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Showing papers on "B vitamins published in 2009"


Journal ArticleDOI
TL;DR: Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin, however, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

477 citations


Journal ArticleDOI
TL;DR: The potato is a carbohydrate-rich, energy-providing food with little fat, and many compounds in potatoes contribute to antioxidant activity and interest in cultivars with pigmented flesh is growing.
Abstract: The potato (Solanum tuberosum L.) tuber follows only rice and wheat in world importance as a food crop for human consumption. Cultivated potatoes have spread from the Andes of South America where they originated to 160 countries around the world. Consumption of fresh potatoes has declined while processed products have increased in popularity. As the potato becomes a staple in the diets of an increasing number of humans, small differences in potato nutritional composition will have major impacts on population health. The potato is a carbohydrate-rich, energy-providing food with little fat. Potato protein content is fairly low but has an excellent biological value of 90-100. Potatoes are particularly high in vitamin C and are a good source of several B vitamins and potassium. The skins provide substantial dietary fiber. Many compounds in potatoes contribute to antioxidant activity and interest in cultivars with pigmented flesh is growing. This review will examine the nutrient and bioactive compounds in potatoes and their impact on human health.

471 citations


Journal ArticleDOI
18 Nov 2009-JAMA
TL;DR: Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic Acid fortification of foods.
Abstract: Context Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk. Objective To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials. Design, Setting, and Participants Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007. Interventions Oral treatment with folic acid (0.8 mg/d) plus vitamin B 12 (0.4 mg/d) and vitamin B 6 (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B 12 (0.4 mg/d) (n = 1703); vitamin B 6 alone (40 mg/d) (n = 1705); or placebo (n = 1721). Main Outcome Measures Cancer incidence, cancer mortality, and all-cause mortality. Results During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B 12 vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B 12 vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B 12 vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B 12 . Vitamin B 6 treatment was not associated with any significant effects. Conclusion Treatment with folic acid plus vitamin B 12 was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods. Trial Registration clinicaltrials.gov Identifier: NCT00671346

377 citations


Journal ArticleDOI
TL;DR: The neurotoxic effects of homocysteine may also play a role in the neurologic and psychiatric disturbances that are associated with folate and vitamin B12 deficiency.
Abstract: Folate and vitamin B12 are required both in the methylation of homocysteine to methionine and in the synthesis of S-adenosylmethionine. S-ad-enosylmethionine is involved in numerous methylation reactions involving proteins, phospholipids, DNA, and neurotransmitter metabolism. Both folate and vitamin B12 deficiency may cause similar neurologic and psychiatric disturbances including depression, dementia, and a demyelinating myelopathy. A current theory proposes that a defect in methylation processes is central to the biochemical basis of the neuropsychiatry of these vitamin deficiencies. Folate deficiency may specifically affect central monoamine metabolism and aggravate depressive disorders. In addition, the neurotoxic effects of homocysteine may also play a role in the neurologic and psychiatric disturbances that are associated with folate and vitamin B12 deficiency.

330 citations


Journal ArticleDOI
13 Aug 2009-Blood
TL;DR: It is hypothesized that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma.

302 citations


Journal ArticleDOI
TL;DR: The method enables quantification of endogenous plasma concentrations of 16 analytes related to B-vitamin status and inflammation, and may prove useful in large-scale epidemiological studies.
Abstract: Vitamins B2 and B6 serve as cofactors in enzymatic reactions involved in tryptophan and homocysteine metabolism. Plasma concentrations of these vitamins and amino acids are related to smoking and inflammation, and correlate with other markers of immune activation. Large-scale studies of these relations have been hampered by lack of suitable analytical methods. The assay described includes riboflavin, five vitamin B6 forms (pyridoxal 5'-phosphate, pyridoxal, 4-pyridoxic acid, pyridoxine and pyridoxamine), tryptophan and six tryptophan metabolites (kynurenine, kynurenic acid, anthranilic acid, 3-hydroxykynurenine, xanthurenic acid and 3-hydroxyanthranilic acid), cystathionine, neopterin and cotinine. Trichloroacetic acid containing 13 isotope-labelled internal standards was added to 60 microL of plasma, the mixture was centrifuged, and the resulting supernatant used for analysis. The analytes were separated within 5 min on a stable-bond C8 column by a gradient-type mobile phase containing acetonitrile, heptafluorobutyric acid and high concentration (650 mmol/L) of acetic acid, and detected using electrospray ionization tandem mass spectrometry (ESI-MS/MS). The mobile phase ensured sufficient separation and high ionization efficiency of all analytes. Recoveries were 75-123% and within-day and between-day coefficients of variance (CVs) were 2.5-9.5% and 5.4-16.9%, respectively. Limits of detection ranged from 0.05 to 7 nmol/L. The method enables quantification of endogenous plasma concentrations of 16 analytes related to B-vitamin status and inflammation, and may prove useful in large-scale epidemiological studies.

287 citations


Journal ArticleDOI
TL;DR: Examination of the role of nutrition in perinatal depression finds a positive association between low n-3 levels and a higher incidence of maternal depression.
Abstract: The purpose of this review is to examine the role of nutrition in perinatal depression. Perinatal (maternal) depression refers to major and minor episodes during pregnancy (termed antenatal) and/or within the first 12 months after delivery (termed postpartum or postnatal). Prevalence of antenatal depression can be as high as 20%, while approximately 12% to 16% of women experience postpartum depression. These are probably conservative estimates, as cases of maternal depression are underreported or underdiagnosed. Risk factors for depression include genetic predisposition and environmental factors, as well as a number of social, psychological, and biological factors. One biological factor given increasing consideration is inadequate nutrition. Credible links between nutrient deficiency and mood have been reported for folate, vitamin B-12, calcium, iron, selenium, zinc, and n-3 fatty acids. For maternal depression, the nutrient that has received the most attention from nutrition researchers has been the n-3 essential fatty acids. Numerous studies, such as randomized controlled trials, cohort studies, and ecological studies, have found a positive association between low n-3 levels and a higher incidence of maternal depression. In addition, nutrient inadequacies in pregnant women who consume a typical western diet might be much more common than researchers and clinicians realize. A number of studies have reported inadequate intakes of n-3, folate, B vitamins, iron, and calcium in pregnant women. Depletion of nutrient reserves throughout pregnancy can increase a woman's risk for maternal depression.

284 citations


Journal ArticleDOI
TL;DR: It is suggested that women have vitamin B12 levels of >300 ng/L (221 pmol/L) before becoming pregnant and improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.
Abstract: OBJECTIVE. Folic acid fortification has reduced neural tube defect prevalence by 50% to 70%. It is unlikely that fortification levels will be increased to reduce neural tube defect prevalence further. Therefore, it is important to identify other modifiable risk factors. Vitamin B12 is metabolically related to folate; moreover, previous studies have found low B12 status in mothers of children affected by neural tube defect. Our objective was to quantify the effect of low B12 status on neural tube defect risk in a high-prevalence, unfortified population. METHODS. We assessed pregnancy vitamin B12 status concentrations in blood samples taken at an average of 15 weeks’ gestation from 3 independent nested case-control groups of Irish women within population-based cohorts, at a time when vitamin supplementation or food fortification was rare. Group 1 blood samples were from 95 women during a neural tube defect–affected pregnancy and 265 control subjects. Group 2 included blood samples from 107 women who had a previous neural tube defect birth but whose current pregnancy was not affected and 414 control subjects. Group 3 samples were from 76 women during an affected pregnancy and 222 control subjects. RESULTS. Mothers of children affected by neural tube defect had significantly lower B12 status. In all 3 groups those in the lowest B12 quartiles, compared with the highest, had between two and threefold higher adjusted odds ratios for being the mother of a child affected by neural tube defect. Pregnancy blood B12 concentrations of CONCLUSIONS. Deficient or inadequate maternal vitamin B12 status is associated with a significantly increased risk for neural tube defects. We suggest that women have vitamin B12 levels of >300 ng/L (221 pmol/L) before becoming pregnant. Improving B12 status beyond this level may afford a further reduction in risk, but this is uncertain.

262 citations


Journal ArticleDOI
TL;DR: The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity, including the primary prevention of atherothrombotic disease in individuals at low or intermediate risk, or those with severe hyperhomocysteinemia.
Abstract: The unique biochemical profile of homocysteine is characterized by chemical reactivity supporting a wide range of molecular effects and by a tendency to promote oxidant stress-induced cellular toxicity. Numerous epidemiological reports have established hyperhomocysteinemia as an independent risk factor for cardiovascular disease, cerebrovascular disease, dementia-type disorders, and osteoporosis-associated fractures. Although combined folic acid and B-vitamin therapy substantially reduces homocysteine levels, results from randomized placebo-controlled clinical trials testing the effect of vitamin therapy on outcome in these diseases have generally fallen short of expectations. These results have led some to abandon homocysteine monitoring in the management of patients with cardiovascular or cognitive disorders. These trials, however, have generally included patients with only mildly elevated homocysteine levels and have not addressed several clinical scenarios in which homocysteine reduction may be effective, including the primary prevention of atherothrombotic disease in individuals at low or intermediate risk, or those with severe hyperhomocysteinemia.

259 citations


Journal ArticleDOI
TL;DR: The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis and the ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of Vitamin B12.
Abstract: The B vitamins are components of one-carbon metabolism (OCM) that contribute to DNA synthesis and methylation. Homocysteine, a by-product of OCM, has been associated with coronary heart disease, stroke and neurological disease. To investigate genetic factors that affect circulating vitamin B6, vitamin B12, folate and homocysteine, a genome-wide association analysis was conducted in the InCHIANTI (N = 1175), SardiNIA (N = 1115), and BLSA (N = 640) studies. The top loci were replicated in an independent sample of 687 participants in the Progetto Nutrizione study. Polymorphisms in the ALPL gene (rs4654748, p = 8.30 × 10−18) were associated with vitamin B6 and FUT2 (rs6022662, p = 2.83 × 10−20) with vitamin B12 serum levels. The association of MTHFR, a gene consistently associated with homocysteine, was confirmed in this meta-analysis. The ALPL gene likely influences the catabolism of vitamin B6 while FUT2 interferes with absorption of vitamin B12. These findings highlight mechanisms that affect vitamin B6, vitamin B12 and homocysteine serum levels.

255 citations


Journal ArticleDOI
12 Mar 2009-Nature
TL;DR: The structural data imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket, which makes the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds.
Abstract: The biosynthesis of several protein cofactors is subject to feedback regulation by riboswitches. Flavin mononucleotide (FMN)-specific riboswitches, also known as RFN elements, direct expression of bacterial genes involved in the biosynthesis and transport of riboflavin (vitamin B(2)) and related compounds. Here we present the crystal structures of the Fusobacterium nucleatum riboswitch bound to FMN, riboflavin and antibiotic roseoflavin. The FMN riboswitch structure, centred on an FMN-bound six-stem junction, does not fold by collinear stacking of adjacent helices, typical for folding of large RNAs. Rather, it adopts a butterfly-like scaffold, stapled together by opposingly directed but nearly identically folded peripheral domains. FMN is positioned asymmetrically within the junctional site and is specifically bound to RNA through interactions with the isoalloxazine ring chromophore and direct and Mg(2+)-mediated contacts with the phosphate moiety. Our structural data, complemented by binding and footprinting experiments, imply a largely pre-folded tertiary RNA architecture and FMN recognition mediated by conformational transitions within the junctional binding pocket. The inherent plasticity of the FMN-binding pocket and the availability of large openings make the riboswitch an attractive target for structure-based design of FMN-like antimicrobial compounds. Our studies also explain the effects of spontaneous and antibiotic-induced deregulatory mutations and provided molecular insights into FMN-based control of gene expression in normal and riboflavin-overproducing bacterial strains.

Journal ArticleDOI
TL;DR: The evidence that single clinically defined cardiovascular risk factors are significantly associated with incident AD is inconsistent at best.
Abstract: Objective The purpose of this study was to conduct a systematic review of the literature of cardiovascular factors pertaining to incident Alzheimer disease (AD). Methods A systematic literature review was conducted of all studies of cardiovascular risk factors for incident AD listed in PubMed in English from 2000 to 2007. Risk factors included hypertension, diabetes, exercise, alcohol intake, smoking, B complex vitamins, homocysteine, stroke, atrial fibrillation, apolipoprotein E (APOE), lipids, and diet. Inclusion criteria consisted of diagnoses of incident AD and longitudinal studies with cohorts of 500 or more. Results Individual clinically defined risk factors such as hypertension and diabetes were not significantly associated with increased risk for AD. The strength of the association for hypertension could be considerably strengthened by changing criteria such as midlife measurements or using higher cutoffs for systolic blood pressure. APOE epsilon4 was the most consistent risk factor. Interactions between risk factors modify risk particularly for hypertension and diabetes. Interactions modifying risk were also found for exercise and physical function, APOE epsilon4, diabetes, and cholesterol. Conclusions In this review, the evidence that single clinically defined cardiovascular risk factors are significantly associated with incident AD is inconsistent at best. The strength of the association of cardiovascular risk factors and AD can be influenced greatly by changing the parameters of measurement of risk factors and by identifying interactions between the factors.

Journal ArticleDOI
TL;DR: Maternal vitamin B12 deficiency is associated with increased adiposity and, in turn, with insulin resistance and GDM, and may be an important factor underlying the high risk of ‘diabesity’ in south Asian Indians.
Abstract: Aims/hypothesis This study was designed to test the hypothesis that low plasma vitamin B12 concentrations combined with high folate concentrations in pregnancy are associated with a higher incidence of gestational diabetes (GDM) and later diabetes.

Journal ArticleDOI
TL;DR: In this paper, the release of riboflavin from soy protein hydrogels of filamentous or particulate microstructure was investigated under gastric and intestinal conditions in the presence or absence of digestive proteases.

Journal ArticleDOI
TL;DR: The copper complexes shown to possess superoxide dismutase (SOD) and antimicrobial activities were well correlated with the theoretical parameters as calculated by density functional theory at the B3LYP/LANL2DZ level of theory.

Journal ArticleDOI
TL;DR: High folate status is associated with impaired activity of the 2 vitamin B-12-dependent enzymes, methionine synthase and MMA-coenzyme A mutase, which implies that, in vitamin Folic acid intake adversely influences the natural history of vitamin B -12 deficiency.

Journal ArticleDOI
TL;DR: Thiamine supplements at high dose may provide improved therapy for early-stage diabetic nephropathy and produce a regression of UAE in type 2 diabetic patients with microalbuminuria in this pilot study.
Abstract: Aims/hypothesis High-dose supplements of thiamine prevent the development of microalbuminuria in experimental diabetes. The aim of this pilot study was to assess whether oral supplements of thiamine could reverse microalbuminuria in patients with type 2 diabetes.

Journal ArticleDOI
TL;DR: This work identifies LMBRD1 as the gene underlying the cblF defect of cobalamin metabolism and suggests that LMBD1 is a lysosomal membrane exporter for cobalamina.
Abstract: Vitamin B(12) (cobalamin) is essential in animals for metabolism of branched chain amino acids and odd chain fatty acids, and for remethylation of homocysteine to methionine. In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes, thus hindering its conversion to cofactors. Using homozygosity mapping in 12 unrelated cblF individuals and microcell-mediated chromosome transfer, we identified a candidate gene on chromosome 6q13, LMBRD1, encoding LMBD1, a lysosomal membrane protein with homology to lipocalin membrane receptor LIMR. We identified five different frameshift mutations in LMBRD1 resulting in loss of LMBD1 function, with 18 of the 24 disease chromosomes carrying the same mutation embedded in a common 1.34-Mb haplotype. Transfection of fibroblasts of individuals with cblF with wild-type LMBD1 rescued cobalamin coenzyme synthesis and function. This work identifies LMBRD1 as the gene underlying the cblF defect of cobalamin metabolism and suggests that LMBD1 is a lysosomal membrane exporter for cobalamin.

Journal ArticleDOI
TL;DR: Animal and human studies suggest that vitamin B6 deficiency affects both humoral and cell-mediated immune responses and should attempt to establish safe intake levels that optimize immune response.
Abstract: Animal and human studies suggest that vitamin B6 deficiency affects both humoral and cell-mediated immune responses. Lymphocyte differentiation and maturation are altered by deficiency, delayed-type hypersensitivity responses are reduced, and antibody production may be indirectly impaired. Although repletion of the vitamin restores these functions, megadoses do not produce benefits beyond those observed with moderate supplementation. Additional human studies indicate that vitamin B6 status may influence tumor growth and disease processes. Deficiency of the vitamin has been associated with immunological changes observed in the elderly, persons infected with human immunodeficiency virus (HIV), and those with uremia or rheumatoid arthritis. Future research efforts should focus on establishing the mechanism underlying the effects of vitamin B6 on immunity and should attempt to establish safe intake levels that optimize immune response.

Journal ArticleDOI
TL;DR: Two patients are reported whose CSF showed the marker of folinic acid–responsive seizures, but who responded clinically to pyridoxine, and genetic and biochemical testing was performed on these patients, and seven others, to determine the relation between these two disorders.
Abstract: Objective Folinic acid-responsive seizures and pyridoxine-dependent epilepsy are two treatable causes of neonatal epileptic encephalopathy. The former is diagnosed by characteristic peaks on cerebrospinal fluid (CSF) monoamine metabolite analysis; its genetic basis has remained elusive. The latter is due to alpha-aminoadipic semialdehyde (alpha-AASA) dehydrogenase deficiency, associated with pathogenic mutations in the ALDH7A1 (antiquitin) gene. We report two patients whose CSF showed the marker of folinic acid-responsive seizures, but who responded clinically to pyridoxine. We performed genetic and biochemical testing of samples from these patients, and seven others, to determine the relation between these two disorders. Methods CSF samples were analyzed for the presence of alpha-AASA and pipecolic acid. DNA sequencing of the ALDH7A1 gene was performed. Results Both patients reported here had increased CSF alpha-AASA, CSF pipecolic acid, and known or likely pathogenic mutations in the ALDH7A1 gene, consistent with alpha-AASA dehydrogenase deficiency. Analysis of CSF samples from seven other anonymous individuals diagnosed with folinic acid-responsive seizures showed similar results. Interpretation These results demonstrate that folinic acid-responsive seizures are due to alpha-AASA dehydrogenase deficiency and mutations in the ALDH7A1 gene. Thus, folinic acid-responsive seizures are identical to the major form of pyridoxine-dependent epilepsy. We recommend consideration of treatment with both pyridoxine and folinic acid for patients with alpha-AASA dehydrogenase deficiency, and consideration of a lysine restricted diet. The evaluation of patients with neonatal epileptic encephalopathy, as well as those with later-onset seizures, should include a measurement of alpha-AASA in urine to identify this likely underdiagnosed and treatable disorder.

Journal ArticleDOI
TL;DR: Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density.
Abstract: Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, recent research has clarified the importance of several additional nutrients and food constituents. Further, results of calcium and vitamin D supplementation trials have been inconsistent, suggesting that reliance on this intervention may be inadequate. In addition to dairy, fruit and vegetable intake has emerged as an important modifiable protective factor for bone health. Several nutrients, including magnesium, potassium, vitamin C, vitamin K, several B vitamins, and carotenoids, have been shown to be more important than previously realized. Rather than having a negative effect on bone, protein intake appears to benefit bone status, particularly in older adults. Regular intake of cola beverages shows negative effects and moderate alcohol intake shows positive effects on bone, particularly in older women. Current research on diet and bone status supports encouragement of balanced diets with plenty of fruit and vegetables, adequate dairy and other protein foods, and limitation of foods with low nutrient density.

Journal ArticleDOI
TL;DR: Dietary intake of dairy products and fish are significant contributors to plasma vitamin B-12 and may improve plasma vitaminB-12 status and guidelines for improving vitamin B -12 status should take this into consideration.

Journal ArticleDOI
TL;DR: This review looks at how vitamin overproduction strategies have been developed, some of which have successfully been tested in animal models and could be relatively easily adapted by the food industry to develop novel vitamin-enhanced functional foods with enhanced consumer appeal.

Journal ArticleDOI
TL;DR: Race, dietary folic acid, and plasma B6 showed associations with global methylation that differed between the right and the left bowel, and no significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes.
Abstract: Background: Global loss of methylated cytosines in DNA, thought to predispose to chromosomal instability and aneuploidy, has been associated with an increased risk of colorectal neoplasia. Little is known about the relationships between global hypomethylation and lifestyle, demographics, dietary measures, and genetic factors. Methods: Our data were collected as part of a randomized clinical trial testing the efficacy of aspirin and folic acid for the prevention of colorectal adenomas. At a surveillance colonoscopy ∼3 years after the qualifying exam, we obtained two biopsies of the normal-appearing mucosa from the right colon and two biopsies from the left colon. Specimens were assayed for global hypomethylation using a pyrosequencing assay for LINE-1 (long interspersed nucleotide elements) repeats. Results: The analysis included data from 388 subjects. There was relatively little variability in LINE methylation overall. Mean LINE-1 methylation levels in normal mucosa from the right bowel were significantly lower than those on the left side ( P < 0.0001). No significant associations were found between LINE-1 methylation and folate treatment, age, sex, body mass index, smoking status, alcohol use, dietary intake, or circulating levels of B vitamins, homocysteine, or selected genotypes. Race, dietary folic acid, and plasma B6 showed associations with global methylation that differed between the right and the left bowel. The effect of folic acid on risk of adenomas did not differ according to extent of LINE-1 methylation, and we found no association between LINE-1 methylation and risk of adenomas. Conclusions: LINE-1 methylation is not influenced by folic acid supplementation but differs by colon subsite. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1041–9)

Journal ArticleDOI
TL;DR: These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD.
Abstract: Background Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of therapy to lower homocysteine levels in AMD are lacking. Our objective was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride (vitamin B 6 ), and cyanocobalamin (vitamin B 12 ) therapy. Methods We conducted a randomized, double-blind, placebo-controlled trial including 5442 female health care professionals 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. A total of 5205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), pyridoxine hydrochloride (50 mg/d), and cyanocobalamin (1 mg/d) or placebo. Our main outcome measures included total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. Results After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47-0.93 [ P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [ P = .03]). Conclusions These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD. Trial Registration clinicaltrials.gov IdentifierNCT00000161

Journal ArticleDOI
TL;DR: Based on pathways of cell dysfunction and death, several approaches toward neuroprotection are being investigated that show promise toward clinical translation, including minimizing oxidative stress by avoiding unnecessary hyperoxia, promoting aerobic energy metabolism by repletion of NAD(+) and by providing alternative oxidative fuels.

Journal ArticleDOI
TL;DR: The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.
Abstract: In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

Journal ArticleDOI
TL;DR: AGE+S is associated with a favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis.

Journal ArticleDOI
TL;DR: Thiamine deficiency represents a model system with which to explore pathological mechanisms inherent in such maladies, with the potential to yield new insights into their possible treatment and prevention and their role in selective vulnerability in TD.
Abstract: Thiamine deficiency (TD) is a well-established model of Wernicke's encephalopathy. Although the neurologic dysfunction and brain damage resulting from the biochemical consequences of TD is well characterized, the mechanism(s) that lead to the selective histological lesions characteristic of this disorder remain a mystery. Over the course of many years, various structural and functional changes have been identified that could lead to cell death in this disorder. However, despite a concerted effort to explain the consequences of TD in terms of these changes, our understanding of the pathophysiology of this disorder remains unclear. This review will focus on three of these processes, i.e. oxidative stress, glutamate-mediated excitotoxicity and inflammation and their role in selective vulnerability in TD. Since TD inhibits oxidative metabolism, a feature of many neurodegenerative disease states, it represents a model system with which to explore pathological mechanisms inherent in such maladies, with the potential to yield new insights into their possible treatment and prevention.

Journal ArticleDOI
TL;DR: Data are presented to support the hypothesis that quinic acid is not responsible for any efficacy, but rather thatQuinic acid nutritionally supports the synthesis of tryptophan and nicotinamide in the gastrointestinal (GI) tract, and that this in turn leads to DNA repair enhancement and NF‐kB inhibition via increased Nicotinamide and tryPTophan production.
Abstract: For over 50 years, hippuric/quinic acids were believed to have no biological efficacy. Here data are presented to support the hypothesis that quinic acid is not responsible for any efficacy, but rather that quinic acid nutritionally supports the synthesis of tryptophan and nicotinamide in the gastrointestinal (GI) tract, and that this in turn leads to DNA repair enhancement and NF-kB inhibition via increased nicotinamide and tryptophan production.Moreover, it is shown that quinic acid is a normal constituent of our diet, capable of conversion to tryptophan and nicotinamide via the GI tract microflora, thus providing an in situ physiological source of these essential metabolic ingredients to humans. The concentrations of quinic and hippuric acids in the diet were dependent on each other when analysed in urine, as was evidenced by a significant linear regression analysis that included unsupplemented control subjects (n = 45, p < 0.001). Thus, these ingredients were identified as major dietary components, and not simply originating from environmental pollution as previously had been thought.