Q J Med 2002; 95: 733-740
© 2002 Association of Physicians
Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age
From the 1 Coombe Womens Hospital, Dublin, Ireland, 2 Branches of Epidemiology and Statistics, NICHD/NIH, Bethesda, Maryland, USA, Departments of 3 Clinical Medicine and 4 Biochemistry, Trinity College Dublin, Ireland, 5 Biochemistry Department, Veterinary Sciences Division, Belfast, UK and 6 Health Research Board, Dublin, Ireland
Received 4 April 2002 Accepted for publication 15 July 2002.
Background: Ongoing clinical trials are investigating whether lowering plasma homocysteine reduces the risk of vascular disease. If so, food fortification with folic acid will be the likely result, and sub-optimal amounts are likely to be preferred, for safety reasons. Dose-finding studies are needed before the outcomes of these trials, to establish the benefits and risks of folic acid consumption over the widest intake range likely to be encountered.
Aim: To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women.
Design: Double-blind, randomized placebo-controlled trial.
Methods: Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 µg/day of folic acid. Red-cell folate and plasma homocysteine were measured at baseline and after 10 weeks supplementation.
Results: Median red cell folate levels increased significantly in the 200 µg (p=0.0001) and 400 µg (p=0.0001) groups; but not in the placebo (0 µg) (p=0.25) or the 100 µg (p=0.5) groups. Only the 200 µg and the 400 µg groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 µmol/l (already optimally low) were removed from the analysis, there were significant plasma homocysteine decreases in all three treatment groups, but not the placebo group.
Discussion: In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.
Address correspondence to Professor J.M. Scott, Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland. e-mail: jscott{at}tcd.ie
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