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Nutrients Aug 2021There is little evidence regarding the association between serum vitamin B6 concentration and subsequent mortality. We aimed to evaluate the association of serum vitamin...
There is little evidence regarding the association between serum vitamin B6 concentration and subsequent mortality. We aimed to evaluate the association of serum vitamin B6 concentration with all-cause, cardiovascular disease (CVD), and cancer mortality in the general population using data from the National Health and Nutrition Examination Survey (NHANES). Our study examined 12,190 adults participating in NHANES from 2005 to 2010 in the United States. The mortality status was linked to National Death Index (NDI) records up to 31 December 2015. Pyridoxal 5'-phosphate (PLP) is the biologically active form of vitamin B6. Vitamin B6 status was defined as deficient (PLP < 20 nmol/L), insufficient (PLP ≥ 20.0 and <30.0 nmol/L), and sufficient (PLP ≥ 30.0 nmol/L). We established Cox proportional-hazards models to estimate the associations of categorized vitamin B6 concentration and log-transformed PLP concentration with all-cause and cause-specific mortality by calculating hazard ratios (HRs) and 95% confidence intervals (95%CIs). In our study, serum vitamin B6 was sufficient in 70.6% of participants, while 12.8% of the subjects were deficient in vitamin B6. During follow-up, a total of 1244 deaths were recorded, including 294 cancer deaths and 235 CVD deaths. After multivariate adjustment in Cox regression, participants with higher serum vitamin B6 had a 15% (HR = 0.85, 95%CI = 0.77, 0.93) reduced risk of all-cause mortality and a 19% (HR = 0.81, 95%CI = 0.68, 0.98) reduced risk for CVD mortality for each unit increment in natural log-transformed PLP. A higher log-transformed PLP was not significantly associated with a lower risk for cancer mortality. Compared with sufficient vitamin B6, deficient (HR = 1.37, 95%CI = 1.17, 1.60) and insufficient (HR = 1.19, 95%CI = 1.02, 1.38) vitamin B6 level were significantly associated with a higher risk for all-cause mortality. There was no significant association for cause-specific mortality. Participants with higher levels of vitamin B6 had a lower risk for all-cause mortality. These findings suggest that maintaining a sufficient level of serum vitamin B6 may lower the all-cause mortality risk in the general population.
Topics: Cardiovascular Diseases; Cause of Death; Cross-Sectional Studies; Female; Health Surveys; Humans; Male; Middle Aged; Neoplasms; Prospective Studies; United States; Vitamin B 6; Vitamin B Complex
PubMed: 34578855
DOI: 10.3390/nu13092977 -
Cancer Cell Jan 2020Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and...
Cancer cells rely on altered metabolism to support abnormal proliferation. We performed a CRISPR/Cas9 functional genomic screen targeting metabolic enzymes and identified PDXK-an enzyme that produces pyridoxal phosphate (PLP) from vitamin B6-as an acute myeloid leukemia (AML)-selective dependency. PDXK kinase activity is required for PLP production and AML cell proliferation, and pharmacological blockade of the vitamin B6 pathway at both PDXK and PLP levels recapitulated PDXK disruption effects. PDXK disruption reduced intracellular concentrations of key metabolites needed for cell division. Furthermore, disruption of PLP-dependent enzymes ODC1 or GOT2 selectively inhibited AML cell proliferation and their downstream products partially rescued PDXK disruption induced proliferation blockage. Our work identifies the vitamin B6 pathway as a pharmacologically actionable dependency in AML.
Topics: Animals; CRISPR-Cas Systems; Cell Line, Tumor; Cell Proliferation; GTP Phosphohydrolases; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute; Membrane Proteins; Mice; Monomeric GTP-Binding Proteins; Phosphotransferases; Phosphotransferases (Alcohol Group Acceptor); Polyamines; Pyridoxal Phosphate; RNA, Small Interfering; Vitamin B 6
PubMed: 31935373
DOI: 10.1016/j.ccell.2019.12.002 -
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 -
Anais Da Academia Brasileira de Ciencias 2019Sepsis is a life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Inflammation and oxidative stress are intrinsically related...
Sepsis is a life-threatening organ dysfunction induced by a disrupted host response to infecting pathogens. Inflammation and oxidative stress are intrinsically related to sepsis progression and organ failure. Vitamin B6 is an important cellular cofactor for metabolic processes and has anti-inflammatory and antioxidant properties. We aimed at evaluating the effect of vit B6 on inflammation and oxidative stress markers in the liver and lung of rats subjected to a relevant animal model of polymicrobial sepsis. Adult male Wistar rats were submitted to cecal ligation and perforation model and immediately after sepsis induction, vit B6 was administered as a single dose (600 mg/kg, subcutaneous). Twenty-four hours later, the lung and liver were harvest for neutrophil infiltration, oxidative markers to lipids and protein and antioxidant activity of endogenous enzyme. Vitamin B6 diminished neutrophil infiltration in both organs, oxidative markers in the liver and restored catalase activity levels in the lung of septic animals. Vitamin B6 exerts anti-inflammatory and antioxidant effects in peripheral organs after polymicrobial sepsis.
Topics: Animals; Antioxidants; Biomarkers; Disease Models, Animal; Inflammation; Lipid Peroxidation; Liver; Lung; Male; Oxidative Stress; Rats; Rats, Wistar; Sepsis; Vitamin B 6
PubMed: 31800708
DOI: 10.1590/0001-3765201920190434 -
Canadian Family Physician Medecin de... Jul 2007A 42-year-old woman with carpal tunnel syndrome tells you she has started taking a vitamin B6 supplement to relieve her symptoms. Her work in an automotive parts... (Review)
Review
QUESTION
A 42-year-old woman with carpal tunnel syndrome tells you she has started taking a vitamin B6 supplement to relieve her symptoms. Her work in an automotive parts department involves both lifting moderately heavy packages and typing at a computer terminal. What does the research indicate about vitamin B6 as a treatment option, and what health issues should you discuss with this patient?
ANSWER
Although its effectiveness is controversial, vitamin B6 is often used as a conservative and adjunct therapy in treatment of carpal tunnel syndrome. Many patients attempt to treat their symptoms with vitamin B6 on their own. Vitamin B6 at less than 200 mg daily is not likely to cause any adverse effects, but patients should be monitored for changes in symptoms, particularly when high doses are taken over long periods.
Topics: Carpal Tunnel Syndrome; Dietary Supplements; Dose-Response Relationship, Drug; Drug Administration Schedule; Family Practice; Female; Follow-Up Studies; Humans; Male; Pain Measurement; Severity of Illness Index; Treatment Outcome; Vitamin B 6
PubMed: 17872812
DOI: No ID Found -
Biomolecules Apr 2022Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker... (Review)
Review
Cardiovascular diseases are the leading cause of death and the main cause of disability. In the last decade, homocysteine has been found to be a risk factor or a marker for cardiovascular diseases, including myocardial infarction (MI) and heart failure (HF). There are indications that vitamin B6 plays a significant role in the process of transsulfuration in homocysteine metabolism, specifically, in a part of the reaction in which homocysteine transfers a sulfhydryl group to serine to form α-ketobutyrate and cysteine. Therefore, an elevated homocysteine concentration (hyperhomocysteinemia) could be a consequence of vitamin B6 and/or folate deficiency. Hyperhomocysteinemia in turn could damage the endothelium and the blood vessel wall and induce worsening of atherosclerotic process, having a negative impact on the mechanisms underlying MI and HF, such as oxidative stress, inflammation, and altered function of gasotransmitters. Given the importance of the vitamin B6 in homocysteine metabolism, in this paper, we review its role in reducing oxidative stress and inflammation, influencing the functions of gasotransmitters, and improving vasodilatation and coronary flow in animal models of MI and HF.
Topics: Animals; Folic Acid; Gasotransmitters; Heart Failure; Homocysteine; Hyperhomocysteinemia; Inflammation; Models, Theoretical; Myocardial Infarction; Vitamin B 6; Vitamins
PubMed: 35454125
DOI: 10.3390/biom12040536 -
Nutrients Aug 2015B vitamins may correlate with Parkinson's disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between... (Meta-Analysis)
Meta-Analysis Review
B vitamins may correlate with Parkinson's disease (PD) through regulating homocysteine level. However, there is no comprehensive assessment on the associations between PD and B vitamins. The present study was designed to perform a meta-analytic assessment of the associations between folate, vitamin B6, and vitamin B12 and PD, including the status of B vitamins in PD patients compared with controls, and associations of dietary intakes of B vitamins and risk of PD. A literature search using Medline database obtained 10 eligible studies included in the meta-analyses. Stata 12.0 statistical software was used to perform the meta-analysis. Pooled data revealed that there was no obvious difference in folate level between PD patients and healthy controls, and PD patients had lower level of vitamin B12 than controls. Available data suggested that higher dietary intake of vitamin B6 was associated with a decreased risk of PD (odds ratio (OR) = 0.65, 95% confidence intervals (CI) = (0.30, 1.01)), while no significant association was observed for dietary intake of folate and vitamin B12 and risk of PD. PD patients had lower level of vitamin B12 and similar level of folate compared with controls. Dietary intake of vitamin B6 exhibited preventive effect of developing PD based on the available data. As the number of included studies is limited, more studies are needed to confirm the findings and elucidate the underpinning underlying these associations.
Topics: Case-Control Studies; Diet; Folic Acid; Humans; Odds Ratio; Parkinson Disease; Protective Factors; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 26343714
DOI: 10.3390/nu7095333 -
Nutrients Apr 2023Vitamins B12 and B6 and folate are known to have implications for pregnancy outcomes. We aimed to describe B6, B12, and folate status in pregnancy and investigate their...
Vitamins B12 and B6 and folate are known to have implications for pregnancy outcomes. We aimed to describe B6, B12, and folate status in pregnancy and investigate their associations with low birth weight and preterm delivery in mothers recruited from public hospitals in urban Bengaluru. Pregnant women between 18 and 45 years were included in the MAASTHI prospective cohort study. Each participant's age, socioeconomic status, and anthropometry were recorded during baseline and followed up after delivery. Blood samples were collected between the 24th and 32nd weeks of gestation and stored at -80° for analysis. B6, B12, folate, homocysteine, and methylmalonic acid (MMA) levels were analyzed in the stored samples. We found low plasma vitamin B12, folate, and B6 levels in 48.5%, 42.0%, and 10.4% of the women ( = 230), respectively. Elevated MMA and homocysteine were observed among 73.6% and 6.1% of the women, respectively. We found B6 levels were significantly associated with birth weight (β(SE) -0.002(0.0), = 0.001) after adjusting for age, parity, adiposity, gestational diabetes, and socioeconomic status of the mother. Those with impaired folate deficiency were twice at risk (AOR 1.95 (1.29, 3.07), = 0.002) of low birth weight. Vitamin B6 levels and impaired folate status were associated with low birth weight in the MAASTHI birth cohort.
Topics: Infant, Newborn; Humans; Female; Pregnancy; Vitamin B 12; Folic Acid; Vitamin B 6; Birth Cohort; Prospective Studies; Pyridoxine; Infant, Low Birth Weight; Birth Weight; India; Homocysteine
PubMed: 37049630
DOI: 10.3390/nu15071793 -
Advances in Nutrition (Bethesda, Md.) Jan 2015
Topics: Diet; Humans; Recommended Dietary Allowances; Vitamin B 6; Vitamin B Complex; Vitamin B Deficiency
PubMed: 25593152
DOI: 10.3945/an.113.005207 -
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