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Brain, Behavior, and Immunity May 2024We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites,...
BACKGROUND AND AIMS
We have previously shown that systemic inflammation was associated with post-stroke cognitive impairment (PSCI). Because neopterin, kynurenine pathway (KP) metabolites, and B6 vitamers are linked to inflammation, in our study we investigated whether those biomarkers were associated with PSCI.
MATERIAL AND METHODS
The Norwegian Cognitive Impairment After Stroke study is a prospective multicenter cohort study of patients with acute stroke recruited from May 2015 through March 2017. Plasma samples of 422 participants (59 % male) with ischemic stroke from the index hospital stay and 3 months post-stroke were available for analyses of neopterin, KP metabolites, and B6 vitamers using liquid chromatography-tandem mass spectrometry. Mixed linear regression analyses adjusted for age, sex, and creatinine, were used to assess whether there were associations between those biomarkers and cognitive outcomes, measured by the Montreal Cognitive Assessment scale (MoCA) at 3-, 18-, and 36-month follow-up.
RESULTS
Participants had a mean (SD) age of 72 (12) years, with a mean (SD) National Institutes of HealthStroke Scale score of 2.7 (3.6) at Day 1. Higher baseline values of quinolinic acid, PAr (i.e., an inflammatory marker based on vitamin B6 metabolites), and HKr (i.e., a marker of functional vitamin B6 status based on selected KP metabolites) were associated with lower MoCA score at 3, 18, and 36 months post-stroke (p < 0.01). Higher baseline concentrations of neopterin and 3-hydroxykynurenine were associated with lower MoCA scores at 18 and 36 months, and higher concentrations of xanthurenic acid were associated with higher MoCA score at 36 months (p < 0.01). At 3 months post-stroke, higher concentrations of neopterin and lower values of pyridoxal 5́-phosphate were associated with lower MoCA scores at 18- and 36-month follow-up, while lower concentrations of picolinic acid were associated with a lower MoCA score at 36 months (p < 0.01).
CONCLUSION
Biomarkers and metabolites of systemic inflammation, including biomarkers of cellular immune activation, indexes of vitamin B6 homeostasis, and several neuroactive metabolites of the KP pathway, were associated with PSCI.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT02650531.
Topics: Aged; Female; Humans; Male; Biomarkers; Cognitive Dysfunction; Cohort Studies; Inflammation; Kynurenine; Neopterin; Prospective Studies; Pyridoxal Phosphate; Stroke; Vitamin B 6; Middle Aged; Aged, 80 and over
PubMed: 38428649
DOI: 10.1016/j.bbi.2024.02.030 -
Plant Signaling & Behavior 2016The essential micronutrient vitamin B6 is best known in its enzymatic cofactor form, pyridoxal 5'-phosphate (PLP). However, vitamin B6 comprises the amine pyridoxamine...
The essential micronutrient vitamin B6 is best known in its enzymatic cofactor form, pyridoxal 5'-phosphate (PLP). However, vitamin B6 comprises the amine pyridoxamine 5'-phosphate (PMP) and the alcohol pyridoxine 5'-phosphate (PNP) in addition to PLP, as well as their corresponding non-phosphorylated forms. The different B6 forms (called vitamers) are enzymatically interconverted in a ubiquitous salvage pathway. Recently, we have shown that balancing the ratio of the different B6 vitamers in particular PMP by the PMP/PNP oxidase PDX3 is essential for growth and development in Arabidopsis thaliana. Intriguingly, nitrate to ammonium conversion is impaired in pdx3 mutants, such that the mutants become ammonium-dependent, suggesting an interaction between vitamin B6 and nitrogen metabolism. In addition, we found a strong up-regulation of genes related to plant defense. Here, we further show that pdx3 mutants display a temperature-sensitive phenotype that is typical of autoimmune mutants and is possibly connected to the impaired nitrogen metabolism.
Topics: Arabidopsis; Arabidopsis Proteins; Autoimmunity; Gene Expression Regulation, Plant; Nitrogen; Phenotype; Reproduction; Temperature; Vitamin B 6
PubMed: 27018849
DOI: 10.1080/15592324.2016.1161876 -
International Journal of Molecular... Aug 2019Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but...
Chronic inflammation can lead to tumour initiation and progression. Vitamin B complex has the ability to regulate the immune response and, therefore, inflammation but many of the mechanistic and molecular processes involved in this regulation are still not fully understood. This study sought to determine some of these processes by studying the effects of vitamin B2 (riboflavin) B6 (pyridoxine) and B9 (folic acid) on un-differentiated pro-monocytic lymphoma cells in regard to their ability to alter the proliferation, migration, apoptosis, cytokines and expression levels of programmed death ligand 1. We show that vitamin B2, B6 and B9, on pro-monocytic lymphoma cells exerted an anti-tumorigenic effect. This data could form the basis for future studies in using vitamin B supplementation to reduce cancer cell growth in vivo.
Topics: Adult; Anticarcinogenic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Folic Acid; Humans; Lymphoma; Male; Riboflavin; Vitamin B 6
PubMed: 31374832
DOI: 10.3390/ijms20153763 -
Bulletin Du Cancer Oct 2011Vitamin B6 is well-known for its role as a cofactor in many enzymatic reactions and recently, several epidemiological studies have highlighted the importance of this... (Review)
Review
Vitamin B6 is well-known for its role as a cofactor in many enzymatic reactions and recently, several epidemiological studies have highlighted the importance of this vitamin as a protective agent against various cancers: elevated vitamin B6 plasma levels were associated with a lower risk of colorectal cancer development, for example. In vivo studies have shown that vitamin B6 decreased cell proliferation and enhanced the immune response. At the cellular level, antioxidant, pro-apoptotic and anti-angiogenic effects have been identified. At the molecular level, vitamin B6 is able to inhibit the transactivation potential of various nuclear receptors. Interestingly, a recent paper has described the conjugation of vitamin B6 to RIP140 (receptor interacting protein of 140 kDa), a protein that acts as a transcriptional corepressor of nuclear receptors. This post-translational modification increases the transcriptional repression of RIP140 and regulates its subcellular localization and its ability to interact with different protein partners. Finally, vitamin B6 is involved in the methyl donor cycle ant thus, some of the antitumor properties of vitamin B6 may involve an indirect effect on the level of DNA or histone methylation. All of these mechanistic and clinical data justify further studies to decipher the mechanism of action of vitamin B6 and its clinical interest in combination with molecules typically used in chemotherapy or hormonal therapy.
Topics: Adaptor Proteins, Signal Transducing; Animals; Colorectal Neoplasms; DNA Methylation; Epigenesis, Genetic; Histones; Humans; Neoplasm Proteins; Neoplasms; Nuclear Proteins; Nuclear Receptor Interacting Protein 1; Protein Processing, Post-Translational; Rats; Receptors, Cytoplasmic and Nuclear; Vitamin B 6
PubMed: 22001823
DOI: 10.1684/bdc.2011.1458 -
Nutrients Jun 2022Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA...
Previous evidence suggests a potential dual impact of aging and vitamin B6 (B6) deficiency on polyunsaturated fatty acid (PUFA) metabolism; gender may influence PUFA biosynthesis. Perturbation of PUFA compositions during B6 deficiency could be linked to age-related health outcomes. However, little is known about the interrelationships between vitamin B6, PUFA, and gender in the older population. Therefore, we investigated whether gender-specific associations of B6 intake and plasma pyridoxal 5’-phosphate (PLP) concentration, respectively, with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, and (EPA + DHA)/AA) existed in older adults. We further examined the relationships of adequate B6 status (PLP ≥ 20 nmol/L) with high (above median) plasma PUFA relative to deficient B6 status. This cross-sectional study analyzed 461 participants aged ≥60 years from NHANES 2003−2004. Nutrient intakes were assessed using two 24-h recalls and supplement questionnaires. PLP and PUFA concentrations were measured. Multivariate linear regression assessed the association of B6 intake and PLP with PUFA; multivariate logistic regression evaluated the relationship of adequate B6 status with high plasma PUFA, adjusting for demographic, socioeconomic, and dietary factors; physical activity; smoking; alcohol; medication; and BMI. There were interactions between gender and B6 intake on EPA (P-interaction = 0.008) and AA (P-interaction = 0.004) only, whereas no interaction existed between gender and PLP on PUFA. PLP was directly associated with EPA (β = 0.181, P = 0.002), DHA (β = 0.109, P = 0.005), EPA + DHA (β = 0.14, P = 0.002), EPA/AA (β = 0.186, P = 0.004), and (EPA + DHA)/AA (β = 0.13, P = 0.026). The odds of having high plasma EPA (adjusted (a) OR: 2.03, P = 0.049) and EPA/AA (aOR: 3.83, P < 0.0001) were greater in those with adequate B6 status compared to those with deficient B6 status. In conclusion, in US older adults, a higher PLP level was associated with a greater level of EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA. Adequate B6 status was associated with high EPA and EPA/AA status. These findings suggest that sufficient vitamin B6 status may positively influence PUFA metabolism in older adults.
Topics: Aged; Arachidonic Acid; Cross-Sectional Studies; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Nutrition Surveys; Phosphates; Pyridoxal Phosphate; Vitamin B 6
PubMed: 35684138
DOI: 10.3390/nu14112336 -
Folia Biologica 2016The role of vitamin B6 as a key component in a number of biological events has been well established. Based on the relationship between chronic inflammation and...
The role of vitamin B6 as a key component in a number of biological events has been well established. Based on the relationship between chronic inflammation and carcinogenesis on the one hand, and the interaction between immune and cancer cells expressed by modulated cytokine production on the other hand, the aim of the present work was to examine the possibility that vitamin B6 affects cancer development by an interference in the cross-talk between human peripheral blood mononuclear cells (PBMC) and those from two colon carcinoma cell lines. Both non-stimulated PBMC and mononuclear cells induced for cytokine production by HT-29 and RKO cells from human colon carcinoma lines were incubated without and with 4, 20 and 100 μg/ml of pyridoxal hydrochloride (vitamin B6) and secretion of TNF-α, IL-1β, IL-6, IFN-γ, IL-10, and IL-1ra was examined. Vit B6 caused a dose-dependent decrease in production of all cytokines examined, except for that of IL-1ra. The results indicate that vitamin B6 exerts an immunomodulatory effect on human PBMC. The finding that production of inflammatory cytokines is more pronounced when PBMC are in contact with malignant cells and markedly inhibited by the vitamin suggests an additional way by which vitamin B6 may exert its carcinopreventive effect.
Topics: Adult; Anti-Inflammatory Agents; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Cytokines; Humans; Interferon-gamma; Leukocytes, Mononuclear; Vitamin B 6
PubMed: 27085010
DOI: No ID Found -
Frontiers in Public Health 2024This study aims to understand the impact of dietary intake through supplementation of vitamins D, B6, and magnesium on elevated depressive symptoms, a mental health...
OBJECTIVE
This study aims to understand the impact of dietary intake through supplementation of vitamins D, B6, and magnesium on elevated depressive symptoms, a mental health illness that is a leading contributor to global disability and a public health concern.
METHODS
Multiple datasets from the National Health and Nutrition Examination Survey 2017-March 2020 investigated the associations between vitamin D, B6, and magnesium on depression screening scores. A cross-sectional sample of adults over 20 was extracted ( = 9,232). Chi-square tests and logistic regression analyses were used to investigate the associations.
RESULTS
Individuals with low amounts of vitamin D ( = 0.0481) were more likely to report elevated depressive symptoms relative to those with low amounts of vitamin B6 ( = 0.0225). These results remained significant among those with high magnesium ( = 0.0133) proportionate to high vitamin B6 ( = 0.0225). In the age-adjusted model, a lower intake of vitamin D, vitamin B6, and magnesium showed a relationship with elevated depressive symptoms (Vitamin D: OR = 0.611, 95% CI 0.382-0.980 Vitamin B6: OR = 0.503, 95% CI 0.291-0.867 Magnesium: OR = 0.458, 95% CI 0.277-0.759). The fully adjusted regression model (gender, race/ethnicity, and household food security) showed that a lower intake of vitamin B6 and magnesium correlated with elevated depressive symptoms (Vitamin B6: OR = 0.439, 95% CI 0.260-0.738 Magnesium: OR = 0.465, 95% CI 0.303-0.714).
CONCLUSION
Preventive measures could be addressed by identifying the risks of vitamin deficiencies. Further epidemiological research is needed for the individual effects of vitamin supplementation and depression screening scores. Future prospective cohort studies exploring these associations, focusing on daily dietary intake, are needed to validate the direction of causation further and understand the underlying mechanisms.
Topics: Adult; Humans; Magnesium; Vitamin B 6; Vitamin D; Depression; Dietary Supplements; Prospective Studies; Cross-Sectional Studies; Nutrition Surveys; Public Health; Vitamins; Eating
PubMed: 38605872
DOI: 10.3389/fpubh.2024.1369666 -
Journal of Cellular Physiology Sep 2022The insulin signaling pathway controls cell growth and metabolism, thus its deregulation is associated with both cancer and diabetes. Phosphatidylinositol 3-kinase...
The insulin signaling pathway controls cell growth and metabolism, thus its deregulation is associated with both cancer and diabetes. Phosphatidylinositol 3-kinase (PI3K) contributes to the cascade of phosphorylation events occurring in the insulin pathway by activating the protein kinase B (PKB/AKT), which phosphorylates several substrates, including those involved in glucose uptake and storage. PI3K inactivating mutations are associated with insulin resistance while activating mutations are identified in human cancers. Here we show that RNAi-induced depletion of the Drosophila PI3K catalytic subunit (Dp110) results in diabetic phenotypes such as hyperglycemia, body size reduction, and decreased glycogen content. Interestingly, we found that hyperglycemia produces chromosome aberrations (CABs) triggered by the accumulation of advanced glycation end-products and reactive oxygen species. Rearing PI3K flies in a medium supplemented with pyridoxal 5'-phosphate (PLP; the catalytically active form of vitamin B6) rescues DNA damage while, in contrast, treating PI3K larvae with the PLP inhibitor 4-deoxypyridoxine strongly enhances CAB frequency. Interestingly, PLP supplementation rescues also diabetic phenotypes. Taken together, our results provide a strong link between impaired PI3K activity and genomic instability, a crucial relationship that needs to be monitored not only in diabetes due to impaired insulin signaling but also in cancer therapies based on PI3K inhibitors. In addition, our findings confirm the notion that vitamin B6 is a good natural remedy to counteract insulin resistance and its complications.
Topics: Animals; DNA Damage; Disease Models, Animal; Drosophila; Glucose; Humans; Hyperglycemia; Insulin; Insulin Resistance; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-akt; Pyridoxal Phosphate; Vitamin B 6
PubMed: 35678366
DOI: 10.1002/jcp.30812 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2019Vitamin B6 has been postulated to play an important role in determining chronic diseases. However, few studies have evaluated associations between dietary vitamin B6 and...
BACKGROUND & AIMS
Vitamin B6 has been postulated to play an important role in determining chronic diseases. However, few studies have evaluated associations between dietary vitamin B6 and cause-specific mortality comprehensively.
METHODS
We investigated the associations between vitamin B6 from diet and risk of all-cause, and cause-specific mortality in 134,480 participants from the Shanghai Men's Health Study (2002-2014) and Shanghai Women's Health Study (1997-2014). The median follow-up periods for men and women were 10.3 and 16.2 years, respectively. We estimated hazard ratio (HR) and 95% confidence interval (CI) using Cox proportional hazards models.
RESULTS
After adjustment for suspected confounders, the multivariable-adjusted HRs for the highest versus lowest quintiles for total, CVD, stroke and CHD mortality among men were 0.83 (95%CI = 0.76, 0.90), 0.73 (95%CI = 0.63, 0.85), 0.71 (95%CI = 0.58, 0.88), 0.66 (95%CI = 0.47, 0.91), accordingly. Women with the highest intake had significantly 17% (HR = 0.83; 95% CI = 0.77, 0.90), 20% (HR = 0.80; 95% CI = 0.70, 0.92), and 28% (HR = 0.72; 95% CI = 0.59, 0.86) lower risks of total, CVD and stroke mortality compared with those of women with lowest vitamin B6 intake. No significant association was observed between dietary vitamin B6 and cancer mortality both among men and women.
CONCLUSIONS
In the current study with two prospective Chinese cohorts, high dietary vitamin B6 consumption was inversely associated with risk of all-cause and CVD mortality.
Topics: Adult; Aged; Cardiovascular Diseases; China; Diet; Female; Humans; Male; Middle Aged; Prospective Studies; Vitamin B 6
PubMed: 29764693
DOI: 10.1016/j.clnu.2018.04.016 -
Biochimie Jul 2016The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the... (Review)
Review
Vitamin B6 nutritional status and cellular availability of pyridoxal 5'-phosphate govern the function of the transsulfuration pathway's canonical reactions and hydrogen sulfide production via side reactions.
The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H2S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H2O2, and by Michaelis-Menten principles whereby substrate concentrations affect reaction rates. Although pyridoxal phosphate (PLP) serves as coenzyme for both CBS and cystathionine γ-lyase (CSE), CSE exhibits much greater loss of activity than CBS during PLP insufficiency. Thus, cellular and plasma cystathionine concentrations increase in vitamin B6 deficiency mainly due to the bottleneck caused by reduced CSE activity. Because of the increase in cystathionine, the canonical production of cysteine (homocysteine → cystathionine → cysteine) is largely maintained even during vitamin B6 deficiency. Typical whole body transsulfuration flux in humans is 3-7 μmol/h per kg body weight. The in vivo kinetics of H2S production via side reactions of CBS and CSE in humans are unknown but they have been reported for cultured HepG2 cells. In these studies, cells exhibit a pronounced reduction in H2S production capacity and rates of lanthionine and homolanthionine synthesis in deficiency. In humans, plasma concentrations of lanthionine and homolanthionine exhibit little or no mean change due to 4-wk vitamin B6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B6 status. Wide individual variation in responses of the H2S biomarkers to such perturbations of human vitamin B6 status suggests that the resulting modulation of H2S production may have physiological consequences in a subset of people. Supported by NIH grant DK072398. This paper refers to data from studies registered at clinicaltrials.gov as NCT01128244 and NCT00877812.
Topics: Animals; Clinical Trials as Topic; Female; Hep G2 Cells; Humans; Hydrogen Sulfide; Male; Nutritional Status; Pyridoxal Phosphate; Vitamin B 6
PubMed: 26765812
DOI: 10.1016/j.biochi.2015.12.020