title: C(1) metabolism and CVD outcomes in older adults.
abstract: CVD is the most common cause of death in people over 65 years. This review considers the latest evidence for a potential protective effect of C(1) donors (folate and the metabolically related B-vitamins) in CVD. Such an effect may or may not be mediated via the role of these nutrients in maintaining plasma homocysteine concentrations within a desirable range. Despite predictions from epidemiological studies that lowering plasma homocysteine would reduce cardiovascular risk, several secondary prevention trials in at-risk patients published since 2004 have failed to demonstrate a benefit of homocysteine-lowering therapy with B-vitamins on CVD events generally. All these trials were performed in CVD patients with advanced disease; thus current evidence suggests that intervention with high-dose folic acid is of no benefit in preventing another event, at least in the case of heart disease. The evidence at this time, however, is stronger for stroke, with meta-analyses of randomised trials showing that folic acid reduces the risk of stroke, particularly in people with no history of stroke. Genetic studies provide convincing evidence to support a causal relationship between sub-optimal B-vitamin status and CVD. People homozygous for the common C677T variant in the gene encoding the folate-metabolising enzyme, methylenetetrahydrofolate reductase (MTHFR), typically have a 14-21% higher risk of CVD. Apart from folate, riboflavin is required as a co-factor for MTHFR. New evidence shows that riboflavin intervention results in marked lowering of blood pressure, specifically in patients with the MTHFR 677TT genotype. This novel gene-nutrient interaction may provide insights as to the mechanism that links C(1) metabolism with CVD outcomes.
authors.affiliation: Northern Ireland Centre for Food and Health, University of Ulster, Cromore Road, Coleraine BT52 1SA, UK. h.mcnulty@ulster.ac.uk
authors.forename: Helene
authors.initials: H
authors.lastname: McNulty
authors.forename: J J
authors.initials: JJ
authors.lastname: Strain
authors.forename: Kristina
authors.initials: K
authors.lastname: Pentieva
authors.forename: Mary
authors.initials: M
authors.lastname: Ward
mesh_terms: D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D002244:Carbon / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics / Q000517:prevention & control*; D005492:Folic Acid / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006331:Heart Diseases / Q000188:drug therapy / Q000235:genetics; D006710:Homocysteine / Q000097:blood; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D012256:Riboflavin / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D020521:Stroke / Q000235:genetics / Q000517:prevention & control*; D014803:Vitamin B Complex / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D006710:Homocysteine; D014803:Vitamin B Complex; D002244:Carbon; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D012256:Riboflavin