B Vitamins and Homocysteine in Cardiovascular Disease and Aging

ABSTRACT: The sulfur‐containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine β synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor.

[1]  S. Vollset,et al.  Plasma homocysteine levels and mortality in patients with coronary artery disease. , 1997, The New England journal of medicine.

[2]  D. Wilcken.  MTHFR 677C→T mutation, folate intake, neural-tube defect, and risk of cardiovascular disease , 1997, The Lancet.

[3]  J. Witteman,et al.  Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. , 1997, JAMA.

[4]  M. Creager,et al.  Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. , 1997, Circulation.

[5]  S. Vasikaran,et al.  Methylenetetrahydrofolate reductase gene and coronary artery disease. , 1997, Circulation.

[6]  W. Willett,et al.  Methylenetetrahydrofolate reductase polymorphism, plasma folate, homocysteine, and risk of myocardial infarction in US physicians. , 1996, Circulation.

[7]  D. Wilcken,et al.  Distribution in healthy and coronary populations of the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[8]  S. Vollset,et al.  Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. , 1995, JAMA.

[9]  G. Omenn,et al.  A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. , 1995, JAMA.

[10]  R. D'Agostino,et al.  Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis. , 1995, The New England journal of medicine.

[11]  D. Wilcken,et al.  Determinants of severity of coronary artery disease in Australian men and women. , 1994, Circulation.

[12]  P. Wilson,et al.  Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. , 1993, JAMA.

[13]  D. Celermajer,et al.  Impaired endothelial function occurs in the systemic arteries of children with homozygous homocystinuria but not in their heterozygous parents. , 1993, Journal of the American College of Cardiology.

[14]  D. Wilcken,et al.  Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. , 1988, Metabolism: clinical and experimental.

[15]  D. Wilcken,et al.  Interrelations between plasma free and protein-bound homocysteine and cysteine in homocystinuria. , 1988, Metabolism: clinical and experimental.

[16]  D. Wilcken,et al.  Homocystinuria--the effects of betaine in the treatment of patients not responsive to pyridoxine. , 1983, The New England journal of medicine.

[17]  D. Wilcken,et al.  Cysteine-homocysteine mixed disulphide: differing plasma concentrations in normal men and women. , 1979, Clinical science.

[18]  D. Wilcken,et al.  The pathogenesis of coronary artery disease. A possible role for methionine metabolism. , 1976, The Journal of clinical investigation.

[19]  K. Mccully.  Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. , 1969, The American journal of pathology.

[20]  V. McKusick,et al.  HOMOCYSTINURIA. STUDIES OF 20 FAMILIES WITH 38 AFFECTED MEMBERS. , 1965 .

[21]  C. Dent,et al.  HOMOCYSTINURIA: CLINICAL AND PATHOLOGICAL REVIEW OF TEN CASES. , 1965, The Journal of pediatrics.

[22]  T. Gerritsen,et al.  The identification of homocystine in the urine. , 1962, Biochemical and biophysical research communications.

[23]  D. W. Neill,et al.  Metabolic Abnormalities Detected in a Survey of Mentally Backward Individuals in Northern Ireland , 1962, Archives of disease in childhood.

[24]  I. Rosenberg,et al.  Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. , 1996, Circulation.

[25]  R. Matthews,et al.  A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase , 1995, Nature Genetics.

[26]  K. Pettigrew,et al.  The natural history of homocystinuria due to cystathionine beta-synthase deficiency. , 1985, American journal of human genetics.