B-vitamins, homocysteine metabolism and CVD.
The present review focuses on the B-vitamins, i.e. folate, vitamin B12, vitamin B6 and 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 B12 and, to a lesser extent, vitamin B6 are 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 C677T 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 677TT genotype are genetically predisposed to elevated plasma homocysteine, and in most populations have a markedly higher risk of CVD.
Strain
J J
JJ
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, UK. JJ.Strain@ulster.ac.uk
Dowey
L
L
Ward
M
M
Pentieva
K
K
McNulty
H
H
D019731:Carbon-Nitrogen Ligases / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D020022:Genetic Predisposition to Disease; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000378:metabolism*; D014804:Vitamin B Deficiency / Q000097:blood / Q000150:complications*
D006710:Homocysteine; D014803:Vitamin B Complex; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase