B-vitamins, homocysteine metabolism and CVD (original) (raw)
Related papers
American Journal of Physiology-endocrinology and Metabolism, 2001
Folate and vitamin B 6 act in generating methyl groups for homocysteine remethylation, but the kinetic effects of folate or vitamin B 6 deficiency are not known. We used an intravenous primed, constant infusion of stable isotope-labeled serine, methionine, and leucine to investigate one-carbon metabolism in healthy control (n ϭ 5), folatedeficient (n ϭ 4), and vitamin B 6-deficient (n ϭ 5) human subjects. The plasma homocysteine concentration in folatedeficient subjects [15.9 Ϯ 2.1 (SD) mol/l] was approximately two times that of control (7.4 Ϯ 1.7 mol/l) and vitamin B6-deficient (7.7 Ϯ 2.1 mol/l) subjects. The rate of methionine synthesis by homocysteine remethylation was depressed (P ϭ 0.027) in folate deficiency but not in vitamin B6 deficiency. For all subjects, the homocysteine remethylation rate was not significantly associated with plasma homocysteine concentration (r ϭ Ϫ0.44, P ϭ 0.12). The fractional synthesis rate of homocysteine from methionine was positively correlated with plasma homocysteine concentration (r ϭ 0.60, P ϭ 0.031), and a model incorporating both homocysteine remethylation and synthesis rates closely predicted plasma homocysteine levels (r ϭ 0.85, P ϭ 0.0015). Rates of homocysteine remethylation and serine synthesis were inversely correlated (r ϭ Ϫ0.89, P Ͻ 0.001). These studies demonstrate distinctly different metabolic consequences of vitamin B6 and folate deficiencies. one-carbon metabolism; remethylation; stable isotopes; human; vitamin B 6; folate MILD ELEVATION OF PLASMA HOMOCYSTEINE is an independent risk factor for cardiovascular disease, peripheral arterial occlusive disease, stroke, and venous thrombosis (1, 2, 5, 12, 29). For example, Boushey et al. (1) calculated in a meta-analysis that the odds ratio for coronary artery disease in males for each 5 mol/l increase in plasma homocysteine is 1.6. However, it is unclear whether homocysteine is directly involved
The effect of a subnormal vitamin B6 status on homocysteine metabolism
Journal of Clinical Investigation, 1996
Homocysteine, an atherogenic amino acid, is either remethylated to methionine or metabolized to cysteine by the transsulfuration pathway. The biochemical conversion of homocysteine to cysteine is dependent upon two consecutive, vitamin B-6-dependent reactions.
Homocysteine, B-vitamins and CVD
Proceedings of the Nutrition Society, 2008
There is considerable interest in plasma homocysteine (tHcy) as a CVD risk factor. Although the secondary prevention trials published to date have been inconclusive in confirming a benefit of tHcy-lowering treatment with B-vitamins on CVD events generally, such studies are widely recognised to have been insufficiently powered to detect a significant effect for the predicted magnitude of association between tHcy and heart disease risk, and therefore cannot be interpreted as evidence that no relationship exists. In fact, a recent meta-analysis of clinical trials has confirmed that folic acid supplementation reduces the risk of stroke, particularly in individuals without a history of stroke. Evidence supporting a causal relationship between elevated tHcy and heart disease also comes from genetic studies. The most important genetic determinant of tHcy in the general population is the common C677T variant in methylenetetrahydrofolate reductase (MTHFR) that results in higher tHcy. Individuals with the homozygous mutant (TT) genotype have a significantly higher (14-21 %) risk of heart disease. Plasma tHcy is very responsive to intervention with the B-vitamins required for its metabolism, in particular folic acid, and to a lesser extent vitamins B 12 and B 6 . Thus, although primarily aimed at reducing neural-tube defects, folic acid fortification may have an important role in the primary prevention of CVD via tHcy lowering. Besides folate, riboflavin is required as a cofactor for MTHFR and enhanced riboflavin status results in a marked lowering in tHcy specifically in individuals with the TT genotype, presumably by neutralising the variant form of the enzyme. About 10 % of the UK and Irish populations have the TT genotype. In the present paper the potential role of folate and related B-vitamins in the primary prevention of CVD and the implications for nutrition policy are explored.
Molecular Medicine Reports, 2013
The role of hyperhomocysteinemia (HHcy) as a cardiovascular risk factor remains a matter of debate, while it correlates with folates, it demonstrates inverse correlation with plasma homocysteine (Hcy) levels and vitamin B12 levels and reduces plasma Hcy levels following supplementation with multivitamins. The purpose of this study was to demonstrate that administering multivitamins at speciic doses for 90 days restores normal plasma Hcy levels in women who are homozygous for the thermolabile variant of 5,10 methylenetetrahydrofolate reductase (MTHFR C677T). We enrolled 106 healthy females aged between 30 and 42 years, who were non-smokers, non-vegetarian, normotensive and who had no history of food abuse in the previous months. Only females were enrolled in order to rule out any bias due to the variation in Hcy plasma concentrations between males and females. Patient blood sampling was performed in order to determine plasma Hcy, serum folic acid and vitamin B12 levels. Furthermore, molecular characterization of the C677T polymorphism present in the MTHFR gene, was also performed.
British Journal of Nutrition, 2000
The 677cytosine (c)→thymine(T) mutation identified in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene has been frequently associated with an elevated plasma homocysteine concentration. The aim of the present study was to determine the impact of this MTHFR common mutation on plasma and erythrocyte folate (RCF) and plasma total homocysteine (tHcy) concentrations in healthy French adults. A cohort of 291 subjects living in the Paris area and participating in the Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX) study were analysed to assess the impact of MTHFR polymorphism 677C→T on folate status and plasma tHcy concentration. The frequency of the mutant homozygote for 677C→T polymorphism (677TT genotype) in the present cohort was 16·8%. There were significant differences in plasma tHcy between 677CC, 677CT and 677TT genotype groups. The RCF concentrations were significantly different between each genotype, the lowest levels being associated with the 677TT gen...
The American Journal of the Medical Sciences, 2006
Background: Observational studies have shown an inverse relationship between vitamin B 2 status and total homocysteine levels, a risk factor for cardiovascular disease. We hypothesize that intervention with riboflavin will lower total homocysteine levels. The total homocysteine lowering by the three genotypes (CC, CT, TT) of methylenetetrahydrofolate reductase polymorphism (677C¡T) was also studied. Methods: The decrease in total homocysteine levels after supplementation with riboflavin (10 mg/d) or folic acid (1 mg/d) for 3 weeks was compared in two groups of healthy subjects (17 per group, matched by age and gender) (Phase 1). Then, both groups received supplementation with folic acid and riboflavin for an additional 3 weeks (Phase 2). Results: During Phase 1, total homocysteine levels were lowered by 2% or 4% after supplementation with riboflavin or fatty acid, respectively, although neither decrease was statistically significant (P ϭ 0.50 and 0.19). Compared to subjects of CC genotype, total homocysteine lowering in subjects of CT genotype was approaching significance (P ϭ 0.059) for the folic acid group, but not for the riboflavin group. After Phase 2, total homocysteine levels were not lowered significantly in either the folic acid (1%) or the riboflavin (2%) group. However, in the folic acid-riboflavin combined group, total homocysteine lowering in subjects of TT type was larger when compared to subjects of CC and CT types (P ϭ 0.007). Conclusions: Riboflavin supplementation did not lower total homocysteine levels in healthy subjects with CC type of C677T polymorphism. However, supplementation with folic acid or with both folic acid and riboflavin may be important for CT and TT subjects in optimizing their homocysteine metabolism. These findings are relevant in characterizing the factors controlling the high total homocysteine levels for subjects of CT and TT genotypes.