Author + information
- Received December 6, 2000
- Revision received August 15, 2001
- Accepted August 29, 2001
- Published online December 1, 2001.
- Catherine H Pullin, BSca,
- Pauline A.L Ashfield-Watt, BAa,
- Michael L Burr, MD, FFPHMa,
- Zoë E Clark, MPhila,
- Malcolm J Lewis, MB, DSc, FESCa,
- Stuart J Moat, PhD†,
- Robert G Newcombe, PhD, C. Stats, MFPHM‡,
- Hilary J Powers, PhD†,
- Jenny M Whiting, RGNa and
- Ian F.W McDowell, MD, MRCP, FRCPath*,a ()
- ↵*Reprint requests and correspondence: Dr. Ian F. W. McDowell, Department of Medical Biochemistry, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, Wales United Kingdom
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.
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 (∼12% of the population) have increased homocysteine levels, particularly in association with suboptimal folate intake.
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-μg folic acid supplement plus natural diet; and 3) increased dietary folate intake to 400 μg/day.
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 μm at baseline, 110 ± 69 μm after a high-folate diet, 114 ± 59 μm after supplementation and 118 ± 68 μm after placebo). Plasma von Willebrand factor antigen was unaltered.
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.
☆ This work was funded by the Ministry of Agriculture, Fisheries and Food (subsequently transferred to the Food Standards Agency), project no. NO5002. Kellogg’s Ltd. (Manchester, United Kingdom) provided reimbursement for fortified foods (cereals).
- Received December 6, 2000.
- Revision received August 15, 2001.
- Accepted August 29, 2001.
- American College of Cardiology