scholarly journals C1 metabolism and CVD outcomes in older adults

2011 ◽  
Vol 71 (2) ◽  
pp. 213-221 ◽  
Author(s):  
Helene McNulty ◽  
J. J. Strain ◽  
Kristina Pentieva ◽  
Mary Ward
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Epidemiological Studies ◽  
Plasma Homocysteine ◽  
Convincing Evidence ◽  
B Vitamins ◽  
Current Evidence ◽  
High Dose ◽  
C1 Metabolism ◽  
Meta Analyses

CVD is the most common cause of death in people over 65 years. This review considers the latest evidence for a potential protective effect of C1 donors (folate and the metabolically related B-vitamins) in CVD. Such an effect may or may not be mediated via the role of these nutrients in maintaining plasma homocysteine concentrations within a desirable range. Despite predictions from epidemiological studies that lowering plasma homocysteine would reduce cardiovascular risk, several secondary prevention trials in at-risk patients published since 2004 have failed to demonstrate a benefit of homocysteine-lowering therapy with B-vitamins on CVD events generally. All these trials were performed in CVD patients with advanced disease; thus current evidence suggests that intervention with high-dose folic acid is of no benefit in preventing another event, at least in the case of heart disease. The evidence at this time, however, is stronger for stroke, with meta-analyses of randomised trials showing that folic acid reduces the risk of stroke, particularly in people with no history of stroke. Genetic studies provide convincing evidence to support a causal relationship between sub-optimal B-vitamin status and CVD. People homozygous for the common C677T variant in the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), typically have a 14–21% higher risk of CVD. Apart from folate, riboflavin is required as a co-factor for MTHFR. New evidence shows that riboflavin intervention results in marked lowering of blood pressure, specifically in patients with the MTHFR 677TT genotype. This novel gene–nutrient interaction may provide insights as to the mechanism that links C1 metabolism with CVD outcomes.

Variations in the Lipid Profile of Patients with Chronic Renal Failure, Treated with Folic Acid

2003 ◽  
Vol 73 (3) ◽  
pp. 215-220 ◽  
Author(s):  
de Gómez Dumm ◽  
Giammona ◽  
Touceda
Keyword(s):  
Renal Failure ◽  
Folic Acid ◽  
Chronic Renal Failure ◽  
Density Lipoprotein ◽  
Plasma Homocysteine ◽  
Lipid Profiles ◽  
Erythrocyte Membranes ◽  
Favorable Effect ◽  
High Dose ◽  
Acid Therapy

Dyslipidemia and increases in plasma homocysteine usually occur at end-stage renal disease; both are recognized as risk factors for atherosclerosis. Folate administration reduces homocysteine concentration. In this study we determined the effect of a high dose of folic acid (40 mg intravenous injection three times a week) on plasma and red blood cell lipid profiles in twelve chronic renal failure patients on regular hemodialysis. Fasting blood samples were taken at the beginning of the study (baseline) and after 21, 42, and 64 days of treatment. Folic acid supplementation decreased plasma homocysteine. Plasma triglyceride levels decreased whereas polyunsaturated fatty acid values increased after 21 days; then they returned to baseline levels at the end of treatment. Total cholesterol and low-density lipoprotein (LDL) cholesterol were higher than those of the baseline during all the study, whereas high-density lipoprotein (HDL) cholesterol was reduced. In erythrocyte membranes, folic acid therapy enhanced cholesterol/phospholipid ratios and the fluorescence anisotropy of diphenyl-hexatriene. We conclude that large doses of folic acid produce a favorable effect, reducing plasma homocysteine levels and protecting patients from atherosclerosis. However, as this therapy induces significant alterations in both plasma and erythrocyte membrane lipid profiles, plasma lipid values should be controlled throughout the treatment of patients with renal failure.

scholarly journals Polyphenols and Cognition In Humans: An Overview of Current Evidence from Recent Systematic Reviews and Meta-Analyses

2020 ◽  
pp. 1-15
Author(s):  
Daniel Joseph Lamport ◽  
Claire Michelle Williams
Keyword(s):  
Systematic Reviews ◽  
Evidence Base ◽  
Epidemiological Studies ◽  
Cognitive Outcome ◽  
Current Evidence ◽  
Duration Of Treatment ◽  
Current Evidence Base ◽  
Cognitive Benefits ◽  
Meta Analyses ◽  
The Impact

There is increasing interest in the impact of dietary influences on the brain throughout the lifespan, ranging from improving cognitive development in children through to attenuating ageing related cognitive decline and reducing risk of neurodegenerative diseases. Polyphenols, phytochemicals naturally present in a host of fruits, vegetables, tea, cocoa and other foods, have received particular attention in this regard, and there is now a substantial body of evidence from experimental and epidemiological studies examining whether their consumption is associated with cognitive benefits. The purpose of this overview is to synthesise and evaluate the best available evidence from two sources, namely meta-analyses and systematic reviews, in order to give an accurate reflection of the current evidence base for an association between polyphenols and cognitive benefits. Four meta-analyses and thirteen systematic reviews published between 2017–2020 were included, and were categorised according to whether they reviewed specific polyphenol-rich foods and classes or all polyphenols. A requirement for inclusion was assessment of a behavioural cognitive outcome in humans. A clear and consistent theme emerged that whilst there is support for an association between polyphenol consumption and cognitive benefits, this conclusion is tentative, and by no means definitive. Considerable methodological heterogeneity was repeatedly highlighted as problematic such that the current evidence base does not support reliable conclusions relating to efficacy of specific doses, duration of treatment, or sensitivity in specific populations or certain cognitive domains. The complexity of multiple interactions between a range of direct and indirect mechanisms of action is discussed. Further research is required to strengthen the reliability of the evidence base.

Abstract P060: Major Dietary Risk Factors for Chronic Diseases: A Systematic Review of the Current Evidence for Causal Effects and Effect Sizes

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Shahab Khatibzadeh ◽  
Renata Micha ◽  
Ashkan Afshin ◽  
Mayuree Rao ◽  
Mohammad Y Yakoob ◽  
...  
Keyword(s):  
Risk Factors ◽  
Dose Response ◽  
Convincing Evidence ◽  
Dietary Factors ◽  
Causal Effects ◽  
Effect Sizes ◽  
Current Evidence ◽  
Dietary Risk Factors ◽  
Dietary Risk ◽  
Meta Analyses

Background: Diet habits contribute to development of CVD and diabetes. Estimating the impact of diet on these diseases requires identification and quantification of causal effects of dietary factors. Objectives: To assess major dietary risk factors for CVD and diabetes, evaluate current evidence for causal effects, and identify the best unbiased effect estimates on risk. Methods: For multiple dietary risk factors, we evaluated WHO and similar criteria as part of the Global Burden of Diseases (GBD) study to assess probable or convincing evidence for causal effects, including consistency, dose-response, plausibility, and temporality. We performed systematic searches of online databases from 2008 to 2011, including hand-searches of references and author contacts, to identify systematic reviews and meta-analyses of well-designed observational or interventional studies. Meta-analyses were evaluated based on number of studies, design, definition of diet factors and outcomes, sample size, number of events, length of follow-up, statistical methods, evidence of bias, and control for confounders. Meta-analyses with largest numbers of studies and events and least evidence for bias were identified. Effect sizes and uncertainty were quantified per defined units of exposure, including pooling of categorical dose-response estimates using fixed-effects generalized least squares for trend estimation (GLST). Results: We identified 15 dietary risk factors having probable or convincing evidence of causal effects on CVD or diabetes. For 13, data were identified to provide the best pooled unbiased effect size on disease (Table). Conclusions: This systematic evaluation provides the best evidence-based quantitative estimates of the effects of major dietary factors on CVD and diabetes. These findings enable estimation of quantitative impacts on diseases burdens of suboptimal intakes of these factors in specific populations, and also highlight gaps in knowledge related to causality or effect sizes of other dietary factors.

scholarly journals B-vitamins, homocysteine metabolism and CVD

2004 ◽  
Vol 63 (4) ◽  
pp. 597-603 ◽  
Author(s):  
J. J. Strain ◽  
L. Dowey ◽  
M. Ward ◽  
K. Pentieva ◽  
H. McNulty
Keyword(s):  
Methylenetetrahydrofolate Reductase ◽  
Independent Predictor ◽  
Systemic Disease ◽  
Plasma Concentrations ◽  
Nutrient Status ◽  
Mthfr Gene ◽  
Plasma Homocysteine ◽  
B Vitamins ◽  
Vitamin B ◽  
Pathophysiological Mechanism

The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6and riboflavin, that are involved in homocysteine metabolism. Homocysteine is a S-containing amino acid and its plasma concentrations can be raised by various constitutive, genetic and lifestyle factors, by inadequate nutrient status and as a result of systemic disease and various drugs. Hyperhomocysteinaemia is a modest independent predictor of CVD and stroke, but causality and the precise pathophysiological mechanism(s) of homocysteine action remain unproven. The predominant nutritional cause of raised plasma homocysteine in most healthy populations is folate insufficiency. Vitamin B12and, to a lesser extent, vitamin B6are also effective at lowering plasma homocysteine, especially after homocysteine lowering by folic acid in those individuals presenting with raised plasma homocysteine. However, riboflavin supplementation appears to be effective at lowering plasma homocysteine only in those individuals homozygous for the T allele of the C677 T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene. This gene codes for the MTHFR enzyme that produces methyltetrahydrofolate, which, in turn, is a substrate for the remethylation of homocysteine by the vitamin B12-dependent enzyme methionine synthase. Individuals with the MTHFR 677 TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.

scholarly journals Methylenetetrahydrofolate Reductase Deficiency Reduces Brain Microglia in Zebrafish During Embryonic Development and Is Not Corrected by Folic Acid

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 925-925
Author(s):  
Rebecca Simonian ◽  
Emanuela Pannia ◽  
Rola Hammoud ◽  
Xiucheng Cui ◽  
Ruslan Kubant ◽  
...  
Keyword(s):  
Folic Acid ◽  
Embryonic Development ◽  
Methylenetetrahydrofolate Reductase ◽  
Fetal Brain ◽  
Neutral Red ◽  
High Dose ◽  
Head Region ◽  
Zebrafish Model ◽  
Mthfr Deficiency

Abstract Objectives Neuronal development and function is dependent on the interaction between the central nervous system and immune system. Microglia are resident macrophages of the brain critical for regulating neuronal activity during embryonic development. 5-methyltetrahydrofolate (5MTHF), the bioactive folate form, is essential for fetal brain development and immune function. Common variants in methylenetetrahydrofolate reductase (MTHFR), required for conversion of folic acid (FA) to 5-MTHF, limits its production. High dose FA supplementation is recommended but high FA may have the converse effect of reducing MTHFR activity. The objective of this study was to determine the effects of mthfr deficiency and its interaction with FA during embryonic development on microglia in a zebrafish model. Methods The mthfr gene in zebrafish was disrupted using two CRISPR mutagenesis methods. A set of 4 guide RNAs (gRNAs) + cas9 protein or cas9 alone (control) were injected to assay F0 zebrafish, or 2 gRNAs + cas9 mRNA were used to induce a germline mutation. To visualize macrophages at 4 days post fertilization (dpf) in live zebrafish, the transgenic mpeg1: mcherry line was used. In a subset of embryos, FA was added at 0, 50, 75, or 100- μM from 0–4dpf. At 4dpf, live neutral red staining for microglia was performed and the number in the optic tectum was quantified. 5MTHF, s-adenosylmethionine (SAM) and s-adenosylhomocysteine (SAH) were assayed in whole zebrafish at 5dpf. Results In vivo imaging revealed a reduction in macrophage number (∼30%, P < 0.001) in the head region of mthfr disrupted zebrafish, but not in the periphery. mthfr zebrafish also had less microglia compared to controls (15%, P < 0.001). These changes were associated with lower 5MTHF (90%, P < 0.0001) and SAM: SAH (∼50%, P < 0.001) at 5dpf indicative of lower methylation potential. Exposure with FA did not correct the phenotype and at 100µM FA, control zebrafish also showed a decrease in microglia similar to mthfr zebrafish, confirming inhibitory effects of the high FA dose. Conclusions mthfr deficiency reduces microglia in zebrafish but supplementation with FA does not prevent and may exacerbate the negative effects. The 5MTHF form of folate may be a better alternative to FA for brain health in patients with underlying genetic conditions. Funding Sources Supported by CIHR-INMD.

scholarly journals Effect of High Dose Folic Acid Therapy on Hyperhomocysteinemia in Hemodialysis Patients

2000 ◽  
Vol 11 (6) ◽  
pp. 1106-1116 ◽  
Author(s):  
GERE SUNDER-PLASSMANN ◽  
MANUELA FÖDINGER ◽  
HEIDI BUCHMAYER ◽  
MENELAOS PAPAGIANNOPOULOS ◽  
JADWIGA WOJCIK ◽  
...  
Keyword(s):  
Folic Acid ◽  
Treatment Period ◽  
Plasma Levels ◽  
Methylenetetrahydrofolate Reductase ◽  
Plasma Concentrations ◽  
Hemodialysis Patients ◽  
High Dose ◽  
Acid Therapy ◽  
Total Homocysteine

Abstract. Homocysteine is associated with atherosclerosis and enhanced cardiovascular risk. In previous studies, treatment with folic acid up to 15 mg/d failed to correct hyperhomocysteinemia in the majority of end-stage renal disease patients. A dose of 30 or 60 mg of folic acid per day was compared with 15 mg/d in an attempt to normalize hyperhomocysteinemia in 150 hemodialysis patients. In a randomized, double-blind, multicenter study, 144 patients completed the 4-wk treatment period and 121 patients completed the 6-mo follow-up. Total homocysteine plasma levels were reduced by 32.1% (15 mg/d), 29.9% (30 mg/d), or 37.8% (60 mg/d) with no significant differences found between the three treatment groups. Baseline total homocysteine plasma concentration was an independent predictor of the response to folic acid therapy (P= 0.0001), whereas the 5,10-methylenetetrahydrofolate reductase polymorphisms (MTHFR677C → T and 1298A → C) had no influence. Nevertheless, patients with theMTHFR677TT genotype more frequently attained normal total homocysteine plasma levels than patients with the CC or CT genotype (P= 0.025). In response to 60 mg of folic acid per day, TT genotype patients had lower folate plasma levels compared to CC or CT genotype patients (P= 0.016). After completion of the 4-wk treatment period with 30 or 60 mg of folic acid per day, there was a marked rebound of total homocysteine plasma levels at the end of the follow-up in patients with theMTHFR677TT genotype, which even exceeded baseline values in several patients (P= 0.0001). This study clearly demonstrates that doses of 30 or 60 mg of folic acid per day are not more effective than 15 mg/d in reducing hyperhomocysteinemia in regular hemodialysis patients. Patients with theMTHFR677TT genotype are more likely to realize normal total homocysteine plasma levels. Folic acid at 30 or 60 mg/d but not 15 mg/d results in a rebound of total homocysteine plasma concentrations when treatment is stopped.

Sign in / Sign up

Export Citation Format

Share Document