Folate status and homocysteine response to folic acid doses and withdrawal among young Chinese women in a large-scale randomized double-blind trial.

Randomized, double-blind trial in healthy young Chinese women from Xianghe County, Hebei Province, northern China. Participants were 24-42 years old and were not pregnant, not anemic, not vitamin B-12 deficient, and not using other supplements; six active intervention arms were analyzed.

Six oral folic acid regimens were tested for 6 months in a double-blind randomized design: 25 µg four times daily, 100 µg once daily, 100 µg four times daily, 400 µg once daily, 4000 µg once daily, and 4000 µg once weekly. The main comparison was daily versus divided or weekly dosing at the same or different total daily intakes.

Overall, folate and homocysteine responses were driven by total folic acid intake rather than whether the dose was given once daily or in divided doses. At 3 months, plasma folate increased by 108% in the 100 µg/day group, 259% in the 400 µg/day group, 460% in the 4000 µg/day group, and 142% in the 4000 µg/week group. At 6 months, RBC folate rose by 27.7%, 71.8%, 137%, and 45.7%, respectively, showing a slower and more gradual response than plasma folate. Homocysteine fell by about 4% with 100 µg/day, 17% with 400 µg/day, and up to about 22% with 4000 µg/day. After folic acid stopped, plasma folate declined rapidly and RBC folate declined more slowly; self-reported adverse events did not differ across intervention groups.

The trial was conducted in a specific group of healthy, nonpregnant Chinese women, which limits generalizability. Follow-up was relatively short, and one arm had no stated sample size in the extracted data. Dietary intake, physical activity, and BMI were not described, and the weekly 4000 µg arm appears less effective than daily dosing, which complicates interpretation of intermittent regimens.