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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 -
International Journal of Molecular... Nov 2020Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular...
Pathological neovascularization in the eye is a leading cause of blindness in all age groups from retinopathy of prematurity (ROP) in children to age-related macular degeneration (AMD) in the elderly. Inhibiting neovascularization via antivascular endothelial growth factor (VEGF) drugs has been used for the effective treatment. However, anti-VEGF therapies may cause development of chorioretinal atrophy as they affect a physiological amount of VEGF essential for retinal homeostasis. Furthermore, anti-VEGF therapies are still ineffective in some cases, especially in patients with AMD. Hypoxia-inducible factor (HIF) is a strong regulator of VEGF induction under hypoxic and other stress conditions. Our previous reports have indicated that HIF is associated with pathological retinal neovascularization in murine models of ROP and AMD, and HIF inhibition suppresses neovascularization by reducing an abnormal increase in VEGF expression. Along with this, we attempted to find novel effective HIF inhibitors from natural foods of our daily lives. Food ingredients were screened for prospective HIF inhibitors in ocular cell lines of 661W and ARPE-19, and a murine AMD model was utilized for examining suppressive effects of the ingredients on retinal neovascularization. As a result, rice bran and its component, vitamin B6 showed inhibitory effects on HIF activation and suppressed mRNA induction under a CoCl-induced pseudo-hypoxic condition. Dietary supplement of these significantly suppressed retinal neovascularization in the AMD model. These data suggest that rice bran could have promising therapeutic values in the management of pathological ocular neovascularization.
Topics: Aged; Animals; Cobalt; Disease Models, Animal; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Infant, Newborn; Macular Degeneration; Mice; Neovascularization, Pathologic; Oryza; Retina; Retinal Pigment Epithelium; Rice Bran Oil; Vascular Endothelial Growth Factor A; Vitamin B 6
PubMed: 33255657
DOI: 10.3390/ijms21238940 -
Nutrients May 2022The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to...
The evidence regarding the intake of dietary folate, vitamin B6, and vitamin B12 in relation to mortality in the general population is limited. This study aimed to examine the relationship between dietary intakes of folate, vitamin B6, and vitamin B12 in relation to all-cause and cause-specific mortality in a large U.S. cohort. This study included a total of 55,569 adults from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 1999-2014. Vital data were determined by linking with the National Death Index records through 31 December 2015. Cox proportional hazards models were used to investigate the relationships of all-cause and cause-specific mortality with dietary folate, vitamin B6, and vitamin B12 intake. Dietary intakes of folate and vitamin B6 were inversely associated with mortality from all-cause, cardiovascular disease, and cancer for men and with mortality from all-cause and cardiovascular disease for women. In men, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.77 (0.71-0.85) and 0.79 (0.71-0.86) for all-cause mortality, 0.59 (0.48-0.72) and 0.69 (0.56-0.85) for CVD mortality, and 0.68 (0.56-0.84) and 0.73 (0.60-0.90) for cancer mortality, respectively. Among women, the multivariable hazard ratios (95% confidence intervals) for the highest versus lowest quintiles of folate and vitamin B6 were 0.86 (0.78-0.95) and 0.88 (0.80-0.97) for all-cause mortality and 0.53 (0.41-0.69) and 0.56 (0.44-0.73) for CVD mortality, respectively. No significant associations between dietary vitamin B12 and all-cause and cause-specific mortality were observed. In conclusion, higher dietary intakes of folate and vitamin B6 were significantly associated with lower all-cause and cardiovascular mortality. Our findings suggest that increasing the intake of folate and vitamin B6 may lower the mortality risk among U.S. adults.
Topics: Adult; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Humans; Male; Nutrition Surveys; Pyridoxine; Vitamin B 12; Vitamin B 6
PubMed: 35684053
DOI: 10.3390/nu14112253 -
JAMA Network Open Jan 2023The associations of B vitamin status with metabolic syndrome (MetS) incidence among the US population remain unclear.
IMPORTANCE
The associations of B vitamin status with metabolic syndrome (MetS) incidence among the US population remain unclear.
OBJECTIVE
To investigate intakes and serum concentrations of folate, vitamin B6, and vitamin B12 in association with MetS risk in a large US cohort.
DESIGN, SETTING, AND PARTICIPANTS
This prospective study included Black and White young adults in the US who were enrolled from 1985 to 1986 and studied until 2015 to 2016. Diet was assessed using a validated diet history at examination years 0, 7, and 20. Serum concentrations of folate, vitamin B6, and vitamin B12 were assayed at examination years 0, 7, and 15 in a subset of 1430 participants. MetS was ascertained by clinic and laboratory measurements and self-reported medication use. Data were analyzed between January and July 2021.
EXPOSURES
Intakes and serum levels of folate, vitamin B6, and vitamin B12.
MAIN OUTCOMES AND MEASURES
Multivariable Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs for the associations of energy-adjusted B vitamin intakes or serum B vitamin levels with incident MetS.
RESULTS
The study included 4414 participants, with 2225 Black individuals (50.4%) and 2331 women (52.8%). The mean (SD) age at baseline was 24.9 (3.6) years. A total of 1240 incident MetS cases occurred during the 30 years (mean [SD], 22.1 [9.5] years) of follow-up. Compared with the lowest quintile of each energy-adjusted B vitamin intake, the HRs for incident MetS in the highest quintile were 0.39 (95% CI, 0.31-0.49) for folate (P for trend < .001), 0.61 (95% CI, 0.46-0.81) for vitamin B6 (P for trend = .002), and 0.74 (95% CI, 0.58-0.95) for vitamin B12 (P for trend = .008) after adjustment for potential confounders. Similarly, significant inverse associations were observed in the subset with serum data on these B vitamins (folate: HR, 0.23; 95% CI, 0.17-0.33; P for trend < .001; vitamin B6: HR, 0.48; 95% CI, 0.34-0.67; P for trend < .001; and vitamin B12: HR, 0.70; 95% CI, 0.51-0.96; P for trend = .01).
CONCLUSIONS AND RELEVANCE
This prospective cohort study found that intakes and serum concentrations of folate, vitamin B6, and vitamin B12 were inversely associated with incident MetS among Black and White young adults in the US.
Topics: Young Adult; Female; Humans; Adult; Folic Acid; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Prospective Studies; Incidence; Metabolic Syndrome
PubMed: 36630134
DOI: 10.1001/jamanetworkopen.2022.50621 -
Nutrients Mar 2015Nutrition is one of the most important modifiable factors involved in the development and maintenance of good bone health. Calcium and Vitamin D have confirmed and... (Review)
Review
Nutrition is one of the most important modifiable factors involved in the development and maintenance of good bone health. Calcium and Vitamin D have confirmed and established roles in the maintenance of proper bone health. However, other nutritional factors could also be implicated. This review will explore the emerging evidence of the supporting role of certain B Vitamins as modifiable factors associated with bone health. Individuals with high levels of homocysteine (hcy) exhibit reduced bone mineral density (BMD), alteration in microarchitecture and increased bone fragility. The pathophysiology caused by high serum homocysteine is not completely clear regarding fractures, but it may involve factors, such as bone mineral density, bone turnover, bone blood flow and collagen cross-linking. It is uncertain whether supplementation with B Vitamins, such as folate, Vitamin B1, and Vitamin B6, could decrease hip fracture incidence, but the results of further clinical trials should be awaited before a conclusion is drawn.
Topics: Bone Density; Bone Remodeling; Bone and Bones; Calcium, Dietary; Folic Acid; Hip Fractures; Homocysteine; Humans; Incidence; Randomized Controlled Trials as Topic; Risk Factors; Thiamine; Vitamin B 6; Vitamin B Complex; Vitamin D
PubMed: 25830943
DOI: 10.3390/nu7042176 -
PLoS Medicine Dec 2023Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from... (Randomized Controlled Trial)
Randomized Controlled Trial
Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial.
BACKGROUND
Maternal vitamin status preconception and during pregnancy has important consequences for pregnancy outcome and offspring development. Changes in vitamin status from preconception through early and late pregnancy and postpartum have been inferred from cross-sectional data, but longitudinal data on vitamin status from preconception throughout pregnancy and postdelivery are sparse. As such, the influence of vitamin supplementation on vitamin status during pregnancy remains uncertain. This study presents one prespecified outcome from the randomized controlled NiPPeR trial, aiming to identify longitudinal patterns of maternal vitamin status from preconception, through early and late pregnancy, to 6 months postdelivery, and determine the influence of vitamin supplementation.
METHODS AND FINDINGS
In the NiPPeR trial, 1,729 women (from the United Kingdom, Singapore, and New Zealand) aged 18 to 38 years and planning conception were randomized to receive a standard vitamin supplement (control; n = 859) or an enhanced vitamin supplement (intervention; n = 870) starting in preconception and continued throughout pregnancy, with blinding of participants and research staff. Supplement components common to both treatment groups included folic acid, β-carotene, iron, calcium, and iodine; components additionally included in the intervention group were riboflavin, vitamins B6, B12, and D (in amounts available in over-the-counter supplements), myo-inositol, probiotics, and zinc. The primary outcome of the study was glucose tolerance at 28 weeks' gestation, measured by oral glucose tolerance test. The secondary outcome reported in this study was the reduction in maternal micronutrient insufficiency in riboflavin, vitamin B6, vitamin B12, and vitamin D, before and during pregnancy. We measured maternal plasma concentrations of B-vitamins, vitamin D, and markers of insufficiency/deficiency (homocysteine, hydroxykynurenine-ratio, methylmalonic acid) at recruitment, 1 month after commencing intervention preconception, in early pregnancy (7 to 11 weeks' gestation) and late pregnancy (around 28 weeks' gestation), and postdelivery (6 months after supplement discontinuation). We derived standard deviation scores (SDS) to characterize longitudinal changes among participants in the control group and measured differences between the 2 groups. At recruitment, the proportion of patients with marginal or low plasma status was 29.2% for folate (<13.6 nmol/L), 7.5% and 82.0% for riboflavin (<5 nmol/L and ≤26.5 nmol/L, respectively), 9.1% for vitamin B12 (<221 pmol/L), and 48.7% for vitamin D (<50 nmol/L); these proportions were balanced between the groups. Over 90% of all participants had low or marginal status for one or more of these vitamins at recruitment. Among participants in the control group, plasma concentrations of riboflavin declined through early and late pregnancy, whereas concentrations of 25-hydroxyvitamin D were unchanged in early pregnancy, and concentrations of vitamin B6 and B12 declined throughout pregnancy, becoming >1 SDS lower than baseline by 28 weeks gestation. In the control group, 54.2% of participants developed low late-pregnancy vitamin B6 concentrations (pyridoxal 5-phosphate <20 nmol/L). After 1 month of supplementation, plasma concentrations of supplement components were substantially higher among participants in the intervention group than those in the control group: riboflavin by 0.77 SDS (95% CI 0.68 to 0.87, p < 0.0001), vitamin B6 by 1.07 SDS (0.99 to 1.14, p < 0.0001), vitamin B12 by 0.55 SDS (0.46 to 0.64, p < 0.0001), and vitamin D by 0.51 SDS (0.43 to 0.60, p < 0.0001), with higher levels in the intervention group maintained during pregnancy. Markers of vitamin insufficiency/deficiency were reduced in the intervention group, and the proportion of participants with vitamin D insufficiency (<50 nmol/L) during late pregnancy was lower in the intervention group (35.1% versus 8.5%; p < 0.0001). Plasma vitamin B12 remained higher in the intervention group than in the control group 6 months postdelivery (by 0.30 SDS (0.14, 0.46), p = 0.0003). The main limitation is that generalizability to the global population is limited by the high-resource settings and the lack of African and Amerindian women in particular.
CONCLUSIONS
Over 90% of the trial participants had marginal or low concentrations of one or more of folate, riboflavin, vitamin B12, or vitamin D during preconception, and many developed markers of vitamin B6 deficiency in late pregnancy. Preconception/pregnancy supplementation in amounts available in over-the-counter supplements substantially reduces the prevalence of vitamin deficiency and depletion markers before and during pregnancy, with higher maternal plasma vitamin B12 maintained during the recommended lactational period.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02509988; U1111-1171-8056.
Topics: Female; Humans; Pregnancy; Cross-Sectional Studies; Dietary Supplements; Folic Acid; Pregnancy Outcome; Riboflavin; Vitamin B 12; Vitamin B 6; Vitamin B Complex; Vitamin D; Adolescent; Young Adult; Adult
PubMed: 38051700
DOI: 10.1371/journal.pmed.1004260 -
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 -
Psychiatry and Clinical Neurosciences Sep 2014Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to... (Review)
Review
Appropriate biological treatment and psychosocial support are essential to achieve and maintain recovery for patients with schizophrenia. Despite extensive efforts to clarify the underlying disease mechanisms, the main cause and pathophysiology of schizophrenia remain unclear. This is due in large part to disease heterogeneity, which results in biochemical differences within a single disease entity. Other factors include variability across clinical symptoms and disease course, along with varied risk factors and treatment responses. Although schizophrenia's positive symptoms are largely managed through treatment with atypical antipsychotics, new classes of drugs are needed to address the unmet medical need for improving cognitive dysfunction and promoting recovery of negative symptoms in these patients. Accumulation of toxic reactive dicarbonyls, such as methylglyoxal, are typical indicators of carbonyl stress, and result in the modification of proteins and the formation of advanced glycation end products, such as pentosidine. In June 2010, we reported on idiopathic carbonyl stress in a subpopulation of schizophrenia patients, leading to a failure of metabolic systems with plasma pentosidine accumulation and serum pyridoxal depletion. Our findings suggest two markers, pentosidine and pyridoxal, as beneficial for distinguishing a specific subgroup of schizophrenics. We believe that this information, derived from in vitro and in vivo studies, is beneficial in the search for personalized and hopefully more effective treatment regimens in schizophrenia. Here, we define a subtype of schizophrenia based on carbonyl stress and the potential for using carbonyl stress as a biomarker in the challenge of overcoming heterogeneity in schizophrenia treatment.
Topics: Arginine; Biomarkers; Glycation End Products, Advanced; Humans; Lactoylglutathione Lyase; Lysine; Mutation; Psychiatric Status Rating Scales; Pyridoxal; Pyridoxamine; Schizophrenia; Stress, Physiological
PubMed: 24995521
DOI: 10.1111/pcn.12216 -
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 -
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