Review: State of the knowledge on the importance of folates and cobalamin for dairy cow metabolism.

Synthesis of B vitamins by the rumen microbiota is usually sufficient to avoid the appearance of clinical deficiency symptoms in dairy cows under normal feeding conditions. Nevertheless, it is now generally accepted that vitamin deficiency is much more than the appearance of major functional and morphological symptoms. Subclinical deficiency, which is present as soon as the supply is lower than the need, causes cellular metabolic changes leading to a loss of metabolic efficiency. Folates and cobalamin, two B vitamins, share close metabolic relationships. Folates act as co-substrates in one-carbon metabolism, providing one-carbon unit for DNA synthesis and de novo synthesis of methyl groups for the methylation cycle. Cobalamin acts as a coenzyme for reactions in the metabolism of amino acids, odd-numbered chain fatty acids including propionate and de novo synthesis of methyl groups. Both vitamins are involved in reactions to support lipid and protein metabolism, nucleotide synthesis, methylation reactions and possibly, maintenance of redox status. Over the last decades, several studies have reported the beneficial effects of folic acid and vitamin B12 supplements on lactation performance of dairy cows. These observations indicate that, even when cows are fed diets adequately balanced for energy and major nutrients, B-vitamin subclinical deficiency could be present. This condition reduces casein synthesis in the mammary gland and milk and milk component yields. Folic acid and vitamin B12 supplements, especially when given together, may alter energy partitioning in dairy cows during early and mid-lactation as indicated by increased milk, energy-corrected milk, or milk component yields without affecting DM intake and BW or even with reductions in BW or body condition loss. Folate and cobalamin subclinical deficiency interferes with efficiency of gluconeogenesis and fatty acid oxidation and possibly alters responses to oxidative conditions. The present review aims to describe the metabolic pathways affected by folate and cobalamin supply and the consequences of a suboptimal supply on metabolic efficiency. The state of knowledge on the estimation of folate and cobalamin supply is also briefly mentioned.

Demand for Water-Soluble Vitamins in a Group of Patients with CKD versus Interventions and Supplementation-A Systematic Review.

BACKGROUND: Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD. METHODS: Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients. RESULTS: The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients. CONCLUSIONS: Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.

MR1: An unconventional twist in the tail.

MR1 is a conserved molecule that binds microbial vitamin B metabolites and presents them to unconventional T cells. Lim and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202110125) uncover the role of AP2 in ensuring MR1 surface presentation, which relies on an atypical motif within the MR1 cytoplasmic tail.

Metabolic adaptation to vitamin auxotrophy by leaf-associated bacteria.

Auxotrophs are unable to synthesize all the metabolites essential for their metabolism and rely on others to provide them. They have been intensively studied in laboratory-generated and -evolved mutants, but emergent adaptation mechanisms to auxotrophy have not been systematically addressed. Here, we investigated auxotrophies in bacteria isolated from Arabidopsis thaliana leaves and found that up to half of the strains have auxotrophic requirements for biotin, niacin, pantothenate and/or thiamine. We then explored the genetic basis of auxotrophy as well as traits that co-occurred with vitamin auxotrophy. We found that auxotrophic strains generally stored coenzymes with the capacity to grow exponentially for 1-3 doublings without vitamin supplementation; however, the highest observed storage was for biotin, which allowed for 9 doublings in one strain. In co-culture experiments, we demonstrated vitamin supply to auxotrophs, and found that auxotrophic strains maintained higher species richness than prototrophs upon external supplementation with vitamins. Extension of a consumer-resource model predicted that auxotrophs can utilize carbon compounds provided by other organisms, suggesting that auxotrophic strains benefit from metabolic by-products beyond vitamins.

Investigations into metabolic properties and selected nutritional metabolic byproducts of different non-Saccharomyces yeast strains when producing nonalcoholic beer.

Nonalcoholic beers are becoming increasingly popular, in part due to consumers' awareness of a healthier lifestyle. Additionally, consumers are demanding diversification in the product range, which can be offered by producing nonalcoholic beers using non-Saccharomyces yeasts for fermentation to create a wide variety of flavors. So far, little is known about the nutritionally relevant byproducts that these yeasts release during wort fermentation and whether these yeasts can be considered safe for food fermentations. To gain insights into this, the B vitamins of four different nonalcoholic beers fermented with the yeast species Saccharomycodes ludwigii, Cyberlindnera saturnus (two strains), and Kluyveromyces marxianus were analyzed. Furthermore, a total of 16 beers fermented with different non-Saccharomyces yeast strains were analyzed for biogenic amines. Additionally, stress tolerance tests were performed at 37°C and in synthetic human gastric juice in vitro. B vitamins were found in the four nonalcoholic beers in nutritionally relevant amounts so they could serve as a supplement for a balanced diet. Biogenic amines remained below the limit of determination in all 16 beers, and thus likely had no influence, while the stress tolerance tests gave a first indication that seven yeast strains could possibly tolerate the human gastric juice milieu.

Meta-analysis of apparent ruminal synthesis and postruminal flow of B vitamins in dairy cows.

As milk production has significantly increased over the past decade(s), existing estimates of the B-vitamin needs of the modern dairy cow are currently being reconsidered, as suboptimal B-vitamin supply may affect metabolic efficiency. At the same time, however, "true" (i.e., biologically active forms, excluding nonfunctional analogs) B-vitamin supply also cannot be adequately estimated by dietary intake, as the rumen microbiota has been shown to play a significant role in synthesis and utilization of B vitamins. Given their complex impact on the metabolism of dairy cows, incorporating these key nutrients into the next generation of mathematical models could help to better predict animal production and performance. Therefore, the purpose of this study was to generate hypotheses of regulation in the absence of supplemental B vitamins by creating empirical models, through a meta-analysis, to describe true B-vitamin supply to the cow (postruminal flow, PRF) and apparent ruminal synthesis (ARS). The database used for this meta-analysis consisted of 340 individual cow observations from 15 studies with 16 experiments, where diet and postruminal digesta samples were (post hoc) analyzed for content of B vitamins (B1, B2, B3, B6, B9, B12). Equations of univariate and multivariate linear form were considered. Models describing ARS considered dry matter intake (DMI, kg/d), B-vitamin dietary concentration [mg/kg of dry matter (DM)] and rumen-level variables such as rumen digestible neutral detergent fiber (NDF) and starch (g/kg of DM), total volatile fatty acids (VFA, mM), acetate, propionate, butyrate, and valerate molar proportions (% of VFA), mean pH, and fractional rates of degradation of NDF and starch (%/h). Models describing PRF considered dietary-level driving variables such as DMI, B-vitamin dietary concentration (mg/kg of DM), starch and crude protein (g/kg of DM) and forage NDF (g/kg of DM). Equations developed were required to contain all significant slope parameters and contained no significant collinearity between driving variables. Concordance correlation coefficient was used to evaluate the models on the developmental data set due to data scarcity. Overall, modeling ARS yielded better-performing models compared with modeling PRF, and DMI was included in all prediction equations as a scalar variable. The B-vitamin dietary concentration had a negative effect on the ARS of B1, B2, B3, and B6 but increased the PRF of B2 and B9. The rumen digestible NDF concentration had a negative effect on the ARS of B2, B3, and B6, whereas rumen digestible starch concentration had a negative effect on the ARS of B1 and a positive effect on the ARS of B9. In the best prediction models, the dietary starch increased PRF of B1, B2, and B9 but decreased PRF of B12. The equations developed may be used to better understand the effect of diet and ruminal environment on the true supply of B vitamins to the dairy cow and stimulate the development of better-defined requirements in the future.

Autophagy Regulates Whitefly-Symbiont Metabolic Interactions.

Nutritional symbionts are restricted to specialized host cells called bacteriocytes in various insect orders. These symbionts can provide essential nutrients to the host. However, the cellular mechanisms underlying the regulation of these insect-symbiont metabolic associations remain largely unclear. The whitefly Bemisia tabaci MEAM1 hosts "Candidatus Portiera aleyrodidarum" (here, "Ca. Portiera") and "Candidatus Hamiltonella defensa" (here, "Ca. Hamiltonella") bacteria in the same bacteriocyte. In this study, the induction of autophagy by chemical treatment and gene silencing decreased symbiont titers and essential amino acid (EAA) and B vitamin contents. In contrast, the repression of autophagy in bacteriocytes via Atg8 silencing increased symbiont titers, and amino acid and B vitamin contents. Furthermore, dietary supplementation with non-EAAs or B vitamins alleviated autophagy in whitefly bacteriocytes, elevated TOR (target of rapamycin) expression, and increased symbiont titers. TOR silencing restored symbiont titers in whiteflies after dietary supplementation with B vitamins. These data suggest that "Ca. Portiera" and "Ca. Hamiltonella" evade autophagy of the whitefly bacteriocytes by activating the TOR pathway via providing essential nutrients. Taken together, we demonstrate that autophagy plays a critical role in regulating the metabolic interactions between the whitefly and two intracellular symbionts. Therefore, this study reveals that autophagy is an important cellular basis for bacteriocyte evolution and symbiosis persistence in whiteflies. The whitefly symbiosis unravels the interactions between cellular and metabolic functions of bacteriocytes. IMPORTANCE Nutritional symbionts, which are restricted to specialized host cells called bacteriocytes, can provide essential nutrients for many hosts. However, the cellular mechanisms of regulation of animal-symbiont metabolic associations have been largely unexplored. Here, using the whitefly-"Ca. Portiera"/"Ca. Hamiltonella" endosymbiosis, we demonstrate autophagy regulates the symbiont titers and thereby alters the essential amino acid and B vitamin contents. For persistence in the whitefly bacteriocytes, "Ca. Portiera" and "Ca. Hamiltonella" alleviate autophagy by activating the TOR (target of rapamycin) pathway through providing essential nutrients. Therefore, we demonstrate that autophagy plays a critical role in regulating the metabolic interactions between the whitefly and two intracellular symbionts. This study also provides insight into the cellular basis of bacteriocyte evolution and symbiosis persistence in the whitefly. The mechanisms underlying the role of autophagy in whitefly symbiosis could be widespread in many insect nutritional symbioses. These findings provide a new avenue for whitefly control via regulating autophagy in the future.

Vitamin B status and association with antiseizure medication in pregnant women with epilepsy.

OBJECTIVE: Antiseizure medication (ASM) use interacts with vitamin B status in nonpregnant epilepsy populations. We aimed to examine the association between ASM and vitamin B status in pregnant women with epilepsy. METHODS: We performed a cross-sectional study of pregnancies in women with epilepsy enrolled in the Norwegian Mother, Father and Child Cohort Study from 1999 to 2008. Data on ASM and vitamin supplement use were collected from questionnaires. We analyzed maternal plasma concentrations of ASM and metabolites of folate, including unmetabolized folic acid (UMFA), riboflavin (vitamin B2), pyridoxine (vitamin B6), and niacin (vitamin B3) during gestational weeks 17-19. RESULTS: We included 227 singleton pregnancies exposed to ASM with available plasma samples (median maternal age 29 years, range 18 to 41 years). From the preconception period to gestational week 20, any supplement of folic acid was reported in 208 of pregnancies (94%), riboflavin in 72 (33%), pyridoxine in 77 (35%), and niacin in 45 (20%). High ASM concentrations correlated with high concentrations of UMFA and inactive folate metabolites, and with low concentrations of riboflavin and metabolically active pyridoxine. There was no association between ASM and niacin status. SIGNIFICANCE: ASM concentrations during pregnancy were associated with vitamin B status in pregnant women with epilepsy. Additional studies are needed to determine the clinical impact of these findings, and to define the optimal vitamin doses that should be recommended to improve pregnancy outcomes.

Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial.

BACKGROUND: Infantile beriberi-related mortality is still common in South and Southeast Asia. Interventions to increase maternal thiamine intakes, and thus human milk thiamine, are warranted; however, the required dose remains unknown. OBJECTIVES: We sought to estimate the dose at which additional maternal intake of oral thiamine no longer meaningfully increased milk thiamine concentrations in infants at 24 wk postpartum, and to investigate the impact of 4 thiamine supplementation doses on milk and blood thiamine status biomarkers. METHODS: In this double-blind, 4-parallel arm randomized controlled dose-response trial, healthy mothers were recruited in Kampong Thom, Cambodia. At 2 wk postpartum, women were randomly assigned to consume 1 capsule, containing 0, 1.2 (estimated average requirement), 2.4, or 10 mg of thiamine daily from 2 through 24 weeks postpartum. Human milk total thiamine concentrations were measured using HPLC. An Emax curve was plotted, which was estimated using a nonlinear least squares model in an intention-to-treat analysis. Linear mixed-effects models were used to test for differences between treatment groups. Maternal and infant blood thiamine biomarkers were also assessed. RESULTS: In total, each of 335 women was randomly assigned to1 of the following thiamine-dose groups: placebo (n = 83), 1.2 mg (n = 86), 2.4 mg (n = 81), and 10 mg (n = 85). The estimated dose required to reach 90% of the maximum average total thiamine concentration in human milk (191 µg/L) is 2.35 (95% CI: 0.58, 7.01) mg/d. The mean ± SD milk thiamine concentrations were significantly higher in all intervention groups (183 ± 91, 190 ± 105, and 206 ± 89 µg/L for 1.2, 2.4, and 10 mg, respectively) compared with the placebo group (153 ± 85 µg/L; P < 0.0001) and did not significantly differ from each other. CONCLUSIONS: A supplemental thiamine dose of 2.35 mg/d was required to achieve a milk total thiamine concentration of 191 µg/L. However, 1.2 mg/d for 22 wk was sufficient to increase milk thiamine concentrations to similar levels achieved by higher supplementation doses (2.4 and 10 mg/d), and comparable to those of healthy mothers in regions without beriberi. This trial was registered at clinicaltrials.gov as NCT03616288.

Antigen Recognition by MR1-Reactive T Cells; MAIT Cells, Metabolites, and Remaining Mysteries.

Mucosal-associated Invariant T (MAIT) cells recognize vitamin B-based antigens presented by the non-polymorphic MHC class I related-1 molecule (MR1). Both MAIT T cell receptors (TCR) and MR1 are highly conserved among mammals, suggesting an important, and conserved, immune function. For many years, the antigens they recognize were unknown. The discovery that MR1 presents vitamin B-based small molecule ligands resulted in a rapid expansion of research in this area, which has yielded information on the role of MAIT cells in immune protection, autoimmune disease and recently in homeostasis and cancer. More recently, we have begun to appreciate the diverse nature of the small molecule ligands that can bind MR1, with several less potent antigens and small molecule drugs that can bind MR1 being identified. Complementary structural information has revealed the complex nature of interactions defining antigen recognition. Additionally, we now view MAIT cells (defined here as MR1-riboflavin-Ag reactive, TRAV1-2+ cells) as one subset of a broader family of MR1-reactive T cells (MR1T cells). Despite these advances, we still lack a complete understanding of how MR1 ligands are generated, presented and recognized in vivo. The biological relevance of these MR1 ligands and the function of MR1T cells in infection and disease warrants further investigation with new tools and approaches.

B-vitamin nutrition in the pea aphid-Buchnera symbiosis.

Various insects that utilize vitamin-deficient diets derive a supplementary supply of these micronutrients from their symbiotic microorganisms. Here, we tested the inference from genome annotation that the symbiotic bacterium Buchnera aphidicola in the pea aphid Acyrthosiphon pisum provides the insect with vitamins B2 and B5 but no other B-vitamins. Contrary to expectation, aphid survival over five days of larval development on artificial diets individually lacking each B-vitamin not synthesized by Buchnera was not significantly reduced, despite significantly lower carcass B1, B3, B6 and B7 concentrations in the aphids on diets lacking each of these B-vitamins than on the vitamin-complete diet. Aphid survival was, however, significantly reduced on diet containing low concentrations (≤0.2 mM) or no pantothenate (B5). Complementary transcriptome analysis revealed low abundance of the sense-transcript, but high abundance of the antisense transcript, of the Buchnera gene panC encoding the enzyme mediating the terminal reaction in pantothenate synthesis. We hypothesize that metabolic constraints or antisense transcripts may reduce Buchnera-mediated production of pantothenate, resulting in poor aphid performance on pantothenate-free diets. The discrepancy between predictions from genome data and empirical data illustrates the need for physiological study to test functional inferences made from genome annotations.

Valproate and folate: Congenital and developmental risks.

Increasing awareness of the congenital and developmental risks associated with the use of sodium valproate (VPA) has led to recent European guidelines designed to avoid the use of this drug in pregnancy if effective alternative treatments are available. In the general population, it is well established that periconceptual folic acid reduces the risk of neural tube defects (NTDs) and possibly other congenital abnormalities. We here review the evidence 1) that VPA interferes with one-carbon metabolism, including the transport of methylfolate into the brain and the placenta by targeting folate receptors; 2) that VPA effects on the folate metabolic system contribute to congenital and developmental problems associated with VPA exposure; and 3) that genetic factors, notably polymorphisms related to one-carbon metabolism, contribute to the vulnerability to these VPA-induced risks. Based on these facts, we propose that the standard periconceptual use of 400 µg of folic acid may not adequately protect against VPA or other antiepileptic drug (AED)-induced congenital or developmental risks. Pending definitive studies to determine appropriate dose, we recommend up to 5 mg of folic acid periconceptually in at-risk women with the caveat that the addition of supplementary vitamin B12 may also be prudent because vitamin B12 deficiency is common in pregnancy in some countries and is an additional risk factor for developmental abnormalities.

Possible Adverse Effects of High-Dose Nicotinamide: Mechanisms and Safety Assessment.

Nicotinamide (NAM) at doses far above those recommended for vitamins is suggested to be effective against a wide spectrum of diseases and conditions, including neurological dysfunctions, depression and other psychological disorders, and inflammatory diseases. Recent increases in public awareness on possible pro-longevity effects of nicotinamide adenine dinucleotide (NAD+) precursors have caused further growth of NAM consumption not only for clinical treatments, but also as a dietary supplement, raising concerns on the safety of its long-term use. However, possible adverse effects and their mechanisms are poorly understood. High-level NAM administration can exert negative effects through multiple routes. For example, NAM by itself inhibits poly(ADP-ribose) polymerases (PARPs), which protect genome integrity. Elevation of the NAD+ pool alters cellular energy metabolism. Meanwhile, high-level NAM alters cellular methyl metabolism and affects methylation of DNA and proteins, leading to changes in cellular transcriptome and proteome. Also, methyl metabolites of NAM, namely methylnicotinamide, are predicted to play roles in certain diseases and conditions. In this review, a collective literature search was performed to provide a comprehensive list of possible adverse effects of NAM and to provide understanding of their underlying mechanisms and assessment of the raised safety concerns. Our review assures safety in current usage level of NAM, but also finds potential risks for epigenetic alterations associated with chronic use of NAM at high doses. It also suggests directions of the future studies to ensure safer application of NAM.

Adaptive Laboratory Evolution and Reverse Engineering of Single-Vitamin Prototrophies in Saccharomyces cerevisiae.

Quantitative physiological studies on Saccharomyces cerevisiae commonly use synthetic media (SM) that contain a set of water-soluble growth factors that, based on their roles in human nutrition, are referred to as B vitamins. Previous work demonstrated that in S. cerevisiae CEN.PK113-7D, requirements for biotin were eliminated by laboratory evolution. In the present study, this laboratory strain was shown to exhibit suboptimal specific growth rates when either inositol, nicotinic acid, pyridoxine, pantothenic acid, para-aminobenzoic acid (pABA), or thiamine was omitted from SM. Subsequently, this strain was evolved in parallel serial-transfer experiments for fast aerobic growth on glucose in the absence of individual B vitamins. In all evolution lines, specific growth rates reached at least 90% of the growth rate observed in SM supplemented with a complete B vitamin mixture. Fast growth was already observed after a few transfers on SM without myo-inositol, nicotinic acid, or pABA. Reaching similar results in SM lacking thiamine, pyridoxine, or pantothenate required more than 300 generations of selective growth. The genomes of evolved single-colony isolates were resequenced, and for each B vitamin, a subset of non-synonymous mutations associated with fast vitamin-independent growth was selected. These mutations were introduced in a non-evolved reference strain using CRISPR/Cas9-based genome editing. For each B vitamin, the introduction of a small number of mutations sufficed to achieve a substantially increased specific growth rate in non-supplemented SM that represented at least 87% of the specific growth rate observed in fully supplemented complete SM.IMPORTANCE Many strains of Saccharomyces cerevisiae, a popular platform organism in industrial biotechnology, carry the genetic information required for synthesis of biotin, thiamine, pyridoxine, para-aminobenzoic acid, pantothenic acid, nicotinic acid, and inositol. However, omission of these B vitamins typically leads to suboptimal growth. This study demonstrates that, for each individual B vitamin, it is possible to achieve fast vitamin-independent growth by adaptive laboratory evolution (ALE). Identification of mutations responsible for these fast-growing phenotypes by whole-genome sequencing and reverse engineering showed that, for each compound, a small number of mutations sufficed to achieve fast growth in its absence. These results form an important first step toward development of S. cerevisiae strains that exhibit fast growth on inexpensive, fully supplemented mineral media that only require complementation with a carbon source, thereby reducing costs, complexity, and contamination risks in industrial yeast fermentation processes.

Critical review of nutrition, blood pressure and risk of hypertension through the lifecycle: do B vitamins play a role?

Hypertension is the leading cause of preventable mortality worldwide, contributing to over 9 million deaths per annum, predominantly owing to cardiovascular disease. The association of obesity, physical inactivity and alcohol with elevated blood pressure (BP) is firmly established. Weight loss or other dietary strategies, such as the Dietary Approaches to Stop Hypertension (DASH) diet, have been shown to be effective in lowering BP. Additionally, specific nutrients are recognised to contribute to BP, with higher sodium intake linked with an increased risk of hypertension, while potassium is associated with a reduced risk of hypertension. Of note, emerging evidence has identified a novel role for one-carbon metabolism and the related B vitamins, particularly riboflavin, in BP. Specifically in adults genetically at risk of developing hypertension, owing to the common C677T polymorphism in MTHFR, supplemental riboflavin (co-factor for MTHFR) was shown in randomised trials to lower systolic BP by up to 13 mmHg. A BP response to intervention of this magnitude could have important clinical impacts, given that a reduction in systolic BP of 10 mmHg is estimated to decrease stroke risk by 40%. This review aims to explore the factors contributing to hypertension across the lifecycle and to critically evaluate the evidence supporting a role for nutrition, particularly folate-related B vitamins, in BP and risk of hypertension. In addition, gaps in our current knowledge that warrant future research in this area, will be identified.

The Link between Homocysteine and Omega-3 Polyunsaturated Fatty Acid: Critical Appraisal and Future Directions.

Omega-3 polyunsaturated fatty acids and B vitamins are linked to metabolic and degenerative disorders, such as cardiovascular disease and cognitive decline. In the last two decades, the interplay between B vitamins and omega-3 polyunsaturated fatty acids gained increasing attention. Expression control on enzymes involved in the pathway of homocysteine by polyunsaturated fatty acids has been proposed. The methylation process seems crucial for the metabolism of polyunsaturated fatty acids and their distribution within the body. This review summarizes the available data in humans about the link between homocysteine and omega-3 polyunsaturated fatty acids, with a special focus on the meta-analyses of randomized clinical trials. Even if the paucity of available information about the topic does not allow for definitive conclusions, a synergic action between polyunsaturated fatty acids and B vitamins may play a key role in regulating several metabolic pathways. This element could explain a stronger action on homocysteine levels when omega-3 polyunsaturated fatty acids and B vitamins are supplemented simultaneously. To date, a robust rationale of intervention to prevent metabolic diseases is lacking and could be beneficial for individual health and healthcare policy.

Involvement of metallothionein, homocysteine and B-vitamins in the attenuation of arsenic-induced uterine disorders in response to the oral application of hydro-ethanolic extract of Moringa oleifera seed: a preliminary study.

The painful invasive chelation therapy makes it challenging to continue the prolonged treatment against arsenic toxicity. Hence, the significance of the present preliminary investigation was to explore a noninvasive treatment strategy against sodium arsenite (As3+) by the use of a hydroethanolic extract of Moringa oleifera (MO) seed. Arsenic treatment (10 mg/kg body-weight) in animals showed significant level of oxidative stress as evidenced by increased serum levels of malondialdehyde (MDA), conjugated dienes (CD) and reduced level of non-protein thiol (NPSH). A significant diminution in the activities of enzymatic antioxidants was noted in As3+-treated rats. As3+ treatment showed a lengthy phase of metestrous in animals followed by significantly diminished ovarian steroidogenesis, increased ovarian follicular degeneration and distortion of uterine tissue histomorphology. In addition, there was a significant depletion of Vitamin-B9 (folate) and B12 following As3+ ingestion. The levels of circulating TNF-α, homocysteine (Hcy), uterine-IL-6, and liver metallothionein (MT-1) were significantly elevated in arsenic treated rats. MO at a dose of 100 mg/kg body-weight could successfully mitigate the uterine ROS generation by maintaining the uterine antioxidant status in As3+- treated rats. This seed extract prevented the deterioration of As3+-mediated ovarian-steroidogenesis and ovarian and uterine histoarchitecture significantly. B9 and B12 levels were also improved following the ingestion of the MO extract in arsenicated animals. Elevation of Hcy, TNF-α and IL-6 was also prevented by this MO seed extract in As3+-treated rats. A further increase of MT-1 level was achieved after MO ingestion in As3+-treated rats. Here, the alleviation of arsenic toxicity might involve via the regulation of the components of S-adenosine methionine (SAM) pool and MT-1.

Water Soluble Vitamins and their Role in Diabetes and its Complications.

BACKGROUND: Diabetes is a metabolic disorder associated with abnormally high levels of glucose in the blood due to inadequate production of insulin or inadequate sensitivity of cells to the action of insulin. Diabetes has become an increasing challenge in the world. The predicted diabetic population according to the World Health Organization is 8.7% between the age group 20-70 years. There are many complications linked to prolonged high blood glucose levels, such as microvascular complications and macrovascular complications. Vitamins play an important role in glucose metabolism and the potential utility of supplementation is relevant for the prevention and/or management of diabetes mellitus and its complications. METHODS: Literature search was performed using various dataset like PUBMED, EBSCO, ProQuest, Scopus and selected websites like the National Institute of Health and the World Health Organization. RESULT: Water-soluble vitamins have been thoroughly studied for their activity in diabetes and diabetic complications. CONCLUSION: Water-soluble vitamins like B1, B3, B6, B7, B9 and B12 have notable effects in diabetes mellitus and its related complications like nephropathy, neuropathy, retinopathy and cardiomyopathy.

Wolbachia supplement biotin and riboflavin to enhance reproduction in planthoppers.

Symbiont-mediated nutritional mutualisms can contribute to the host fitness of insects, especially for those that feed exclusively on nutritionally unbalanced diets. Here, we elucidate the importance of B group vitamins in the association of endosymbiotic bacteria Wolbachia with two plant-sap feeding insects, the small brown planthopper, Laodelphax striatellus (Fallén), and the brown planthopper, Nilaparvata lugens (Stål). Infected planthoppers of both species laid more eggs than uninfected planthoppers, while the experimental transfer of Wolbachia into uninfected lines of one planthopper species rescued this fecundity deficit. The genomic analysis showed that Wolbachia strains from the two planthopper species encoded complete biosynthesis operons for biotin and riboflavin, while a metabolic analysis revealed that Wolbachia-infected planthoppers of both species had higher titers of biotin and riboflavin. Furthermore, experimental supplementation of food with a mixture of biotin and riboflavin recovered the fecundity deficit of Wolbachia-uninfected planthoppers. In addition, comparative genomic analysis suggested that the riboflavin synthesis genes are conserved among Wolbachia supergroups. Biotin operons are rare in Wolbachia, and those described share a recent ancestor that may have been horizontally transferred from Cardinium bacteria. Our research demonstrates a type of mutualism that involves a facultative interaction between Wolbachia and plant-sap feeding insects involving vitamin Bs.

[Lipoic acid: physiological role and prospects for clinical application].

α-Lipoic acid (also known as thioctic acid) is a natural vitamin-like compound. Lipoic acid contains asymmetrical carbon, which causes the presence of two possible optical isomers (enantiomers): R-lipoic acid (levogyrate isomer) and S-lipoic acid (rightspinning isomer). Lipoic acid functions as a cofactor for several important mitochondrial multienzyme complexes, enhances the uptake of glucose by the cells, and modulates the activity of various signaling molecules and transcription factors. It was shown that α-lipoic acid and its derivative, dihydrolipoic acid, have a direct antioxidant effect due to the neutralization of reactive oxygen species that are destructive to DNA, proteins and lipids of cells. Dihydrolipoic acid enhances the antioxidant properties of ascorbic acid, glutathione and ubiquinone. Available evidence suggests that supplementation with lipoic acid reduces the symptoms of peripheral diabetic neuropathy. Results from randomized controlled trials show that high doses of lipoic acid can improve the glycemic profile of subjects with metabolic disorders. Lipoic acid can be used to control body weight in people with obesity. R-Lipoic acid is synthesized in the human body and is contained in foods in a form covalently associated with lysine (lipoyllysine). Its dose in dietary supplements significantly exceeds the amount in the diet. Most dietary supplements contain a racemic mixture of R- and S-lipoic acid.