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Homocysteine: An Indicator of Methylation Pathway Alternation in Down Syndrome Children and its Regulation by Folic Acid Therapy  [PDF]
Hala D. El-Gindi,Hala M. Hussien
Journal of Medical Sciences , 2007,
Abstract: The purpose of this research was to evaluate the total homocysteine (t-Hcy) metabolism in Down Syndrome (DS) children and to determine whether the supplementation with folic acid therapy would shift the genetically induced metabolic imbalance. Thirty-five infants with DS (17 male and 18 females), their mean age 17.66"12.24 months were included in this study. They were selected among those attending the Genetic out Patients Clinic, Children Hospital. Present results revealed that Down syndrome=s children had a significant increase of serum folic acid after treatment with folic acid therapy (18.91±3.59 vs 11.95±1.55 ng mLG1), while no significant change in vitamin B12 (323.17±38.42 vs 358.36±57.43 pg mLG1). There was a significant decrease in plasma t-Hcy level after treatment with folic acid therapy (11.79±0.92 vs 14.41±4.93 μ mol LG1). A significant negative correlation was found between t-Hcy and folic acid serum levels (r = -0.112; p< 0.05). The present study concluded that, the regulation of methylation pathways in Down syndrome becomes important in light of possible normalization of the metabolic imbalance and the detection of increased sensitivity to therapeutic interventions.
No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine  [PDF]
Audrey Y. Jung, Yvo Smulders, Petra Verhoef, Frans J. Kok, Henk Blom, Robert M. Kok, Ellen Kampman, Jane Durga
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024976
Abstract: A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = ?0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes. ClinicalTrials.gov NCT00110604
Methoxistasis: Integrating the Roles of Homocysteine and Folic Acid in Cardiovascular Pathobiology  [PDF]
Jacob Joseph,Joseph Loscalzo
Nutrients , 2013, DOI: 10.3390/nu5083235
Abstract: Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or “methoxistasis”, exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.
Neural Tube Defects, Folic Acid and Methylation  [PDF]
Apolline Imbard,Jean-Fran?ois Benoist,Henk J. Blom
International Journal of Environmental Research and Public Health , 2013, DOI: 10.3390/ijerph10094352
Abstract: Neural tube defects (NTDs) are common complex congenital malformations resulting from failure of the neural tube closure during embryogenesis. It is established that folic acid supplementation decreases the prevalence of NTDs, which has led to national public health policies regarding folic acid. To date, animal studies have not provided sufficient information to establish the metabolic and/or genomic mechanism(s) underlying human folic acid responsiveness in NTDs. However, several lines of evidence suggest that not only folates but also choline, B12 and methylation metabolisms are involved in NTDs. Decreased B12 vitamin and increased total choline or homocysteine in maternal blood have been shown to be associated with increased NTDs risk. Several polymorphisms of genes involved in these pathways have also been implicated in risk of development of NTDs. This raises the question whether supplementation with B12 vitamin, betaine or other methylation donors in addition to folic acid periconceptional supplementation will further reduce NTD risk. The objective of this article is to review the role of methylation metabolism in the onset of neural tube defects.
Effect of Homocysteine ,Vitamin B12 , Folic acid during pregnancy
Arpita Patel,Chandan Chakrabarty,Arjun Singh,Jatin Patel
NHL Journal of Medical Sciences , 2012,
Abstract: Vitamin B12, folic acid and homocysteine are metabolically closely related. At the same time homocysteine is found to be offending factor for vascular pathology causing preeclampsia. On the other hand periconceptional nutritional status influences the vitamin B12 & folic acid level. Which further affect the homocysteine level thus may affect pregnancy outcome. Various contributory factors lead these vitamin deficiencies, maternal nutrition is one of them. Ahmedabad being a predominantly vegetarian city, its population is at higher risk of vitamin B12 deficiency. But no systematic study has been done in Ahmedabad to know whether B12, folic acid and homocysteine levels influence pregnancy. To know this answer this study was planned to know total homocysteine level and its correlation in preeclampsia and normotensive pregnant women.Vitamin B12, folic acid and homocysteine were measured in all the subjects using fluorescence polarized immunoassay in AxSym Immunochemistry analyzer on 60 non vitamin supplemented vegetarian women. Vitamin levels were within lower normal limit. Homocysteine level was higher among preeclampsia patient. From the findings of the present study it can be concluded that measurement of these biochemical parameter in ante natal care are useful for further management and prevention of complication of pregnancy like preeclampsia
Homocysteine in Gestational Diabetes and Normal Pregnancy plus Effects of Folic Acid
F Davari-Tanha,F Khan-Mohamadi,M Kaveh,M Shariat
Iranian Journal of Public Health , 2008,
Abstract: "nBackground: The aim of study was to assess serum homocysteine and its relation with serum folate, vit B12 and lipid pro-files in gestational diabetes mellitus and comparison with normal pregnant women as well as effect of different doses of fo-lic acid on Homocysteine (Hcy) and pregnancy outcome."nMethods: In a biphasic study first prospective controlled study 80 pregnant women were chosen at 24-28 weeks of gesta-tion. In case group pregnant women with gestational diabetes mellitus and control group who had normal Oral Glucose Toler-ance test (GTT) results. Levels of fasting glucose, homocysteine, vit B12, and folic acid, uric acid, total cholesterol, triglyc-eride, LDL, HDL, were measured. In phase II study a randomized clinical trial was done with diabetic women 15 with 1mg folic acid and 15 with 5 mg folic acid for six weeks and then above variables and pregnancy outcome was evalu-ated."nResults: The mean levels of homocysteine in Gestational Diabetes Mellitus (GDM) group were significantly higher but fo-lic acid and vit B12 were significantly lower. Hcy levels were decreased in both groups after six weeks folic acid but de-crease in Hcy for group 5mg was significantly more than 1mg group. "nConclusion: Homocysteine levels were higher in GDM than normal pregnancy. High dose folic acid can reduce Hcy levels more than low dose and it may be a safe, simple, inexpensive intervention that prevents major pregnancy complications. "n
Homocysteine, Vitamin B12 and Folic Acid in Children with Acute Glomerulonephritis  [PDF]
Duangkamol Viroonudomphol, Saowanee Kanjanachumpol, Sarinya Sirisate
World Journal of Engineering and Technology (WJET) , 2018, DOI: 10.4236/wjet.2018.63042
Abstract: Homocysteine (Hcy) is an intermediate product of methionine formed by its demethylation. Hcy can be metabolized via remethylation to methionine or transsulfuration to cysteine which is dependent on several enzymes and cofactors. It is deleterious to blood vessel including glomeruli. Kidney is a major organ that metabolizes Hcy. More than 80% of patients with chronic renal disease develop hyperhomocysteinemia (hHcy). Accessible data of plasma Hcy in nephritic syndrome (NS) patients are controversial with increased, decreased and unchanged values reported. In renal patients, plasma Hcy concentration can be reduced by administration of folic acid. Absolute or relative deficiencies of folate, vitamin B6, or vitamin B12 may also play a role. Therefore, plasma Hcy, folic acid, vitamin B6, and vitamin B12 in children with acute glomerulonephritis (AGN) were accessed in this study. Hcy, folic acid vitamin B12, B6 and renal function such as blood urea nitrogen (BUN), creatinine (Cr) were analyzed 12 pediatric patients with AGN and 15 age and sex matched healthy children served as controls. The results revealed that a?significant increase in plasma Hcy in children with acute AGN when compared with controls. For simple regression analysis, Hcy was positively correlated with BUN, Cr, ferritin and uric acid but negatively correlated with serum glutathione. This research indicated hHcy suggests enhanced risks for inflammation and endothelial injury,?which lead to kidney disease. Folic acid has also been shown to improve endothelial function, suggesting an alternative explanation for the effect of folic acid on endothelial function. Careful considerations of not only dietary measures are necessary but also folate and vitamin B supplementation for reducing hHcy in AGN need to be investigated.
Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children
ON Eldeen, SH Abd Eldayem, RH Shatla, NA Omara, SS Elgammal
Egyptian Journal of Medical Human Genetics , 2012,
Abstract: The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.
Levels of serum B12, folic acid and homocysteine in thromboembolic diseases on admission to the Emergency Department
A Bay?r, K U?ar Karabulut, A Ak
Critical Care , 2011, DOI: 10.1186/cc9434
Abstract: This study included 100 subjects with acute myocardial infarctus (AMI), acute pulmonary embolism, deep vein thrombosis, ischemic cerebrovascular disease (ICD), acute mesentery embolism, and peripheric artery embolism (PAE), and 110 healthy voluntary subjects were included in the control group. Vitamin B12, folic acid and homocysteine levels were examined in the blood samples obtained at admission, The data were loaded onto SPSS 16 for Windows program. P ≤ 0.05 was considered significant.Mean serum homocysteine and plasma vitamin B12 levels were significantly higher in the patient group than the control group (P = 0.002 and 0.000 respectively). There was no significant difference in the levels of folic acid between the patient and control groups. Mean serum B12 values of the AMI and ICD groups in the patient group were significantly lower than those of the control group (P < 0.05). Serum folic acid values of the PAE and AMI groups were considerably lower than the control group (P < 0.05). Plasma homocysteine levels were significantly higher in all patient groups according to their diagnosis than the control group (P < 0.05).Mean serum homocysteine and plasma vitamin B12 levels were significantly higher in the patient group than the control group (P = 0.002 and 0.000 respectively). There was no significant difference in the levels of folic acid between the patient and control groups. Mean serum B12 values of the AMI and ICD groups in the patient group were significantly lower than those of the control group (P < 0.05). Serum folic acid values of the PAE and AMI groups were considerably lower than the control group (P < 0.05). Plasma homocysteine levels were significantly higher in all patient groups according to their diagnosis than the control group (P < 0.05).
Homocysteine, folic acid and vitamin B12 serum levels in hemodialysis patients referring to hemodialysis unit of Jahrom hospital
abdoreza Sotoodeh Jahromi,Mohammad Reza Farjam,Mohammad Shojaei
Journal of Jahrom University of Medical Sciences , 2011,
Abstract: Homocysteine, folic acid and vitamin B12 serum levels in hemodialysis patients referring to hemodialysis unit of Jahrom hospitalSotoodeh Jahromi A1,2, Farjam MR*3, Shojaei M4Received: 09/25/2010Revised: 01/27/2011Accepted: 01/29/20111. Dept. of Immunology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran2. Research Center for Zoonotic Diseases, Jahrom University of Medical Sciences, Jahrom, Iran 3. Dept. of Biochemistry, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran4. Dept. of Internal Medicine, School of Medicine, Jahrom University of Medical Sciences, Jahrom, IranJournal of Jahrom University of Medical Sciences, Vol. 9, No. 1, Spring 2011 AbstractIntroduction:Homocysteine is an amino acid yielded from methionin to cysteine metabolism. Increased level of homocysteine can increase the risk of cardiovascular diseases. Several factors such as uremia, genetic factors, dialysis related factors and vitamin B group deficiency lead to increased plasma level of homocysteine in dialysis patients. This study aimed to evaluate plasma levels of homocysteine, vitamin B12 and folic acid in Jahrom hemodialysis patients.Materials and Methods:This cross-sectional study was carried out on a total of 43 hemodialysis patients and 43 age and sex matched healthy individuals without any underlying renal disease as control group during December 2008 and September 2009. The serum level of homocysteine was measured using ELISA method and the serum levels of vitamin B12 and folic acid were measured by radioimmunoassay method.Results:Comparing the patients with the control group, there were significant differences between the two groups in mean serum levels of homocysteine (22.709±5.765 μmol/L vs. 16.518±5.425 μmol/L), folic acid (513.814±15.378 ng/ml vs. 22.976±7.462 ng/ml) and vitamin B12 (5366.814±1734.752 pg/ml vs. 868.907±251.484 pg/ml) (P<0.001). A significant positive correlation was found between mean serum level of homocysteine and duration of hemodialysis therapy (r=0.893, P<0.001).Conclusion:Although in the present study the homocysteine level in the patients was more than that of the healthy subjects, it was lower than that of hemodialysis patients in other countries.
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