Effects of quintuply-fortified salt on the micronutrient status of females of reproductive age in Punjab, India: a randomized, community-based trial

Innovative fortification solutions are needed to address micronutrient deficiencies, which remain highly prevalent among adult females in India. The objective of this trial was to evaluate the effects of quintuply-fortified salt (QFS) compared with iodized salt on the micronutrient status of nonpregnant females of reproductive age (NPFRA) in Punjab, India. We conducted a double-blind, randomized, controlled, community-based trial. A total of 998 NPFRA were randomly assigned to receive: 1 ) QFS with iron as encapsulated ferrous fumarate, zinc, vitamin B 12 , folic acid, and iodine (eFF-QFS); 2 ) QFS with the same micronutrients, but iron as encapsulated ferric pyrophosphate plus ethylenediaminetetraacetic acid (eFePP-QFS); or 3 ) iodized salt. Biomarkers of micronutrient status were assessed at enrollment, 6 mo and 12 mo. At enrollment, the prevalence of anemia, iron deficiency, hypozincemia, vitamin B 12 insufficiency, and folate insufficiency among trial participants was 47.9%, 59.7%, 35.5%, 61.5%, and 69.7%, respectively. Mean household salt disappearance, measured at monthly home visits, was 6.0 g/adult female equivalent/day 95% confidence interval (CI): 5.9, 6.1 and did not vary across groups or time. At 6 mo, the odds of vitamin B 12 insufficiency, folate insufficiency, and hypozincemia were, respectively, 80% odds ratio (OR): 0.20; 95% CI: 0.13, 0.31, 86% (OR: 0.14; 95% CI: 0.09, 0.21), and 38% (OR: 0.62; 95% CI: 0.41, 0.93) lower in the eFF-QFS compared with the iodized salt group. Effects on vitamin B 12 and folate status were sustained at 12 mo, and were comparable in the eFePP-QFS compared with the iodized salt group. There was a small, marginally significant, reduction in iron deficiency in the eFF-QFS compared with the iodized salt group at 6 (OR: 0.64; 95% CI: 0.42, 0.98; P = 0.08) and 12 mo (OR: 0.58; 95% CI: 0.35, 0.95; P = 0.06), but not in the eFePP-QFS compared with the iodized salt group. There were no groupwise differences in anemia at either time point. Multiple micronutrient salt fortification may be an effective strategy to improve micronutrient status, especially vitamin B 12 and folate, among NPFRA at high risk of deficiency. This study was registered at clinicaltrials.gov , with NCT05166980 and at Clinical Trials Registry-India with CTRI/2022/02/040333.