Effect of dietary factors and time of day on iron absorption from oral iron supplements in iron deficient women

Abstract Guidelines generally recommend taking iron supplements in the morning away from meals and with ascorbic acid (AA) to increase iron absorption. However, there is little direct evidence on the effects of dietary factors and time of day on absorption from iron supplements. In iron‐depleted women ( n = 34; median serum ferritin 19.4 μg/L), we administered 100 mg iron doses labeled with 54 Fe, 57 Fe, or 58 Fe in each of six different conditions with: (1) water (reference) in the morning; (2) 80 mg AA; (3) 500 mg AA; (4) coffee; (5) breakfast including coffee and orange juice (containing ~90 mg AA); and (6) water in the afternoon. Fractional iron absorption (FIA) from these n = 204 doses was calculated based on erythrocyte incorporation of multiple isotopic labels. Compared to the reference: 80 mg AA increased FIA by 30% ( p < .001) but 500 mg AA did not further increase FIA ( p = .226); coffee decreased FIA by 54% ( p = .004); coffee with breakfast decreased FIA by 66% ( p < .001) despite the presence of ~90 mg of AA. Serum hepcidin was higher ( p < .001) and FIA was 37% lower ( p = .059) in the afternoon compared to the morning. Our data suggest that to maximize efficacy, ferrous iron supplements should be consumed in the morning, away from meals or coffee, and with an AA‐rich food or beverage. Compared to consuming a 100 mg iron dose in the morning with coffee or breakfast, consuming it with orange juice alone results in a ~ 4‐fold increase in iron absorption, and provides ~20 more mg of absorbed iron per dose. The trial was registered at Clinicaltrials.gov (NCT04074707).