Vitamin B6 deficiency cooperates with oncogenic Ras to induce malignant tumors in Drosophila.

Vitamin B6 is a water-soluble vitamin which possesses antioxidant properties. Its catalytically active form, pyridoxal 5'-phosphate (PLP), is a crucial cofactor for DNA and amino acid metabolism. The inverse correlation between vitamin B6 and cancer risk has been observed in several studies, although dietary vitamin B6 intake sometimes failed to confirm this association. However, the molecular link between vitamin B6 and cancer remains elusive. Previous work has shown that vitamin B6 deficiency causes chromosome aberrations (CABs) in Drosophila and human cells, suggesting that genome instability may correlate the lack of this vitamin to cancer. Here we provide evidence in support of this hypothesis. Firstly, we show that PLP deficiency, induced by the PLP antagonists 4-deoxypyridoxine (4DP) or ginkgotoxin (GT), promoted tumorigenesis in eye larval discs transforming benign RasV12 tumors into aggressive forms. In contrast, PLP supplementation reduced the development of tumors. We also show that low PLP levels, induced by 4DP or by silencing the sgllPNPO gene involved in PLP biosynthesis, worsened the tumor phenotype in another Drosophila cancer model generated by concomitantly activating RasV12 and downregulating Discs-large (Dlg) gene. Moreover, we found that RasV12 eye discs from larvae reared on 4DP displayed CABs, reactive oxygen species (ROS) and low catalytic activity of serine hydroxymethyltransferase (SHMT), a PLP-dependent enzyme involved in thymidylate (dTMP) biosynthesis, in turn required for DNA replication and repair. Feeding RasV12 4DP-fed larvae with PLP or ascorbic acid (AA) plus dTMP, rescued both CABs and tumors. The same effect was produced by overexpressing catalase in RasV12 DlgRNAi 4DP-fed larvae, thus allowing to establish a relationship between PLP deficiency, CABs, and cancer. Overall, our data provide the first in vivo demonstration that PLP deficiency can impact on cancer by increasing genome instability, which is in turn mediated by ROS and reduced dTMP levels.

A retrospective analysis of vitamin B6 deficiency and associated changes of gut microbes in Crohn's disease.

BACKGROUND: Patients with inflammatory bowel diseases (IBD) are at risk of micronutrient deficiencies, particularly during flares. Vitamin B6 is required for the proper development of brain, nerves, and many other parts of the body. However, limited studies are available to describe the prevalence, relevance and consequences of vitamin B6 deficiencies in IBD. We aim to estimate the prevalence of vitamin B6 deficiencies in Crohn's disease (CD) patients, to identify associated risk factors and to explore the alteration of intestinal microbiota related to vitamin B6 status. METHODS: A total of 360 CD patients and 55 ulcerative colitis (UC) patients from Shanghai Tenth People's Hospital of Tongji University were included. Serum vitamin B6 concentrations were collected from the computerized laboratory data. The logistic regression was used for statistical analysis. Fecal-associated microbiota was also analyzed using 16S rRNA sequencing in another 20 CD patients (10 of vitamin B6 normal, 10 of vitamin B6 deficiency). RESULTS: The prevalence of vitamin B6 abnormality was significantly higher in CD than in UC patients. Logistic regression analysis showed that small bowel lesion, ileocolonic lesion (L3), extraintestinal manifestations, ileal resection, and usage of immunosuppressor were independently associated with abnormal vitamin B6 in CD. Interestingly, the microbial structure presented significant differences between two CD groups. PICRUSt2 prediction revealed that some enzymes and metabolic pathways between the two groups were significantly different. CONCLUSIONS: Collectively, our analysis showed that vitamin B6 reduction occurred frequently in patients with CD and affected the intestinal flora of patients.

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.

Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.

BACKGROUND: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. METHODS: we measured plasma pyridoxal 5'-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1-57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8-8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47-0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51-1.01) and 0.74 (95% confidence interval, 0.53-1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27-0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65-1.51). CONCLUSIONS: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.

Vitamin B-6 Status Correlates with Disease Activity in Rheumatoid Arthritis Patients During Treatment with TNFα Inhibitors.

BACKGROUND: A frequent observation in inflammatory conditions, including rheumatoid arthritis (RA), is low circulating amounts of pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B-6. Recently, a functional marker of vitamin B-6 status, the ratio of 3-hydroxykynurenine (HK): xanthurenic acid (XA) in plasma (HK: XA), was proposed. OBJECTIVE: We investigated vitamin B-6 status in patients with RA before and after established treatment with TNFα inhibitors. METHODS: We performed a longitudinal study of RA patients (n = 106, 36% men, median age 54 y) starting first treatment with a TNFα inhibitor (infliximab, etanercept, adalimumab, golimumab, or certolizumab). Clinical assessment (Disease Activity Score for 28 standard joints, DAS28), joint ultrasonography, and blood draw were performed at baseline and after 3 mo treatment. Plasma concentrations of PLP, HK, and XA were measured by liquid chromatography-tandem mass spectrometry. Associations of changes in vitamin B-6 markers with change in DAS28 were assessed by generalized additive models regression and with European League Against Rheumatism (EULAR) response categories by linear regression. RESULTS: At baseline PLP was inversely correlated with CRP (ρ = -0.27, P = 0.007), whereas HK: XA correlated with DAS28 (ρ = 0.46, P < 0.001), CRP (ρ = 0.36, P < 0.001), and ultrasonography scores (ρ = 0.29-0.35, P ≤ 0.003). After 3 mo treatment, the change (a 33% overall reduction) in DAS28 was related to changes in both PLP (ß = -0.28, P = 0.01) and HK: XA (ß = 0.33, P < 0.001). Good responders (45%) according to EULAR criteria experienced a 31% increase in PLP (P = 0.003) and an 11% decrease in HK: XA (P = 0.1), whereas nonresponders (24%) experienced a 25% increase in HK: XA (P = 0.02). CONCLUSION: Two independent measures of vitamin B-6 status confirm an association with disease activity in RA patients. The association of HK: XA with disease activity may also imply perturbations in kynurenine metabolism in RA. This trial was registered at helseforskning.etikkom.no as 2011/490.

Accumulation of Liver Lipids Induced by Vitamin B6 Deficiency Was Effectively Ameliorated by Choline and, to a Lesser Extent, Betaine.

Despite previous studies suggesting that choline and betaine ameliorate lipid accumulation in rat livers, the relative effectiveness of the two nutrients is unclear. We examined the efficacy of dietary supplementation with choline or betaine in ameliorating lipid accumulation induced by vitamin B6 (B6) deficiency in the rat liver. Male Wistar rats were fed control, B6-deficient, choline-supplemented B6-deficient, betaine-supplemented B6-deficient, or both choline and betaine-supplemented B6-deficient diets (all containing 9 g of l-methionine (Met)/kg) for 35 d. Two experiments were performed, i.e., one using 17 mmol/kg diet choline bitartrate, betaine anhydrous, and the combination and another using 8.5 mmol/kg diet. Rats fed a B6-deficient diet developed lipid accumulation in the liver with a reduction of plasma lipids induced by the disruption of Met metabolism. However, the addition of 17 mmol/kg diet choline or betaine was sufficient to ameliorate the disruptions of lipid and Met metabolism. Additionally, 8.5 mmol/kg diet choline ameliorated liver lipid deposition, while the same amount of betaine had no significant effects on liver or plasma lipid profiles. Supplementation with choline resulted in a higher liver betaine than that found using the same amount of betaine alone, although the overall liver betaine content was reduced in B6-deficient rats. Our findings indicate that choline is more effective than betaine in ameliorating B6 deficiency-related disruptions in Met metabolism and liver lipid accumulation by increasing liver betaine levels.

Disorders affecting vitamin B6 metabolism.

Vitamin B6 is present in our diet in many forms, however, only pyridoxal 5'-phosphate (PLP) can function as a cofactor for enzymes. The intestine absorbs nonphosphorylated B6 vitamers, which are converted by specific enzymes to the active PLP form. The role of PLP is enabled by its reactive aldehyde group. Pathways reliant on PLP include amino acid and neurotransmitter metabolism, folate and 1-carbon metabolism, protein and polyamine synthesis, carbohydrate and lipid metabolism, mitochondrial function and erythropoiesis. Besides the role of PLP as a cofactor B6 vitamers also play other cellular roles, for example, as antioxidants, modifying expression and action of steroid hormone receptors, affecting immune function, as chaperones and as an antagonist of Adenosine-5'-triphosphate (ATP) at P2 purinoceptors. Because of the vital role of PLP in neurotransmitter metabolism, particularly synthesis of the inhibitory transmitter γ-aminobutyric acid, it is not surprising that various inborn errors leading to PLP deficiency manifest as B6 -responsive epilepsy, usually of early onset. This includes pyridox(am)ine phosphate oxidase deficiency (a disorder affecting PLP synthesis and recycling), disorders affecting PLP import into the brain (hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects), a disorder of an intracellular PLP-binding protein (PLPBP, previously named PROSC) and disorders where metabolites accumulate that inactivate PLP, for example, ALDH7A1 deficiency and hyperprolinaemia type II. Patients with these disorders can show rapid control of seizures in response to either pyridoxine and/or PLP with a lifelong dependency on supraphysiological vitamin B6 supply. The clinical and biochemical features of disorders leading to B6 -responsive seizures and the treatment of these disorders are described in this review.

Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.

Background: Low vitamin B-6 status has been linked to depressive symptomatology. We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3-time points over ∼5-7 years in a cohort of older Hispanic adults. Methods: We used two-level hierarchical linear regression models for continuous outcomes. Vitamin B-6 status was associated with depressive symptomatology across these time points. Results: Plasma pyridoxyl-5-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies-Depression Scale (CES-D) score of 22 ± 14, vs. 20 ± 13); this differential remained constant over time and persisted after controlling for age, sex, education, body mass index, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events, allostatic load, and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time. Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Hispanic of Puerto Rican descent and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive approach in this population.

Pseudotumor cerebral asociado a hipovitaminosis A, B6 y D: A propósito de dos casos / Pseudotumor cerebri associated with hypovitaminosis A, B6 and D: About two cases

La hipertensión endocraneana idiopàtica se asocia infrecuentemente con la hipovitaminosis A y D. Se presenta el caso de una paciente femenina de 8 años con visión borrosa de 24 horas y papiledema bilateral. Resonancia magnética nuclear normal. Presión de apertura de líquido cefalorraquídeo: 260 mm^O. Presentó déficit de vitamina A y D, e inició un tratamiento sustitutivo. El segundo caso corresponde a un paciente masculino de 12 años con fiebre y odinofagia de 3 días. Con antecedente de glomerulonefritis y sobrepeso. Presentaba edema bipalpebral y papiledema. Tomografia axial computada de la órbita: aumento de líquido en la vaina de ambos nervios ópticos. Resonancia magnética nuclear: aracnoidocele intraselar. Presión de apertura de líquido cefalorraquídeo: 400 mm^O. Presentó déficit de vitamina D y B6, e inició el tratamiento sustitutivo. La elevación de la presión intracraneal desencadena mecanismos de compensación que, al fallar, pueden comprometer la vida o provocar graves discapacidades neurológicas. Reconocer la causa para un enfoque terapéutico preciso es clave para disminuir la morbimortalidad asociada a esta patología.

Idiopathic endocranial hypertension is infrequently associated with hypovitaminosis A and D. The case of an 8-year-old female with 24-hour blurred vision and bilateral papilledema is presented. Nuclear magnetic resonance was normal. Opening pressure of cerebrospinal fluid: 260 mm^O. She presented vitamin A and D deficiency and started replacement therapy. The second case corresponds to a 12-year-old male with fever and odynophagia of 3 days. History of glomerulonephritis and overweight. He had bipalpebral edema and papilledema. Computed tomography scan of the orbit: increase of fluid in the sheath of both optic nerves. Nuclear magnetic resonance: intrasellar arachnoidocele. Opening pressure of cerebrospinal fluid: 400 mmH2O. He presented vitamin D and B6 deficiency and started replacement treatment. The elevation of intracranial pressure triggers compensation mechanisms that, when they fail, can compromise life or cause serious neurological disabilities. Recognizing the cause for an accurate therapeutic approach is key to reduce the morbidity and mortality associated with this pathology.

[Pseudotumor cerebri associated with hypovitaminosis A, B6 and D. About two cases]. / Pseudotumor cerebral asociado a hipovitaminosis A, B6 y D. A propósito de dos casos.

Idiopathic endocranial hypertension is infrequently associated with hypovitaminosis A and D. The case of an 8-year-old female with 24-hour blurred vision and bilateral papilledema is presented. Nuclear magnetic resonance was normal. Opening pressure of cerebrospinal fluid: 260 mmH2O. She presented vitamin A and D deficiency and started replacement therapy. The second case corresponds to a 12-year-old male with fever and odynophagia of 3 days. History of glomerulonephritis and overweight. He had bipalpebral edema and papilledema. Computed tomography scan of the orbit: increase of fluid in the sheath of both optic nerves. Nuclear magnetic resonance: intrasellar arachnoidocele. Opening pressure of cerebrospinal fluid: 400 mmH2O. He presented vitamin D and B6 deficiency and started replacement treatment. The elevation of intracranial pressure triggers compensation mechanisms that, when they fail, can compromise life or cause serious neurological disabilities. Recognizing the cause for an accurate therapeutic approach is key to reduce the morbidity and mortality associated with this pathology.

La hipertensión endocraneana idiopática se asocia infrecuentemente con la hipovitaminosis A y D. Se presenta el caso de una paciente femenina de 8 años con visión borrosa de 24 horas y papiledema bilateral. Resonancia magnética nuclear normal. Presión de apertura de líquido cefalorraquídeo: 260 mmH2O. Presentó déficit de vitamina A y D, e inició un tratamiento sustitutivo. El segundo caso corresponde a un paciente masculino de 12 años con fiebre y odinofagia de 3 días. Con antecedente de glomerulonefritis y sobrepeso. Presentaba edema bipalpebral y papiledema. Tomografía axial computada de la órbita: aumento de líquido en la vaina de ambos nervios ópticos. Resonancia magnética nuclear: aracnoidocele intraselar. Presión de apertura de líquido cefalorraquídeo: 400 mmH2O. Presentó déficit de vitamina D y B6, e inició el tratamiento sustitutivo. La elevación de la presión intracraneal desencadena mecanismos de compensación que, al fallar, pueden comprometer la vida o provocar graves discapacidades neurológicas. Reconocer la causa para un enfoque terapéutico preciso es clave para disminuir la morbimortalidad asociada a esta patología.

Acute nutritional axonal neuropathy.

INTRODUCTION: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. METHODS: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. RESULTS: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. DISCUSSION: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018.

Functional vitamin B-6 status and long-term mortality in renal transplant recipients.

Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8-6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK:XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status.Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29-60 nmol/L), 40.1 nmol/L (IQR: 33.0-48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5-24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17-50 nmol/L), 61.5 nmol/L (IQR: 45.6-86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2-40.0 nmol/L), respectively, in RTRs (all P < 0.001). RTRs had a higher median 3-HK:XA ratio (2.38; IQR: 1.68-3.49) than did healthy controls (2.13; IQR: 1.63-2.71) (P < 0.05). In RTRs, the 3-HK:XA ratio was inversely associated with plasma PLP (ß = -0.21, P < 0.001). Moreover, a higher 3-HK:XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs.Conclusions: Vitamin B-6-deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6-sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease. This trial was registered at clinicaltrials.gov as NCT02811835.

Vitamin B-6 and colorectal cancer risk: a prospective population-based study using 3 distinct plasma markers of vitamin B-6 status.

Background: Higher plasma concentrations of the vitamin B-6 marker pyridoxal 5'-phosphate (PLP) have been associated with reduced colorectal cancer (CRC) risk. Inflammatory processes, including vitamin B-6 catabolism, could explain such findings.Objective: We investigated 3 biomarkers of vitamin B-6 status in relation to CRC risk.Design: This was a prospective case-control study of 613 CRC cases and 1190 matched controls nested within the Northern Sweden Health and Disease Study (n = 114,679). Participants were followed from 1985 to 2009, and the median follow-up from baseline to CRC diagnosis was 8.2 y. PLP, pyridoxal, pyridoxic acid (PA), 3-hydroxykynurenine, and xanthurenic acids (XAs) were measured in plasma with the use of liquid chromatography-tandem mass spectrometry. We calculated relative and absolute risks of CRC for PLP and the ratios 3-hydroxykynurenine:XA (HK:XA), an inverse marker of functional vitamin B-6 status, and PA:(PLP + pyridoxal) (PAr), a marker of inflammation and oxidative stress and an inverse marker of vitamin B-6 status.Results: Plasma PLP concentrations were associated with a reduced CRC risk for the third compared with the first quartile and for PLP sufficiency compared with deficiency [OR: 0.60 (95% CI: 0.44, 0.81) and OR: 0.55 (95% CI: 0.37, 0.81), respectively]. HK:XA and PAr were both associated with increased CRC risk [OR: 1.48 (95% CI: 1.08, 2.02) and OR: 1.50 (95% CI: 1.10, 2.04), respectively] for the fourth compared with the first quartile. For HK:XA and PAr, the findings were mainly observed in study participants with <10.5 y of follow-up between sampling and diagnosis.Conclusions: Vitamin B-6 deficiency as measured by plasma PLP is associated with a clear increase in CRC risk. Furthermore, our analyses of novel markers of functional vitamin B-6 status and vitamin B-6-associated oxidative stress and inflammation suggest a role in tumor progression rather than initiation.

Low serum concentrations of vitamin B6 and iron are related to panic attack and hyperventilation attack.

Patients undergoing a panic attack (PA) or a hyperventilation attack (HVA) are sometimes admitted to emergency departments (EDs). Reduced serotonin level is known as one of the causes of PA and HVA. Serotonin is synthesized from tryptophan. For the synthesis of serotonin, vitamin B6 (Vit B6) and iron play important roles as cofactors. To clarify the pathophysiology of PA and HVA, we investigated the serum levels of vitamins B2, B6, and B12 and iron in patients with PA or HVA attending an ED. We measured each parameter in 21 PA or HVA patients and compared the values with those from 20 volunteers. We found that both Vit B6 and iron levels were significantly lower in the PA/HVA group than in the volunteer group. There was no significant difference in the serum levels of vitamins B2 or B12. These results suggest that low serum concentrations of Vit B6 and iron are involved in PA and HVA. Further studies are needed to clarify the mechanisms involved in such differences.

Plasma pyridoxal 5'-phosphate is not associated with inflammatory and immune responses after adjusting for serum albumin in patients with rheumatoid arthritis: a preliminary study.

BACKGROUND/AIMS: Plasma pyridoxal 5'-phosphate (PLP) has been shown to be associated with inflammatory and immune responses.Rheumatoid arthritis (RA) is an autoimmune and chronic systemic inflammatory disease and patients with RA have lower plasma PLP levels. We studied the relationship between plasma PLP and inflammatory or immune responses in patients with RA. METHODS: This study was designed as an observational cross-sectional study. Forty-three patients with RA were allocated to the adequate (PLP ≥20 nmol/l) (n = 30) or deficient vitamin B(6) (PLP <20 nmol/l) (n = 13) group according to their fasting plasma PLP concentration on the day blood was taken. Plasma PLP, inflammatory parameters [i.e. high-sensitivity CRP (hs-CRP), erythrocyte sedimentation rate, interleukin-6, tumor necrosis factor-α] and immune parameters (i.e. white blood cells, total lymphocytes, neutrophils, T lymphocytes, B lymphocytes, T helper cells and T suppressor cells) were measured. RESULTS: Patients with deficient plasma PLP concentration were mostly considered to have a systemic inflammatory status (hs-CRP >3 mg/l) and apparently had significantly higher mean hs-CRP levels and immune parameters than patients with adequate plasma PLP concentration. There was no significant association between plasma PLP levels and inflammatory parameters. The significantly inverse correlation of plasma PLP with the numbers of white blood cells, neutrophils, total lymphocytes, T lymphocytes and T helper cells remained after adjusting for serum hemoglobin concentration, but the significant correlation disappeared after serum albumin concentration was also considered. CONCLUSIONS: RA patients with deficient plasma PLP concentration had more severe inflammatory and immune responses than patients with adequate plasma PLP concentration. However, there was a lack of association of low plasma PLP concentration with inflammatory and immune parameters after serum albumin concentration was considered in patients with RA.

Vitamin B6 deficiency, genome instability and cancer.

Vitamin B6 functions as a coenzyme in >140 enzymatic reactions involved in the metabolism of amino acids, carbohydrates, neurotransmitters, and lipids. It comprises a group of three related 3-hydroxy-2-methyl-pyrimidine derivatives: pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM) and their phosphorylated derivatives [pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP)], In the folate metabolism pathway, PLP is a cofactor for the mitochondrial and cytoplasmic isozymes of serine hydroxymethyltransferase (SHMT2 and SHMT1), the P-protein of the glycine cleavage system, cystathionine ß-synthase (CBS) and γ-cystathionase, and betaine hydroxymethyltransferase (BHMT), all of which contribute to homocysteine metabolism either through folate- mediated one-carbon metabolism or the transsulfuration pathway. Folate cofactors carry and chemically activate single carbons for the synthesis of purines, thymidylate and methionine. So the evidence indicates that vitamin B6 plays an important role in maintenance of the genome, epigenetic stability and homocysteine metabolism. This article focuses on studies of strand breaks, micronuclei, or chromosomal aberrations regarding protective effects of vitamin B6, and probes whether it is folate-mediated one-carbon metabolism or the transsulfuration pathway for vitamin B6 which plays critical roles in prevention of cancer and cardiovascular disease.

Nutritional intake and prevalence of nutritional deficiencies prior to surgery in a Spanish morbidly obese population.

BACKGROUND: The prevalence of obesity in Spain is on the rise with the consequent increase in bariatric surgery. Studies in non-Mediterranean populations have shown that micronutrient deficits are present before surgery. However, there is no data on this topic in a Spanish population. METHODS: We evaluated food intake and the prevalence of nutritional deficiencies in 231 obese patient (72.3% women, 45.6 ± 9.9 years, BMI 48.2 ± 7.8 kg/m(2)) candidates for bariatric surgery. Forty-six normal weight individuals with similar demographic variables except BMI were included for comparison of deficiencies. RESULTS: In obese subjects, the mean estimated energy intake was 2,584 ± 987 kcal/day in males and 2,094 ± 669 kcal/day in females (p < 0.05). After adjusting for kilocalorie intake, carbohydrate intake was of 38.7% [CI 36.2 to 41.1] and 39.9% [CI 37.8 to 40.8] (n.s.), lipid intake was 41.9% [CI 39.6 to 44.2] and 43.0% [CI 41.7 to 44.8] (n.s.) and protein intake was 19.1% [CI 17.7 to 20.5] and 17.3% [CI 16.4 to 18.1] (n.s.) for men and women, respectively. The most prevalent deficiency was vitamin D25(OH): obese 94%, control 24%; (p < 0.0001). Above normal PTH levels were observed in 41.0% and 20.0% of obese and normal weight subjects, respectively (p < 0.0497). Increased prevalence of deficiencies in obese patients included magnesium, vitamin B6 and anaemia (p < 0.05). Other vitamin deficiencies were observed although did not reach statistical significance. CONCLUSIONS: Nutritional deficiencies are commonly found in the Spanish obese population undergoing bariatric surgery and are significantly more prevalent than in normal weight individuals.

B vitamins and the aging brain.

Deficiencies of the vitamins folate, B(12) , and B(6) are associated with neurological and psychological dysfunction and with congenital defects. In the elderly, cognitive impairment and incident dementia may be related to the high prevalence of inadequate B vitamin status and to elevations of plasma homocysteine. Plausible mechanisms include homocysteine neurotoxicity, vasotoxicity, and impaired S-adenosylmethionine-dependent methylation reactions vital to central nervous system function. In light of this, it is imperative to find safe ways of improving vitamin B status in the elderly without exposing some individuals to undue risk.

Acceleration of brain amyloidosis in an Alzheimer's disease mouse model by a folate, vitamin B6 and B12-deficient diet.

Epidemiological and clinical studies indicate that elevated circulating level of homocysteine (Hcy) is a risk factor for developing Alzheimer's disease (AD). Dietary deficiency of folate, vitamin B6 and B12 results in a significant increase of Hcy levels, a condition also known as hyperhomocysteinemia (HHcy). In the present study we tested the hypothesis that a diet deficient for these three important factors when administered to a mouse model of AD, i.e. Tg2576, will result in HHcy and in an acceleration of their amylodotic phenotype. Compared with Tg2576 mice on regular chow, the ones receiving the diet deficient for folate, B6 and B12 developed HHcy. This condition was associated with a significant increase in Abeta levels in the cortex and hippocampus, and an elevation of Abeta deposits in the same regions. No significant changes were observed for steady-state levels of total APP, BACE-1, ADAM-10, PS1 and nicastrin in the brains of mice with HHcy. No differences were observed for the main Abeta catabolic pathways, i.e. IDE and neprilysin proteins, or the Abeta chaperone apolipoprotein E. Our findings demonstrate that a dietary condition which leads to HHcy may also result in increased Abeta levels and deposition in a transgenic mouse model of AD-like amylodosis. They further support the concept that dietary factors can contribute to the development of AD neuropathology.

[Does diet affect our mood? The significance of folic acid and homocysteine]. / Czy dieta ma wplyw na nasz nastrój? Znaczenie kwasu foliowego i homocysteiny.

UNLABELLED: In recent years, there has been growing interest in the association between national diet and the possibility of developing various mental disorders, as well as between deficiency of such vitamins as, e.g. folic acid, vitamin B12, B6, and others (e.g., omega-3 fatty acids), elevated serum homocysteine level and the functioning of human brain as well as the occurrence of such disorders as dementia, central nervous system vascular disorders and depression. THE AIM OF THE STUDY: was to present the current state of knowledge about the role of folic acid and homocysteine in the human organism as well as the significance of vitamin deficiency, mainly folic acid and hyperhomocysteinemy for the occurrence of mood disorders. METHOD: The authors conducted the search of the Internet database Medline (www.pubmed.com) using as key words: depression, mood, homocysteine, vitamin deficiencies: folic acid, B6 and 812 and time descriptors: 1990-2007. RESULTS: In depression, folate, vitamins B12 and B6, as well as unsaturated omega-3 fatty acids deficiency affects the biochemical processes in the CNS, as folic acid and vitamin B12, participate in the metabolism of S-adenosylmethionine (SAM), a donator of methyl groups, which play a decisive role in the functioning of the nervous system; they are, among others, active in the formation of neurotransmitters (e.g. serotonin), phospholipids that are a component of neuronal myelin sheaths, and cell receptors. The deficiency of the vitamins in question results in hyperhomocysteinemia (the research shows that approximately 45-55% of patients with depression develop significantly elevated serum homocysteine), which causes a decrease in SAM, followed by impaired methylation and, consequently, impaired metabolism of neurotransmitters, phospholipids, myelin, and receptors. Hyperhomocysteinemia also leads to activation of NMDA receptors, lesions in vascular endothelium, and oxidative stress. All this effects neurotoxicity and promotes the development of various disorders, including depression. Vitamins B12 and B6, folic acid and omega-3 fatty acids supplementation is thus important in patients suffering from their deficiency; national diet as a significant factor in prevention of numerous CNS disorders, including depression, is also worth consideration.