Low-dose folic acid lowers plasma homocysteine levels in women of child-bearing age

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 mug/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 mug (p=0.0001) and 400 mug (p=0.0001) groups; but not in the placebo (0 mug) (p=0.25) or the 100 mug (p=0.5) groups. Only the 200 mug and the 400 mug groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 mumol/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.