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Annual Review of Nutrition 2015Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes,... (Review)
Review
Measures of B6 status are categorized as direct biomarkers and as functional biomarkers. Direct biomarkers measure B6 vitamers in plasma/serum, urine and erythrocytes, and among these plasma pyridoxal 5'-phosphate (PLP) is most commonly used. Functional biomarkers include erythrocyte transaminase activities and, more recently, plasma levels of metabolites involved in PLP-dependent reactions, such as the kynurenine pathway, one-carbon metabolism, transsulfuration (cystathionine), and glycine decarboxylation (serine and glycine). Vitamin B6 status is best assessed by using a combination of biomarkers because of the influence of potential confounders, such as inflammation, alkaline phosphatase activity, low serum albumin, renal function, and inorganic phosphate. Ratios between substrate-products pairs have recently been investigated as a strategy to attenuate such influence. These efforts have provided promising new markers such as the PAr index, the 3-hydroxykynurenine:xanthurenic acid ratio, and the oxoglutarate:glutamate ratio. Targeted metabolic profiling or untargeted metabolomics based on mass spectrometry allow the simultaneous quantification of a large number of metabolites, which are currently evaluated as functional biomarkers, using data reduction statistics.
Topics: Amino Acids; Biomarkers; Body Mass Index; Female; Health Status; Humans; Infant; Infant, Newborn; Inflammation; Kynurenine; Life Style; Male; Metabolome; Metabolomics; Nutritional Status; Pregnancy; Pyridoxal; Pyridoxal Phosphate; Pyridoxic Acid; Transaminases; Vitamin B 6; Vitamin B 6 Deficiency
PubMed: 25974692
DOI: 10.1146/annurev-nutr-071714-034330 -
Nutrients Feb 2017Vitamin B₆ (B₆) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the... (Review)
Review
Vitamin B₆ (B₆) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the glutathione peroxidase (GPX) system. In fact, B₆-dependent enzymes catalyse most reactions of the transsulfuration pathway, driving homocysteine to cysteine and further into GPX proteins. Considering that mammals metabolize sulfur- and seleno-amino acids similarly, B₆ plays an important role in the fate of sulfur-homocysteine and its seleno counterpart between transsulfuration and one-carbon metabolism, especially under oxidative stress conditions. This is particularly important in reproduction because ovarian metabolism may generate an excess of reactive oxygen species (ROS) during the peri-estrus period, which may impair ovulatory functions and early embryo development. Later in gestation, placentation raises embryo oxygen tension and may induce a higher expression of ROS markers and eventually embryo losses. Interestingly, the metabolic accumulation of ROS up-regulates the flow of one-carbon units to transsulfuration and down-regulates remethylation. However, in embryos, the transsulfuration pathway is not functional, making the understanding of the interplay between these two pathways particularly crucial. In this review, the importance of the maternal metabolic status of B₆ for the flow of one-carbon units towards both maternal and embryonic GPX systems is discussed. Additionally, B₆ effects on GPX activity and gene expression in dams, as well as embryo development, are presented in a pig model under different oxidative stress conditions.
Topics: Amino Acids; Animals; Antioxidants; Carbon; Disease Models, Animal; Embryonic Development; Glutathione Peroxidase; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Selenium; Swine; Vitamin B 6
PubMed: 28245568
DOI: 10.3390/nu9030189 -
Frontiers in Cellular and Infection... 2021Malaria is still today one of the most concerning diseases, with 219 million infections in 2019, most of them in Sub-Saharan Africa and Latin America, causing approx.... (Review)
Review
Malaria is still today one of the most concerning diseases, with 219 million infections in 2019, most of them in Sub-Saharan Africa and Latin America, causing approx. 409,000 deaths per year. Despite the tremendous advances in malaria treatment and prevention, there is still no vaccine for this disease yet available and the increasing parasite resistance to already existing drugs is becoming an alarming issue globally. In this context, several potential targets for the development of new drug candidates have been proposed and, among those, the biosynthesis pathway for the B6 vitamin was identified to be a promising candidate. The reason behind its significance is the absence of the pathway in humans and its essential presence in the metabolism of major pathogenic organisms. The pathway consists of two enzymes i.e. Pdx1 (PLP synthase domain) and Pdx2 (glutaminase domain), the last constituting a transient and dynamic complex with Pdx1 as the prime player and harboring the catalytic center. In this review, we discuss the structural biology of Pdx1 and Pdx2, together with and the understanding of the PLP biosynthesis provided by the crystallographic data. We also highlight the existing evidence of the effect of PLP synthesis inhibition on parasite proliferation. The existing data provide a flourishing environment for the structure-based design and optimization of new substrate analogs that could serve as inhibitors or even suicide inhibitors.
Topics: Glutaminase; Humans; Malaria; Plasmodium; Plasmodium falciparum; Vitamin B 6
PubMed: 34327152
DOI: 10.3389/fcimb.2021.688380 -
Nutrition Journal Oct 2020Nutrients involved in one-carbon metabolism may play a key role in pancreatic carcinogenesis. The aim of this study was to examine the association between pancreatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Nutrients involved in one-carbon metabolism may play a key role in pancreatic carcinogenesis. The aim of this study was to examine the association between pancreatic cancer risk and intake or blood levels of vitamins B6, B12 and methionine via meta-analysis.
METHODS
A systematic search was performed in PubMed, Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI) up to April 2020 to identify relevant studies. Risk estimates and their 95% confidence intervals (CIs) were retrieved from the studies and combined by a random-effect model.
RESULTS
A total of 18 studies were included in this meta-analysis on the association of vitamin B6, B12 and methionine with pancreatic cancer risk. The combined risk estimate (95% CI) of pancreatic cancer for the highest vs lowest category of vitamin B6 intake and blood pyridoxal 5'-phosphate (PLP, active form of vitamin B6) levels was 0.63 (0.48-0.79) and 0.65 (0.52-0.79), respectively. The results indicated a non-linear dose-response relationship between vitamin B6 intake and pancreatic risk. Linear dose-response relationship was found, and the risk of pancreatic cancer decreased by 9% for every 10 nmol/L increment in blood PLP levels. No significant association were found between pancreatic cancer risk and vitamin B12 intake, blood vitamin B12 levels, methionine intake and blood methionine levels.
CONCLUSION
Our study suggests that high intake of vitamin B6 and high concentration of blood PLP levels may be protective against the development of pancreatic cancer. Further research are warranted to confirm the results.
Topics: Diet; Folic Acid; Humans; Methionine; Pancreatic Neoplasms; Risk Factors; Vitamin B 12; Vitamin B 6
PubMed: 33012287
DOI: 10.1186/s12937-020-00628-7 -
Frontiers in Immunology 2022Targeting T cell metabolism is an established method of immunomodulation. Following activation, T cells engage distinct metabolic programs leading to the uptake and...
Targeting T cell metabolism is an established method of immunomodulation. Following activation, T cells engage distinct metabolic programs leading to the uptake and processing of nutrients that determine cell proliferation and differentiation. Redirection of T cell fate by modulation of these metabolic programs has been shown to boost or suppress immune responses and . Using publicly available T cell transcriptomic and proteomic datasets we identified vitamin B6-dependent transaminases as key metabolic enzymes driving T cell activation and differentiation. Inhibition of vitamin B6 metabolism using the pyridoxal 5'-phosphate (PLP) inhibitor, aminoxyacetic acid (AOA), suppresses CD8+ T cell proliferation and effector differentiation in a dose-dependent manner. We show that pyridoxal phosphate phosphatase (PDXP), a negative regulator of intracellular vitamin B6 levels, is under the control of the hypoxia-inducible transcription factor (HIF1), a central driver of T cell metabolism. Furthermore, by adoptive transfer of CD8 T cells into a C57BL/6 mouse melanoma model, we demonstrate the requirement for vitamin B6-dependent enzyme activity in mediating effective anti-tumor responses. Our findings show that vitamin B6 metabolism is required for CD8+ T cell proliferation and effector differentiation and . Targeting vitamin B6 metabolism may therefore serve as an immunodulatory strategy to improve anti-tumor immunotherapy.
Topics: Aminooxyacetic Acid; Animals; CD8-Positive T-Lymphocytes; Hypoxia-Inducible Factor 1, alpha Subunit; Melanoma; Mice; Mice, Inbred C57BL; Neoplasms; Phosphoprotein Phosphatases; Proteomics; Pyridoxal Phosphate; Vitamin B 6
PubMed: 35251031
DOI: 10.3389/fimmu.2022.837669 -
The Journal of Clinical Endocrinology... Sep 2022There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus...
CONTEXT
There is little evidence regarding the association between serum vitamin B6 status and catabolism and all-cause mortality in patients with type-2 diabetes mellitus (T2DM).
OBJECTIVE
We aimed to ascertain if the serum level of vitamin B6 and catabolism, including pyridoxal 5'-phosphate (PLP) and 4-pyridoxic acid (4-PA), were associated with risk of all-cause mortality in T2DM patients.
METHODS
This prospective cohort study involved 2574 patients with T2DM who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The serum concentrations of PLP and 4-PA were used to assess the serum level of vitamin B6. Mortality status was determined by routine follow-up using the National Death Index through December 31, 2015.
RESULTS
Over a median follow-up of 85 months, there were 588 deaths. The fully adjusted Cox model indicated that the highest serum PLP concentrations (> 63.6 nmol/L) were associated with a decrease in all-cause mortality (hazard ratio [HR], 0.74; 95% CI, 0.55-0.99, P trend = .035). The risk for all-cause mortality was 59% higher for participants with the highest quartile of 4-PA level compared with the lowest quartile (HR, 1.62; 95% CI, 1.12-2.35; P trend = .003). The sensitivity and specificity of the combination of PLP and 4-PA levels for the prediction of all-cause mortality were 59.5% and 60.9%, respectively (area under the receiver operating characteristic curve = 0.632). The Kaplan-Meier method was used to estimate overall survival for patients based on different combinations of PLP level and 4-PA level. Patients with PLP less than 24.3 nmol/L and 4-PA greater than or equal to 25.4 nmol/L had the worst outcomes (log-rank P < .001).
CONCLUSION
Overall, our data suggest that a low serum level of PLP and high serum level of 4-PA, which represent the serum level of vitamin B6, increases the risk of all-cause mortality significantly in patients with T2DM.
Topics: Diabetes Mellitus, Type 2; Humans; Nutrition Surveys; Phosphates; Prospective Studies; Pyridoxal Phosphate; Pyridoxic Acid; Vitamin B 6
PubMed: 35907182
DOI: 10.1210/clinem/dgac429 -
Molecules (Basel, Switzerland) Jul 2021Water-soluble B vitamins participate in numerous crucial metabolic reactions and are critical for maintaining our health. Vitamin B deficiencies cause many different...
Water-soluble B vitamins participate in numerous crucial metabolic reactions and are critical for maintaining our health. Vitamin B deficiencies cause many different types of diseases, such as dementia, anaemia, cardiovascular disease, neural tube defects, Crohn's disease, celiac disease, and HIV. Vitamin B3 deficiency is linked to pellagra and cancer, while niacin (or nicotinic acid) lowers low-density lipoprotein (LDL) and triglycerides in the blood and increases high-density lipoprotein (HDL). A highly sensitive and robust liquid chromatography-tandem mass spectroscopy (LC/MS-MS) method was developed to detect and quantify a vitamin B3 vitamer (nicotinamide) and vitamin B6 vitamers (pyridoxial 5'-phosphate (PLP), pyridoxal hydrochloride (PL), pyridoxamine dihydrochloride (PM), pridoxamine-5'-phosphate (PMP), and pyridoxine hydrochloride (PN)) in human hair samples of the UAE population. Forty students' volunteers took part in the study and donated their hair samples. The analytes were extracted and then separated using a reversed-phase Poroshell EC-C18 column, eluted using two mobile phases, and quantified using LC/MS-MS system. The method was validated in human hair using parameters such as linearity, intra- and inter-day accuracy, and precision and recovery. The method was then used to detect vitamin B3 and B6 vitamers in the human hair samples. Of all the vitamin B3 and B6 vitamers tested, only nicotinamide was detected and quantified in human hair. Of the 40 samples analysed, 12 were in the range 100-200 pg/mg, 15 in the range 200-500 pg/mg, 9 in the range of 500-4000 pg/mg. The LC/MS-MS method is effective, sensitive, and robust for the detection of vitamin B3 and its vitamer nicotinamide in human hair samples. This developed hair test can be used in clinical examination to complement blood and urine tests for the long-term deficiency, detection, and quantification of nicotinamide.
Topics: Chromatography, High Pressure Liquid; Hair; Humans; Niacinamide; Tandem Mass Spectrometry; Vitamin B 6
PubMed: 34361640
DOI: 10.3390/molecules26154487 -
Nutrients Jan 2024Marginal vitamin B6 (B6) deficiency is a widespread global concern. Inadequate B6 levels have been linked to an increased risk of age-related chronic diseases such as... (Review)
Review
Marginal vitamin B6 (B6) deficiency is a widespread global concern. Inadequate B6 levels have been linked to an increased risk of age-related chronic diseases such as cardiovascular diseases and cancers. In recent years, the growing concern over sarcopenia (the age-related loss of muscle mass and strength) and frailty (a decline in physiological resilience and increased vulnerability associated with aging) is particularly relevant due to the emergence of super-aged societies in developed countries. Notably, among the thirty-one studies included in this review, twenty-five showed a significant association of B6 status with sarcopenia, frailty, and all-cause mortality in adults ( < 0.05), while six showed no association. Emerging studies have suggested novel mechanisms underlying this association. These mechanisms involve P2X7 receptor-mediated NLRP3 inflammasome signaling, AMPK signaling, PD-L1 signaling, and satellite cell-mediated myogenesis. Furthermore, the modulation of PLP-dependent enzymes due to B6 deficiency is associated with impaired metabolic processes, affecting energy utilization, imidazole peptide production, and hydrogen sulfide production, as well as the kynurenine pathway, all of which play vital roles in skeletal muscle health and pathophysiology. This narrative review provides an up-to-date assessment of our current understanding of the potential role of nutritional B6 status in combating sarcopenia, frailty, and mortality.
Topics: Adult; Humans; Aged; Vitamin B 6; Sarcopenia; Frailty; Pyridoxine; Aging
PubMed: 38202006
DOI: 10.3390/nu16010177 -
Urolithiasis Jun 2018Higher vitamin B6 intake might reduce urinary excretion of oxalate, one of the major determinants of risk for calcium oxalate kidney stones. Previous studies...
Higher vitamin B6 intake might reduce urinary excretion of oxalate, one of the major determinants of risk for calcium oxalate kidney stones. Previous studies investigating the association between intake of vitamin B6 and risk of stones found conflicting results. We sought to investigate the association in three large prospective cohorts. We prospectively examined the association in the Health Professionals Follow-up Study (HPFS; n = 42,919 men), Nurses' Health Study I (NHS I; n = 60,003 older women), and Nurses' Health Study II (NHS II; n = 90,629 younger women). Hazard ratios (HRs) and 95% confidence intervals (CIs) for incident stones across categories of total vitamin B6 intake (<3.0, 3.0-4.9, 5.0-9.9, 10.0-39.9, ≥40.0 mg/day) were generated with Cox proportional hazards regression models adjusted for potential confounders. During 3,316,846 person-years of follow-up, 6576 incident kidney stones were confirmed. In univariate and multivariate analyses, there was no association between intake of vitamin B6 and incident stones. The HR for stones in the highest category compared with the lowest was 1.05 (95% CI 0.85, 1.30; p value for trend = 0.61) for HPFS, 0.95 (95% CI 0.76, 1.18; p value for trend = 0.42) for NHS I, and 1.06 (95% CI 0.91, 1.24; p value for trend = 0.34) for NHS II. The pooled adjusted HR for the highest category compared with the lowest was 1.03 (95% CI 0.92, 1.15; p value for trend = 0.60). Intake of vitamin B6 is not associated with risk of incident kidney stones.
Topics: Adult; Aged; Female; Follow-Up Studies; Humans; Incidence; Kidney Calculi; Male; Middle Aged; Oxalates; Proportional Hazards Models; Prospective Studies; Renal Elimination; Risk Assessment; Risk Factors; Vitamin B 6
PubMed: 28674784
DOI: 10.1007/s00240-017-0999-5 -
European Journal of Nutrition Mar 2023Pyridoxal 5´-phosphate (PLP) is the main form of vitamin B6 in humans and functions a coenzyme for more than 160 different enzymatic reactions. The purpose of the study...
PURPOSE
Pyridoxal 5´-phosphate (PLP) is the main form of vitamin B6 in humans and functions a coenzyme for more than 160 different enzymatic reactions. The purpose of the study was to find plasma PLP concentrations, which ensure an optimal vitamin B6 status determined by a metabolic marker, in never-pregnant, pregnant and lactating women and their infants.
METHODS
In an observational, prospective study, plasma PLP and the metabolic marker, HKr (hydroxykynurenine/(kynurenic acid + anthranilic acid + xanthurenic acid + hydroxyanthranilic acid) were assessed in women (n = 114) from pregnancy week 18 to 6 months postpartum and related to infant status. Never-pregnant women 18-40 years (n = 127) were included as controls.
RESULTS
Compared to controls, plasma PLP decreased during pregnancy and increased postpartum, while HKr increased from week 18 to 6 weeks postpartum, indicating maternal vitamin B6 insufficiency during this period. In never-pregnant women, HKr increased gradually with plasma PLP < 100 nmol/L, and in pregnancy week 28 a sharp increase in HKr was seen at plasma PLP < 30 nmol/L. Despite correcting for maternal vitamin B6 status, infant median plasma PLP decreased with months of exclusive breastfeeding.
CONCLUSIONS
Plasma PLP and kynurenine concentrations differ substantially between never-pregnant, pregnant and postpartum women and infants. A plasma PLP concentration in the range of 50-100 nmol/L seems to ensure an optimal vitamin B6 status for never-pregnant women, whereas a plasma PLP > 30 nmol/L in pregnancy week 28 ensures an adequate vitamin B6 status during pregnancy and lactation. Infant vitamin B6 status at age 6 months is inversely correlated to number of months of exclusive breastfeeding.
Topics: Humans; Female; Infant; Pregnancy; Vitamin B 6; Prospective Studies; Lactation; Pyridoxal Phosphate; Postpartum Period
PubMed: 36318283
DOI: 10.1007/s00394-022-03033-4