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

Ingebor A. Brouwer, Marijke van Dusseldorp, Chris MG Thomas, Marinus Duran, Joseph GAJ Hautvast, Tom KAB Eskes, and Regine PM Steegers-Theunissen

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.

Am J Clin Nutr 1999;69:99-104