Low-dose folic acid supplementation decreases plasma homocysteine concentrations: A randomized trial

Abstract

Background: An elevated plasma total homocysteine concentration is a risk factor for cardiovascular disease and neural tube defects. A high daily intake of supplemental folic acid is known to decrease total homocysteine concentrations. Objective: We studied the effect of low-dose folic acid administration (250 or 500 μg/d) for 4 wk on plasma total homocysteine concentrations and folate status. We also investigated whether total homocysteine concentrations and blood folate concentrations returned to baseline after an 8-wk washout period. Design: In this placebo-controlled study, 144 healthy women aged 18-40 y received 500 μg folic acid/d, 500 μg folic acid every second day (250 μg/d), or a placebo tablet with their habitual diet (mean dietary folate intake: 280 μg/d). Results: Administration of 250 and 500 μg folic acid/d for 4 wk significantly increased folate concentrations in plasma (P < 0.001) and red blood cells (P < 0.01). Total homocysteine concentrations decreased significantly (P < 0.001) in women (n = 50) who took 250 μg folic acid/d [mean (±SEM) deviation from baseline: -11.4 ± 1.98%] and in women (n = 45) who took 500 μg folic acid/d (-21.8 ± 1.49%). Eight weeks after the end of the intervention period (week 12), plasma total homocysteine concentrations in the folic acid-supplemented groups had not returned to baseline (week 0). Conclusions: Doses of folic acid as low as 250 μg/d, on average, in addition to usual dietary intakes of folate significantly decreased plasma total homocysteine concentrations in healthy, young women. An 8-wk washout period was not sufficient for blood folate and plasma total homocysteine concentrations to return to baseline concentrations.