Optimization of dietary folate or low-dose folic acid supplements lower homocysteine but do not enhance endothelial function in healthy adults, irrespective of the methylenetetrahydrofolate reductase (C677T) genotype

[摘要] Objectives We sought to study the effect of low-dose folic acid supplementation or optimization of dietary folate intake on plasma homocysteine and endothelial function in healthy adults. Background Elevated homocysteine is associated with cardiovascular disease, but it is not known whether this relationship is causal. Individuals homozygous (TT) for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene (similar to 12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake. Methods Healthy subjects (n=126; 42 of each MTHFR genotype) were included in this cross-over study of three interventions of four months each: 1) placebo plus natural diet; 2) daily 400-mug folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 mug/day. Results At baseline, homocysteine was inversely related to plasma folate and was higher in TT homozygotes. For the whole group, plasma folate increased by 46% after dietary folate and by 79% after supplementation, with reductions of homocysteine of 14% and 16%, respectively. Within the genotype, TT homozygotes exhibited the most marked changes in these variables. Brachial artery endothelial function, as determined by a change in end-diastolic diameter in response to increased flow, was not changed by increased folate intake (98 +/- 73 mum at baseline, 110 +/- 69 mum after a high-folate diet, 114 +/- 59 mum after supplementation and 118 +/- 68 mum after placebo). Plasma von Willebrand factor antigen was unaltered. Conclusions Optimization of dietary folate or low-dose folic acid supplementation reduces plasma homocysteine but does not enhance endothelial function, irrespective of the MTHFR (C667T) genotype. (J Am Coll Cardiol 2001;38:1799-805) (C) 2001 by the American College of Cardiology.

[发布日期] 2001-12-01