Homocysteine and Cardiovascular Disease: Interactions Between Nutrition, Genetics and Lifestyle

2004 ◽  
Vol 29 (6) ◽  
pp. 773-780 ◽  
Author(s):  
John T. Brosnan
Keyword(s):  
Cardiovascular Disease ◽  
Folic Acid ◽  
Renal Disease ◽  
Methylenetetrahydrofolate Reductase ◽  
Coffee Consumption ◽  
Plasma Homocysteine ◽  
Folate Intake ◽  
Vitamin B ◽  
Methionine Metabolism ◽  
Vitamin Deficiencies

Homocysteine is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar, even moderate hyperhomocysteinemia is associated with increased incidence of cardiovascular disease and Alzheimer's disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. Pyridoxal, folic acid, riboflavin, and Vitamin B12 are all required for methionine metabolism, and deficiences of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15%, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable life style factors, in affecting methionone metabolism and in determining plasma homocysteine levels is discussed. Key words: methionine, liver metabolism, folic acid, vitamin B12, polymorphisms, neural tube defects, end-stage renal disease, coffee consumption

scholarly journals Genetics of hyperhomocysteinaemia in cardiovascular disease

2003 ◽  
Vol 40 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Karin J.A. Lievers ◽  
Leo A.J. Kluijtmans ◽  
Henk J. Blom
Keyword(s):  
Cardiovascular Disease ◽  
High Plasma ◽  
Plasma Homocysteine ◽  
Genetic Defects ◽  
Vitamin B ◽  
Methionine Metabolism ◽  
Elevated Plasma ◽  
Genetic Determinants ◽  
Genes Encoding ◽  
Very High

Homocysteine, a sulphur amino acid, is a branch-point intermediate of methionine metabolism. It can be degraded in the transsulphuration pathway to cystathionine, or remethylated to methionine via the remethylation pathway. In both pathways, major genetic defects that cause enzyme deficiencies are associated with very high plasma homocysteine concentrations and excretion of homocystine into the urine. Mildly elevated plasma homocysteine concentrations are thought to be an independent and graded risk factor for both arterial occlusive disease and venous thrombosis. Genetic defects in genes encoding enzymes involved in homocysteine metabolism, or depletion of important cofactors or (co)substrates for those enzymes, including folate, vitamin B12 and vitamin B6, may result in elevated plasma homocysteine concentrations. Plasma homocysteine concentrations are also influenced by dietary and lifestyle factors. In the last decade, several studies have been conducted to elucidate the genetic determinants of hyperhomocysteinaemia in patients with cardiovascular disease. We report on both environmental and genetic determinants of hyperhomocysteinaemia and give a detailed overview of all the genetic determinants that have been reported to date.

scholarly journals A Novel Review of Homocysteine and Pregnancy Complications

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chuce Dai ◽  
Yiming Fei ◽  
Jianming Li ◽  
Yang Shi ◽  
Xiuhua Yang
Keyword(s):  
Folic Acid ◽  
Pregnancy Complications ◽  
Methylenetetrahydrofolate Reductase ◽  
Normal Pregnancy ◽  
Positive Outcome ◽  
Mthfr Gene ◽  
Folate Intake ◽  
Daily Diet ◽  
B12 Deficiency ◽  
Work Done

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

scholarly journals Homocysteine and vitamins in cardiovascular disease

1998 ◽  
Vol 44 (8) ◽  
pp. 1833-1843 ◽  
Author(s):  
Donald W Jacobsen
Keyword(s):  
Cardiovascular Disease ◽  
Folic Acid ◽  
Vascular Endothelium ◽  
Intervention Studies ◽  
Genetic Mutation ◽  
Plasma Homocysteine ◽  
Total Plasma ◽  
Homocysteine Concentration ◽  
Atherothrombotic Disease ◽  
Lines Of Evidence

Abstract On the basis of recent retrospective and prospective studies, it is now widely accepted that increased total plasma homocysteine is a risk factor for cardiovascular disease. Impaired enzyme function as a result of genetic mutation or deficiency of the essential B vitamins folic acid, B12, and B6 can lead to hyperhomocysteinemia. Oxidized forms of homocysteine account for 98–99% of total plasma homocysteine. Although there is uncertainty as to whether increased homocysteine is causal or merely a proxy for cardiovascular disease, several lines of evidence suggest that it may play a role in atherothrombotic disease. Homocysteine appears to alter the anticoagulant properties of endothelial cells to a procoagulant phenotype. Mildly increased homocysteine causes dysfunction of the vascular endothelium. Folic acid effectively lowers homocysteine concentration in the plasma. Intervention studies are urgently needed to determine if lowering homocysteine is effective in decreasing the morbidity and mortality of cardiovascular disease.

Effect of Folic Acid Combined with Fluoxetine in Patients with Major Depression on Plasma Homocysteine and Vitamin B12, and Serotonin Levels in Lymphocytes

2008 ◽  
Vol 15 (3) ◽  
pp. 145-152 ◽  
Author(s):  
Gustavo Resler ◽  
Renée Lavie ◽  
Julio Campos ◽  
Salvador Mata ◽  
Mary Urbina ◽  
...  
Keyword(s):  
Folic Acid ◽  
Major Depression ◽  
Plasma Homocysteine ◽  
Vitamin B

scholarly journals Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer: a case–control study in a population with relatively low folate intake

2008 ◽  
Vol 99 (2) ◽  
pp. 379-389 ◽  
Author(s):  
Linda Sharp ◽  
Julian Little ◽  
Nigel T. Brockton ◽  
Seonaidh C. Cotton ◽  
Lindsey F. Masson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Carbon Metabolism ◽  
Methylenetetrahydrofolate Reductase ◽  
Case Control Study ◽  
Case Control ◽  
B Vitamins ◽  
Folate Intake ◽  
Vitamin B ◽  
One Carbon Metabolism ◽  
Control Study

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case–control study of folate intake, related dietary factors andMTHFRpolymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CTv.CC = 0·77 (95 % CI 0·52, 1·16); OR for TTv.CC = 0·62 (95 % CI 0·31, 1·24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0·81 (95 % CI 0·45, 1·49)). There were significant interactions between total folate and C677T (P = 0·029) and A1298C (P = 0·025), and total vitamin B6and both polymorphisms (C677T,P = 0·016; A1298C,P = 0·033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.

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.

Homocysteine, folic acid and vitamin B12 in relation to pre- and postnatal health aspects

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Rima Obeid ◽  
Wolfgang Herrmann
Keyword(s):  
Folic Acid ◽  
Vitamin B12 ◽  
Pregnancy Outcomes ◽  
Pregnancy Complications ◽  
Plasma Homocysteine ◽  
Vitamin B ◽  
Total Plasma ◽  
Vitamin Status ◽  
B Vitamin ◽  
Early Abortion

AbstractStudies linking hyperhomocysteinemia (HHCY) and B-vitamin deficiency to some health aspects in children have been accumulating. Low B-vitamin status inearly life, even as early as the time of conception, may endanger the potential for new life and may negatively influence the health of the offspring. Early abortion, pregnancy complications and poor pregnancy outcomes have been linked to elevated concentrations of total plasma homocysteine (tHcy) and low folate or vitamin B

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