Serum Folate Forms Show Dose-Dependent Increases in Nonpregnant Ethiopian Women of Reproductive Age Participating in a Randomized Controlled Trial with Double-Fortified Salt Containing Iodine and Folic Acid

Information is limited regarding the response of serum folate forms (FOL-forms) to intake of folic acid (FA)-fortified foods. A randomized, 3-arm, dose-response trial of nonpregnant Ethiopian females assessed the effect of double-fortified salt containing iodine and FA on folate status. This report focuses on changes in FOL-forms {5-methyltetrahydrofolate (5-methylTHF), unmetabolized FA (UMFA), nonmethyl folate (NMFOL; sum of 3 minor FOL-forms), and the oxidation product of 5-methylTHF [pyrazino-s-triazine derivative of 4α-hydroxy-5-methyltetrahydrofolate (MeFox)]} after consumption of iodized salt (IS), lower FA IS (LFS; ∼200 μg additional FA/d), or higher FA IS (HFS; ∼600 μg additional FA/d) from baseline to endline ∼6 mo later. At endline, median concentrations of 5-methylTHF, UMFA, NMFOL, and MeFox were significantly different among treatment arms in a dose-response manner, whereas no differences were observed at baseline [5-methylTHF: 5.1-fold (HFS), 3.2-fold (LFS) baseline to endline increase]. The response of serum FOL-forms to the intervention was consistent with limited information from previous supplementation trials. This trial was registered at clinicaltrials.gov as NCT06223854; https://clinicaltrials.gov/study/NCT06223854?term=NCT06223854&viewType=Card&rank=1.