Abstract
The threshold for population-level optimal red blood cell (RBC) folate concentration among women of reproductive age for the prevention of neural tube defects has been estimated at 906 nmol/L; however, the dose-response relationship between folic acid intake and blood folate concentrations is uncharacterized. To estimate the magnitude of blood folate concentration increase in response to specific dosages of folic acid under steady-state conditions (as could be achieved with food fortification), a systematic review of the literature and meta-analysis was conducted. Of the 14,002 records we identified, 533 were selected for full-text review, and data were extracted from 108 articles. The steady-state concentrations (homeostasis) of both serum/plasma and RBC folate concentrations were estimated using a Bayesian meta-analytic approach and one-compartment physiologically-based pharmacokinetic models. RBC folate concentrations increased 1.78 fold (95% credible interval (CI): 1.66, 1.93) from baseline to steady-state at 375–570 µg folic acid/day, and it took a median of 36 weeks of folic acid intake (95% CI: 27, 52) to achieve steady-state RBC folate concentrations. Based on regression analysis, we estimate that serum/plasma folate concentrations increased 11.6% (95% CI: 8.4, 14.9) for every 100 µg/day folic acid intake. These results will help programs plan and monitor folic acid fortification programs.
Highlights
Neural tube defects (NTDs), such as anencephaly, encephalocele and spina bifida, often have devastating effects on infants and their families and can result in death or life-long disability
Nutrients 2019, 11, 71 folic acid per day, in addition to having a diet rich in natural food folate [1,2]. This recommendation was informed by randomized controlled trials [3,4] and has been confirmed by fortification and supplementation programs showing that folic acid intake before and during early pregnancy prevents many NTDs [5,6,7,8,9,10,11]
In the sensitivity analyses (Table 2), we found that studies with a high Risk of bias (ROB) had a lower ratio of baseline to steady-state (1.50; 95% Credible Intervals (CI): 1.35, 1.66) than those studies with low or medium risk of bias (1.81; 95% CI: 1.66, 2.00)
Summary
Neural tube defects (NTDs), such as anencephaly, encephalocele and spina bifida, often have devastating effects on infants and their families and can result in death or life-long disability. Nutrients 2019, 11, 71 folic acid per day, in addition to having a diet rich in natural food folate [1,2]. This recommendation was informed by randomized controlled trials [3,4] and has been confirmed by fortification and supplementation programs showing that folic acid intake before and during early pregnancy prevents many NTDs [5,6,7,8,9,10,11]. At least 70 other countries have legislation to mandate folic acid fortification a staple grain product the effectiveness and coverage of most of these policies are not established nor widely monitored (http://www.ffinetwork.org/global_progress/)
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