Folate Status of Reproductive Age Women and Neural Tube Defect Risk: The Effect of Long-Term Folic Acid Supplementation at Doses of 140 µg and 400 µg per Day
What this study found
Both folic acid doses improved folate status over 40 weeks, and there was no evidence of a difference in red blood cell folate between 140 µg/day and 400 µg/day at 40 weeks. RBC folate increased by 51% (95% CI: 29, 78) with 140 µg/day and by 63% (95% CI: 39, 92) with 400 µg/day, each showing a significant time-by-treatment interaction versus placebo (P < 0.001). Plasma folate rose by 50% with 140 µg/day and by 107% with 400 µg/day; the 400 µg/day dose produced higher plasma folate than 140 µg/day (P = 0.007). The prevalence of RBC folate below 906 nmol/L fell from 67% at baseline to 35% at…
- Study & population
- Randomized interventional study in healthy reproductive-age women in New Zealand.
- Intervention
- Oral folic acid was given once daily for 40 weeks in two active doses: 133 µg tablet folic acid/day (target 140 µg/day) and 359 µg tablet folic acid/day (target 400 µg/day).
- Key limitation
- The active-arm sample sizes were modest, which limits precision and detection of smaller between-dose differences.
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Open PDFOriginal abstract
Primary prevention of most folate-responsive neural tube defects (NTDs) may not require 400 μg folic acid/day but may be achieved by attaining a high maternal folate status. Using RBC folate ≥906 nmol/L as a marker for NTD risk reduction, the study aimed to determine the change in blood folate concentrations in reproductive age women in response to long-term folic acid supplementation at 400 µg/day and 140 µg/day (dose designed to mimic the average daily folic acid intake received from New Zealand’s proposed mandatory bread fortification program). Participants were randomly assigned to a daily folic acid supplement of 140 µg (n = 49), 400 µg (n = 48) or placebo (n = 47) for 40 weeks. RBC folate concentrations were measured at baseline, and after 6, 12, 29 and 40 weeks. At 40 weeks, the overall prevalence of having a RBC folate <906 nmol/L decreased to 18% and 35% in the 400 µg and 140 µg groups, respectively, while remaining relatively unchanged at 58% in the placebo group. After 40 weeks, there was no evidence of a difference in RBC folate between the two treatment groups (P = 0.340), nor was there evidence of a difference in the odds of a RBC folate <906 nmol/L (P = 0.078). In conclusion, the average daily intake of folic acid received from the proposed fortification program would increase RBC folate concentrations in reproductive age women to levels associated with a low risk of NTDs.