INTRODUCTION: The prevalence of neural tube defects (NTDs) is higher in Ethiopia than most other countries, and ~84% of Ethiopian women of reproductive age (WRA) have folate insufficiency, a major risk factor for NTDs. Salt fortification with folic acid is a potential strategy to improve womens folate status, but data are needed on the acceptability, nutritional impact and safety of folic acid fortification of iodised salt. METHODS AND ANALYSIS: The study is designed as a community-based, household-randomised, dose-response trial. A total of 360 non-pregnant WRA 18-49 years of age will be randomly assigned to one of three intervention arms: (1) iodised salt fortified with 30 ppm folic acid to provide ~200 µg folic acid/day; (2) iodised salt fortified with 90 ppm folic acid to provide ~600 µg folic acid/day; or (3) iodised salt (comparator). The preweighed salts will be delivered to participants homes biweekly for 26 weeks; unused salt will be collected and weighed. Fasting, venous blood samples will be collected at baseline, end line and a randomly assigned intermediate time point for assessment of folate, iodine, vitamin B12 and other micronutrient status biomarkers. Womens dietary intakes, including discretionary salt consumption, will be measured using weighed food records; 24-hour urine specimens will be analysed for sodium and iodine excretion. Primary outcomes are womens consumption of study salts, change in biomarkers of folate and iodine status and prevalence of adverse events. Results will be analysed using analysis of covariance models to estimate group mean differences for continuous outcomes, controlling for baseline measurements, and log-binomial or modified Poisson regressions for categorical outcomes. Prespecified effect modifications will be explored. ETHICS AND DISSEMINATION: The study has been approved by the Ethiopian Public Health Institutes Institutional Review Board, and the protocol has been registered with ClinicalTrials.gov (registration number NCT06223854). Study results will be published in open access scientific journals and disseminated nationally in Ethiopia. TRIAL REGISTRATION NUMBER: NCT06223854.

Recognizing the broader accessibility of iodized salt compared to wheat flour, the Ethiopian government is considering fortification of iodized salt with folic acid, and possibly vitamin B12, to address the high incidence of neural tube defects (NTDs) in Ethiopia. To prepare for this program, we assessed practices related to edible salt procurement and consumption, and the acceptability of novel salts fortified with iodine and folic acid (double-fortified salt, DFS) or iodine, folic acid, and vitamin B12 (triple-fortified salt, TFS) compared to iodized salt (IS). We surveyed 840 women of reproductive age in urban (Addis Ababa) and rural (Gimbichu Woreda) areas to describe their salt preferences and practices and used a three-point hedonic scale to evaluate the sensory acceptability of fine and coarse forms of DFS, TFS, and IS for color, taste, aroma, texture and overall acceptability. We found that women were the primary salt purchasers (72.8% rural, 97.4% urban) for household. Rural women preferred coarse salt (76.1%), whereas urban women preferred fine salt (42.4%) or both types (30.0%). All salts received favorable mean sensory ratings (≥ 2.1), with fine salt preferred for all sensory characteristics (p < 0.05). Fine IS (2.8 ± 0.5) was rated slightly higher than DFS (2.6 ± 0.8) and TFS (2.5 ± 0.8) (p < 0.05). Rural women were more willing to purchase DFS (79.2%) and TFS (73.0%) than urban women (65.0% DFS, 63.8% TFS). In conclusion, DFS and TFS are highly acceptable in Ethiopia, with women being the key target for their introduction. Mandatory fortification of both coarse and fine salts is recommended to maximize reach.