Physicians and Surgeons, New York, NY
Key Points• Iron supplements at doses of 60 mg Fe as FeSO 4 or higher increase hepcidin for up to 24 hours and are associated with lower iron absorption on the following day.• The soluble transferrin receptor/ferritin ratio and hepcidin are equivalent predictors of iron absorption from supplements.Iron supplements acutely increase hepcidin, but the duration and magnitude of the increase, its dose dependence, and its effects on subsequent iron absorption have not been characterized in humans. Better understanding of these phenomena might improve oral iron dosing schedules. We investigated whether the acute iron-induced increase in hepcidin influences iron absorption of successive daily iron doses and twice-daily iron doses. We recruited 54 nonanemic young women with plasma ferritin £20 mg/L and conducted: (1) (study 1, n 5 25; study 2, n 5 16); and (2) a study giving three 60-mg Fe doses (twice-daily dosing) within 24 hours (study 3, n 5 13). In studies 1 and 2, 24 hours after doses ‡60 mg, serum hepcidin was increased (P < .01) and fractional iron absorption was decreased by 35% to 45% (P < .01). With increasing dose, fractional absorption decreased (P < .001), whereas absolute absorption increased (P < .001). A sixfold increase in iron dose (40-240 mg) resulted in only a threefold increase in iron absorbed (6.7-18.1 mg). In study 3, total iron absorbed from 3 doses (2 mornings and an afternoon) was not significantly greater than that from 2 morning doses. Providing lower dosages (40-80 mg Fe) and avoiding twice-daily dosing maximize fractional absorption. The duration of the hepcidin response supports alternate day supplementation, but longer-term effects of these schedules require further investigation. These clinical trials were registered at www.ClinicalTrials.gov as #NCT01785407 and #NCT02050932. (Blood.
Background: Overweight is increasing in transition countries, while iron deficiency remains common. In industrialized countries, greater adiposity increases risk of iron deficiency. Higher hepcidin levels in obesity may reduce dietary iron absorption. Therefore, we investigated the association between body mass index (BMI) and iron absorption, iron status and the response to iron fortification in populations from three transition countries (Thailand, Morocco and India). Methods: In Thai women (n ¼ 92), we examined the relationship between BMI and iron absorption from a reference meal containing B4 mg of isotopically labeled fortification iron. We analyzed data from baseline (n ¼ 1688) and intervention (n ¼ 727) studies in children in Morocco and India to look for associations between BMI Z-scores and baseline hemoglobin, serum ferritin and transferrin receptor, whole blood zinc protoporphyrin and body iron stores, and changes in these measures after provision of iron. Results: In the Thai women, 20% were iron deficient and 22% were overweight. Independent of iron status, a higher BMI Z-score was associated with decreased iron absorption (P ¼ 0.030). In the Indian and Moroccan children, 42% were iron deficient and 6.3% were overweight. A higher BMI Z-score predicted poorer iron status at baseline (Po0.001) and less improvement in iron status during the interventions (Po0.001). Conclusions: Adiposity in young women predicts lower iron absorption, and pediatric adiposity predicts iron deficiency and a reduced response to iron fortification. These data suggest the current surge in overweight in transition countries may impair efforts to control iron deficiency in these target groups. Interactions of the 'double burden' of malnutrition during the nutrition transition may have adverse consequences.
Low iron absorption from common beans might contribute to iron deficiency in countries where beans are a staple food. High levels of phytic acid (PA) and polyphenols (PP) inhibit iron absorption; however, the effect of bean PP on iron absorption in humans has not been demonstrated and, with respect to variety selection, the relative importance of PP and PA is unclear. To evaluate the influence of bean PP relative to PA on iron absorption in humans, 6 stable iron isotope absorption studies were conducted in women (16 or 17 per study). Bean PP (20, 50, and 200 mg) were added in studies 1-3 as red bean hulls to a bread meal. Studies 4- 6 investigated the influence on iron absorption of PP removal and dephytinization of whole red bean porridge and PP removal from dephytinized porridge. Iron absorption was lowered by 14% with 50 mg PP (P < 0.05) and by 45% with 200 mg PP (P < 0.001). The mean iron absorption from whole bean porridge was 2.5%. PP and PA removal increased absorption 2.6-fold (P < 0.001) and removal of PP from dephytinized porridge doubled absorption (P < 0.001). Between-study comparisons indicated that dephytinization did not increase iron absorption in the presence of PP, but in their absence, absorption increased 3.4-fold (P < 0.001). These data suggest that in countries where beans are a staple food, PP and PA concentrations should be considered when selecting bean varieties for human consumption. Lowering only one inhibitor will have a modest influence on iron absorption.
Dietary iron absorption is reduced by ≈ 40% in asymptomatic P. falciparum parasitemia, likely because of low-grade inflammation and its modulation of circulating hepcidin. Because asymptomatic parasitemia has a protracted course and is very common in malarial areas, this effect may contribute to IDA and blunt the efficacy of iron supplementation and fortification programs. This trial was registered at clinicaltrials.gov as NCT01108939.
Optimization of the micronutrient powder increased iron absorption from a highly inhibitory meal approximately 5-fold. This approach may allow for effective, untargeted in-home fortification of complementary foods with low amounts of highly bioavailable iron.
Iron biofortification of pearl millet (Pennisetum glaucum) is a promising approach to combat iron deficiency (ID) in the millet-consuming communities of developing countries. To evaluate the potential of iron-biofortified millet to provide additional bioavailable iron compared with regular millet and post-harvest iron-fortified millet, an iron absorption study was conducted in 20 Beninese women with marginal iron status. Composite test meals consisting of millet paste based on regular-iron, iron-biofortified, or post-harvest iron-fortified pearl millet flour accompanied by a leafy vegetable sauce or an okra sauce were fed as multiple meals for 5 d. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. Fractional iron absorption from test meals based on regular-iron millet (7.5%) did not differ from iron-biofortified millet meals (7.5%; P = 1.0), resulting in a higher quantity of total iron absorbed from the meals based on iron-biofortified millet (1125 vs. 527 μg; P < 0.0001). Fractional iron absorption from post-harvest iron-fortified millet meals (10.4%) was higher than from regular-iron and iron-biofortified millet meals (P < 0.05 and P < 0.01, respectively), resulting in a higher quantity of total iron absorbed from the post-harvest iron-fortified millet meals (1500 μg; P < 0.0001 and P < 0.05, respectively). Results indicate that consumption of iron-biofortified millet would double the amount of iron absorbed and, although fractional absorption of iron from biofortification is less than that from fortification, iron-biofortified millet should be highly effective in combatting ID in millet-consuming populations.
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