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Abstract Pyridoxal kinase (PdxK, EC 2.7.1.35) is an important enzyme of vitamin B6 salvage pathway which is required for phosphorylation of B6 vitamers. In the present study, pyridoxal kinase (pdxK) gene from Leishmania donovani (Ld PdxK) was cloned and a 33 kDa protein was expressed and kinetically characterized. Site-directed mutagenesis was performed to determine the functional significance of conserved GXGD motif. Mutation of Thr229 to Ala did not affect the catalytic function of Ld PdxK however Gly228, Gly230 and Asp231 were found to be indispensible for enzyme activity. To determine the role of Ld PdxK in Leishmania promastigotes, Ld PdxK overexpressing parasites were generated by episomal expression of the enzyme. The overexpression studies revealed the role of this enzyme in growth and infection of the parasite. In silico analysis of the human and parasite PdxK structure revealed significant differences in the active site region thus highlighting its potential as an antileishmanial drug target. Homology model of Ld PdxK was built and was subjected to molecular dynamics simulations. Based on the above information, a pharmacophore was developed and shape based virtual screening was performed to identify potential and selective inhibitors against this essential enzyme. The current data suggests that Ld PdxK could be a promising antileishmanial drug target. [ABSTRACT FROM AUTHOR]

Purpose: Gyrate atrophy (GA) is a rare chorioretinal degeneration that results in the deterioration of night and peripheral vision, eventually leading to blindness. The disorder is caused by mutations in the gene encoding ornithine aminotransferase (OAT), causing increased levels of plasma ornithine. Treatment revolves around lowering plasma ornithine levels, with vitamin B6 supplementation being the preferred treatment. Nevertheless, most patients do not respond to this therapy. Here, we report a rare case of vitamin B6-responsive GA caused by a novel mutation in OAT and characterize the presentation with multimodal imaging. Methods: This is a single-patient case report with a clinical diagnosis based on history, multimodal retinal imaging, laboratory findings, and DNA sequencing analysis. We include a 3D structure prediction of the novel mutant protein. Results: DNA sequencing analysis demonstrated that there is a homozygous, novel variant c.473A>C: p.Y158S in OAT. Upon undergoing two weeks of vitamin B6 supplementation, the patient exhibited a 28.5% reduction in plasma ornithine levels. In a follow-up visit two years later, plasma ornithine levels were reduced by 24.1% from the levels at initial presentation and disease progression was retarded based on clinical findings. Conclusion: One novel homozygous missense mutation in OAT was identified and considered to be pathogenic in a patient with GA. The response for the vitamin B6 supplementation was positive, which is rare in all the GA cases reported in the literature. Our data suggests that further studies regarding the relationship between genotype and responsiveness to vitamin B6 should be conducted. [ABSTRACT FROM AUTHOR]

Tahfiz education has been well accepted by Muslims in Malaysia. Memorizing the Quran through rote learning can assist in improving the brain ability to process, store information and build memory. In addition, dietary intakes were reported to contribute in the process of memorizing the Quran and to increase the levels of intelligence (IQ) among huffaz students. This cross-sectional study was conducted to measure and to determine the correlation between IQ and dietary intake as well as between IQ and the level of trace elements among students in selected tahfiz schools and non-tahfiz school in Selangor. Questionnaires were used to obtain demographic data. Dietary intake was assessed via 3 days dietary record. Levels of trace elements in the nail samples were analyzed by using ICP-MS. Test for intelligence using WASI-II was conducted to measure the students' IQ. The results showed that there was a moderate positive correlation between IQ and carbohydrate (r = 0.425, p < 0.001, a weak positive correlation between IQ and energy (r = 0.260, p < 0.05), vitamin B6 (r = 0.189, p < 0.05), vitamin B12 (r = 0.207, p < 0.05) and vitamin C (r = 0.211, p < 0.05). The levels of trace elements in nail samples showed no correlation with IQ, whereas there were moderate positive correlations between IQ and dietary zinc (r = 0.375, p < 0.001) as well as between IQ and dietary iron (r = 0.303, p < 0.001). There was also a moderate positive correlation between IQ and the level of memorization (r = 0.375, p < 0.001). The results of stepwise multiple linear regression showed that al-Quran memorization influence the level of IQ by 20 %. As a conclusion, dietary intake of certain nutrients including energy, vitamins and selected trace elements can potentially improve memorization activities and also IQ. [ABSTRACT FROM AUTHOR]

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. Inhibition of GABA aminotransferase (GABA-AT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, has been established as a possible strategy for the treatment of substance abuse. The raised GABA levels that occur as a consequence of this inhibition have been found to antagonize the rapid release of dopamine in the ventral striatum (nucleus accumbens) that follows an acute challenge by an addictive substance. In addition, increased GABA levels are also known to elicit an anticonvulsant effect in patients with epilepsy. We previously designed the mechanism-based inactivator (1S,3S)-3-amino-4-difluoromethylenyl-1-cyclopentanoic acid (2), now called CPP-115, that is 186 times more efficient in inactivating GABA-AT than vigabatrin, the only FDA-approved drug that is an inactivator of GABA-AT. CPP-115 was found to have high therapeutic potential for the treatment of cocaine addiction and for a variety of epilepsies, has successfully completed a Phase I safety clinical trial, and was found to be effective in the treatment of infantile spasms (West syndrome). Herein we report the design, using molecular dynamics simulations, synthesis, and biological evaluation of a new mechanism-based inactivator, (S)-3-amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (5), which was found to be almost 10 times more efficient as an inactivator of GABA-AT than CPP-115. We also present the unexpected crystal structure of 5 bound to GABA-AT, as well as computational analyses used to assist the structure elucidation process. Furthermore, 5 was found to have favorable pharmacokinetic properties and low off-target activities. In vivo studies in freely moving rats showed that 5 was dramatically superior to CPP-115 in suppressing the release of dopamine in the corpus striatum, which occurs subsequent to either an acute cocaine or nicotine challenge. Compound 5 also attenuated increased metabolic demands (neuronal glucose metabolism) in the hippocampus, a brain region that encodes spatial information concerning the environment in which an animal receives a reinforcing or aversive drug. This multidisciplinary computational design to preclinical efficacy approach should be applicable to the design and improvement of mechanism-based inhibitors of other enzymes whose crystal structures and inactivation mechanisms are known. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that vitamin B6 is an ergogenic factor. However, the role of dietary vitamin B6 in skeletal muscle has not been widely researched. The aim of the present study was to investigate the effects of dietary vitamin B6 on the gene expression of 19 myokines, 14 nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated factors, 8 myogenesis-related factors and 4 heat shock proteins (HSPs), which may serve important roles in skeletal muscles. Rats were fed a diet containing 1 (marginal vitamin B6 deficiency), 7 (recommended dietary level) or 35 mg/kg of pyridoxine (PN) HCl/for 6 weeks. Gene expressions were subsequently analysed using reverse transcription-quantitative polymerase chain reaction. Food intake and growth were unaffected by this dietary treatment. The rats in the 7 and 35 mg/kg PN HCl groups exhibited a significant increase in the concentration of pyridoxal 5'-phosphate in the gastrocnemius muscle compared with the 1 mg/kg PN HCl diet (P<0.01). The expressions of myokines, such as IL-7, IL-8, secreted protein acidic and rich in cysteine, IL-6, growth differentiation factor 11, myonectin, leukaemia inhibitory factor, apelin and retinoic acid receptor responder (tazarotene induced) 1, the expression of Nrf2 and its regulated factors, such as heme oxygenase 1, superoxide dismutase 2, glutathione peroxidase 1 and glutathione S-transferase, and the expression of myogenin and HSP60 were significantly elevated in the 7 mg/kg PN HCl group compared with the 1 mg/kg PN HCl diet (P<0.05). No significant differences in levels of these genes were observed between the 35 and 1 mg/kg PN HCl, with the exception of GDF11 and myonectin, whose expressions were significantly increased in the 35 mg/kg PN HCl (P<0.05). Notably, the majority of gene expressions that were affected responded to dietary supplemental vitamin B6 in a similar manner. The results suggest that compared with the marginal vitamin B6 deficiency, the recommended dietary intake of vitamin B6 upregulates the gene expression of a number of factors that promote the growth and repair of skeletal muscle. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported low circulating concentrations of pyridoxal-5-phospate (PLP) in renal transplant recipients (RTRs). It is unknown whether this is because of low intake or altered handling, and it is also unknown whether variation in circulating concentrations of PLP influences long-term outcome. Objective: We compared vitamin B-6 intake and circulating PLP concentrations of RTRs with those of healthy controls and investigated long-term clinical implications of vitamin B-6 deficiency in stable outpatient RTRs. Design: In a longitudinal cohort of 687 stable RTRs (57% male; mean ± SD age: 53 ± 13 y) with a median (IQR) follow-up of 5.3 y (4.8-6.1 y) and 357 healthy controls (47% male; age 54 ± 11 y), baseline vitamin B-6 was measured as plasma PLP by high-performance liquid chromatography (HPLC). Vitamin B-6 deficiency was defined as PLP <20 nmol/L, and insufficiency as PLP 20-30 nmol/L. Dietary intake was assessed by validated food-frequency questionnaires. Results: At inclusion [5.3 y (1.8-12.1 y) after transplantation], the mean vitamin B-6 intakes in RTRs and healthy controls were 1.77 ± 0.49 and 1.85 ± 0.56 mg/d, respectively (P = 0.23). In these groups, the median plasma PLP concentrations were 29 nmol/L (17-50 nmol/L) and 41 nmol/L (29-60 nmol/L), respectively (P < 0.001). Accordingly, deficiency was present in 30% of RTRs compared with 11% of healthy controls. PLP concentrations were inversely associated with glucose homeostasis variables and inflammation variables (all P < 0.01). During follow-up, 149 (21%) RTRs died and 82 (12%) developed graft failure. In RTRs, vitamin B-6 deficiency was associated with considerably higher mortality risk (HR 2.14; 95% CI: 1.48, 3.08) than a sufficient vitamin B-6 status, independent of potential confounders. No associations were observed for graft failure (P = 0.18). Conclusions: Vitamin B-6 deficiency is common in RTRs and does not seem to be a consequence of inadequate intake. In addition, this deficient state is clinically relevant and independently associated with an increased risk of mortality in RTRs. The cohort on which the study was based [TransplantLines Food and Nutrition Biobank and Cohort Study (TxL-FN)] was registered at clinicaltrials.gov as NCT02811835. [ABSTRACT FROM AUTHOR]

The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism. [ABSTRACT FROM AUTHOR]

The transsulfuration pathway (TS) acts in sulfur amino acid metabolism by contributing to the regulation of cellular homocysteine, cysteine production, and the generation of H 2 S for signaling functions. Regulation of TS pathway kinetics involves stimulation of cystathionine β-synthase (CBS) by S-adenosylmethionine (SAM) and oxidants such as H 2 O 2 , 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 B 6 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 B 6 deficiency. Typical whole body transsulfuration flux in humans is 3–7 μmol/h per kg body weight. The in vivo kinetics of H 2 S 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 H 2 S 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 B 6 restriction, nor do they respond to pyridoxine supplementation of subjects in chronically low-vitamin B 6 status. Wide individual variation in responses of the H 2 S biomarkers to such perturbations of human vitamin B 6 status suggests that the resulting modulation of H 2 S 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. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies ( NDA) derives Dietary Reference Values ( DRVs) for vitamin B6. The Panel considers that plasma pyridoxal 5′-phosphate ( PLP) concentration is the biomarker of status suitable for deriving DRVs for vitamin B6. Considering that a plasma PLP concentration of 30 nmol/L, as a population mean, is indicative of an adequate vitamin B6 status, the Panel proposes to use this cut-off value to set Average Requirements ( ARs). Population Reference Intakes ( PRIs) are derived for adults and children from ARs, assuming a coefficient of variation ( CV) of 10%. For women, the AR and PRI are set at 1.3 and 1.6 mg/day. For men, the AR of 1.5 mg/day is derived by an allometric scaling from the AR for women, and a PRI of 1.7 mg/day is set. For all infants aged 7-11 months, an Adequate Intake of 0.3 mg/day is set, averaging the results of two extrapolation approaches based on an allometric scaling: upwards extrapolation from the estimated vitamin B6 intake of exclusively breastfed infants from birth to 6 months, and downwards extrapolation from the ARs for adults applying a growth factor. For all children, ARs are derived from adult ARs using an allometric scaling and growth factors. For children of both sexes aged 1-14 years, ARs range between 0.5 and 1.2 mg/day. For children aged 15-17 years, the Panel derives the same ARs as for adults. PRIs for children aged 1-17 years range between 0.6 and 1.7 mg/day. Extrapolation of ARs by an allometric scaling considered differences in reference body weight. For pregnant and lactating women, additional requirements are considered, based on the uptake of vitamin B6 by the fetal and maternal tissues and the losses through breast milk, and PRIs of 1.8 and 1.7 mg/day, respectively, are derived. [ABSTRACT FROM AUTHOR]

Vitamin B6 plays a crucial role in the nervous system as the amino acid decarboxylases involved in the synthesis of all putative neurotransmitters requires the coenzyme pyridoxal phosphate. Vitamin B6 in its various forms has antioxidant properties. Pyridoxal phosphate has a role in regulating cellular calcium transport through both the voltage-mediated and ATP-mediated purinergic mechanisms of cellular calcium influx and, hence, has a role in the control of hypertension. Pharmacological doses of vitamin B6 appear to decrease the high blood pressure associated with both genetic and nongenetic models of hypertension. Vitamin B6 has a crucial role in the normal function of the central and peripheral nervous systems. It also protects against ischemia and glutamate-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

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Prospective cohort studies have found that prediagnostic circulating vitamin B6 is inversely associated with both risk of kidney cancer and kidney cancer prognosis. We investigated whether circulating concentrations of vitamin B6 at kidney cancer diagnosis are associated with risk of death using a case-cohort study of 630 renal cell carcinoma (RCC) patients. Blood was collected at the time of diagnosis, and vitamin B6 concentrations were quantified using LC-MS/MS. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. After adjusting for stage, age, and sex, the hazard was 3 times lower among those in the highest compared to the lowest fourth of B6 concentration (HR4vs1 0.33, 95% CI [0.18, 0.60]). This inverse association was solely driven by death from RCC (HR4vs1 0.22, 95% CI [0.11, 0.46]), and not death from other causes (HR4vs1 0.89, 95% CI [0.35, 2.28], p-interaction = 0.008). These results suggest that circulating vitamin B6 could provide additional prognostic information for kidney cancer patients beyond that afforded by tumour stage. [ABSTRACT FROM AUTHOR]

Background: Deficiency of vitamin B-6, vitamin B-12, folate, folic acid, or methionine may lead to dysregulation of DNA methylation, which might lead to disturbed energy and lipid metabolism. Objective: We aimed to explore whether intakes of vitamin B-6, vitamin B-12, folate, folic acid, and methionine at 1 y are associated with measures of growth and body composition at the age of 6 y. Methods: This study was performed in 2922 children participating in The Generation R Study, a population-based prospective cohort study. Dietary intakes of vitamins B-6 and B-12, folate, folic acid, and methionine were assessed at a median age of 12.9 mo by using a validated food-frequency questionnaire. At the age of 6 y, height and weight were measured, and body mass index (BMI; in kg/m²) was calculated. Body fat was measured with dual-energy X-ray absorptiometry, and body fat percentage and the ratio of android fat mass to gynoid fat mass (android:gynoid) were calculated. Results: In models adjusted for maternal and child characteristics, children with folic acid intakes in the highest tertile had a 0.16 SD score (SDS) lower weight (95% CI: -0.31, -0.02 SDS) and a 0.14 SDS lower BMI (95% CI: -0.26, -0.01 SDS) than children in the lowest tertile. Children with vitamin B-12 intakes in the highest tertile had a 0.13 SDS higher android:gynoid (95% CI: 0.00, 0.25 SDS) than children in the lowest tertile. In addition, children with intakes in the highest tertile of methionine had a 0.09 SDS higher BMI (95% CI: 0.01, 0.17) and a 0.12 SDS higher android:gynoid (95% CI: 0.02, 0.22) than children in the lowest tertile. Vitamin B-6 and folate intakes were not associated with any of the body composition outcomes measured. Conclusions: In this population of children, early high folic acid intakes were associated with a lower body weight and BMI at the age of 6 y. In contrast, early higher methionine intakes were associated with unfavorable body composition at the age of 6 y. Future studies should investigate long-term consequences of these outcomes on health. [ABSTRACT FROM AUTHOR]

Background: Folate, vitamin B-6, vitamin B-12, and choline are involved in one-carbon metabolism and play critical roles in pregnancy including prevention of birth defects and promotion of neurodevelopment. However, excessive intakes may adversely affect disease susceptibility in offspring. Intakes of these nutrients during pregnancy are not well characterized. Objective: Our aim was to determine dietary and supplemental intakes and major dietary sources of one-carbon nutrients during pregnancy. Methods: In pregnant women (n = 368) at ≤16 wk postconception, supplement use >30 d before pregnancy was assessed by maternal recall and supplement and dietary intakes in early (0-16 wk) and late pregnancy (23-37 wk) were assessed by food-frequency questionnaire. Results: Preconception, 60.1 % (95% CI: 55.8, 64.3) of women used B vitamin-containing supplements. This increased to 92.8% (95% CI: 89.6, 95.2) in early and 89.0% (95% CI: 85.0, 92.3) in late pregnancy. Median supplemental folic acid, vitamin B-12, and vitamin B-6 were 1000 mg/d, 2.6 mg/d, and 1.9 mg/d, respectively. Forty-one percent and 50% of women had dietary intakes of folate and vitamin B-6 less than the estimated average requirement (520 mg/d dietary folate equivalents and 1.6 mg/d, respectively). Eight-seven percent of women had choline intakes less than the Adequate Intake (450 mg/d). Dietary intakes did not change appreciably during pregnancy. Fruits and vegetables and fortified foods contributed ~57% to total dietary folate intake. Fruits and vegetables contributed ~32% to total dietary vitamin B-6 intake and dairy and egg products contributed ~37% to total dietary vitamin B-12 intake. Conclusions: Vitamin supplements were an important source of one-carbon nutrients during pregnancy in our sample. Without supplements, many women would not have consumed quantities of folate and vitamin B-6 consistent with recommendations. Given the importance of choline in pregnancy, further research to consider inclusion in prenatal supplements is warranted. This trial was registered at clinicaltrials.gov as NCT02244684. [ABSTRACT FROM AUTHOR]

Background: Abnormalities of tryptophan (Trp) metabolism through the kynurenine (Kyn) pathway have been reported in various diseases; however, nutritional and lifestyle factors that affect this pathway in healthy individuals are not well documented. Objective: Our aim was to examine the effect of vitamin B-6 status and lifestyle factors including the use of vitamin B-6 supplements, alcohol, smoking, and oral contraceptives on Trp and its Kyn metabolites in a cohort of 2436 healthy young adults aged 18-28y. Methods: Anthropometric and lifestyle data were collected by questionnaire. Participants provided blood samples for analysis of Trp, Kyn, anthranilic acid, kynurenic acid (KA), 3-hydroxykynurenine (HK), 3-hydroxyanthranilic acid (HAA), and xanthurenic acid (XA). Vitamin B-6 species were also measured. Results: Serum Trp metabolites were 10-15% higher among men (n = 993) compared with women (n = 1443; P < 0.0001), except for HKandXA. In all participants, serum Trp was positively associated with plasma pyridoxal 5'-phosphate (PLP; r= 0.28, P< 0.0001), reaching a plateau at PLP concentrations of ;83 nmol/L HK was inversely associated with PLP (r= 20.14, P< 0.01). Users of vitamin B-6 supplements (n = 671) had 6% lower concentrations of HK than nonusers (n = 1765; P= 0.0006). Oral contraceptive users (n = 385) had lower concentrations of KA (20.7%) but higher XA (24.1%) and HAA (9.0%) than did nonusers (n = 1058; P< 0.0001). After adjustment for gender and other lifestyle variables, XA concentrations were 16% higher in heavy drinkers (n = 713) than in never or occasional drinkers (n = 975; P = 0.0007). Concentrations of 2 other essential amino acids, methionine and arginine, also were positively associated with serum Trp (r = 0.65 and 0.33, respectively; P < 0.0001). Conclusions: In this population of healthy young adults, gender has the largest influence on serum Kyn metabolite concentrations. The significant covariance of Trp with unrelated amino acids suggests that protein intake may be an important consideration in evaluating Kyn metabolism. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether functional vitamin B-6 insufficiency occurs in OC users and is attributable to OCs, we investigated the associations of PLP with metabolites of one-carbon metabolism, tryptophan catabolism, and inflammation in OC users, and evaluated the effects of OCs on these metabolites. Methods: Plasma metabolite concentrations were measured in 157 OC users (20-40 y of age). Associations between PLP and the metabolites were analyzed through use of generalized additive models and partial least squares-discriminant analysis (PLS-DA). Additionally, data from 111 of the 157 OC users were compared to previously reported data from 11 nonusers, at adequate and low vitamin B-6 status, with use of multivariate ANOVA. Results: PLP showed significant (P < 0.05) negative nonlinear association with homocysteine, glutathione, and ratios of asymmetric dimethylarginine to arginine, 3-hydroxykynurenine to 3-hydroxyanthranilic acid, and 3-hydroxykynurenine to kynurenic acid. PLS-DA supported these conclusions and identified 3-hydroxykynurenine and the 3-hydroxykynurenine-to-kynurenine ratio as discriminating biomarkers in women with PLP ≤30 nmol/L. Among the many differences, OC users had significantly higher plasma pyridoxal (157% at adequate and 195% at low vitamin B-6 status), 4-pyridoxic acid (154% at adequate and 300% at low vitamin B-6 status), xanthurenic acid (218% at low vitamin B-6 status), 3-hydroxyanthranilic acid (176% at adequate and 166% at low vitamin B-6 status), quinolinic acid (127% at low vitamin B-6 status), and nicotinamide (197% at low vitamin B-6 status). Biomarkers of inflammation were not associated with PLP, and no differences were found between the 2 groups. Conclusions: PLP is associated with biomarkers of one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in OC users. Independent of vitamin B-6 status, OCs have effects on metabolites and ratios of one-carbon metabolism and tryptophan catabolism but not on biomarkers of inflammation. [ABSTRACT FROM AUTHOR]

Background: Nausea and vomiting are the most common complicated issues in pregnancy period, but they have not been paid much attention. Herb based formulations can be effectively used for the treatment nausea and vomiting observed during pregnancy. Aim: To investigate the effect of ginger in nausea and vomiting during pregnancy in comparison with vitamin B6 and placebo. Materials and Methods: This is a randomized and double-blind clinical trial. The women who had nausea and vomiting and did not take any medications were included in this study. 120 women were selected by simple random sampling method, and divided into three groups and were given vitamin B6, placebo, and ginger, respectively. 97 women completed the treatment. They were given treatment for 4 days and were followed after a week. The instrument used in this study was a questionnaire, including demographic characteristic and determining severity nausea and vomiting based on the analog visual scale. Data were analyzed with SPSS software and t-test and Kruskal-Wallis test. Results: There was significant difference between groups in severity of nausea and frequency of vomiting (P < 0.001). Conclusion: Ginger was effective in treating nausea and vomiting in pregnancy, but its use needs further studies to determine the proper dosage and the confirmation about the safety of this drug for a pregnant mother and her fetus. [ABSTRACT FROM AUTHOR]

Background Multivitamin/multimineral (MVM) supplements are commonly consumed by the general population, but little is known regarding their composition and compliance with local regulations. We assessed the composition and compliance with regulations [no indication in the label of vitamin/minerals amounting <15% of the acceptable daily intake (ADI)] of MVM available in Switzerland. Methods The composition of vitamin/minerals supplements was obtained from the Swiss drug compendium, the Internet, pharmacies, parapharmacies and supermarkets. MVM was defined as the presence of at least 5 vitamins and/or minerals. Results Of the 254 vitamin/mineral supplements collected, 95 (37%) were considered as MVM. The most frequent vitamins were B 6 (73.7%), C (71.6%), B 2 (69.5%) and B 1 (67.4%); the least frequent were K (17.9%), biotin (51.6%), pantothene (55.8%) and E (56.8%). Approximately half of MVMs provided >150% of the ADI for vitamins. The most frequent minerals were zinc (66.3%), calcium (55.8%), magnesium (54.7%) and copper (48.4%), and the least frequent were fluoride (3.2%), phosphorous (17.9%), chrome (22.1%) and iodine (25%). More than two thirds of MVMs provided between 50 and 150% of the ADI for minerals, and few MVMs provided >150% of the ADI. While few MVMs provided <15% of the ADI for vitamins, a considerable fraction did so for minerals (32.7% for magnesium, 26.1% for copper and 22.6% for calcium). Conclusion There is a great variability regarding the composition of MVMs available in Switzerland. Several MVM do not comply with Swiss regulations, which calls for monitoring and corrective measures. [ABSTRACT FROM AUTHOR]

High folate intake has been suggested as an important factor in cancer prevention; however, previous studies on the relation among folate intake, serum folate, and plasma homocysteine (hcy) are controversial. We conducted a hospitalbased, case-control study in Brazil investigating associations between dietary and circulating vitamins B-6 and B-12 and folate, hcy, genotypes of folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR C677T, A1298C), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), methionine synthase reductase (MTRR A66G), and reduced folate carrier (RFC1 G80A) and risk of cervical intraepithelial neoplasia (CIN) grades 1 (CIN1), 2 (CIN2), and (CIN3). The study was composed by 453 controls, 140 CIN1, 126 CIN2, and 231 CIN3. We investigated the joint effects of genetic variants of folate-related genes using genetic risk scores (GRSs) by summing the number of risk alleles for CIN1 and CIN2+ (CIN2 and CIN3 cases). The OR (95% CI) for CIN1 and CIN2+ per each risk allele were 1.29 (1.01, 1.65) and 1.22 (1.01, 1.46), respectively. An association between folate intake and CIN2+ was observed only after stratification according to GRS: crude OR (95% CI) for lower folate intake and GRS ≥4 was 1.67 (0.92, 3.04) (P-trend < 0.001) compared with higher folate intake (above the median) and GRS ≤3. The CIN2+ risk of lower serum vitamin B-6 and GRS ≥4 was 2.14 (0.92, 5.02) (P-trend = 0.05) and lower serum folate (below the median) and GRS ≥4 was 0.49 (0.20, 1.17) (P-trend = 0.05) after adjustment for confounding variables and human papillomavirus infection. Our data suggest that polymorphisms in genes related to folate metabolism modify the association of dietary and circulating folate and vitamin B-6 with cervical neoplasia. [ABSTRACT FROM AUTHOR]

Abstract: Background: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. Aim: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. Methods: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). Results: 181 patients (73% >16years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1–10years, 90%; 11–16years, 82%; and >16years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1–10years, 12g; 11–16years, 11g; and >16years, 45g. With diet and betaine, median natural protein intake (g/day) by age was: 1–10years, 13g; 11–16years, 20g; and >16years, 38g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. Conclusion: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines. [Copyright &y& Elsevier]

Background/objectives:Vitamin B6 is suggested to have a protective role against depression. However, the association between vitamin B6 intake and depression remains inconclusive, and few studies have examined the relationship between circulating vitamin B6 concentrations and depressive symptoms. Here, we investigated the cross-sectional and prospective associations between serum pyridoxal concentrations and depressive symptoms among Japanese workers. Subjects/methods: Participants were 422 municipal employees (aged 21-67 years) who participated in a baseline survey in 2006 for cross-sectional analysis, and 210 subjects without depressive symptoms at baseline (2006) who completed both baseline and follow-up (2009) surveys for prospective analysis. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. Logistic regression analysis was used to estimate the odds ratio of depressive symptoms (CES-D scale of ≥19) according to tertile of serum pyridoxal with adjustment for potential confounding variables. Results:In the cross-sectional analysis, serum pyridoxal concentrations were significantly associated with a decreased prevalence of depressive symptoms (P for trend=0.03); the multivariable-adjusted odds ratio of depressive symptoms for the highest tertile of pyridoxal was 0.54 (95% confidence interval 0.30-0.96) compared with the lowest tertile. In longitudinal analyses, higher serum pyridoxal concentrations at baseline were associated with a trend toward reduced depressive symptoms after 3 years; the multivariable-adjusted odds ratio of depressive symptoms for the highest versus the lowest tertile of pyridoxal concentration was 0.55 (95% confidence interval 0.13-2.32).Conclusions:A higher vitamin B6 status may be associated with a decreased risk of depressive symptoms in Japanese. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the impact of fortification by comparing food records and selected biochemical indicators of nutritional status pre- and post-fortification.DesignMean intake from 24 h recalls (n 142) was compared with the Estimated Average Requirement (EAR) to determine the proportion with inadequate intake. In a subsample (n 34), diet and serum retinol, folate, ferritin and Zn were compared pre- and post-fortification for fortified nutrients vitamin A, thiamin, riboflavin, niacin, folic acid, Fe and Zn.SettingSouth Africa.SubjectsBreast-feeding women (ninety-four HIV-infected, forty eight HIV-uninfected) measured at ∼6, 14, 24 weeks, and 9 and 12 months postpartum.ResultsPre-fortification, >80 % of women did not meet the EAR for vitamins A, C, D, thiamin, riboflavin, niacin, B6, B12 and folate and minerals Zn, iodine and Ca. Dietary intake post-fortification increased for all fortified nutrients. In post-fortification food records, >70 % did not meet the EAR for Zn and vitamins A, riboflavin and B6. Serum folate and Zn increased significantly post-fortification (P < 0·001 for both), with no change in ferritin and a reduction in retinol. Post-fortification marginal/deficient folate status was reduced (73·5 % pre v. 3·0 % post; P < 0·001), as was Zn deficiency (26·5 % pre v. 5·9 % post; P < 0·05). Pre- and post-fortification, >93 % were retinol replete. There was no change in Fe deficiency (16·7 % pre v. 19·4 % post; P = 0·728).ConclusionsMicronutrient intake improved with fortification, but >70 % of lactating women did not meet the EAR for Zn, vitamins A, riboflavin and B6. Although 100 % exceeded the EAR for Fe after fortification, Fe status did not improve. [ABSTRACT FROM PUBLISHER]

The contents of six natural vitamin B6 forms in popular Japanese sushi toppings were determined by a 4-pyridoxolactone-conversion HPLC method. The half-baked bonito exhibited the highest total vitamin B6 content and the northern shrimp sashimi the lowest. Pyridoxal 5′-phosphate plus pyridoxal was predominant in nine samples, and pyridoxamine 5′-phosphate plus pyridoxamine in two other samples. Pyridoxine 5′-phosphate plus pyridoxine was minor. The raw meats (sashimi) of fatty seawater fishes contain a lot of pyridoxal 5′-phosphate and/or pyridoxamine 5′-phosphate. Five portions of sushi with 20 g of fatty seawater sashimi toppings would supply with vitamin B6 recommended by the Japanese Recommended Daily Allowance. [ABSTRACT FROM AUTHOR]

Few studies have evaluated the relationship between the consumption of dietary folate and one-carbon metabolism-related nutrients and breast cancer risk defined by oestrogen receptor (ER) and progesterone receptor (PR) status. The objective of the present study was to examine the associations between dietary folate, vitamin B6, vitamin B12, and methionine intake and the risk of breast cancer by ER and PR status among Chinese women in Guangdong. A hospital-based case–control study was conducted from June 2007 to August 2008, with 438 cases and 438 age (5-year interval)- and residence (rural/urban)-matched controls. Dietary intake information was assessed using a validated FFQ administered through a face-to-face interview. Unconditional logistic regression models were used to calculate multivariate-adjusted OR and 95 % CI. A significant inverse association was found between dietary folate and vitamin B6 intake and breast cancer risk. The adjusted OR of the highest v. the lowest quartile were 0·32 (95 % CI 0·21, 0·49; Ptrend < 0·001) for dietary folate and 0·46 (95 % CI 0·30, 0·69; Ptrend < 0·001) for vitamin B6. No associations were observed for vitamin B12 and methionine intake. A significant inverse association between dietary folate intake and breast cancer risk was observed in all subtypes of ER and PR status. These findings suggest that dietary folate and vitamin B6 intakes were inversely associated with breast cancer risk. The inverse association did not differ by ER and/or PR status. [ABSTRACT FROM PUBLISHER]

ABSTRACT: Vitamin B6 is a water-soluble vitamin, important for the normal functioning of multiple organ systems. In patients receiving haemodialysis, vitamin B6 deficiency has been reported. The impact of ongoing advances in renal medicine on vitamin B6 status has not been evaluated. The aims of this review were (i) to determine the current level of vitamin B6 deficiency in the haemodialysis population; (ii) to determine the effect of current haemodialysis prescriptions on vitamin B6 levels; and (iii) to consider the impact of recent medical advances in haemodialysis on vitamin B6 levels. Electronic databases were used to locate studies with biochemical measures of vitamin B6 between the years 2000 and 2010. Inclusion exclusion criteria were applied by two independent reviewers. Of 316 articles identified, 53 were selected for detailed review. Appropriate vitamin B6 measures and information were extracted. Eleven final studies were included. Vitamin B6 deficiency was shown to be between 24% and 56%. Dialysis reduced plasma levels by 28-48% depending on the dialyser used. Advances in renal medicine including the use of erythropoietin stimulating agents and ion exchange phosphate binding resins were shown to negatively affect vitamin B6 status. Current recommendations for supplementation range from 10-50 mg. These figures are based on older studies often with small numbers of patients. Suboptimal vitamin B6 status is common in the haemodialysis population. Advances in renal medicine and engineering of dialysis membranes may contribute to increased levels of deficiency. [ABSTRACT FROM AUTHOR]

Abstract: Vitamin B6 (B6) is an essential cofactor of glutamate decarboxylase and catalyzes the decarboxylation of the excitatory neurotransmitter glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Although immediate administration of B6 to patients with acute encephalopathy with febrile convulsive status epilepticus (AEFCSE) is effective, it is not known whether prolonged seizures in status epilepticus (SE) children prevent the transport of B6 to the central nervous system (CNS) and/or induce the consumption of B6 inside the CNS. We evaluated the B6 concentration in cerebrospinal fluid (CSF) and serum in SE children. Further, we performed a sequential serum B6 analysis on days 1 and 2 after admission and on the day before discharge. Among the several vitamers of B6, we used pyridoxal (PL) as a representative of B6 in this study. We enrolled 15 SE children (8 boys and 7 girls; age range,1–11years; average age, 3.3years) and 21 control children (3 boys and 18 girls; age range, 7months–14years; average age, 3.0years) and each group was divided into 2 subgroups according to age (4months–1year and 2–14years). We found no significant differences in the CSF PL levels, CSF/serum PL ratios, and serum PL levels in the SE and control subgroups. Our results suggest that prolonged seizures do not result in B6 deficiency in CSF and serum in SE children. Whenever necessary, B6 should be administered to SE children with caution to prevent possible adverse effects. [Copyright &y& Elsevier]

Objective: To investigate serum concentrations and the prevalence of inadequate folate intake and also vitamin B6 and vitamin B12 intakes and to identify those foods that make a major contribution to intake levels of these nutrients. Methods: This was a cross-sectional, observational study of adolescents of both sexes aged 16 to 19 years from the town of Indaiatuba, SP, Brazil. Data collection was by non-consecutive 3-day dietary record. The samples' habitual diet was estimated by removing intraindividual variability, and the prevalence rates of inadequate intakes were calculated using the estimated average requirement as cutoff points. Biochemical assays for folate, vitamin B6 and vitamin B12 were conducted in accordance with the methods accepted in the literature. Results: The study sample comprised 99 adolescents, the majority of whom were female (58.6%), with a mean age of 17.6 [standard deviation, (SD) 0.9]. Mean serum concentrations for folate, vitamin B6 and vitamin B12 were 9.2 (SD 3.4) ng/mL, 18.7 (SD 5.1) nmol/L and 397.5 (SD 188.4) pg/mL, respectively; and the prevalence rates of inadequate intake for these vitamins were 15.2, 10.2 and < 1%, respectively. The foods that made a major contribution to vitamin intakes were French bread, pasta and beans for folate; white rice, chicken and beef for vitamin B6; and lean beef, whole milk and fatty beef for vitamin B12. Conclusions: The prevalence rates of inadequate folate, vitamin B6 and vitamin B12 intakes were low, which is possibly the result of improved access to and availability of foods that are dietary sources of these vitamins. Beans, which are a part of the traditional Brazilian diet, remain one of the primary food items that contribute to folate intake, even after mandatory fortification with folic acid in Brazil. [ABSTRACT FROM AUTHOR]

Low circulating pyridoxal 5'-phosphate (PLP) concentrations have been linked to inflammatory markers and the occurrence of inflammatory diseases. However, the implications of these findings are unclear. The measurement of PLP and C-reactive protein (CRP) in blood samples collected from participants in the 2003-2004 NHANES afforded us the opportunity to investigate this relationship in the general U.S. population. Dietary and laboratory data were available for 3864 of 5041 interviewed adults, 2686 of whom were eligible lie, provided reliable dietary data and were not diabetic, pregnant, lactating, or taking hormones or steroidal antiinflammatory drugs). Vitamin B-6 intake was assessed using 2 24-h diet recalls and supplement use data. After multivariate adjustment for demographics, smoking, BMI, alcohol use, antioxidant vitamin status, intakes of protein and energy, and serum concentrations of creatinine and albumin, high vitamin B-6 intake was associated with protection against serum CRP concentrations >10 mg/L compared with ⩽3 mg/L. However, plasma PLP ⩾⩾ 20 nmol/L compared with <20 nmol/L was inversely related to serum CAP independently of vitamin 8-6 intake (P< 0.0011. Among participants with vitamin B-6 intakes from 2 to 3 mg/d, the multivariate-adjusted prevalence of vitamin B-6 inadequacy was <10% in participants with serum CRP ⩽3 mg/L but close to 50% in those with serum CAP > 10 mg/L (P < 0.001). In conclusion, higher vitamin B-6 intakes were linked to protection against inflammation and the vitamin El-6 intake associated with maximum protection against vitamin B-6 inadequacy was increased in the presence compared to absence of inflammation [ABSTRACT FROM AUTHOR]

Low circulating pyridoxal 5'-phosphate (PLP) concentrations have been linked to inflammatory markers and the occurrence of inflammatory diseases. However, the implications of these findings are unclear. The measurement of PLP and C-reactive protein (CRP) in blood samples collected from participants in the 2003-2004 NHANES afforded us the opportunity to investigate this relationship in the general U.S. population. Dietary and laboratory data were available for 3864 of 5041 interviewed adults, 2686 of whom were eligible lie, provided reliable dietary data and were not diabetic, pregnant, lactating, or taking hormones or steroidal antiinflammatory drugs). Vitamin B-6 intake was assessed using 2 24-h diet recalls and supplement use data. After multivariate adjustment for demographics, smoking, BMI, alcohol use, antioxidant vitamin status, intakes of protein and energy, and serum concentrations of creatinine and albumin, high vitamin B-6 intake was associated with protection against serum CRP concentrations >10 mg/L compared with ⩽3 mg/L. However, plasma PLP ⩾⩾ 20 nmol/L compared with <20 nmol/L was inversely related to serum CAP independently of vitamin 8-6 intake (P< 0.0011. Among participants with vitamin B-6 intakes from 2 to 3 mg/d, the multivariate-adjusted prevalence of vitamin B-6 inadequacy was <10% in participants with serum CRP ⩽3 mg/L but close to 50% in those with serum CAP > 10 mg/L (P < 0.001). In conclusion, higher vitamin B-6 intakes were linked to protection against inflammation and the vitamin El-6 intake associated with maximum protection against vitamin B-6 inadequacy was increased in the presence compared to absence of inflammation [ABSTRACT FROM AUTHOR]

The article presents a study which examines the association of low serum B vitamins with human bone's structural and biomechanical properties. The study was conducted to the heads of 94 men and women, who underwent hip arthroplasty, using dual-energy X-ray absorptiometry (DXA), biomechanical testing, and histomorphometry. Findings reveal that low serum folate and vitamin B-6 concentrations were associated with altered morphology of the bone.

The article presents a study which examines the effect of marginal vitamin B-6 deficiency on the rate of red blood cell glutathione synthesis. Subjects and methods of the study are offered, along with a discussion on the protective roles of glutathione in the human body. Result of the study reveals that dietary vitamin B-6 restriction reduces the red blood cell glutathione synthesis rate without affecting glutathione concentration in plasma.

Glycine is a precursor of purines, protein, glutathione, and 1-carbon units as 5,10-methylenetetrahydrofolate. Glycine decarboxylation through the glycine cleavage system (GCS) and glycine-serine transformation by serine hydroxymethyl-transferase (SHMT) require pyridoxal 5'-phosphate (PLP; active form of vitamin B-6) as a coenzyme. The intake of vitamin B-6 is frequently low in humans. Therefore, we determined the effects of vitamin B-6 restriction on whole-body glycine flux, the rate of glycine decarboxylation, glycine-to-serine conversion, use of glycine carbons in nucleoside synthesis, and other aspects of 1-carbon metabolism. We used a primed, constant infusion of (1,2-13C2lgIycine and [5,5,5-2H3]Ieucine to quantify in vivo kinetics in healthy adults (7 males, 6 females; 20-39 y) of normal vitamin B-6 status or marginal vitamin B-6 deficiency. Vitamin B-6 restriction lowered the plasma PLP concentration from 55 ± 4 nmol/L (mean ± SEM( to 23 ± 1 nmol/L (P< 0.0001), which is consistent with marginal deficiency, whereas the plasma glycine concentration increased <0.01). SHMT-mediated conversion of glycine to serine increased from 182 ± 7 to 205 ± 9 μmol·kg-1·h-1 (P< 0.05), but serine production using a GCS-derived 1-carbon unit (93 ± 9 vs. 91 ± 6 μmol·kg-1·h-1) and glycine cleavage (163 ± 11 vs. 151 ± 8 μmol·kg-1·h-1 were not changed by vitamin B-6 restriction. The GCS produced 1 -carbon units at a rate (~140-170 μmol·.kg-1·h-1) that greatly exceeds the demand for remethylation and transmethylation processes (~4-7 ¼mol·kg-1·h-1). We conclude that the in vivo GCS and SHMT reactions are quite resilient to the effects of marginal vitamin B-6 deficiency, presumably through a compensatory effect of increasing substrate concentration. [ABSTRACT FROM AUTHOR]

The article presents a study on the incidence, risk factors and management of pyridoxal-5′ -phosphate (PLP) deficiency following the multivisceral and intestinal transplantation in adult. It highlights the clinical nutritional autonomy (CNA) measurement of serum PLP and homocysteine concentrations before and after transplant to prevent deficiency. It also emphasizes the establishment of an effective repletion algorithmic protocol for the achievement of full CNA.

Although fasting and post-methionine loading (PML) homocysteine concentrations are not necessarily related, a high percentage of hyperhomocysteinemia cases would be missed if methionine loading was not performed. The influences of B-vitamins and genetic polymorphism (methylenetetrahydrofolate reductase 677C → T, MTHFR 677C → T) on fasting and PML homocysteine concentrations and the relationship between fasting and PML homocysteine were studied. This study was a cross-sectional study. Healthy subjects were divided into either fasting hyper-homocysteinemia (≥12.2 µmol/l) (fasting hyper-hcy, n = 51), PML hyper-homocysteinemia (fasting homocysteine <12.2 µmol/l but PML homocysteine ≥25.6 µmol/l) (PML hyper-hcy, n = 29), or normo-homocysteinemia (fasting homocysteine <12.2 µmol/l and PML homocysteine <25.6 µmol/l) (normo-hcy, n = 118) group based on elevated fasting and PML homocysteine levels of the 75th percentile of the population. The concentrations of plasma fasting and PML homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5′- phosphate (PLP) were measured. The genetic polymorphisms were determined. Fasting homocysteine, but not PML homocysteine and MTHFR 677C → T genotype, was significantly and inversely affected by serum folate concentration after adjusting for potential confounders ( β = −0.062, P < 0.01). Fasting and PML homocysteine were highly associated in the fasting hyper-hcy and pooled groups ( P < 0.01) but not in the PML hyper-hcy and normo-hcy groups. PML homocysteine did not interact with either serum folate ( P = 0.302), vitamin B-12 ( P = 0.465), plasma PLP ( P = 0.996) or MTHFR 677C → T genotype ( P = 0.136) to affect fasting homocysteine concentration. Approximately one-third (36.3%) of hyperhomocysteinemia cases would be missed if methionine loading were not performed. Even though subjects may have a normal fasting homocysteine concentration, they need further screening for their PML homocysteine. [ABSTRACT FROM AUTHOR]

Adequate intake of folate, methionine, riboflavin, and vitamin B-6 may prevent aberrant DNA methylation and thereby protect against colorectal cancer (CRC). However, previous epidemiological studies investigating associations between dietary intakes of these nutrients and CRC have been inconsistent. We investigated the associations between intakes of folate, methionine, riboflavin, and vitamin B-6 and CRC risk, accounting for the sublocalization of the tumor. Within the Netherlands Cohort Study on diet and cancer (n = 120,852), 2349 cases and 4168 subcohort members were available for data analyses from a follow-up period of 13.3 y after baseline. Gender-specific adjusted incidence rate ratios (RR) were calculated over quintiles of dietary intake in case-cohort analyses. Folate intake was not associated with CRC risk in either men or women. However, methionine was associated with decreased risk of proximal colon cancer among men (RR = 0.57 for highest vs. lowest quintile of intake; P-trend = 0.03) and rectal cancer among women (highest vs. lowest quintile; RR = 0.45; P-trend = 0.05). Riboflavin tended to be associated with decreased proximal colon cancer risk among women (RR = 0.61; P-trend = 0.07). Conversely, there was a strong positive association between vitamin B-6 and rectal cancer among women (RR = 3.57; P-trend = 0.01). Our findings suggest that relatively high methionine intake may protect against proximal colon cancer in men and rectal cancer in women but that folate may not have a protective effect. This is the 2nd prospective cohort study in which vitamin B-6 intake was associated with increased risk of rectal tumors in women, which might suggest that this vitamin enhances rectal cancer in women. [ABSTRACT FROM AUTHOR]

Background: No large-scale, population-based study has considered the descriptive epidemiology of vitamin B-6 status with use of plasma pyridoxal 5'-phosphate (PLP), the indicator of vitamin B-6 adequacy used to set the current Recommended Dietary Allowance, which is ⩽2 mg/d for all subgroups. Objectives: We sought to examine the epidemiology of vitamin B-6 status in the US population. Methods: In >6000 participants aged >1 y in the National Health and Nutrition Examination Survey (2003-2004), we considered relations between plasma PLP and various subject characteristics and examined trends in plasma PLP and homocysteine with vitamin B-6 intake, both overall and in selected subgroups. Results: In males, plasma PLP decreased with age after adolescence only in nonusers of supplemental vitamin B-6. Regardless of supplement use, plasma PLP concentrations of women of childbearing age were significantly lower than those of comparably aged men, and most oral contraceptive users had plasma PLP <20 nmol/L. The prevalenceof low plasma PLP was significantly >3% atvitaminB-6 intakes from 2 to 2.9 mg/d in all subgroups and at intakes from 3 to 4.9 mg/d in smokers, the elderly, non-Hispanic blacks, and current and former oral contraceptive users. Intakes from 3 to 4.9 mg/d compared with <2 mg/d were associated with significant protection from low plasma PLP in most subgroups and from hyperhomocys-teinemia in the elderly. Conclusions: Vitamin B-6 intakes of 3 to 4.9 mg/d appear consistent with the definition of a Recommended Dietary Allowance for most Americans. However, at that intake level, substantial proportions of some population subgroups may not meet accepted criteria for adequate vitamin B-6 status [ABSTRACT FROM AUTHOR]

The article presents a study that investigated the association of dietary folate, vitamin B6 and vitamin B12 with the risk of coronary heart disease among middle-aged persons. Coronary heart disease and myocardial infarction were reportedly inversely associated with dietary folate and vitamin B6 and vitamin B12. Use of dietary intake of B vitamins as protective risk factor for cardiovascular disease is discussed.

Background: During the last decades, many basic and clinical research have pointed to the role of B vitamins (folate, vitamins B6 and B12) and n-3 fatty acids as nutritional factors that might have a protective effect on the development of cardiovascular diseases (CVD). Methods/design: The SU.FOL.OM3 (SUpplementation with FOlate, vitamin B6 and B12 and/or OMega-3 fatty acids) trial is a randomized double-blind, placebo-controlled, secondary-prevention trial designed to test the efficacy of 5-methyl tetra-hydro-folates (5-MTHF) supplementation, in combination with vitamin B6 and B12 and/or n-3 fatty acids, at nutritional doses, on fatal and non fatal ischemic CVD in a 2 x 2 factorial design. A total of 2501 patients aged between 45 and 80 years who had a past history, in the previous year, of myocardial infarction (n = 1151) or instable angina pectoris (n = 711) or an ischemic stroke (n = 639) were included. Subjects have to be supplemented and followed up for five years. Daily supplementation comprised nutritional doses of 5-MTHF (560 µg), vitamin B6 (3 mg) and B12 (20 µg) and/or n-3 fatty acids (600 mg with an EPA:DHA ratio of 2:1). A factorial design 2 x 2 has been applied to investigate the separate effects of the B-vitamins, and the n-3 fatty acids, as well as their interaction as compared to the placebo. The primary endpoint is a combination of myocardial infarction, ischemic stroke and cardiovascular death. Secondary endpoints are events of the composite endpoint taken separately, total mortality, and other cardiovascular events such as acute coronary syndromes, coronary revascularization, cardiac failure, arrhythmia... Conclusion: Baseline socio-demographic and medical characteristics of participants are totally comparable in the four randomized groups. Trial registration: Current Controlled Trials ISRCTN41926726 [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the associations and distribution of vitamin B-6 species in plasma and their relation to transsulfuration metabolites concentrations in plasma. Authors of the study examined nonfasting blood samples from healthy subjects for all known vitamin B-6 forms including cobalamin, folate, and riboflavin. Results showed that plasma concentrations of the main vitamin B-6 vitamers were strongly correlated.

Objective: Homebound elderly are at increased risk for micronutrient deficiencies and nutritional status in this population has not been adequately described. There is evidence for beneficial effects of multivitamin use and a greater understanding of their nutritional contribution could identify behaviors that may help alleviate excess chronic disease. The purpose of this analysis is to investigate, in a racially diverse group of homebound elders, the association of multivitamin use with measures of plasma B vitamin concentrations. Design: We examined the cross-sectional association between multivitamin use and plasma concentrations of B vitamins and homocysteine in 236 white and 182 black homebound elders (65-99y). Dietary intake was assessed and demographic and health information was ascertained. Results: White and black elders had a high prevalence of dietary intakes below the Estimated Average Requirement for folate (38.1 and 40.7%), vitamin B6 (16.9 and 19.2%.), and vitamin B12 (3 and 3.9%) respectively. Multivitamin use was associated with higher mean plasma B vitamin concentrations in each group. In whites, multivitamin users had higher concentrations of vitamin B6 (64.6 vs. 32.4 nmol/L; p<0.00l), vitamin B12 (398 vs. 324 pmol/L;p<0.001) and folate (39.4 vs. 30.4 nmol/L;p<0.001). Black multivitamin users had higher concentrations of vitamin B6 (53.7 vs. 29.5 nmol/L; p<0.001), B12 (427 vs. 372 pmol/L; p<0.05) and folate (35.7 vs. 25.4 nmol/L;p<0.001) than non-users. Conclusions: Multivitamin supplementation was associated with higher mean plasma concentrations of vitamins B6, B12, and folate and lower prevalence of low plasma B vitamin status in a biracial homebound elderly population. [ABSTRACT FROM AUTHOR]

Assessments of the relation between folate intake and ovarian cancer risk have been limited and inconsistent. Therefore, the authors prospectively examined the association of dietary and supplemental intakes of folate, methionine, and vitamin B6 with ovarian cancer risk among 80,254 Nurses' Health Study participants. Beginning in 1976, women completed biennial questionnaires assessing ovarian cancer risk factors; starting in 1980, food frequency questionnaires were administered every 2–4 years. During 22 years of follow-up (1980–2002), the authors confirmed 481 incident epithelial ovarian cancers. There were no associations between total folate (top quintile vs. bottom: relative risk (RR) = 1.21, 95% confidence interval (CI): 0.92, 1.60), methionine (RR = 1.00, 95% CI: 0.76, 1.33), dietary vitamin B6 (RR = 1.09, 95% CI: 0.81, 1.47), or total vitamin B6 (RR = 1.13, 95% CI: 0.85, 1.51) intake and ovarian cancer risk. Higher dietary folate was associated with a modestly decreased risk after exclusion of cases diagnosed during the 4 follow-up years after dietary assessment (RR = 0.66, 95% CI: 0.43, 1.03) and for the serous subtype (RR = 0.51, 95% CI: 0.31, 0.84). Results did not vary by alcohol intake, multivitamin use, menopausal status, or oral contraceptive use. There was little evidence that folate, methionine, and vitamin B6 are important in ovarian cancer risk, although dietary folate was inversely associated with risk in some analyses. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: This study assessed the effect of vitamin B6 status on immune responses in mechanically ventilated, critically ill patients and compared the results with those of healthy controls. Methods: This was designed as a cross-sectional observational study. Forty patients in the intensive care unit successfully completed this study. Vitamin B6 intake was recorded for 8 d. Severity of illness (Second Acute Physiology and Chronic Health Evaluation score) was recorded. Thirty-eighty healthy controls were recruited from the physical check unit of Taichung Veterans General Hospital (Taichung, Taiwan). All control subjects were given instruction on how to complete a 24-d diet recall. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5′-phosphate [PLP] and 4-pyridoxic acid) and indirect measures (erythrocyte alanine and aspartate aminotransferase activity coefficients). Levels of serum albumin, hemoglobin, hematocrit, high-sensitivity C-reactive protein, and immune responses (white blood cell, neutrophil, total lymphocytes, T lymphocytes [CD3], B lymphocytes [CD19], T-helper cells [CD4], and suppressor cells [CD8]) were determined. Results: Critically ill patients had sufficient vitamin B6 intake but showed marginal PLP deficiency (20.9 ± 1.5 nmol/L). In addition, critically ill patients had significantly lower and abnormal immune responses than did healthy controls. There was no significant correlation of vitamin B6 intake and erythrocyte alanine and aspartate aminotransaminase activity coefficients with immune indices. Plasma PLP concentration was strongly negatively correlated with high-sensitivity C-reactive protein level. However, plasma PLP was significantly associated with immune responses after adjustment for age, sex, high-sensitivity C-reactive protein, and the other four vitamin B6 indicators. Conclusions: Plasma PLP is a significant indicator of immune responses in human subjects. Further research is warranted to study whether vitamin B6 supplementation in critically ill patients improves their immune responses. [Copyright &y& Elsevier]

Experimental and human studies describe the adverse effect of iron or vitamin B6 deficiencies on polyunsaturated fatty acid metabolism. Iron is present in end proteins of the δ6-desaturase enzyme complex, and vitamin B6 deficiency can affect the transmethylation reaction of proteins. Plasma polyunsaturated fatty acid content was estimated in apparently healthy subjects of the general population with no consumption of fish and low vitamin B6 serum levels (<3 μg/l; n = 21) or with low iron serum levels (men: <12 μmol/l; women: <10 μmol/l; n = 16) and compared to a control group (n = 22) with normal vitamin B6 and iron serum levels (in reference range). The activities of the δ6-desaturase enzyme complex were calculated as product/precursor (conversion indices). In groups of subjects with low vitamin B6 and low iron levels, δ6-desaturase activity together with δ5-desaturase activity (conversion of α-linolenic/18:3,n–3/ into eicosapentaenoic acid/20:5,n–3/) as well as the conversion index of docosahexaenoic acid formation (22:6,n–3) from 22:5,n–3 (second δ6-desaturase activity) were significantly reduced. The inhibition effect on fatty acid synthesis was more pronounced in subjects with low iron levels than in those with low vitamin B6 levels. The conversion indices correlated significantly positively with vitamin B6 or iron levels. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To assess vitamin B6 intake and status of critically ill patients. The relationship between vitamin B6 status indicators and the severity of illness and outcome in these patients was also examined. Design: Prospective clinical study. Setting: The study was performed at the Taichung Veteran General Hospital, in the central part of Taiwan. Subjects: Ninety-four patients in the intensive care unit (ICU) entered the study and 46 patients successfully completed this study. Interventions: No intervention. Main outcome measures: Vitamin B6 intake was recorded for 14 days. Vitamin B6 status was assessed by direct measures (plasma pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and urinary 4-pyridoxic acid (4-PA)) and indirect measures (erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient). The severity of illness (APACHE II score), the length of ventilation dependency, and the length of ICU and hospital stay were recorded. Results: Patients had an adequate mean vitamin B6 intake (16.26 ± 19.39 mg) during the 14 day study. Mean vitamin B6 intake was significantly higher on day 14 than on day 1 (P<0.001). However, plasma PLP and PL concentrations significantly decreased at the 14th day after admission (P < 0.05). Erythrocyte alanine aminotransaminase activity coefficient and EAST-AC did not change significantly. Urinary 4-PA significantly increased at the 14th day (P < 0.001 ). No significant relationships were found between APACHE II scores and clinical outcomes (the length of ICU and hospital stay, the length of ventilation dependency) of patients, vitamin B6 intake or status indicators. Conclusions: Critically ill patients received nutritional support in the ICU, and had sufficient mean vitamin B6 intake and adequate vitamin B6 status. Therefore, the severity of illness and the results should not be affected by vitamin B6 status. However, we have noted that plasma PLP and PL concentrations significantly decreased... [ABSTRACT FROM AUTHOR]

The present study was conducted to investigate the precaecal digestibility of vitamin B[sub 6] from selected food sources including eggs, bananas, white cabbage, corn, milk powder, fish, barley, soybeans, brown rice, wheat bran, brewer's yeast, rye and soybean meal. These foods were chosen for their relevance in human and animal nutrition and prepared as they are usually eaten by humans. As confirmed by further investigations the precaecal digestibility is a valuable measure for determining the availability of native B-vitamins. Therefore, pigs were fitted with an end-to-end ileo–rectal anastomosis for digesta passing straight from ileum to rectum, thus avoiding endogenous vitamin synthesis by the colon. Three weeks after surgery the digestibility experiments were carried out during which the animals were fed various experimental diets for a period of 12 days and digesta were collected quantitatively twice a day during the final 5 days of this period. The concentration of vitamin B[sub 6] in foods and chyme was determined by high pressure liquid chromatography. Precaecal digestibility of vitamin B[sub 6] from all tested food sources ranged from 51 to 91% in the following order: cabbage diet > banana diet > fish diet > milk powder diet > brewer's yeast diet > soybeans diet > soybean meal diet > egg diet/corn diet > barley diet > wheat bran diet > rye diet. Only boiled brown rice had a very low vitamin B[sub 6] availability of 16%. The digestibility of vitamin B[sub 6] from plant products (excluding the rice) was on average 10% lower when compared with animal products (71 versus 79%). [ABSTRACT FROM AUTHOR]

OBJECTIVE: Dietary factors have been considered as a possible risk factor for ulcerative colitis (UC). However, available data are inconsistent. The aim of the present study was to evaluate the etiological role of dietary factors in the development of UC. METHODS: Recently diagnosed (<6 Months) UC patients (n = 43) and age- and gender-matched population controls (n = 43) were studied in a case-control design. The cross-check dietary history method was used to assess dietary intake of 5 yr before the study. Adipose tissue fatty acid composition was used as a biomarker of long-term fat intake. Conditional logistic regression-derived odds ratios (OR), and 95% confidence intervals (CI) were used for statistical analysis. Dietary intake ORs were adjusted for energy intake. RESULTS: High intakes of monounsaturated fat (OR: 33.9 [95% CI 2.6-443.1]), polyunsaturated fat (OR; 5.1 [95% CI 1.0-26.7]), and vitamin B6 (OR: 6.9 [95% CI 1.6-30.7]) were associated with an increased risk to develop UC. No other significant associations were found with UC risk. CONCLUSIONS: High intakes of mono- and polyunsaturated fat and vitamin B6 may enhance the risk of developing UC. Whether this observation is a true risk factor in the development of UC or rather a reflection of a certain dietary lifestyle needs to be investigated. [ABSTRACT FROM AUTHOR]

The administration of high doses of pyridoxine (6 mg%) resulted in the suppression of hepatic cathepsin B activity. Therefore, we conclude that ovalbumin-dependent antibody productions (IgG[sub 1], IgE) were suppressed by pyridoxine excess diet (6 mg%), because hepatic cathepsin B activity was suppressed by the excess pyridoxine in diet. [ABSTRACT FROM AUTHOR]

Presents information on a study which determined plasma pyridoxal-5-phosphate concentrations as an indicator of vitamin B6 deficiency through the application of a high performance liquid chromatography. Materials and methods; Results; Discussion; Conclusion.

Assesses the effects of increased dietary folate and recommended intakes of vitamin B12 and B6 on serum total homocysteine in individuals at high risk of cardiovascular disease. Participation of ten medical research centers in the United States and Canada; Increase in intake of folate, vitamin B12 and B6 with increased folate and vitamin B12 concentrations.