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

Abstract

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 μg (6 weeks), to 200 μg (6 weeks), to 400 μg (14 weeks). Fasting 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 showed significant (p ≤ 0.001) homocysteine lowering in the top (10.90 ± 0.83 μmol/l) and middle (9.11 ± 0.49 μmol/l) tertiles only. In the low tertile, where the mean baseline homocysteine level was 7.07 ± 0.84 μmol/l, no significant response was observed. Of the three folic acid doses, 200 μg appeared to be as effective as 400 μg, while 100 μg 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 μg/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.