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.


OBJECTIVE
To find the lowest dose of folic acid that effectively reduces plasma homocysteine in premenopausal women.


METHODS
Double-blind, randomized placebo-controlled trial.


METHODS
Women of child-bearing age (n=95) were randomly allocated to 0, 100, 200, or 400 microg/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 microg(p=0.0001) and 400 microg(p=0.0001) groups; but not in the placebo (0 microg) (p=0.25) or the 100 microg (p=0.5) groups. Only the 200 microg and the 400 microg groups had significant decreases in plasma homocysteine, (p=0.04 and p=0.0008, respectively). However, when subjects whose initial plasma homocysteine was <8 micromol/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.


CONCLUSIONS
In this sub-population, low doses of folic acid significantly lower plasma homocysteine. This could be achieved safely by fortification.
Daly
S
S
Coombe Womens Hospital, Dublin, Ireland.
Mills
J L
JL
Molloy
A M
AM
Conley
M
M
McPartlin
J
J
Lee
Y J
YJ
Young
P B
PB
Kirke
P N
PN
Weir
D G
DG
Scott
J M
JM
D000328:Adult; D003430:Cross-Sectional Studies; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006397:Hematinics / Q000008:administration & dosage*; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D006801:Humans; D018579:Patient Selection; D012985:Software Design; D016896:Treatment Outcome
D006397:Hematinics; D006710:Homocysteine; D005492:Folic Acid