based reconstruction of biogenesis, salvage and uptake for eight B vitamins (B1, B2, B3, B5, B6, B7, B9, and B12) and queuosine (essential factor in tRNA modification) over a reference set of 2,228 bacterial genomes representing 690 cultured species of the human gastrointestinal microbiota. This allowed us to classify the studied organisms with respect to their pathway variants and infer their prototrophic vs. auxotrophic phenotypes. In addition to canonical vitamin pathways, several conserved partial pathways were identified pointing to alternative routes of syntrophic metabolism and expanding a microbial vitamin "menu" by several pathway intermediates (vitamers) such as thiazole, quinolinate, dethiobiotin, pantoate. A cross-species comparison was applied to assess the extent of conservation of vitamin phenotypes at distinct taxonomic levels (from strains to families). The obtained reference collection combined with 16S rRNA gene-based phylogenetic profiles was used to deduce phenotype profiles of the human gut microbiota across in two large cohorts. This analysis provided the first estimate of B-vitamin requirements, production and sharing capabilities in the human gut microbiome establishing predictive phenotype profiling as a new approach to classification of microbiome samples. Future expansion of our reference genomic collection of metabolic phenotypes will allow further improvement in coverage and accuracy of predictive phenotype profiling of the human microbiome.

89 citations


Journal ArticleDOI
TL;DR: Two genome duplication events before the divergence from walnut were found in these species, and key genes in biotic and abiotic tolerance, oil, polyphenols, essential amino acids, and B vitamins were highlighted.
Abstract: BACKGROUND Pecan (Carya illinoinensis) and Chinese hickory (C. cathayensis) are important commercially cultivated nut trees in the genus Carya (Juglandaceae), with high nutritional value and substantial health benefits. RESULTS We obtained >187.22 and 178.87 gigabases of sequence, and ∼288× and 248× genome coverage, to a pecan cultivar ("Pawnee") and a domesticated Chinese hickory landrace (ZAFU-1), respectively. The total assembly size is 651.31 megabases (Mb) for pecan and 706.43 Mb for Chinese hickory. Two genome duplication events before the divergence from walnut were found in these species. Gene family analysis highlighted key genes in biotic and abiotic tolerance, oil, polyphenols, essential amino acids, and B vitamins. Further analyses of reduced-coverage genome sequences of 16 Carya and 2 Juglans species provide additional phylogenetic perspective on crop wild relatives. CONCLUSIONS Cooperative characterization of these valuable resources provides a window to their evolutionary development and a valuable foundation for future crop improvement.

82 citations


Journal ArticleDOI
TL;DR: A nuanced view of bacterial–phytoplankton interactions is provided, emphasising the complexity of the sources, sinks and dynamic cycling between marine microbes of these important organic micronutrients.
Abstract: Ostreococcus tauri, a picoeukaryotic alga that contributes significantly to primary production in oligotrophic waters, has a highly streamlined genome, lacking the genetic capacity to grow without the vitamins thiamine (B1) and cobalamin (B12). Here we demonstrate that the B12 and B1 auxotrophy of O. tauri can be alleviated by co-culturing with a heterotrophic bacterial partner Dinoroseobacter shibae, a member of the Rhodobacteraceae family of alpha-proteobacteria, genera of which are frequently found associated with marine algae. D. shibae lacks the complete pathway to synthesise three other B-vitamins: niacin (B3), biotin (B7), and p-aminobenzoic acid (a precursor for folate, B9), and the alga is in turn able to satisfy the reciprocal vitamin requirements of its bacterial partner in a stable long-term co-culture. Bioinformatics searches of 197 representative marine bacteria with sequenced genomes identified just nine species that had a similar combination of traits (ability to make vitamin B12, but missing one or more genes for niacin and biotin biosynthesis enzymes), all of which were from the Rhodobacteraceae. Further analysis of 70 species from this family revealed the majority encoded the B12 pathway, but only half were able to make niacin, and fewer than 13% biotin. These characteristics may have either contributed to or resulted from the tendency of members of this lineage to adopt lifestyles in close association with algae. This study provides a nuanced view of bacterial-phytoplankton interactions, emphasising the complexity of the sources, sinks and dynamic cycling between marine microbes of these important organic micronutrients.

78 citations


Journal ArticleDOI
TL;DR: This narrative review provides a comprehensive overview of the present knowledge of mitochondrial function during and after critical illness and the role and potential therapeutic applications of specific micronutrients to restore mitochondrial function.

Journal ArticleDOI
TL;DR: A diverse diet and regular exposure to sunlight are the best sources for a balanced nutrient supply to maintain an optimal immune defence.
Abstract: Objective This narrative review gives an overview on the essential role of adequate nutrition to an optimally functioning immune defence. Micronutrients act as regulators of the immune response, with the focus of this review on the immunomodulatory effects of the trace elements iron, zinc and selenium, and the vitamins A, D, E, C, B6 and B12 and folic acid. Results Iron deficiency especially impairs the Th1 cell-borne cellular immunity. T lymphocytes are also most affected by a deficiency of zinc, needed for their maturation and the balance between the different T cell subpopulations and acting as a redox signal in the regulation of many enzymes. Selenium is also involved in redox reactions as the glutathione peroxidases and other redox enzymes are selenoproteins. Selenium status has shown special effects on cellular immunity and resistance to viral infections. Vitamin A in the form of retinoic acid induces a humoral Th2 cell response via antigen-presenting cells and is involved in maintaining intestinal immune defence and tolerance through its nuclear receptor RAR and via kinase signalling cascades. Immune tolerance is particularly promoted by vitamin D acting through dendritic cells to stimulate the differentiation of regulatory T cells. Vitamin E has antiinflammatory effects and stimulates naive T cells especially in the elderly. Besides its antioxidative properties, vitamin C has effects on cell signalling and epigenetic regulation. The B vitamins are required for cytotoxic cellular immunity and modulate T cell responses. Conclusion A diverse diet and regular exposure to sunlight are the best sources for a balanced nutrient supply to maintain an optimal immune defence.

Journal ArticleDOI
TL;DR: The stability of gut microbiota is reported using humanized gnotobiotic mice and in vitro anaerobic fecal culture in the context of extreme variations of dietary B-vitamin supply as revealed by phylotype-to-phenotype prediction from 16S rRNA profiling and metabolomic measurements.
Abstract: Cross-feeding on intermediary and end-point metabolites plays an important role in the dynamic interactions of host-associated microbial communities. While gut microbiota possess inherent resilience to perturbation, variations in the intake of certain nutrients may lead to changes in the community composition with potential consequences on host physiology. Syntrophic relationships and mutualism at the level of major carbon and energy sources have been documented, however, relatively little is known about metabolic interactions involving micronutrients, such as B-vitamins, biosynthetic precursors of essential cofactors in the mammalian host and numerous members of the gut microbiota alike. In silico genomic reconstruction and prediction of community-wide metabolic phenotypes for eight major B-vitamins (B1, B2, B3, B5, B6, B7, B9, and B12), suggests that a significant fraction of microbial gut communities (>20% by abundance) are represented by auxotrophic species whose viability is strictly dependent on acquiring one or more B-vitamins from diet and/or prototrophic microbes via committed salvage pathways. Here, we report the stability of gut microbiota using humanized gnotobiotic mice and in vitro anaerobic fecal culture in the context of extreme variations of dietary B-vitamin supply as revealed by phylotype-to-phenotype prediction from 16S rRNA profiling and metabolomic measurements. The observed nearly unaltered relative abundance of auxotrophic species in gut communities in the face of diet or media lacking B-vitamins or containing them in great excess (∼30-fold above normal) points to a strong contribution of metabolic cooperation (B-vitamin exchange and sharing) to the stability of gut bacterial populations.

Journal ArticleDOI
TL;DR: Light is shed on the contributions of microbial folate to overall folate status and mammalian host metabolism through the evaluation of expression of select folate synthesis genes, quantification of total folate production, and analysis of folate polyglutamylation.
Abstract: Microbial metabolites, including B complex vitamins contribute to diverse aspects of human health. Folate, or vitamin B9, refers to a broad category of biomolecules that include pterin, para-aminobenzoic acid (pABA), and glutamate subunits. Folates are required for DNA synthesis and epigenetic regulation. In addition to dietary nutrients, the gut microbiota has been recognized as a source of B complex vitamins, including folate. This study evaluated the predicted folate synthesis capabilities in the genomes of human commensal microbes identified in the Human Microbiome Project and folate production by representative strains of six human intestinal bacterial phyla. Bacterial folate synthesis genes were ubiquitous across 512 gastrointestinal reference genomes with 13% of the genomes containing all genes required for complete de novo folate synthesis. An additional 39% of the genomes had the genetic capacity to synthesize folates in the presence of pABA, an upstream intermediate that can be obtained through diet or from other intestinal microbes. Bacterial folate synthesis was assessed during exponential and stationary phase growth through the evaluation of expression of select folate synthesis genes, quantification of total folate production, and analysis of folate polyglutamylation. Increased expression of key folate synthesis genes was apparent in exponential phase, and increased folate polyglutamylation occurred during late stationary phase. Of the folate producers, we focused on the commensal Lactobacillus reuteri to examine host-microbe interactions in relation to folate and examined folate receptors in the physiologically relevant human enteroid model. RNAseq data revealed segment-specific folate receptor distribution. Treatment of human colonoid monolayers with conditioned media (CM) from wild-type L. reuteri did not influence the expression of key folate transporters proton-coupled folate transporter (PCFT) or reduced folate carrier (RFC). However, CM from L. reuteri containing a site-specific inactivation of the folC gene, which prevents the bacteria from synthesizing a polyglutamate tail on folate, significantly upregulated RFC expression. No effects were observed using L. reuteri with a site inactivation of folC2, which results in no folate production. This work sheds light on the contributions of microbial folate to overall folate status and mammalian host metabolism.

Journal ArticleDOI
TL;DR: The equation between abundance of vitamin-biosynthetic enzymes and vitamin-dependent enzymes suggests that the production and utilization potential of these enzymes seems way more complex usage allocations than just mere direct linear associations.
Abstract: Human gut microbial communities have been known to produce vitamins, which are subsequently absorbed by the host in the large intestine. However, the relationship between species with vitamin pathway associated functional features or their gene abundance in different states of health and disease is lacking. Here, we analyzed shotgun fecal metagenomes of individuals from four different countries for genes that are involved in vitamin biosynthetic pathways and transport mechanisms and corresponding species’ abundance. We found that the prevalence of these genes were found to be distributed across the dominant phyla of gut species. The number of positive correlations were high between species harboring genes related to vitamin biosynthetic pathways and transporter mechanisms than that with either alone. Although, the range of total gene abundances remained constant across healthy populations at the global level, species composition and their presence for metabolic pathway related genes determine the abundance and functional genetic content of vitamin metabolism. Based on metatranscriptomics data, the equation between abundance of vitamin-biosynthetic enzymes and vitamin-dependent enzymes suggests that the production and utilization potential of these enzymes seems way more complex usage allocations than just mere direct linear associations. Our findings provide a rationale to examine and disentangle the interrelationship between B-vitamin dosage (dietary or microbe-mediated) on gut microbial members and the host, in the gut microbiota of individuals with under- or overnutrition.

Journal ArticleDOI
TL;DR: In this article, the effects of glow discharge plasma on siriguela juice quality were investigated through an experimental design changing the processing time (5-15min) and the nitrogen gas flow rate (10-30mL/min). Selected physicochemical properties and bioactive compounds were evaluated pre and post-processing.
Abstract: The effects of glow discharge plasma on siriguela (purple mombin) juice quality were investigated through an experimental design changing the processing time (5–15 min) and the nitrogen gas flow rate (10–30 mL/min). Selected physicochemical properties and bioactive compounds were evaluated pre- and post-processing. No significant changes were found for vitamin C, and the processing did not affect the color of the product. Pigments, total phenolics, antioxidant activity, and B vitamins were increased due to the plasma processing. An increase in antioxidant activity was also observed. Polyphenol oxidase activity showed a decrease of about 20% (20 mL/min of N2/15 min), whereas peroxidase presented a slight activation (6%) in some processing conditions. The plasma processing imparted a positive or an adverse effect on the bioactive compounds in siriguela juice showing the importance of the optimization of food processing by cold plasma for real application. This behavior is related to the time intensity of the treatment, which can promote the extraction of the bioactive compound from the juice pulp followed by degradation at higher times or processing intensity. Due to the low pH of siriguela juice, no microbial contamination was found in the processed juices.

Journal ArticleDOI
TL;DR: The ecological role of essential nutritional biomolecules (fatty acids (FA), amino acids (AA), sterols, vitamins) in aquatic and terrestrial food webs, encompassing the forces behind their environmental distribution is reviewed, offering a great advantage for their use as trophic markers.
Abstract: We here review the ecological role of essential nutritional biomolecules (fatty acids (FA), amino acids (AA), sterols, vitamins) in aquatic and terrestrial food webs, encompassing the forces behind their environmental distribution. Across ecosystems, mutualistic relationships frequently ensure exchanges of vitamins between producer and demander, especially between B12 and other B vitamins as well as the AA methionine. In contrast, FA, sterols and most AA are transferred up the food chain via classical predator-prey interactions, and therefore have good biomarker potential for trophic interactions. As biomass-flow depends on the absolute amounts of potential limiting biomolecules, considering solely their relative proportion in resources may under- or overestimate the availability for consumers. Moreover, if not accounted for, “hidden” trophic channels such as gut symbionts as well as metabolic conversion of precursor molecules can hamper food web analyses. Fundamental differences exist between aquatic and terrestrial ecosystems: Vitamin B12 produced by ammonium oxidizing Archaea is essential to many aquatic algae, whereas terrestrial plants escaped this dependency by using B12 independent enzymes. Long-chain 3 polyunsaturated FA (LC-3 PUFA) in aquatic systems mainly originate from planktonic algae, while in terrestrial systems belowground invertebrates can well be a source, also supporting aboveground biota. Interlinks from terrestrial to aquatic ecosystems are biochemically of total different nature than vice versa. While biomass rich in proteins and LC-3 PUFA is transferred to land, e.g. by trophic relationships, the link from terrestrial to aquatic ecosystems provides recalcitrant plant carbon, mainly devoid of essential nutrients, fuelling detrital food chains. Recent global changes influence food webs via altered input and transfer of essential biomolecules, but separating the effects of nutrients, CO2, and warming is not trivial. Current evolutionary concepts (e.g. Black Queen, relaxed selection) considering the costs of metabolic production partly explain food web dynamics, especially for vitamins, whereas adaptations to potential oxidative stress seem to be more important for LC-PUFA. Overall, for both heterotrophs and auxotrophs, the provision with essential biomolecules is precious. As these valuable nutrients often are kept unaltered in consumer metabolism, even in their stable isotope composition, offers a great advantage for their use as trophic markers.

Journal ArticleDOI
TL;DR: Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocy steine using B vitamins.
Abstract: Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. The objectives of this study were to examine the efficacy of treatment with vitamin B12, vitamin B6, or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval − 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval − 0.10 to 0.18) cognitive impairment compared to placebo. Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

Journal ArticleDOI
TL;DR: Both the pulp and the other parts of the plant (leaves and seeds) present antioxidant, anti-hypertensive, hypoglycemic, and hypolipidemic actions, which, in turn, can contribute to the prevention and treatment of obesity and associated metabolic disorders.
Abstract: Carica papaya L. is a well-known fruit worldwide, and its highest production occurs in tropical and subtropical regions. The pulp contains vitamins A, C, and E, B complex vitamins, such as pantothenic acid and folate, and minerals, such as magnesium and potassium, as well as food fibers. Phenolic compounds, such as benzyl isothiocyanate, glucosinolates, tocopherols (α and δ), β-cryptoxanthin, β-carotene and carotenoids, are found in the seeds. The oil extracted from the seed principally presents oleic fatty acid followed by palmitic, linoleic and stearic acids, whereas the leaves have high contents of food fibers and polyphenolic compounds, flavonoids, saponins, pro-anthocyanins, tocopherol, and benzyl isothiocyanate. Studies demonstrated that the nutrients present in its composition have beneficial effects on the cardiovascular system, protecting it against cardiovascular illnesses and preventing harm caused by free radicals. It has also been reported that it aids in the treatment of diabetes mellitus and in the reduction of cholesterol levels. Thus, both the pulp and the other parts of the plant (leaves and seeds) present antioxidant, anti-hypertensive, hypoglycemic, and hypolipidemic actions, which, in turn, can contribute to the prevention and treatment of obesity and associated metabolic disorders.

Journal ArticleDOI
TL;DR: The aim of this review is to explain in detail the perioperative complications of sleeve gastrectomy, their prevention and treatment, referring to the most recent available literature.
Abstract: Sleeve gastrectomy (SG) has known a spectacular rise worldwide during the last decade. The absence of digestive anastomosis simplifies the surgical technique, reducing anastomosis-related complications such as fistula, stricture and marginal ulcer. Furthermore, the respect for digestive continuity preserves the functions of pylorus, that regulates gastric emptying, and duodenum, where calcium, B vitamins and iron are absorbed. Despite the multiple advantages, SG also has specific complications such as bleeding, stenosis, portal thrombosis and leak. The staple line leak at the oesophagogastric junction is the most feared complication and its prevention remains difficult, as the involved mechanisms have been only partially elucidated. Its management is long and requires a multidisciplinary technical platform including Intensive Care Unit, digestive endoscopy and interventional radiology as well as a specialised surgeon. The aim of this review is to explain in detail the perioperative complications of SG, their prevention and treatment, referring to the most recent available literature.

Journal ArticleDOI
TL;DR: It is found that the Erwinia vitamin-biosynthetic genes not only compensate for Buchnera ’s deficiencies, but also provide a new nutritional function; whose genes have been horizontally acquired from a Sodalis -related bacterium.
Abstract: Many insects depend on obligate mutualistic bacteria to provide essential nutrients lacking from their diet. Most aphids, whose diet consists of phloem, rely on the bacterial endosymbiont Buchnera aphidicola to supply essential amino acids and B vitamins. However, in some aphid species, provision of these nutrients is partitioned between Buchnera and a younger bacterial partner, whose identity varies across aphid lineages. Little is known about the origin and the evolutionary stability of these di-symbiotic systems. It is also unclear whether the novel symbionts merely compensate for losses in Buchnera or carry new nutritional functions. Using whole-genome endosymbiont sequences of nine Cinara aphids that harbour an Erwinia-related symbiont to complement Buchnera, we show that the Erwinia association arose from a single event of symbiont lifestyle shift, from a free-living to an obligate intracellular one. This event resulted in drastic genome reduction, long-term genome stasis, and co-divergence with aphids. Fluorescence in situ hybridisation reveals that Erwinia inhabits its own bacteriocytes near Buchnera’s. Altogether these results depict a scenario for the establishment of Erwinia as an obligate symbiont that mirrors Buchnera’s. Additionally, we found that the Erwinia vitamin-biosynthetic genes not only compensate for Buchnera’s deficiencies, but also provide a new nutritional function; whose genes have been horizontally acquired from a Sodalis-related bacterium. A subset of these genes have been subsequently transferred to a new Hamiltonella co-obligate symbiont in one specific Cinara lineage. These results show that the establishment and dynamics of multi-partner endosymbioses can be mediated by lateral gene transfers between co-ocurring symbionts.

Journal ArticleDOI
TL;DR: The importance of supplementing vitamin B12 (methylcobalamin, vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD is emphasized.
Abstract: DNA methylation and other epigenetic factors are important in the pathogenesis of late-onset Alzheimer’s disease (LOAD). Methylenetetrahydrofolate reductase (MTHFR) gene mutations occur in most elderly patients with memory loss. MTHFR is critical for production of S-adenosyl-l-methionine (SAM), the principal methyl donor. A common mutation (1364T/T) of the cystathionine-γ-lyase (CTH) gene affects the enzyme that converts cystathionine to cysteine in the transsulfuration pathway causing plasma elevation of total homocysteine (tHcy) or hyperhomocysteinemia—a strong and independent risk factor for cognitive loss and AD. Other causes of hyperhomocysteinemia include aging, nutritional factors, and deficiencies of B vitamins. We emphasize the importance of supplementing vitamin B12 (methylcobalamin), vitamin B9 (folic acid), vitamin B6 (pyridoxine), and SAM to patients in early stages of LOAD.

Journal ArticleDOI
TL;DR: It is indicated that marine AOA exude a suite of organic compounds with potentially varying reactivities, dominated by nitrogen‐containing compounds, which typically limit prokaryotic heterotrophic activity in open ocean waters.
Abstract: Ammonia‐oxidizing archaea (AOA) constitute a considerable fraction of microbial biomass in the global ocean, comprising 20%–40% of the ocean's prokaryotic plankton. However, it remains enigmatic to what extent these chemolithoautotrophic archaea release dissolved organic carbon (DOC). A combination of targeted and untargeted metabolomics was used to characterize the exometabolomes of three model AOA strains of the Nitrosopumilus genus. Our results indicate that marine AOA exude a suite of organic compounds with potentially varying reactivities, dominated by nitrogen‐containing compounds. A significant fraction of the released dissolved organic matter (DOM) consists of labile compounds, which typically limit prokaryotic heterotrophic activity in open ocean waters, including amino acids, thymidine and B vitamins. Amino acid release rates corresponded with ammonia oxidation activity and the three Nitrosopumilus strains predominantly released hydrophobic amino acids, potentially as a result of passive diffusion. Despite the low contribution of DOC released by AOA (~0.08%–1.05%) to the heterotrophic prokaryotic carbon demand, the release of physiologically relevant metabolites could be crucial for microbes that are auxotrophic for some of these compounds, including members of the globally abundant and ubiquitous SAR11 clade.

Journal ArticleDOI
TL;DR: This work assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization.
Abstract: Objective Trials of B vitamin therapy to lower blood total homocysteine (tHcy) levels for prevention of stroke are inconclusive. Secondary analyses of trial data and epidemiological studies suggest that tHcy levels may be particularly associated with small vessel stroke (SVS). We assessed whether circulating tHcy and B vitamin levels are selectively associated with SVS, but not other stroke subtypes, using Mendelian randomization. Methods We used summary statistics data for single-nucleotide polymorphisms (SNPs) associated with tHcy (n = 18), folate (n = 3), vitamin B6 (n = 1), and vitamin B12 (n = 14) levels, and the corresponding data for stroke from the MEGASTROKE consortium (n = 16,952 subtyped ischemic stroke cases and 404,630 noncases). Results Genetically predicted tHcy was associated with SVS, with an odds ratio of 1.34 (95% confidence interval [CI], 1.13-1.58; p = 6.7 × 10-4 ) per 1 standard deviation (SD) increase in genetically predicted tHcy levels, but was not associated with large artery or cardioembolic stroke. The association was mainly driven by SNPs at or near the MTHFR and MUT genes. The odds ratios of SVS per 1 SD increase in genetically predicted folate and vitamin B6 levels were 0.49 (95% CI, 0.34-0.71; p = 1.3 × 10-4 ) and 0.70 (95% CI, 0.52-0.94; p = 0.02), respectively. Genetically higher vitamin B12 levels were not associated with any stroke subtype. Interpretation These findings suggest that any effect of homocysteine-lowering treatment in preventing stroke will be confined to the SVS subtype. Whether genetic variants at or near the MTHFR and MUT genes influence SVS risk through pathways other than homocysteine levels and downstream effects require further investigation. Ann Neurol 2019;85:495-501.

Journal ArticleDOI
TL;DR: Adequate dietary folate at baseline predicted a better cognitive reserve, while decreased serum levels of B vitamins may contribute to cognitive impairment by affecting methylation levels of specific redox-related genes.
Abstract: B vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether B vitamin deficiency and increased Hcy could interact with DNA methylation of oxidative-related genes and exacerbate cognitive impairment. Participants were selected from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study. We included 2533 participants who completed a selection of comprehensive cognitive tests and a semiquantitative food frequency questionnaire (FFQ) and were followed for an average of 2.3 years. The longitudinal effects of B vitamin intake on cognitive decline were examined using linear mixed-effect models. Seven mild cognitive impairment (MCI) patients, in the predementia stage of Alzheimer’s disease (AD), and fivev healthy controls were selected for the discovery of genome-wide differentially methylated CpG sites. Candidate oxidative stress-related genes significantly correlated with serum levels of B vitamins were selected for validation in 102 MCI patients and 68 controls. The correlations between DNA methylation levels and serum concentrations of B vitamins and oxidative biomarkers were analyzed with Spearman’s correlation. The interactive effects of DNA methylation and B vitamins on cognitive performance were further evaluated by multiple linear regression. In the prospective analysis, inadequate dietary intake of vitamin B12 was significantly associated with accelerated cognitive decline, whereas adequate folate, vitamin B6, and vitamin B12 intakes were significantly associated with better cognitive reserve. In the case-control analysis, the DNA methylation levels of NUDT15 and TXNRD1 were examined, and significantly hypermethylated sites were identified in MCI patients. Significant correlations of hypermethylated sites with serum levels of folate, homocysteine (Hcy), and oxidative biomarkers were observed, and interactive effects of B vitamins and hypermethylated sites were significantly associated with cognitive performance. Adequate dietary folate at baseline predicted a better cognitive reserve, while decreased serum levels of B vitamins may contribute to cognitive impairment by affecting methylation levels of specific redox-related genes. EMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610

Journal ArticleDOI
21 Jun 2019
TL;DR: The purpose of this state-of-the-art review was to update current information on deficiencies of vitamins and public health approaches to addressing them.
Abstract: Vitamin deficiencies remain major etiological factors in the global burden of disease, especially in low- and middle-income countries. The purpose of this state-of-the-art review was to update current information on deficiencies of vitamins and public health approaches to addressing them. Some stages of life present a higher risk of deficiency than others: risks are higher in pregnant women, children (from conception to young childhood), adolescents, the elderly, and all of the over 800 million people globally who are undernourished. At risk are approximately 125 million preschool children with vitamin A deficiency, as well as sub-populations at risk of deficiencies of folate, thiamin, vitamin B12, niacin, riboflavin, other B vitamins. and vitamin D. Addressing micronutrient deficiencies requires identifying those at risk and then working to prevent and manage that risk. Public health approaches include improved, diversified diets; supplementation; fortification and biofortification; and other supportive public health measures. Historically, as with pellagra and beriberi and, in the last 3 decades, with vitamin A and folic acid, there has been encouraging progress, but much remains to be done.

Journal ArticleDOI
TL;DR: The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety.
Abstract: A systematic review and meta-analysis was undertaken to examine and quantify the effects of B vitamin supplementation on mood in both healthy and ‘at-risk’ populations. A systematic search identified all available randomised controlled trials (RCTs) of daily supplementation with ≥3 B group vitamins with an intervention period of at least four weeks. Random effects models for a standardized mean difference were used to test for overall effect. Heterogeneity was tested using the I2 statistic. Eighteen articles (16 trials, 2015 participants) were included, of which 12 were eligible for meta-analysis. Eleven of the 18 articles reported a positive effect for B vitamins over a placebo for overall mood or a facet of mood. Of the eight studies in ‘at-risk’ cohorts, five found a significant benefit to mood. Regarding individual facets of mood, B vitamin supplementation benefited stress (n = 958, SMD = 0.23, 95% CI = 0.02, 0.45, p = 0.03). A benefit to depressive symptoms did not reach significance (n = 568, SMD = 0.15, 95% CI = −0.01, 0.32, p = 0.07), and there was no effect on anxiety (n = 562, SMD = 0.03, 95% CI = −0.13, 0.20, p = 0.71). The review provides evidence for the benefit of B vitamin supplementation in healthy and at-risk populations for stress, but not for depressive symptoms or anxiety. B vitamin supplementation may particularly benefit populations who are at risk due to (1) poor nutrient status or (2) poor mood status.

Journal ArticleDOI
TL;DR: It is now clear that B vitamins to lower homocysteine reduce the risk of stroke, but the authors should probably be using methylcobalamin instead of cyanocobalamin.
Abstract: Nutrition is far more important in stroke risk than most physcians suppose. Healthy lifestyle choices reduce the risk of stroke by ~80%, and of the factors that increase the risk of stroke, the worst is diet: only ~0.1% of Americans consume a healthy diet, and only 8.3% consume a somewhat healthy diet. The situation is probably not much better in most other countries. A Cretan Mediterranean diet, high in olive oil, whole grains, fruits, vegetables and legumes, and low in cholesterol and saturated fat, can reduce stroke by 40% or more in high-risk patients. The role of the intestinal microbiome in cardiovascular risk is emerging; high levels of toxic metabolites produced by intestinal bacteria from meat (particularly red meat) and egg yolk are renally excreted. Patients with renal impairment, including the elderly, should limit red meat and avoid egg yolk, as should other patients at high risk of stroke. Salt intake should be limited to 2–3 grams per day. Metabolic B12 deficiency is common and usually missed. It has serious neurological consequences, including an increase in the risk of stroke. It now clear that B vitamins to lower homocysteine reduce the risk of stroke, but we should probably be using methylcobalamin instead of cyanocobalamin.

Journal ArticleDOI
TL;DR: It is suggested that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer and should be limited to patients with a known indication, such as a proven deficiency.
Abstract: Background: Folic acid and vitamin B12 play key roles in one-carbon metabolism. Disruption of one-carbon metabolism may be involved in the risk of cancer. Our aim was to assess the long-term effect of supplementation with both folic acid and vitamin B12 on the incidence of overall cancer and on colorectal cancer in the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) trial. Methods: Long-term follow-up of B-PROOF trial participants (N = 2,524), a multicenter, double-blind randomized placebo-controlled trial designed to assess the effect of 2 to 3 years daily supplementation with folic acid (400 μg) and vitamin B12 (500 μg) versus placebo on fracture incidence. Information on cancer incidence was obtained from the Netherlands cancer registry (Integraal Kankercentrum Nederland), using the International Statistical Classification of Disease (ICD-10) codes C00–C97 for all cancers (except C44 for skin cancer), and C18–C20 for colorectal cancer. Results: Allocation to B vitamins was associated with a higher risk of overall cancer [171 (13.6%) vs. 143 (11.3%); HR 1.25; 95% confidence interval (CI), 1.00–1.53, P = 0.05]. B vitamins were significantly associated with a higher risk of colorectal cancer [43(3.4%) vs. 25(2.0%); HR 1.77; 95% CI, 1.08–2.90, P = 0.02]. Conclusions: Folic acid and vitamin B12 supplementation was associated with an increased risk of colorectal cancer. Impact: Our findings suggest that folic acid and vitamin B12 supplementation may increase the risk of colorectal cancer. Further confirmation in larger studies and in meta-analyses combining both folic acid and vitamin B12 are needed to evaluate whether folic acid and vitamin B12 supplementation should be limited to patients with a known indication, such as a proven deficiency.

Journal ArticleDOI
TL;DR: Fortified foods when eaten regularly had a positive impact on all relevant B-vitamin biomarkers, even with hyperglycaemia, and may be beneficial for maintaining better cognitive health in older people with or at risk of diabetes.
Abstract: CONTEXT Emerging evidence suggests that deficiencies of folate-related B vitamins can arise with metformin treatment and are independently linked with cognitive dysfunction, a comorbidity of diabetes. OBJECTIVE To determine the impact of hyperglycemia and metformin use on relevant B vitamin biomarkers and cognitive outcomes in older adults. SETTING AND PARTICIPANTS Community-dwelling older adults (74.1 ± 8.3 years, n = 4160) without dementia, recruited to the Trinity, Ulster and Department of Agriculture cohort study in 2008 to 2012, were classified as normoglycemic (n = 1856) or hyperglycemic, based on HbA1c ≥5.7% (39 mmol/mol), either with (n = 318) or without (n = 1986) metformin treatment. MAIN OUTCOME MEASURES Biomarkers of folate, vitamin B12, vitamin B6, and riboflavin were measured. Cognitive assessments included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) and the Frontal Assessment Battery (FAB). RESULTS Metformin use was associated with higher risk of deficiency of vitamin B12 (combined B12 index ≤-1; OR 1.45; 95% CI, 1.03 to 2.02) and vitamin B6 (plasma pyridoxal 5-phosphate <30.0 nmol/L; OR 1.48; 95% CI, 1.02 to 2.15). Fortified foods when eaten regularly had a positive impact on all relevant B vitamin biomarkers, even with hyperglycemia. After adjustment for relevant covariates, metformin use was associated with an increased risk of cognitive dysfunction as assessed with the RBANS (OR 1.36; 95% CI, 1.03 to 1.80) and FAB (OR 1.34; 95% CI, 1.03 to 1.74). CONCLUSIONS Use of metformin by older adults is associated with poorer cognitive performance; B vitamin deficiency may be implicated. Fortified foods can optimize B vitamin status and may be beneficial for maintaining better cognitive health in older people with or at risk for diabetes.