Effects of wheat-flour biscuits fortified with iron and EDTA, alone and in combination, on blood lead concentration, iron status, and cognition in children: a double-blind randomized controlled trial.

BACKGROUND: Lead is a common neurotoxicant and its absorption may be increased in iron deficiency (ID). Thus, iron fortification to prevent ID in populations is a promising lead mitigation strategy. Two common fortificants are ferrous sulfate (FeSO4) and ferric sodium EDTA (NaFeEDTA). EDTA can chelate iron and lead. OBJECTIVES: Our study objective was to determine the effects of iron and EDTA, alone and in combination, on blood lead (BPb) concentration, iron status, and cognition. DESIGN: In this 2 × 2 factorial, double-blind placebo-controlled trial, 457 lead-exposed Moroccan children were stratified by school and grade and randomly assigned to consume biscuits (6 d/wk at school) containing 1) ∼8 mg Fe as FeSO4, 2) ∼8 mg Fe as NaFeEDTA that contained ∼41 mg EDTA, 3) ∼41 mg EDTA as sodium EDTA (Na2EDTA), or 4) placebo for 28 wk. The primary outcome was BPb concentration; secondary outcomes were iron status and cognitive outcomes from subtests of the Kaufman Assessment Battery for Children and the Hopkins Verbal Learning Test. These outcomes were measured at baseline and endpoint. All data were analyzed by intention-to-treat. RESULTS: The adjusted geometric mean BPb concentration at baseline was 4.3 μg/dL (95% CI: 4.2, 4.3 μg/dL), and at endpoint these values were 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for FeSO4, 2.9 μg/dL (95% CI: 2.7, 3.0 μg/dL) for NaFeEDTA, 3.3 μg/dL (95% CI: 3.1, 3.5 μg/dL) for EDTA, and 3.7 μg/dL (95% CI: 3.5, 3.9 μg/dL) for placebo. We found an effect of iron (P = 0.009) and EDTA (P = 0.012) for reduced BPb concentrations at endpoint, but no iron × EDTA interaction. Iron fortification improved iron status, but there were no positive effects of iron or EDTA on cognitive test scores. CONCLUSIONS: Food fortification with iron and EDTA additively reduces BPb concentrations. Our findings suggest that NaFeEDTA should be the iron fortificant of choice in lead-exposed populations. This trial was registered at clinicaltrials.gov as NCT01573013.