Showing papers on "B vitamins published in 2010"

Wolbachia as a bacteriocyte-associated nutritional mutualist

Abstract: Many insects are dependent on bacterial symbionts that provide essential nutrients (ex. aphid–Buchnera and tsetse–Wiglesworthia associations), wherein the symbionts are harbored in specific cells called bacteriocytes that constitute a symbiotic organ bacteriome. Facultative and parasitic bacterial symbionts like Wolbachia have been regarded as evolutionarily distinct from such obligate nutritional mutualists. However, we discovered that, in the bedbug Cimex lectularius, Wolbachia resides in a bacteriome and appears to be an obligate nutritional mutualist. Two bacterial symbionts, a Wolbachia strain and an unnamed γ-proteobacterium, were identified from different strains of the bedbug. The Wolbachia symbiont was detected from all of the insects examined whereas the γ-proteobacterium was found in a part of them. The Wolbachia symbiont was specifically localized in the bacteriomes and vertically transmitted via the somatic stem cell niche of germalia to oocytes, infecting the incipient symbiotic organ at an early stage of the embryogenesis. Elimination of the Wolbachia symbiont resulted in retarded growth and sterility of the host insect. These deficiencies were rescued by oral supplementation of B vitamins, confirming the essential nutritional role of the symbiont for the host. The estimated genome size of the Wolbachia symbiont was around 1.3 Mb, which was almost equivalent to the genome sizes of parasitic Wolbachia strains of other insects. These results indicate that bacteriocyte-associated nutritional mutualism can evolve from facultative and prevalent microbial associates like Wolbachia, highlighting a previously unknown aspect of the parasitism-mutualism evolutionary continuum.

Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial.

Abstract: Background: An increased rate of brain atrophy is often observed in older subjects, in particular those who suffer from cognitive decline. Homocysteine is a risk factor for brain atrophy, cognitive impairment and dementia. Plasma concentrations of homocysteine can be lowered by dietary administration of B vitamins. Objective: To determine whether supplementation with B vitamins that lower levels of plasma total homocysteine can slow the rate of brain atrophy in subjects with mild cognitive impairment in a randomised controlled trial (VITACOG, ISRCTN 94410159). Methods and Findings: Single-center, randomized, double-blind controlled trial of high-dose folic acid, vitamins B6 and B12 in 271 individuals (of 646 screened) over 70 y old with mild cognitive impairment. A subset (187) volunteered to have cranial MRI scans at the start and finish of the study. Participants were randomly assigned to two groups of equal size, one treated with folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), the other with placebo; treatment was for 24 months. The main outcome measure was the change in the rate of atrophy of the whole brain assessed by serial volumetric MRI scans. Results: A total of 168 participants (85 in active treatment group; 83 receiving placebo) completed the MRI section of the trial. The mean rate of brain atrophy per year was 0.76% [95% CI, 0.63–0.90] in the active treatment group and 1.08% [0.94– 1.22] in the placebo group (P=0.001). The treatment response was related to baseline homocysteine levels: the rate of atrophy in participants with homocysteine .13 mmol/L was 53% lower in the active treatment group (P=0.001). A greater rate of atrophy was associated with a lower final cognitive test scores. There was no difference in serious adverse events according to treatment category. Conclusions and Significance: The accelerated rate of brain atrophy in elderly with mild cognitive impairment can be slowed by treatment with homocysteine-lowering B vitamins. Sixteen percent of those over 70 y old have mild cognitive impairment and half of these develop Alzheimer’s disease. Since accelerated brain atrophy is a characteristic of subjects with mild cognitive impairment who convert to Alzheimer’s disease, trials are needed to see if the same treatment will delay the development of Alzheimer’s disease.

Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals.

Abstract: Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.

Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial

Abstract: Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids, or both, could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke. Design Double blind, randomised, placebo controlled trial; factorial design. Setting Recruitment throughout France via a network of 417 cardiologists, neurologists, and other physicians. Participants 2501 patients with a history of myocardial infarction, unstable angina, or ischaemic stroke. Intervention Daily dietary supplement containing 5-methyltetrahydrofolate (560 μg), vitamin B-6 (3 mg), and vitamin B-12 (20 μg) or placebo; and containing omega 3 fatty acids (600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1) or placebo. Median duration of supplementation was 4.7 years. Main outcome measures Major cardiovascular events, defined as a composite of non-fatal myocardial infarction, stroke, or death from cardiovascular disease. Results Allocation to B vitamins lowered plasma homocysteine concentrations by 19% compared with placebo, but had no significant effects on major vascular events (75 v 82 patients, hazard ratio, 0.90 (95% confidence interval 0.66 to 1.23, P=0.50)). Allocation to omega 3 fatty acids increased plasma concentrations of omega 3 fatty acids by 37% compared with placebo, but also had no significant effect on major vascular events (81 v 76 patients, hazard ratio 1.08 (0.79 to 1.47, P=0.64)). Conclusion This study does not support the routine use of dietary supplements containing B vitamins or omega 3 fatty acids for prevention of cardiovascular disease in people with a history of ischaemic heart disease or ischaemic stroke, at least when supplementation is introduced after the acute phase of the initial event. Trial registration Current Controlled Trials ISRCTN41926726.

Copper deficiency myelopathy

Abstract: Acquired copper deficiency has been recognised as a rare cause of anaemia and neutropenia for over half a century. Copper deficiency myelopathy (CDM) was only described within the last decade, and represents a treatable cause of non-compressive myelopathy which closely mimics subacute combined degeneration due to vitamin B12 deficiency. Here, 55 case reports from the literature are reviewed regarding their demographics, aetiology, haematological and biochemical parameters, spinal imaging, treatment and outcome. The pathophysiology of disorders of copper metabolism is discussed. CDM most frequently presented in the fifth and sixth decades and was more common in women (F:M = 3.6:1). Risk factors included previous upper gastrointestinal surgery, zinc overload and malabsorption syndromes, all of which impair copper absorption in the upper gastrointestinal tract. No aetiology was established in 20% of cases. High zinc levels were detected in some cases not considered to have primary zinc overload, and in this situation the contribution of zinc to the copper deficiency state remained unclear. Cytopenias were found in 78%, particularly anaemia, and a myelodysplastic syndrome may have been falsely diagnosed in the past. Spinal MRI was abnormal in 47% and usually showed high T2 signal in the posterior cervical and thoracic cord. In a clinically compatible case, CDM may be suggested by the presence of one or more risk factors and/or cytopenias. Low serum copper and caeruloplasmin levels confirmed the diagnosis and, in contrast to Wilson’s disease, urinary copper levels were typically low. Treatment comprised copper supplementation and modification of any risk factors, and led to haematological normalisation and neurological improvement or stabilisation. Since any neurological recovery was partial and case numbers of CDM will continue to rise with the growing use of bariatric gastrointestinal surgery, clinical vigilance will remain the key to minimising neurological sequelae. Recommendations for treatment and prevention are made.

Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity

Abstract: Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondrial content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH oxidase activity of mitochondrial electron transport chain (ETC), and activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD), key enzymes of TCA cycle and β-oxidation pathway, respectively. Frozen biopsies collected from obese or T2DM individuals in our previous studies were used to estimate activity of β-HAD. The obtained data were complemented by data from our previous studies and statistically analyzed to compare mitochondrial content and mitochondrial enzyme profile in lean, obese, or T2DM cohort. The total activity of NADH oxidase was reduced significantly in obese or T2DM subjects. The cardiolipin content for lean or obese group was similar, and although for T2DM group cardiolipin showed a tendency to decline, it was statistically insignificant. The total activity of citrate synthase for lean and T2DM group was similar; however, it was increased significantly in the obese group. Activity of β-HAD and mtDNA content was similar for all three groups. We conclude that the total activity of NADH oxidase in biopsy for lean group is significantly higher than corresponding activity for obese or T2DM cohort. The specific activity of NADH oxidase (per mg cardiolipin) and NADH oxidase/citrate synthase and NADH oxidase/β-HAD ratios are reduced two- to threefold in both T2DM and obesity.

Nutrient Intakes of US Infants, Toddlers, and Preschoolers Meet or Exceed Dietary Reference Intakes

Abstract: Objectives To assess the usual nutrient intakes of 3,273 US infants, toddlers, and preschoolers, aged 0 to 47 months, surveyed in the Feeding Infants and Toddlers Study (FITS) 2008; and to compare data on the usual nutrient intakes for the two waves of FITS conducted in 2002 and 2008. Design The FITS 2008 is a cross-sectional survey of a national random sample of US children from birth through age 47 months. Usual nutrient intakes derived from foods, beverages, and supplements were ascertained using a telephone-administered, multiple-pass 24-hour dietary recall. Subjects Infants aged birth to 5 months (n=382) and 6 to 11 months (n=505), toddlers aged 12 to 23 months (n=925), and preschoolers aged 24 to 47 months (n=1,461) were surveyed. Methods All primary caregivers completed one 24-hour dietary recall and a random subsample (n=701) completed a second 24-hour dietary recall. The personal computer version of the Software for Intake Distribution Estimation was used to estimate the 10th, 25th, 50th, 75th, and 90th percentiles, as well as the proportions below and above cutoff values defined by the Dietary Reference Intakes or the 2005 Dietary Guidelines for Americans. Results Usual nutrient intakes met or exceeded energy and protein requirements with minimal risk of vitamin and mineral deficiencies. The usual intakes of antioxidants, B vitamins, bone-related nutrients, and other micronutrients were adequate relative to the Adequate Intakes or Estimated Average Requirements, except for iron and zinc in a small subset of older infants, and vitamin E and potassium in toddlers and preschoolers. Intakes of synthetic folate, preformed vitamin A, zinc, and sodium exceeded Tolerable Upper Intake Level in a significant proportion of toddlers and preschoolers. Macronutrient distributions were within acceptable macronutrient distribution ranges, except for dietary fat, in some toddlers and preschoolers. Dietary fiber was low in the vast majority of toddlers and preschoolers, and saturated fat intakes exceeded recommendations for the majority of preschoolers. The prevalence of inadequate intakes, excessive intake, and intakes outside the acceptable macronutrient distribution range was similar in FITS 2002 and FITS 2008. Conclusions In FITS 2008, usual nutrient intakes were adequate for the majority of US infants, toddlers, and preschoolers, except for a small but important number of infants at risk for inadequate iron and zinc intakes. Diet quality should be improved in the transition from infancy to early childhood, particularly with respect to healthier fats and fiber in the diets of toddlers and preschoolers.

B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial

Abstract: The VITATOPS Trial Study Group* Summary Background Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events. Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown. We aimed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke, non-fatal myocardial infarction, and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye. Methods In this randomised, double-blind, parallel, placebo-controlled trial, we assigned patients with recent stroke or transient ischaemic attack (within the past 7 months) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins (2 mg folic acid, 25 mg vitamin B6, and 0·5 mg vitamin B12). Patients were randomly allocated by means of a central 24-h telephone service or an interactive website, and allocation was by use of random permuted blocks stratifi ed by hospital. Participants, clinicians, carers, and investigators who assessed outcomes were masked to the assigned intervention. The primary endpoint was the composite of stroke, myocardial infarction, or vascular death. All patients randomly allocated to a group were included in the analysis of the primary endpoint. This trial is registered with ClinicalTrials.gov , NCT00097669, and Current Controlled Trials, ISRCTN74743444. Findings Between Nov 19, 1998, and Dec 31, 2008, 8164 patients were randomly assigned to receive B vitamins (n=4089) or placebo (n=4075). Patients were followed up for a median duration of 3·4 years (IQR 2·0–5·5). 616 (15%) patients assigned to B vitamins and 678 (17%) assigned to placebo reached the primary endpoint (risk ratio [RR] 0·91, 95% CI 0·82 to 1·00, p=0·05; absolute risk reduction 1·56%, –0·01 to 3·16). There were no unexpected serious adverse reactions and no signifi cant diff erences in common adverse eff ects between the treatment groups. Interpretation Daily administration of folic acid, vitamin B6, and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more eff ective than placebo in reducing the incidence of major vascular events. These results do not support the use of B vitamins to prevent recurrent stroke. The results of ongoing trials and an individual patient data meta-analysis will add statistical power and precision to present estimates of the eff ect of B vitamins.

Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy: A Randomized Controlled Trial

Abstract: Context Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B(6), and vitamin B(12)) has been shown to lower the plasma concentration of homocysteine. Objective To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications. Design, setting, and participants A multicenter, randomized, double-blind, placebo-controlled trial (Diabetic Intervention with Vitamins to Improve Nephropathy [DIVINe]) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy. Intervention Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B(6) (25 mg/d), and vitamin B(12) (1 mg/d), or matching placebo. Main outcome measures Change in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes were dialysis and a composite of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured. Results The mean (SD) follow-up during the trial was 31.9 (14.4) months. At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m(2) in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m(2) in the placebo group (mean difference, -5.8; 95% confidence interval [CI], -10.6 to -1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04). Plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) micromol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) micromol/L in the placebo group (mean difference, -4.8; 95% CI, -6.1 to -3.7; P Conclusion Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events. Trial registration isrctn.org Identifier: ISRCTN41332305.

Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies.

Abstract: Context Mounting evidence indicates that vitamin B 6 , a coenzyme involved in nearly 100 enzymatic reactions, may reduce the risk of colorectal cancer. Objective To conduct a systematic review with meta-analysis of prospective studies assessing the association of vitamin B 6 intake or blood levels of pyridoxal 5′-phosphate (PLP; the active form of vitamin B 6 ) with risk of colorectal cancer. Data Sources Relevant studies were identified by a search of MEDLINE and EMBASE databases to February 2010, with no restrictions. We also reviewed reference lists from retrieved articles. Study Selection We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between vitamin B 6 intake or blood PLP levels and the risk of colorectal, colon, or rectal cancer. Data Extraction Two authors independently extracted data and assessed study quality. Study-specific RRs were pooled using a random-effects model. Data Synthesis Nine studies on vitamin B 6 intake and 4 studies on blood PLP levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest vs lowest category of vitamin B 6 intake and blood PLP levels were 0.90 (95% CI, 0.75-1.07) and 0.52 (95% CI, 0.38-0.71), respectively. There was heterogeneity among studies of vitamin B 6 intake (P = .01) but not among studies of blood PLP levels (P = .95). Omitting 1 study that contributed substantially to the heterogeneity among studies of vitamin B 6 intake yielded a pooled RR of 0.80 (95% CI, 0.69-0.92). The risk of colorectal cancer decreased by 49% for every 100-pmol/mL increase (approximately 2 SDs) in blood PLP levels (RR, 0.51; 95% CI, 0.38-0.69). Conclusion Vitamin B 6 intake and blood PLP levels were inversely associated with the risk of colorectal cancer in this meta-analysis.

Most harmful algal bloom species are vitamin B1 and B12 auxotrophs

Abstract: Eutrophication can play a central role in promoting harmful algal blooms (HABs), and therefore many HAB studies to date have focused on macronutrients (N, P, Si). Although a majority of algal species require exogenous B vitamins (i.e., auxotrophic for B vitamins), the possible importance of organic micronutrients such as B vitamins (B1, B7, B12) in regulating HABs has rarely been considered. Prior investigations of vitamins and algae have examined a relatively small number of dinoflagellates (n = 26) and a paucity of HAB species (n = 4). In the present study, the vitamin B1, B7, and B12 requirements of 41 strains of 27 HAB species (19 dinoflagellates) were investigated. All but one species (two strains) of harmful algae surveyed required vitamin B12, 20 of 27 species required B1, and 10 of 27 species required B7, all proportions higher than the previously reported for non-HAB species. Half-saturation (Ks) constants of several HAB species for B1 and B12 were higher than those previously reported for other phytoplankton and similar to vitamin concentrations reported in estuaries. Cellular quotas for vitamins suggest that, in some cases, HAB demands for vitamins may exhaust standing stocks of vitamins in hours to days. The sum of these findings demonstrates the potentially significant ecological role of B-vitamins in regulating the dynamics of HABs.

Genotypic and phenotypic spectrum of pyridoxine-dependent epilepsy (ALDH7A1 deficiency)

Abstract: Pyridoxine-dependent epilepsy was recently shown to be due to mutations in the ALDH7A1 gene, which encodes antiquitin, an enzyme that catalyses the nicotinamide adenine dinucleotide-dependent dehydrogenation of l-α-aminoadipic semialdehyde/l-Δ1-piperideine 6-carboxylate. However, whilst this is a highly treatable disorder, there is general uncertainty about when to consider this diagnosis and how to test for it. This study aimed to evaluate the use of measurement of urine l-α-aminoadipic semialdehyde/creatinine ratio and mutation analysis of ALDH7A1 (antiquitin) in investigation of patients with suspected or clinically proven pyridoxine-dependent epilepsy and to characterize further the phenotypic spectrum of antiquitin deficiency. Urinary l-α-aminoadipic semialdehyde concentration was determined by liquid chromatography tandem mass spectrometry. When this was above the normal range, DNA sequencing of the ALDH7A1 gene was performed. Clinicians were asked to complete questionnaires on clinical, biochemical, magnetic resonance imaging and electroencephalography features of patients. The clinical spectrum of antiquitin deficiency extended from ventriculomegaly detected on foetal ultrasound, through abnormal foetal movements and a multisystem neonatal disorder, to the onset of seizures and autistic features after the first year of life. Our relatively large series suggested that clinical diagnosis of pyridoxine dependent epilepsy can be challenging because: (i) there may be some response to antiepileptic drugs; (ii) in infants with multisystem pathology, the response to pyridoxine may not be instant and obvious; and (iii) structural brain abnormalities may co-exist and be considered sufficient cause of epilepsy, whereas the fits may be a consequence of antiquitin deficiency and are then responsive to pyridoxine. These findings support the use of biochemical and DNA tests for antiquitin deficiency and a clinical trial of pyridoxine in infants and children with epilepsy across a broad range of clinical scenarios.

Reduced folic acid, vitamin B12 and docosahexaenoic acid and increased homocysteine and cortisol in never-medicated schizophrenia patients: implications for altered one-carbon metabolism.

Abstract: Abnormal one-carbon metabolism has long been suggested as one of the mechanisms for neuropathology and psychopathology of schizophrenia. Variable levels of components of one-carbon metabolism (folic acid and vitamin B12) and consequent altered levels of homocysteine and phospholipid docosahexaenoic acid (DHA) have been independently reported, mostly in medicated patients. This study examined the simultaneous levels of these key components of one-carbon metabolism and its consequences in unique, medication-naive first-episode psychotic patients (FEP, n=31) and healthy controls (HC, n=48) matched for confounds such as race, diet and lifestyle to reduce the variability. Significantly lower levels of folate and vitamin B12 in plasma and folate in red blood cells were observed in FEP compared to HC. These reductions paralleled the significant increase in plasma homocysteine and cortisol levels. Significantly reduced levels of membrane DHA were also observed in FEP compared to HC. This study, using a unique cohort, provided a broader mechanism (disturbed folic acid-vitamin B12-DHA balance) of altered one-carbon metabolism and one of its key consequential components, an increased homocysteine level that together with cortisol, can contribute to the neuropathology of psychosis. These data may have important implications for the amelioration of psychopathology in schizophrenia.

Advances in the understanding of cobalamin assimilation and metabolism

Abstract: The haematological and neurological consequences of cobalamin deficiency define the essential role of this vitamin in key metabolic reactions. The identification of cubilin-amnionless as the receptors for intestinal absorption of intrinsic factor-bound cobalamin and the plasma membrane receptor for cellular uptake of transcobalamin bound cobalamin have provided a clearer understanding of the absorption and cellular uptake of this vitamin. As the genes involved in the intracellular processing of cobalamins and genetic defects of these pathways are identified, the metabolic disposition of cobalamins and the proteins involved are being recognized. The synthesis of methylcobalamin and 5'-deoxyadenosylcobalamin, their utilization in conjunction with methionine synthase and methylmalonylCoA mutase, respectively, and the metabolic consequences of defects in these pathways could provide insights into the clinical presentation of cobalamin deficiency.

The prevalence of nutritional anemia in pregnancy in an east Anatolian province, Turkey

Abstract: Anemia is considered a severe public health problem by World Health Organization when anemia prevalence is equal to or greater than 40% in the population. The purpose of this study was to determine the anemia prevalence with the associated factors in pregnant women and to determine the serum iron, folate and B12 vitamin status in anaemic pregnants in Malatya province. This is a cross-sectional survey. A multi-sage stratified probability-proportional-to-size cluster sampling methodology was used. A total of 823 pregnant women from sixty clusters were studied. Women were administered a questionnaire related with the subject and blood samples were drawn. Total blood count was performed within four hours and serum iron, folate and B12 vitamin were studied after storing sera at -20 C for six months. Anemia prevalence was 27.1% (Hb < 11.0 gr/dl). Having four or more living children (OR = 2.2), being at the third trimester (OR = 2.3) and having a low family income (OR = 1.6) were determined as the independent predictors of anemia in pregnancy. Anemia was also associated with soil eating (PICA) in the univariate analysis (p < 0.05). Of anaemic women, 50.0% had a transferrin saturation less than 10% indicating iron deficiency, 34.5% were deficient in B12 vitamin and 71.7% were deficient in folate. Most of the anemias were normocytic-normochromic (56.5%) indicating mixed anemia. In Malatya, for pregnant women anemia was a moderate public health problem. Coexisting of iron, folate and B vitamin deficiencies was observed among anaemics. To continue anemia control strategies with reasonable care and diligence was recommended.

Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption

Abstract: After a long period of quiescence at dictyate prophase I, termed the germinal vesicle (GV) stage, mammalian oocytes reenter meiosis by activating the Cdc2–cyclin B complex (maturation-promoting factor [MPF]). The activity of MPF is regulated by Wee1/Myt1 kinases and Cdc25 phosphatases. In this study, we demonstrate that the sequestration of components that regulate MPF activity in distinct subcellular compartments is essential for their function during meiosis. Down-regulation of either Wee1B or Myt1 causes partial meiotic resumption, and oocytes reenter the cell cycle only when both proteins are down-regulated. Shortly before GV breakdown (GVBD), Cdc25B is translocated from the cytoplasm to the nucleus, whereas Wee1B is exported from the nucleus to the cytoplasm. These movements are regulated by PKA inactivation and MPF activation, respectively. Mislocalized Wee1B or Myt1 is not able to maintain meiotic arrest. Thus, cooperation of Wee1B, Myt1, and Cdc25 is required to maintain meiotic arrest and relocation of these components before GVBD is necessary for meiotic reentry.

Caffeine-mediated inhibition of calcium release channel inositol 1,4,5-trisphosphate receptor subtype 3 blocks glioblastoma invasion and extends survival.

Abstract: Calcium signaling is important in many signaling processes in cancer cell proliferation and motility including indeadlyglioblastomasofthebrainthataggressivelyinvadeneighboringtissue.Wehypothesizedthatdisturbing Ca 2+ signaling pathways might decrease the invasive behavior of giloblastoma, extending survival. Evaluating a panel of small-molecule modulators of Ca 2+ signaling, we identified caffeine as an inhibitor of glioblastoma cell motility. Caffeine, which is known to activate ryanodine receptors, paradoxically inhibits Ca 2+ increase by inositol 1,4,5-trisphospate receptor subtype 3 (IP3R3), the expression of which is increased in glioblastoma cells. Consequently, by inhibiting IP3R3-mediated Ca 2+ release, caffeine inhibited migration of glioblastoma cells in various in vitro assays. Consistent with these effects, caffeine greatly increased mean survival in a mouse xenograft model of glioblastoma. These findings suggest IP3R3 as a novel therapeutic target and identify caffeine as a possible adjunct therapy to slow invasive growth of glioblastoma. Cancer Res; 70(3); 1173–83. ©2010 AACR.

Dietary Folate, Alcohol, and B Vitamins in Relation to LINE-1 Hypomethylation in Colon Cancer

Abstract: Background and aims Although critical for methylation reactions, how dietary folate and B vitamins affect global DNA methylation level in colorectal cancers is currently unknown. Long interspersed nucleotide element-1 (LINE-1) is an emerging indicator of genome-wide DNA methylation level that has previously been linked to colon cancer survival. Methods We examined the association between dietary intake of folate, alcohol and B vitamins and LINE-1 hypomethylation in 609 incident colon cancers, utilising the database of two independent prospective cohort studies. Results Participants with ≥400 μg folate intake per day were significantly less likely to develop LINE-1 hypomethylated colon cancers than those reporting interaction =0.01). By contrast, high alcohol consumption conferred a higher risk of LINE-1 hypomethylated cancers (≥15 g alcohol per day versus none, RR=1.67, 95% CI=1.04 to 2.67 for 6 , B 12 or methionine were not significantly associated with colon cancers, regardless of LINE-1 methylation level. Conclusion The influence of dietary folate intake and alcohol consumption on colon cancer risk differs significantly according to tumoral LINE-1 methylation level.

Serum B Vitamin Levels and Risk of Lung Cancer

Abstract: CONTEXT: B vitamins and factors related to 1-carbon metabolism help to maintain DNA integrity and regulate gene expression and may affect cancer risk. OBJECTIVE: To investigate if 1-carbon metabolism factors are associated with onset of lung cancer. DESIGN, SETTING, AND PARTICIPANTS: The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 519,978 participants from 10 countries between 1992 and 2000, of whom 385,747 donated blood. By 2006, 899 lung cancer cases were identified and 1770 control participants were individually matched by country, sex, date of birth, and date of blood collection. Serum levels were measured for 6 factors of 1-carbon metabolism and cotinine. MAIN OUTCOME MEASURE: Odds ratios (ORs) of lung cancer by serum levels of 4 B vitamins (B(2), B(6), folate [B(9)], and B(12)), methionine, and homocysteine. RESULTS: Within the entire EPIC cohort, the age-standardized incidence rates of lung cancer (standardized to the world population, aged 35-79 years) were 6.6, 44.9, and 156.1 per 100,000 person-years among never, former, and current smokers for men, respectively. The corresponding incidence rates for women were 7.1, 23.9, and 100.9 per 100,000 person-years, respectively. After accounting for smoking, a lower risk for lung cancer was seen for elevated serum levels of B(6) (fourth vs first quartile OR, 0.44; 95% confidence interval [CI], 0.33-0.60; P for trend <.000001), as well as for serum methionine (fourth vs first quartile OR, 0.52; 95% CI, 0.39-0.69; P for trend <.000001). Similar and consistent decreases in risk were observed in never, former, and current smokers, indicating that results were not due to confounding by smoking. The magnitude of risk was also constant with increasing length of follow-up, indicating that the associations were not explained by preclinical disease. A lower risk was also seen for serum folate (fourth vs first quartile OR, 0.68; 95% CI, 0.51-0.90; P for trend = .001), although this was apparent only for former and current smokers. When participants were classified by median levels of serum methionine and B(6), having above-median levels of both was associated with a lower lung cancer risk overall (OR, 0.41; 95% CI, 0.31-0.54), as well as separately among never (OR, 0.36; 95% CI, 0.18-0.72), former (OR, 0.51; 95% CI, 0.34-0.76), and current smokers (OR, 0.42; 95% CI, 0.27-0.65). CONCLUSION: Serum levels of vitamin B(6) and methionine were inversely associated with risk of lung cancer.

Effects of high-dose B vitamin complex with vitamin C and minerals on subjective mood and performance in healthy males.

Abstract: Rationale A significant proportion of the general population report supplementing their diet with one or more vitamins or minerals, with common reasons for doing so being to combat stress and fatigue and to improve mental functioning. Few studies have assessed the relationship between supplementation with vitamins/minerals and psychological functioning in healthy cohorts of non-elderly adults.

Enhanced Carbonyl Stress in a Subpopulation of Schizophrenia

Abstract: Context: Various factors are involved in the pathogenesis of schizophrenia. Accumulation of advanced glycation end products, including pentosidine, results from carbonyl stress, a state featuring an increase in reactive carbonyl compounds (RCOs) and their attendant protein modifications. Vitamin B6 is known to detoxify RCOs, including advanced glycation end products. Glyoxalase I (GLO1) is one of the enzymes required for the cellular detoxification of RCOs. Objectives: To examine whether plasma levels of pentosidine and serum vitamin B6 are altered in patients with schizophrenia and to evaluate the functionality ofGLO1 variations linked to concomitant carbonyl stress. Design: An observational biochemical and genetic analysis study. Setting: Multiple centers in Japan. Participants: One hundred six individuals (45 schizophrenic patients and 61 control subjects) were recruited for biochemical measurements. Deep resequencing ofGLO1 derived from peripheral blood or postmortem brain tissue was performed in 1761 patients with schizophrenia and 1921 control subjects. Main Outcome Measures: Pentosidine and vitamin B6 concentrations were determined by high-performance liquid chromatographic assay. Protein expression and enzymatic activity were quantified in red blood cells and lymphoblastoid cells using Western blot and spectrophotometric techniques. Results: We found that a subpopulation of individuals with schizophrenia exhibit high plasma pentosidine and low serum pyridoxal (vitamin B6) levels. We also detected genetic and functional alterations inGLO1. Marked reductions in enzymatic activity were associated with pentosidine accumulation and vitamin B6 depletion, except in some healthy subjects. Most patients with schizophrenia who carried the genetic defects exhibited high pentosidine and low vitamin B6 levels in contrast with control subjects with the genetic defects, suggesting the existence of compensatory mechanisms. Conclusions: Our findings suggest that GLO1 deficits and carbonyl stress are linked to the development of a certain subtype of schizophrenia. Elevated plasma pentosidine and concomitant low vitamin B6 levels could be the most cogent and easily measurable biomarkers in schizophrenia and should be helpful for classifying heterogeneous types of schizophrenia on the basis of their biological causes.

Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis

Abstract: To better understand the compositional and structural dynamics of the human spliceosome during its activation, we set out to isolate spliceosomal complexes formed after precatalytic B but prior to catalytically active C complexes. By shortening the polypyrimidine tract of the PM5 pre-mRNA, which lacks a 3′ splice site and 3′ exon, we stalled spliceosome assembly at the activation stage. We subsequently affinity purified human Bact complexes under the same conditions previously used to isolate B and C complexes, and analyzed their protein composition by mass spectrometry. A comparison of the protein composition of these complexes allowed a fine dissection of compositional changes during the B to Bact and Bact to C transitions, and comparisons with the Saccharomyces cerevisiae Bact complex revealed that the compositional dynamics of the spliceosome during activation are largely conserved between lower and higher eukaryotes. Human SF3b155 and CDC5L were shown to be phosphorylated specifically during the B to Bact and Bact to C transition, respectively, suggesting these modifications function at these stages of splicing. The two-dimensional structure of the human Bact complex was determined by electron microscopy, and a comparison with the B complex revealed that the morphology of the human spliceosome changes significantly during its activation. The overall architecture of the human and S. cerevisiae Bact complex is similar, suggesting that many of the higher order interactions among spliceosomal components, as well as their dynamics, are also largely conserved.

Dietary intake and depressive symptoms: a systematic review of observational studies.

Abstract: The importance of research into the possible role of dietary intake in depressive symptoms is emphasized by the fact that diet is modifiable. We systematically reviewed observational studies investigating the association between dietary intake and depressive symptoms published in English as of December 2008. Using the PubMed database, 34 publications (23 cross-sectional, 10 prospective cohort, and 1 case-control studies) were identified. The number of subjects (n=80–27 111), age of subjects (15–97 years), dietary assessment method (dietary record, diet history interview, and validated and non-validated dietary questionnaire), depressive symptom assessment (discharge diagnosis, established scale, and self-reported information) varied among studies. Dietary variables most frequently investigated included long chain n-3 PUFA, fish, folate, and other B vitamins. Most studies found no association between dietary variables and depressive symptoms. However, most studies included at least one important methodological limitation, such as no inference for causality, unreliable or rough assessment of diet or depressive symptoms, inadequate treatment of potential confounding factors, and ignorance of the possible mediating or confounding influence of other dietary variables. Further evidence from well-designed observational studies is required to confirm or refute the association between dietary intake and depressive symptoms in free-living settings.

Circulating Folate, Vitamin B12, Homocysteine, Vitamin B12 Transport Proteins, and Risk of Prostate Cancer: a Case-Control Study, Systematic Review, and Meta-analysis

Abstract: Background: Disturbed folate metabolism is associated with an increased risk of some cancers. Our objective was to determine whether blood levels of folate, vitamin B12, and related metabolites were associated with prostate cancer risk. Methods: Matched case-control study nested within the U.K. population–based Prostate testing for cancer and Treatment (ProtecT) study of prostate-specific antigen–detected prostate cancer in men ages 50 to 69 years. Plasma concentrations of folate, B12 (cobalamin), holo-haptocorrin, holo-transcobalamin total transcobalamin, and total homocysteine (tHcy) were measured in 1,461 cases and 1,507 controls. ProtecT study estimates for associations of folate, B12, and tHcy with prostate cancer risk were included in a meta-analysis, based on a systematic review. Results: In the ProtecT study, increased B12 and holo-haptocorrin concentrations showed positive associations with prostate cancer risk [highest versus lowest quartile of B12 odds ratio (OR) = 1.17 (95% confidence interval, 0.95-1.43); Ptrend = 0.06; highest versus lowest quartile of holo-haptocorrin OR = 1.27 (1.04-1.56); Ptrend = 0.01]; folate, holo-transcobalamin, and tHcy were not associated with prostate cancer risk. In the meta-analysis, circulating B12 levels were associated with an increased prostate cancer risk [pooled OR = 1.10 (1.01-1.19) per 100 pmol/L increase in B12; P = 0.002]; the pooled OR for the association of folate with prostate cancer was positive [OR = 1.11 (0.96-1.28) per 10 nmol/L; P = 0.2) and conventionally statistically significant if ProtecT (the only case-control study) was excluded [OR = 1.18 (1.00-1.40) per 10 nmol/L; P = 0.02]. Conclusion: Vitamin B12 and (in cohort studies) folate were associated with increased prostate cancer risk. Impact: Given current controversies over mandatory fortification, further research is needed to determine whether these are causal associations. Cancer Epidemiol Biomarkers Prev; 19(6); 1632–42. ©2010 AACR.

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis

Abstract: Summary Background Narrowband ultraviolet B (NB-UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. Objectives To examine whether NB-UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB-UVB on antimicrobial peptide and cytokine expression in the skin. Methods Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB-UVB exposures on the whole body, given three times a week. Serum calcidiol (25-hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real-time quantitative polymerase chain reaction. Results At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L−1). NB-UVB treatment significantly increased (P < 0·001) serum calcidiol. The increase was 59·9 nmol L−1 (95% confidence interval, CI 53·5–66·9) in psoriasis, 68·2 nmol L−1 (95% CI 55·4–80·1) in AD and 90·7 nmol L−1 (95% CI 63·8–123·4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0·001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human β-defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB-UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB-UVB caused a marked but nonsignificant decrease of interleukin (IL)-1β and IL-17 in psoriasis lesions. Conclusions The present study shows that in addition to a significant improvement of psoriasis and AD, NB-UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.