Folic acid fortification of iodized salt improves the folate status of nonpregnant adult Ethiopian females and does not impair their iodine status: a community-based, household-randomized, dose-response trial.

BACKGROUND

Folic acid (FA) fortification of cereal grains reduces the prevalence of folate insufficiency among adult females and related neural tube defects (NTDs) in their offspring. However, fortifiable cereal grains have limited reach in many lower-income countries, so additional fortification options need to be developed and evaluated.

OBJECTIVES

This study assessed the effects of FA fortification of iodized salt on women's discretionary salt intakes, biomarkers of folate and iodine status, and the occurrence of adverse events.

METHODS

We conducted a community-based, 3-arm, household-randomized dose-response trial among 360 nonpregnant Ethiopian females 18 to 49 y of age. We delivered iodized salts containing 32 parts per million (ppm) iodine and 99, 36, or 0 ppm FA to households bi-weekly for 26 wk. We measured participants' fasting red blood cell (RBC) folate, serum folate, homocysteine, thyroglobulin, vitamin B-12 biomarkers, glucose, and insulin, and urinary iodine/creatinine ratios before and during the intervention. We quantified participants' salt intakes using weighed food records, and we systematically recorded adverse events.

RESULTS

The overall median (IQR) RBC folate concentration at baseline was 476 (371, 580) nmol/L. Participants' mean usual intakes of study salts (7.8 ± 1.8 g/d) did not differ by study arm (P = 0.58). The final median (IQR) RBC folate concentrations were 1275 (1120, 1521) nmol/L, 1004 (819, 1212) nmol/L, and 468 (366, 596) nmol/L in the respective study arms (all significantly different, P < 0.001). There were no group-wise differences in urinary iodine/creatinine ratios, serum thyroglobulin, insulin resistance, or reported adverse events.

CONCLUSIONS

FA fortification of salt is an effective and safe method to improve women's folate status and thereby reduce the risk of NTD-affected pregnancies. This trial was registered on the ClinicalTrials.gov website (registration number NCT06223854): https://clinicaltrials.gov/study/NCT06223854?term=Transcobalamin%20Deficiency&viewType=Table&rank=4.