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 (microgram/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 microgram folic acid/d, 500 microgram folic acid every second day (250 microgram/d), or a placebo tablet with their habitual diet (mean dietary folate intake: 280 microgram/d).

Results: Administration of 250 and 500 microgram 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 microgram folic acid/d [mean (+/-SEM) deviation from baseline: - 11.4 +/- 198%] and in women (n = 45) who took 500 microgram 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 microgram/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.