We report the first measurements of long-term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57 Fe). After uniform labelling of body iron with 57 Fe, iron absorption is proportional to the rate of decrease in the 57 Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57 Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57 Fe orally to equilibrate with total body iron over 8-11 months. After assignment to the positive control arm of the HIGH study, 22 toddlers consumed a micronutrient powder containing 12 mg iron for 12 weeks followed by 12 weeks without iron supplementation. Their daily iron absorption increased 3Á8-fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1Á00 (0Á82; 1Á28) mg/day vs. 0Á26 (0Á22; 0Á35) mg/day; P = 0Á001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3Á4-fold [0Á75 (0Á55; 0Á87) mg/day vs. 0Á22 (0Á19; 0Á29) mg/day; P = 0Á005]. Consequently, most (~72%) of the absorbed iron was lost during supplementation. Long-term studies of iron absorption and loss are a promising and accurate method for assessing and quantifying long-term iron balance and may provide a reference method for evaluating iron intervention programs in vulnerable population groups. This study was registered as ISRCTN 0720906.
Iron deficiency and anemia are prominent contributors to the preventable disease burden worldwide. A substantial proportion of people with inadequate dietary iron rely on rice as a staple food, but fortification efforts are limited by low iron bioavailability. Furthermore, using high iron fortification dosages may not always be prudent in tropical regions. To identify alternative fortification formulations with enhanced absorption, we screened different iron compounds for their suitability as rice fortificants, measured in vitro gastric solubility, and assessed dietary iron bioavailability using stable isotopic labels in rural Ghanaian children. Isotopic incorporation in red blood cells indicates that in the two age groups of children investigated (4 to 6 and 7 to 10 years), formulations provided 36 and 51% of the median daily requirement in absorbed iron, respectively. We describe approaches to enhancing iron bioavailability from fortified rice, which can substantially contribute to the prevention of iron deficiency in rice-eating populations.
Background Long-term isotopic dilution measurements of body iron may allow quantification of basal body iron balance and iron gains during an iron intervention with higher precision and accuracy than conventional iron indices. Objectives We compared body iron balance before, during, and after oral iron supplementation in women in Benin and in Switzerland. Methods In prospective studies, Beninese (n = 11) and Swiss (n = 10) women previously labeled with stable iron isotopes were followed preintervention for 90–120 d, then received 50-mg iron daily for 90–120 d and were followed postintervention for 90–120 d. We used changes in blood isotopic composition to calculate iron absorption (Feabs), iron loss (Feloss), and net iron balance (Fegain). Results Compliance with supplementation was >90%. In Benin, during the preintervention, intervention, and postintervention periods, Fe means ± SDs were as follows: 1) Feabs: 0.92 ± 1.05, 3.75 ± 2.07, and 0.90 ± 0.93 mg/d; 2) Feloss: 1.46 ± 1.95, 1.58 ± 1.57, and 1.84 ± 1.61 mg/d; and 3) Fegain: −0.55 ± 1.56 mg/d, 2.17 ± 1.81 mg/d, and −0.94 ± 1.13 mg/d. In Switzerland, the corresponding values were: 1) 1.51 ± 0.37, 4.09 ± 1.52, and 0.97 ± 0.41 mg/d; 2) 0.76 ± 1.37, 2.54 ± 1.43, and 2.08 ± 1.05 mg/d; and 3) 0.75 ± 1.37, 1.55 ± 1.75, and −1.11 ± 1.06 mg/d. Inflammation was low in both settings, and isotopically calculated iron balance was comparable to that calculated from changes in conventional iron indices. Conclusion Without iron supplementation, Beninese women had lower long-term dietary iron absorption and higher iron losses in the preintervention period than Swiss women. During iron supplementation, both groups had high iron absorption and similar iron gains. However, there was a 3-fold increase in iron losses in the Swiss women during the supplementation and postintervention period compared with the preintervention period. Body iron isotope dilution is a promising new method for quantifying long-term body iron balance and for assessing the impact of iron interventions. The studies were registered at clinicaltrials.gov as NCT02979080 and NCT02979132, respectively.
Background: Reference intakes for iron are derived from physiological requirements, with an assumed value for dietary iron absorption. A new approach to estimate iron bioavailability, calculated from iron intake, status, and requirements was used to set European dietary reference values, but the values obtained cannot be used for low- and middle-income countries where diets are very different. Objective: We aimed to test the feasibility of using the model developed from United Kingdom and Irish data to derive a value for dietary iron bioavailability in an African country, using data collected from women of child-bearing age in Benin. We also compared the effect of using estimates of iron losses made in the 1960s with more recent data for whole body iron losses. Methods: Dietary iron intake and serum ferritin (SF), together with physiological requirements of iron, were entered into the predictive model to estimate percentage iron absorption from the diet at different levels of iron status. Results: The results obtained from the 2 different methods for calculating physiological iron requirements were similar, except at low SF concentrations. At a SF value of 30 µg/L predicted iron absorption from the African maize-based diet was 6%, compared with 18% from a Western diet, and it remained low until the SF fell below 25 µg/L. Conclusions: We used the model to estimate percentage dietary iron absorption in 30 Beninese women. The predicted values agreed with results from earlier single meal isotope studies; therefore, we conclude that the model has potential for estimating dietary iron bioavailability in men and nonpregnant women consuming different diets in other countries.
Background Prevention of iron deficiency in African children is a public health priority. Current WHO/FAO estimations of iron requirements are derived from factorial estimates based on healthy, iron-sufficient “model” children using data derived mainly from adults. Objectives In this study, we aimed to quantify iron absorption, loss, and balance in apparently healthy 5- to 7-y-old children living in rural Africa. Methods We directly measured long-term iron absorption and iron loss in a 2-y observational study in Malawian children (n = 48) using a novel stable iron isotope method. Results Of the 36 children with height-for-age and weight-for-age z scores ≥−2, 13 (36%) were iron deficient (soluble transferrin receptor >8.3 mg/L) and 23 were iron sufficient. Iron-deficient children weighed more than iron-sufficient children [mean difference (95% CI): +2.1 (1.4, 2.7) kg; P = 0.01]. Mean iron losses did not differ significantly between iron-deficient and iron-sufficient children and were comparable to WHO/FAO median estimates of 19 µg/(d × kg). In iron-sufficient children, median (95% CI) dietary iron absorption was 32 (28, 34) µg/(d × kg), comparable to WHO/FAO-estimated median requirements of 32 µg/(d × kg). In iron-deficient children, absorption of 28 (25, 30) µg/(d × kg) was not increased to correct their iron deficit, likely because of a lack of bioavailable dietary iron. Twelve children (25%) were undernourished (underweight, stunted, or both). Conclusions Our results suggest that WHO/FAO iron requirements are adequate for healthy iron-sufficient children in this rural area of Malawi, but iron-deficient children require additional bioavailable iron to correct their iron deficit.
Rice can be fortified with the use of hot or cold extrusion or coating, but the nutritional qualities of the resulting rice grains have never been directly compared. Using fortified rice produced by coating or hot or cold extrusion, we compared ) iron and zinc absorption with the use of stable isotopes,) iron and zinc retention during cooking, and ) starch microstructure. We conducted 2 studies in young women: in study 1 [ = 19; mean ± SD age: 26.2 ± 3.4 y; body mass index (BMI; in kg/m): 21.3 ± 1.6], we compared the fractional iron absorption (FAFe) from rice meals containing isotopically labeled ferric prophosphate (FePP), zinc oxide (ZnO), citric acid, and micronutrients fortified through hot extrusion (HER1) with rice meals fortified through cold extrusion containing FePP, ZnO, citric acid, and micronutrients (CER); in study 2 ( = 22; age: 24 ± 4 y; BMI: 21.2 ± 1.3), we compared FAFe and fractional zinc absorption (FAZn) from rice meals fortified through hot extrusion (HER2) compared with rice meals fortified through coating containing FePP, ZnO, a citric acid and trisodium cirate mixture (CA/TSC), and micronutrients (COR) relative to rice meals extrinsically fortified with ferrous sulfate (reference). Rice types HER1 and CER contained citric acid, whereas types HER2 and COR contained CA/TSC. We assessed retention during standardized cooking experiments and characterized the rice starch microstructure. FAFe (95% CI) was greater from CER [2.2% (1.4%, 3.4%)] than from HER1 [1.2% (0.7%, 2.0%)] ( = 0.036). There was no difference in FAFe between HER2 [5.1% (3.7%, 7.1%)] and COR [4.0% (2.9%, 5.4%)] ( = 0.14), but FAFe from COR was lower than that from the reference meal [6.6% (4.9%, 9.0%)] ( = 0.003), and the geometric mean FAZn (95% CI) did not differ between HER2 [9.5% (7.9%, 11.6%)] and COR [9.6% (8.7%, 10.7%)] ( = 0.92). Cooking in a rice-to-water ratio of 1:2 resulted in iron and zinc retentions >80%, and cooking in excess water did not affect iron retention from hot-extruded rice but caused iron losses of 25% from CER and COR. Distinct variations in starch microstructure were found in CER and HER1. Iron absorption was 64% higher from CER than from hot-extruded rice, with no difference between COR compared with hot-extruded rice. Lower extrusion temperatures may generate a more readily digestible starch structure, allowing for greater iron release in vivo but lower mineral retention during cooking. This trial was registered at clinicaltrials.gov as NCT02176759.
Rice fortification can be a viable approach to combat iron deficiency in rice‐consuming populations, but it is crucial to identify micronutrient formulations with high iron bioavailability and acceptable sensory properties. To date, ferric phosphates are the only iron compounds resulting in sensory acceptable iron fortified rice grains.We measured fractional iron absorption (FAFe) from isotopically labeled ferric‐pyrophosphate (54FePP, 57FePP, 58FePP) in a cross‐over multiple meal absorption study. Fortified extruded rice meals either contained: zinc oxide (ZnO; 54FePP+ZnO), zinc sulphate (ZnSO4; 57FePP+ZnSO4), alone or in combination with a citrate buffer CA/TSC (54FePP+ZnO+CA/TSC or 57FePP+ZnSO4+CA/TSC) or ZnO, CA and edetate (EDTA; 58FePP+ZnO+CA+EDTA).Iron depleted school‐age children with and without anemia (N=26) in Northern Ghana were fed six different rice meals (all meals containing 2mg iron) over the course of six weeks. Each type of meal was administered twice daily for five consecutive days. FAFe was compared from meals 54FePP+ZnO, 57FePP+ZnSO4, 54FePP+ZnO+CA/TSC, 57FePP+ZnSO4+CA/TSC, 58FePP+ZnO+CA+EDTA versus non‐fortified extruded rice with 58FeSO4 (reference) added after cooking. FAFe was measured as erythrocyte‐incorporation of stable iron isotopes at least 11 days after meal‐administration.Geometric mean FAFe (95% CI) from meals 54FePP+ZnSO4+CA/TSC (6.3%; 5.3,7.4) and 58FePP+ZnO+CA+EDTA (6.5%; 5.3,8.1) did not differ from the reference (6.6%; 5.4,8.1). FAFe between 57FePP+ZnSO4 (3.5%; 2.7,4.5) and 54FePP+ZnO+CA/TSC (4.4%; 3.6,5.5) was not different, but both differed from 54FePP+ZnSO4+CA/TSC, 58FePP+ZnO+CA+EDTA and the reference (P<0.038), however, 54FePP+ZnO (2.3%; 1.9,2.8) showed the lowest FAFe and significantly differed from all other meals (P<.035).ConclusionsIron absorption from FePP‐fortified rice is affected by both the zinc source (ZnO or ZnSO4) and absorption enhancers (CA/TSC and CA+EDTA). For maximal iron absorption, rice fortification should be implemented using ZnSO4 as the zinc fortificant and CA/TSC or CA+EDTA as iron absorption enhancers.Support or Funding InformationThis study was funded by the Laboratory of Human Nutrition, DSM Nutritional Products, USAID and Abbott Nutrition.
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