5-11-methenyltetrahydrohomofolate and Hyperhomocysteinemia

Uremia represents a state where hyperhomocysteinemia is resistant to folate therapy, thus undermining intervention trials' efficacy. N-acetylcysteine (NAC), an antioxidant, in addition to folates (5-methyltetrahydrofolate, MTHF), was tested in a population of hemodialysis patients.. The study is an open, parallel, intervention study.. Ambulatory chronic hemodialysis patients.. Clinically stable chronic hemodialysis patients, on hemodialysis since more than 3 months, undergoing a folate washout. Control group on standard therapy (n = 50).. One group was treated with intravenous MTHF (MTHF group, n = 48). A second group was represented by patients treated with MTHF, and, during the course of 10 hemodialysis sessions, NAC was administered intravenous (MTHF + NAC group, n = 47).. Plasma homocysteine measured before and after dialysis at the first and the last treatment.. At the end of the study, there was a significant decrease in predialysis plasma homocysteine levels in the MTHF group and MTHF + NAC group, compared with the control group, but no significant difference between the MTHF group and MTHF + NAC group. A significant decrease in postdialysis plasma homocysteine levels in MTHF + NAC group (10.27 ± 0.94 μmol/L, 95% confidence interval: 8.37-12.17) compared with the MTHF group (16.23 ± 0.83, 95% confidence interval: 14.55-17.90) was present. In the MTHF + NAC group, 64% of patients reached a postdialysis homocysteine level <12 μmol/L, compared with 19% in the MTHF group and 16% in the control group.. NAC therapy induces a significant additional decrease in homocysteine removal during dialysis. The advantage is limited to the time of administration.

Topics: Acetylcysteine; Aged; Drug Therapy, Combination; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

There are only very few epidemiological data about homocysteine levels in patients suffering from cardiovascular (CV) disease in Hungary, however, homocysteine is a newly recognized, independent risk factor of CV diseases.. Therefore, in the present study, data of 1010 East-Hungarian patients with signs of CV disease were analyzed retrospectively for correlation between the level of homocysteine and CV diseases, laboratory parameters, as well as genetic differences.. From the studied patient population a control ("healthy") group has been selected according to the following criteria: lack of previous stroke or stenosis of the carotid arteries or the lower extremities, lack of coronary artery stenosis more than 50%, no previous coronary intervention or an angiography diagnosed progression of the coronary atherosclerosis.. The level of homocysteine showed statistically significant negative linear correlation with HDL-cholesterol and the anti-atherogenic ApoAI, and showed a positive correlation with CRP and FXIII activities in the entire patient population. When compared to the control group, homocysteine level was significantly higher in patients with previous stroke or acute myocardial infarction, coronary stenosis, progressive coronary disease, physical inactivity, MTHFR gene polymorphism, low folate or vitamin B12 level in both men and women. In patients with type II diabetes the level of homocysteine was significantly higher only in women.. It can be concluded that the level of homocysteine in patients suffering from various CV diseases is high in Hungary. This may have a prognostic value, and shows that reduction of homocysteine level in these patients may be beneficial.

Topics: Adult; Aged; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; COUP Transcription Factor II; Diabetes Mellitus, Type 2; Factor XIII; Female; Folic Acid; Homocysteine; Humans; Hungary; Hyperhomocysteinemia; Linear Models; Male; Middle Aged; Patient Selection; Polymorphism, Genetic; Retrospective Studies; Risk Factors; Vitamin B 12

Methylenetetrahydrofolate reductase (MTHFR) deficiency is an autosomal recessive disorder resulting in elevated homocysteine levels in plasma and urine. MTHFR catalyses the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a cofactor for homocysteine remethylation to methionine. MTHFR deficiency may be diagnosed from infancy to adulthood with a broad spectrum of clinical symptoms. A molecular analysis of the MTHFR gene combined with an assessment of MTHFR activity, plasma homocysteine and folate in plasma and red blood cells (RBC), especially methylfolate, was assessed in the members of 11 families from children affected with this disorder. This study was performed to try to define the impact of the mutations found in the MTHFR gene on symptoms and biological abnormalities. A total of 14 mutations were found and 10 of them were identified for the first time. Two were found in two families, two more in two other families and one in three families. The position of the mutation spread all over the gene does not predict the degree of biological abnormalities found in parents or healthy siblings bearing the mutation. Two different mutations located not far apart on the same exon may cause mild or severe abnormalities. The thermolabile variant C677T when expressed in an homozygote state in some parents was associated with lower MTHFR activity, higher homocysteine levels, lower folate levels, mainly methylfolate in RBC than in parents without the mutation; conversely, two or more mutations on the same allele had mild effects when the other allele was normal.. Given the heterogeneity of mutations, no one seems preponderant to predict neurological and/or vascular symptoms.

Topics: Child; Female; Folic Acid; Genes, Recessive; Homocysteine; Humans; Hyperhomocysteinemia; Male; Metabolism, Inborn Errors; Methylenetetrahydrofolate Reductase (NADPH2); Mutation; Polymorphism, Genetic; RNA Splice Sites