Elevated plasma total homocysteine (tHcy) concentrations are a risk factor for neural tube defects and vascular diseases. Supplementation with folic acid decreases tHcy. We investigated whether supplementation with 500 ?g folic acid every other day is as effective in lowering tHcy as 250 ?g folic acid each day. Methods: In a 4-week intervention study, 22 healthy young women (18-40 years old) took either 500 ?g folic acid every other day (500-?g/2d group) or 250 ?g folic acid each day (250-?g/d group). Fasting blood was collected on days 0 and 28. Results: Plasma folate concentrations increased by 11.4 nmol/l (6.8-15.9) in the 250-?g/d group and by 9.1 nmol/l (95␌l 1.9-16.3) in the 500-?g/2d group. These increases were not significantly different from each other. THcy concentrations decreased by 1.52 ?mol/l (95␌l -2.09 to -0.95; p < 0.001) in the 250-?g/d group and by 0.88 ?mol/l (-1.53 to -0.23; p < 0.05) in the 500-?g/2d group. The difference in decrease between the 250-?g/d group and the 500-?g/2d group was 0.64 ?mol/l (p = 0.11). Conclusion: Although not conclusive, this study suggests that supplying subjects with folic acid each day decreases tHcy more effectively than a double dose every other day.