Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid

Elevated plasma homocysteine, an independent risk factor for cardiovascular disease (CVD) can be lowered by administration of pharmacological doses of folic acid. The effect of lower doses in apparently normal subjects is currently unknown but is highly relevant to the question of food fortification. Healthy male volunteers (n=30) participated in a chronic intervention study (26 weeks). Folic acid supplements were administered daily at doses increasing from 100 mu g (6 weeks), to 200 mu g (6 weeks), to 400 mu g (14 weeks). Easting blood samples collected before, during and 10 weeks post intervention were analysed for plasma homocysteine, serum and red-cell folate levels. Results, expressed as tertiles of baseline plasma homocysteine concentration, showed significant (p less than or equal to 0.001) homocysteine lowering in the top (10.90+/-0.83 mu mol/l) and middle (9.11 +/- 0.49 mu mol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 +/- 0.84 mu mol/l, no significant response was observed. Of the three folic acid doses, 200 mu g appeared to be as effective as 400 mu g, while 100 mu g was clearly not optimal. There is thus a minimal level of plasma homocysteine below which folic acid has no further lowering effect, probably because an optimal folate status has been reached. A dose as low as 200 mu g/day of folic acid is effective in lowering plasma homocysteine concentrations in apparently normal subjects. Any public health programme for lowering homocysteine levels, with the goal of diminishing CVD risk, should not be based on unnecessarily high doses of folic acid.