Non-causal relationship of polycystic ovarian syndrome with homocysteine and B vitamins: evidence from a two-sample Mendelian randomization.

Objective: Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level. Methods: A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels (P<5×10-8) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results. Results: The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), P = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), P = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), P = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), P = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes. Conclusion: Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS.

Impact of Serum Vitamin D, B6, and B12 and Cognitive Functions on Quality of Life in Peri- and Postmenopausal Polish Women.

BACKGROUND Menopause initiates or accelerates health problems in a woman’s life, and affects cognitive processes and quality of life. We aimed to assess the quality of life, cognitive functions, and serum vitamin D, B6, and B12 concentrations in perimenopausal and postmenopausal Polish women. Also, we correlated the assessment of the quality of life with these vitamin concentrations and cognitive functions. MATERIAL AND METHODS The study was conducted in 287 perimenopausal and postmenopausal women. Serum levels of vitamin D, B6, and B12, cognitive functions using CNS Vital Signs software, and quality of life using WHO Quality of Life Brief were tested. RESULTS Almost all of the perimenopausal and postmenopausal women had normal concentrations of serum vitamin B12 (96%), 80% of them had normal B6 concentration, while only 9% had optimal serum vitamin D concentration. Postmenopausal women had lower Neurocognitive Index, psychomotor speed, motor speed, reaction time, and lower assessment of overall quality of life, physical health, and social relationships compared to perimenopausal women. In comparison to postmenopausal women, perimenopausal women had a lower serum vitamin B6 concentration, and the lower the concentration of this vitamin in serum they had, the lower they assessed their environment. Perimenopausal women assessed their social relationships the better, the better the visual memory, and the lower the processing speed they had. Postmenopausal women assessed the environment the better, the higher their Neurocognition Index was, and the better the reaction time they had. CONCLUSIONS Assessment of quality of life was associated with some cognitive functions in both perimenopausal and postmenopausal women.

Associations of serum vitamin B6 status with the risks of cardiovascular, cancer, and all-cause mortality in the elderly.

Background: There are few studies investigating the relationship between serum vitamin B6 and mortality risk in the elderly. This study hereby evaluated the associations between biomarkers of serum vitamin B6 status and cardiovascular, cancer, and all-cause mortality risks in the elderly. Methods: Our study included a total of 4,881 participants aged 60 years or older from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Serum vitamin B6 status was estimated based on levels of pyridoxal 5'-phosphate (PLP), 4-pyridoxic acid (4-PA), and vitamin B6 turnover rate (4-PA/PLP) detected by high-performance liquid chromatography. Survival status and corresponding causes of death were matched through the National Death Index records through December 31, 2019. Multivariate Cox regression model was adopted to assess the relationships between serum vitamin B6 status and the risk of mortality. Results: During a median follow-up period of 10.33 years, 507 cardiovascular deaths, 426 cancer deaths, and 1995 all-cause deaths were recorded, respectively. In the multivariate-adjusted Cox model, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest versus the lowest quartiles of PLP, 4-PA, and 4-PA/PLP were 0.70(0.54-0.90), 1.33(0.88-2.02), and 2.01(1.41-2.79) for cardiovascular mortality, 0.73(0.52-1.02), 1.05(0.71-1.57), and 1.95(1.25-3.05) for cancer mortality, and 0.62(0.53-0.74), 1.05(0.82-1.34), and 2.29(1.87-2.79) for all-cause mortality, respectively. Conclusion: Our study found that lower serum PLP levels were associated with increased risks of cardiovascular and all-cause mortality among the elderly population. And higher vitamin B6 turnover rate was associated with increased risks of cardiovascular, cancer, and all-cause mortality.

Genetically predicted circulating concentrations of micronutrients and risk of hypertensive disorders of pregnancy: a Mendelian randomization study.

PURPOSE: Epidemiological studies examining the association between circulating micronutrients and the risk of hypertensive disorders during pregnancy (HDP) have produced inconsistent results. Therefore, we conducted a Mendelian randomization (MR) analysis to evaluate the potential causal relationship between micronutrients and HDP. METHODS: Nine micronutrients (beta-carotene, vitamin B6, vitamin B12, calcium, zinc, selenium, copper, folate, and phosphorus) were selected as the exposure factors. Summary data for gestational hypertension (14,727 cases and 196,143 controls) and preeclampsia/eclampsia (7212 cases and 174,266 controls) were extracted from the FinnGen consortium. The MR analysis employed the inverse variance weighted method and conducted a range of sensitivity analyses. RESULTS: The inverse variance weighted method indicated no significant causal relationship between nine genetically predicted micronutrient concentrations and gestational hypertension, as well as preeclampsia/eclampsia. Sensitivity analyses suggested the absence of pleiotropy. CONCLUSION: There is no strong evidence to support the causation between circulating micronutrients and hypertensive disorder during pregnancy.

Kynurenine pathway activation and deviation to anthranilic and kynurenic acid in fibrosing chronic graft-versus-host disease.

Fibrosing chronic graft-versus-host disease (cGVHD) is a debilitating complication of allogeneic stem cell transplantation (alloSCT). A driver of fibrosis is the kynurenine (Kyn) pathway, and Kyn metabolism patterns and cytokines may influence cGVHD severity and manifestation (fibrosing versus gastrointestinal [GI] cGVHD). Using a liquid chromatography-tandem mass spectrometry approach on sera obtained from 425 patients with allografts, we identified high CXCL9, high indoleamine-2,3-dioxygenase (IDO) activity, and an activated Kyn pathway as common characteristics in all cGVHD subtypes. Specific Kyn metabolism patterns could be identified for non-severe cGVHD, severe GI cGVHD, and fibrosing cGVHD, respectively. Specifically, fibrosing cGVHD was associated with a distinct pathway shift toward anthranilic and kynurenic acid, correlating with reduced activity of the vitamin-B2-dependent kynurenine monooxygenase, low vitamin B6, and increased interleukin-18. The Kyn metabolite signature is a candidate biomarker for severe fibrosing cGVHD and provides a rationale for translational trials on prophylactic vitamin B2/B6 supplementation for cGVHD prevention.

Vitamin B6 as a novel risk biomarker of fractured ankles.

ABSTRACT: Ankle fractures are the most common intra-articular fractures. Osteoporosis is a common and frequent disease among the elderly with a poor prognosis and high risk of fractured ankles. However, the relationship between vitamin B6 and the incidence of fractured ankles in patients with osteoporosis is unclear.A total of 101 patients with osteoporosis were recruited. Clinical and followed-up information was recorded. And the vitamin B6, albumin, globulin, and hemoglobin in the blood were tested. Pearson's chi-squared and spearman test were performed to analyze the correlation between fractured ankles and relative parameters. Univariate and multivariate logistic regression, receiver operating characteristic curve analysis, univariate and multivariate Cox proportional hazards regression analysis, and Kaplan-Meier method were also performed.There exist strong relation between the expression level of vitamin B6 and fractured ankle (P < .001). The expression of vitamin B6 [Odd ratio (OR) = 12.071, 95% confidence interval (CI): 4.69-31.143, P < .001] has a clear correlation with whether the patients have fractured ankles via the univariate logistic regression analysis. In terms of multivariate logistic regression level, vitamin B6 (OR = 15.384, 95% CI:5.195-45.556, P < .001) was significantly associated with fractured ankle. In addition, expression level of vitamin B6 [hazard ratio (HR) = 11.684, 95% CI: 6.419-21.267, P < .001] was significantly associated with Maintenance time from recovery to recurrence (MRTT) of patients with osteoporosis.Enhanced vitamin B6 is significantly correlated with the poor prognosis of patients with osteoporosis and the increasing incidence of fractured ankles.

Association of Serum Vitamin B6 with All-Cause and Cause-Specific Mortality in a Prospective Study.

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.

Vitamin B6 in Health and Disease.

Vitamin B6 is a fascinating molecule involved in the vast majority of changes in the human body because it is a coenzyme involved in over 150 biochemical reactions. It is active in the metabolism of carbohydrates, lipids, amino acids, and nucleic acids, and participates in cellular signaling. It is an antioxidant and a compound with the ability to lower the advanced glycation end products (AGE) level. In this review, we briefly summarize its involvement in biochemical pathways and consider whether its deficiency may be associated with various diseases such as diabetes, heart disease, cancer, or the prognosis of COVID-19.

Regular intake of energy drinks and multivitamin supplements is associated with elevated plasma vitamin B6 levels in post-bariatric patients.

The aim of the present survey was to analyze plasma vitamin B6 levels in post-bariatric patients and to elucidate the causal factors associated with elevated plasma vitamin B6 levels. This is a retrospective analysis of electronic patient data of all post-bariatric patients evaluated at the endocrine outpatient clinic of the University Hospital Basel in 2017, for which plasma vitamin B6 values were assessed during regular follow-up visits. In total, 205 patients were included in the study, whereof a minority of 43% had vitamin B6 levels in the normal range. 50% of the patients had vitamin B6 levels up to fourfold higher than the upper normal limit and 7% had levels more than fourfold above the upper normal limit. Vitamin B6 deficiency was not observed in any patient. While multivitamin supplementation in general was associated with elevated plasma vitamin B6 levels, the highest vitamin B6 levels were found after biliopancreatic diversion (BPD) and in patients who reported daily energy drink intake. Elevated plasma vitamin B6 levels up to fourfold above the upper normal limit are common in postbariatric patients and are associated with regular multivitamin supplementation, while highly elevated plasma vitamin B6 levels were seen primarily upon regular energy drink intake. Thus, a regular follow-up of vitamin B6 plasma levels and critical evaluation of vitamin B6 supplementation, either as part of the multivitamin preparation or related to regular energy drink intake, is highly warranted and should be an integral part of the routine post-bariatric follow-up.

Quantification of the B6 vitamers in human plasma and urine in a study with pyridoxamine as an oral supplement; pyridoxamine as an alternative for pyridoxine.

BACKGROUND AND AIMS: Vitamin B6 is involved in a large spectrum of physiological processes and comprises of the vitamers pyridoxamine (PM), pyridoxal (PL), pyridoxine (PN), and their phosphorylated derivatives including the biological active pyridoxal 5'-phosphate (PLP). While PN toxicity is known to complicate several treatments, PM has shown promise in relation to the treatment of metabolic and age-related diseases by blocking oxidative degradation and scavenging toxic dicarbonyl compounds and reactive oxygen species. We aimed to assess the metabolization of oral PM supplements in a single and three daily dose. MATERIALS AND METHODS: We optimized and validated a method for the quantification of the B6 vitamers in plasma and urine using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Five healthy volunteers were recruited to study PM metabolization after a single oral dose of 200 mg PM or a three daily dose of 67 mg PM. A third protocol was implemented as control for dietary intake. Venous blood samples, 24 h urine and fasted second void urine samples were collected. RESULTS: After a single oral dose of 200 mg PM, plasma PM increased in the first 3 h to a maximum of 2324 ± 266 nmol/L. While plasma PM levels returned to baseline after ~10 h of PM intake, PLP increased to a maximum of 2787 ± 329 nmol/L and reached a plateau. We found a small increase of PN to a maximum of 13.5 ± 2.1 nmol/L; it was nearly undetectable after ~12 h. With a three daily dose of 67 mg PM we observed an increase and decline of plasma PM, PL, and PN concentrations after each PM intake. PLP showed a similar increase as in the single dose protocol and accumulated over time. CONCLUSION: In this study we showed high plasma levels of PM after oral PM supplementation. We found steadily increasing levels of the biologically active PLP, with minimal formation of PN. The B6 vitamer PM is an interesting supplement as an inhibitor of harmful processes in metabolic diseases and for the treatment of vitamin B6 deficiency. CLINICAL TRIAL REGISTRY: The study was approved by the Medical Ethics Committee of Maastricht University (NL) and was registered at ClinicalTrials.gov as NCT02954588.

Vitamin B6 Status among Vegetarians: Findings from a Population-Based Survey.

Vitamin B6 from plant foods may have lower bioavailability than vitamin B6 from animal foods, but studies on objectively measured vitamin B6 status among vegetarians compared to non-vegetarians are lacking. Thus, the vitamin B6 status among vegetarians, but also pescatarians, and flexitarians, compared to meat-eaters was assessed in the population-based NHANES study (cycles 2007-2008 and 2009-2010). Data on serum pyridoxal-5'-phosphate (PLP) and 4-pyridoxic acid (4-PA) measured by high-performance liquid chromatography (HPLC) as well as dietary intakes from 24-h recalls were available for 8968 adults aged 20-80 years. Geometric mean (±standard error) PLP concentrations were 58.2 ± 6.0, 52.1 ± 3.7, 49.2 ± 4.6 and 51.0 ± 1.1 nmol/L among vegetarians, pescatarians, flexitarians, and meat-eaters. The 4-PA concentrations were 32.7 ± 4.0, 29.0 ± 2.5, 34.8 ± 5.6 and 33.0 ± 0.7, respectively. There were no statistically significant differences in PLP, 4-PA, and their ratio across the groups in multivariable linear regression models. Overall, the use of vitamin B6 supplements was the strongest predictor of the vitamin B6 status, followed by the dietary vitamin B6 intake. Interestingly, several other covariates were significantly associated with vitamin B6 biomarker levels, particularly serum albumin, creatinine and alkaline phosphatase, and should be considered when assessing the vitamin B6 status. In summary, our findings suggest that a vegetarian diet does not pose a risk for vitamin B6 deficiency.

A Novel Review of Homocysteine and Pregnancy Complications.

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

Genetic variants modify the associations of concentrations of methylmalonic acid, vitamin B-12, vitamin B-6, and folate with bone mineral density.

BACKGROUND: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine ß-synthase (CBS). OBJECTIVES: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength. METHODS: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing. RESULTS: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified. CONCLUSIONS: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture.

Association Between Homocysteine and Vitamin Levels in Demented Patients.

BACKGROUND: Although it is known that the nutritional status among elderly persons and, in particular, patients with dementia, is compromised, malnutrition that results in insufficient uptake of several vitamins is often not diagnosed. OBJECTIVE: An elevated homocysteine level is a known strong risk factor for vascular dementia (VaD) and Alzheimer's disease (AD). Several B vitamins are involved in the metabolism of homocysteine. Therefore, we investigated the serum levels of vitamin B1, vitamin B6, folate, and vitamin B12 in 97 patients with mild cognitive impairment (MCI) or different forms of dementia and 54 elderly control persons without dementia. RESULTS: Compared to aged non-demented people, vitamins B1, B6, B12, and folate were decreased in serum of patients with AD, and patients with Lewy body dementia had reduced vitamin B12 level. Vitamin B6 was diminished in VaD. Patients with frontotemporal dementia showed no alterations in vitamin levels. Age was identified as an important factor contributing to the concentrations of vitamin B1 and B6 in serum, but not vitamin B12 and folate. Increased levels of total homocysteine were detected especially in MCI and AD. Homocysteine correlated negatively with levels of vitamins B6, B12, and folate and positively with Q Albumin. CONCLUSION: Our data suggest that despite increased homocysteine already present in MCI, vitamin levels are decreased only in dementia. We propose to determine the vitamin levels in patients with cognitive decline, but also elderly people in general, and recommend supplementing these nutrients if needed.

Plasma B Vitamers: Population Epidemiology and Parent-Child Concordance in Children and Adults.

SCOPE: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent-child dyads are scarce. Profiling B vitamers in parent-child dyads enables an insightful determination of gene-environment contributions to their circulating concentrations. We aimed to characterise: (a) parent-child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28-71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. METHODS AND RESULTS: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia's Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent-child pairs (10-31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. CONCLUSION: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.

Genetically predicted circulating B vitamins in relation to digestive system cancers.

BACKGROUND: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. METHODS: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. RESULTS: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. CONCLUSIONS: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.

Associations of Plasma Folate and Vitamin B6 With Blood DNA Methylation Age: An Analysis of One-Carbon Metabolites in the VA Normative Aging Study.

One-carbon metabolism is an important contributor to aging-related diseases; nevertheless, relationships of one-carbon metabolites with novel DNA methylation-based measures of biological aging remain poorly characterized. We examined relationships of one-carbon metabolites with 3 DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. We measured plasma levels of 4 common one-carbon metabolites (vitamin B6, vitamin B12, folate, and homocysteine) in 715 VA Normative Aging Study participants with at least 1 visit between 1999 and 2008 (observations = 1153). DNA methylation age metrics were calculated using the HumanMethylation450 BeadChip. We utilized Bayesian Kernel Machine Regression models adjusted for chronological age, lifestyle factors, age-related diseases, and study visits to determine metabolites important to the aging outcomes. Bayesian Kernel Machine Regression models allowed for the estimation of the relationships of single metabolites and the cumulative metabolite mixture with methylation age. Log vitamin B6 was selected as important to PhenoAge (ß = -1.62 years, 95% CI: -2.28, -0.96). Log folate was selected as important to GrimAge (ß = 0.75 years, 95% CI: 0.41, 1.09) and PhenoAge (ß = 1.62 years, 95% CI: 0.95, 2.29). Compared to a model where each metabolite in the mixture is set to its 50th percentile, the log cumulative mixture with each metabolite at its 30th (ß = -0.13 years, 95% CI: -0.26, -0.005) and 40th percentile (ß = -0.06 years, 95% CI: -0.11, -0.005) was associated with decreased GrimAge. Our results provide novel characterizations of the relationships between one-carbon metabolites and DNA methylation age in a human population study. Further research is required to confirm these findings and establish their generalizability.

Effects of the intake of craft or industrial beer on serum homocysteine.

Beer is a source of folate, vitamin B6 and B12, molecules involved in the pathways of homocysteine (HCY), a risk factor for cardiovascular disease. This research evaluated if a consumption of craft or industrial beer could reduce serum HCY. In a randomised cross-over study, 12 men (28.7 ± 6.0 years) and 12 women (29.4 ± 7.5 years), healthy, omnivorous, with normal body mass index, non-smoking and not taking oral supplements or contraceptives, followed a free-living diet and received, daily, for 3 weeks, 330 ml of industrial (4.5% of alcohol) or craft beer (9% of alcohol). Anthropometric measures and blood samples were taken at the beginning and at the end of each period. The consumption of industrial beer reduced (p < 0.05) HCY (7.35 vs. 6.50 µmol/L) and increased folic acid (3.46 vs. 3.94 ng/mL). Craft beer increased gamma-gluamyl transpeptidase (GGT) (16.6 vs. 18.6 U/L) and reduced vitamin B6 (20.9 vs. 16.9 ng/mL).

Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial.

Primary findings from a recent study reported that magnesium supplementation significantly reduced stress in severely stressed subjects with low magnesemia, and additional vitamin B6 enhanced this effect. The mechanism by which combining magnesium and vitamin B6 leads to reduced stress in these subjects remains to be elucidated. This secondary analysis investigated the impact of magnesium and vitamin B6 supplementation and perceived stress on erythrocyte magnesium levels, as a marker of body magnesium status. This was a secondary analysis from an 8-week randomized controlled trial comparing oral magnesium (300 mg) and magnesium-vitamin B6 (300 mg + 30 mg) supplementation. Stress level and erythrocyte magnesium level at baseline, and change in erythrocyte magnesium and serum vitamin B6 levels at weeks 4 and 8, were analyzed. Overall, 264 subjects were randomized to treatment and had evaluable Depression Anxiety Stress Scale scores (132 in each treatment arm). At baseline, stress scores, and mean serum magnesium, erythrocyte magnesium, and serum vitamin B6 concentrations were similar between arms. Although not significant between groups, a significant increase over time in erythrocyte magnesium levels was observed in the subgroup of subjects with low baseline erythrocyte magnesium levels (<1.6 mmol/L) following treatment with magnesium and magnesium-vitamin B6 (week 4:0.21 mmol/L [95% confidence interval (CI), 0.10 to 0.31], p = 0.0003; and 0.13 mmol/L [95% CI, 0.02 to 0.23], p = 0.0233, respectively). Change from baseline in circulating vitamin B6 levels at weeks 4 and 8 in the magnesium-vitamin B6 supplemented group (314.96 nmol/L [95%CI, 294.61 to 335.31]) was significantly different (p < 0.0001) compared with the magnesium supplemented group (-0.39 nmol/L [95% CI, -20.73 to 19.94]). Magnesium alone and magnesium-vitamin B6 provided statistically significant increases in erythrocyte magnesium in subjects with low magnesium status (<1.6mmol/L). Vitamin B6 supplementation did not further increase magnesium levels.