SummaryIncreased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron‐depleted Kenyan children, 24–27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long‐term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48–0.78]) but not with iron dose (r = 0.16 [95% CI −0.10–0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

AIMS OF THE STUDY: Listeriosis is a notifiable disease in Switzerland. In summer 2022, the Swiss Federal Office of Public Health noticed an increase in reports of listeriosis cases, indicating a possible ongoing outbreak. Here we present the approaches applied for rapidly confirming the outbreak, detecting the underlying source of infection and the measures put in place to eliminate it and contain the outbreak. METHODS: For close surveillance and early detection of outbreak situations with their possible sources, listeriosis patients in Switzerland are systematically interviewed about risk behaviours and foods consumed prior to the infection. Listeria monocytogenes isolates derived from patients in medical laboratories are sent to the National Reference Laboratory for Enteropathogenic Bacteria and Listeria, where they routinely undergo whole-genome sequencing. Interview and whole-genome sequencing data are continuously linked for comparison and analysis. RESULTS: In summer 2022, 20 patient-derived L. monocytogenes serotype 4b sequence type 388 strains were found to belong to an outbreak cluster (≤10 different alleles between neighbouring isolates) based on core genome multilocus sequence typing analysis. Geographically, 18 of 20 outbreak cases occurred in northeastern Switzerland. The median age of patients was 77.4 years (range: 58.1–89.7), with both sexes equally affected. Rolling analysis of the interview data revealed smoked trout from a local producer as a suspected infection source, triggering an on-site investigation of the production facility and sampling of the suspected products by the responsible cantonal food inspection team on 15 July 2022. Seven of ten samples tested positive for L. monocytogenes and the respective cantonal authority ordered a ban on production and distribution as well as a product recall. The Federal Food Safety and Veterinary Office released a nationwide public alert covering the smoked fish products concerned. Whole-genome sequencing analysis confirmed the interrelatedness of the L. monocytogenes smoked trout product isolates and the patient-derived isolates. Following the ban on production and distribution and the product recall, reporting of new outbreak-related cases rapidly dropped to zero. CONCLUSIONS: This listeriosis outbreak could be contained within a relatively short time thanks to identification of the source of contamination through the established combined approach of timely interviewing of every listeriosis patient or a representative and continuous molecular analysis of the patient- and food-derived L. monocytogenes isolates. These findings highlight the effectiveness of this well-established, joint approach involving the federal and cantonal authorities and the research institutions mandated to contain listeriosis outbreaks in Switzerland.

The double burden of malnutrition (DBM) is escalating in low- and middle-income countries (LMICs), including in Rwanda, most notably in urbanizing areas. The 2019–2020 Rwanda Demographic Health Survey (DHS) revealed that 33% of children under 5 years old are stunted while 42% of women in urban areas are overweight or obese. This coexistence has contributed to a surge in non-communicable diseases (NCDs), particularly in secondary cities. Using the World Health Organization’s (WHOs) “double-duty action” (DDA) concept, this study aims to identify and evaluate interventions with double-duty potential in Rwanda’s Rusizi and Rubavu districts and generate key recommendations for their improvement. A desk review of national policies pinpointed four programs with the greatest DDA potential: early childhood development (ECD) centers, the school feeding program, farmer field schools (FFS), and the provision of nutrition-sensitive direct support. In-person interviews with key stakeholders assessed the implementation of each program and a Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis was used to generate context-specific recommendations for their improvement. The main finding of this research is that Rwanda’s potential to address the DBM can be improved across multiple sectors by implementing a few key changes: targeting beliefs surrounding nutrition, improving trainings for community educators, enhancing parent–particularly father–involvement, and engaging in close monitoring and follow-up. These findings offer actionable streps that governments and nutrition stakeholders can take to improve similar interventions in other rapidly urbanizing LMICs.

Background: Suboptimal diet is responsible that one-third of the world’s population suffers from malnutrition. However, in cities, current food systems cannot guarantee sustainable availability, accessibility and affordability of nutritious foods for the entire population. Digitalization can be a key driver for sustainable food system transformation for better outcomes in food and nutrition. Objective: In the frame of the Nutrition in City Ecosystems (NICE) project connecting the demand and supply of urban food systems, 16’000 Kenyan farmers should be connected to specific marketplaces in Busia and Bungoma, Western Kenya, using the Soluta-ag digital tool in order to improve availability, accessibility and affordability of nutritious foods for urban consumers. Results: In NICE, the Farmers’ Hub social business model is applied to increase the production of nutritious and agroecologically produced foods. Farmers’ Hubs are ‘one-stop-shops’ offering a range of services to farmers, e.g., access to quality inputs, mechanization, advisory services and a market place for sale for produce contributing to better dietary quality. The Soluta-ag application supports buying and selling activities of the Farmers’ Hubs, provides data-driven insights on market trends, and monitors Farmers’ Hubs performance for more informed decisions. Since the initiation of the NICE project in 2021, 92 NICE Farmers’ Hubs owners serving 10,528 farmers have been trained on the utilization of Soluta-ag in Busia and Bungoma and transacting an average of KES 100,000 per month via Soluta-ag between January to April 2023. Conclusion: Close connection between all food systems stakeholders and evidence-based data for decision-making are key for sustainable food system transformation. A sustainable and equitable food system is a priority to tackle nutrition challenges in city ecosystems. Digitalization can play a key role in these processes. Soluta-ag, applied and introduced to foster production of nutritious and agroecologically produced food in secondary cities and to better link producers and consumers clearly contributes to an increased availability, accessibility, and affordability of nutritious foods for city populations through improved connection of farmers’ produce to markets ensuring fair prices for all involved. Key words Nutritious and agroecologically produced foods, digitalization, city ecosystems, social business model, Soluta-ag

Abstract Background By 2050, approximately 68% of the global population will live in cities, but nutrition data on urban populations of low- and middle-income countries are scarce. Fast growing secondary cities, combining characteristics and hurdles of urban and rural settings, are hotspots for the double burden of malnutrition. The Nutrition in City Ecosystems (NICE) project focuses on 6 secondary cities in Bangladesh, Kenya and Rwanda, to improve health and nutrition, and reduce poverty. To assess the baseline situation and guide future interventions, food insecurity, dietary diversity, nutrition status, and food production and purchasing patterns were explored. Methods In a cross-sectional study design, data were collected from urban and peri-urban households of Dinajpur and Rangpur in Bangladesh, Bungoma and Busia in Kenya, and Rubavu and Rusizi in Rwanda. Approximately 1200 households, in neighborhoods prone to malnutrition, were involved from April to June 2021. We assessed Household Food Insecurity Access Score (HFIAS), both current and before COVID-19, Household Dietary Diversity Score (HDDS), Minimum Dietary Diversity for Women (MDD-W), anthropometric measurements, household and socioeconomic information, and questions related to food production and consumer behavior. Further we collected secondary data on low birthweight and anemia during pregnancy. Results All cities experienced a substantial increase in food insecurity during the COVID-19 pandemic. Stunting rates in children under 5 years varied among the cities and ranged from 7.8% in Busia to 46.6% in Rubavu, while half of adult women were overweight (between 42.1% in Rusizi and 55.8% in Bungoma). Furthermore, many women did not consume an adequately diverse diet (MDD-W < 5 for 29.3% in Bangladesh, 47.5% in Kenya, and 67.0% in Rwanda), however many of the urban and peri-urban households were engaged in farming (58–78%). Conclusions The double burden of malnutrition is high in secondary cities and the COVID-19 pandemic has exacerbated levels of food insecurity. Demand for, and access to, an affordable healthy diverse diet that comprises local, nutritious, and agroecologically produced foods present a pathway for overcoming the complex challenges of malnutrition.

BackgroundSecondary cities tend to be better linked with local food systems than primate cities, acting as important platforms to trade agricultural produce with rural surrounding. COVID-19, conflicts and climate change continue to expose inefficiencies in food systems and have further exacerbated malnutrition, calling for substantial food systems transformations. However, tackling current food systems' challenges requires new approaches to ensure food and nutrition security. Nutritious and agroecologically produced food offer the potential to transform food systems by improving diets and alleviating pressure on the environment, as well as by creating jobs and reducing poverty. This paper describes the design of a project by a Swiss public-private consortium to improve food and nutrition security and to reduce poverty in city ecosystems in six secondary cities in Bangladesh, Kenya and Rwanda through governance/policy and supply and demand side interventions.MethodsThe Nutrition in City Ecosystems (NICE) project promotes well-balanced nutrition for city populations through interdisciplinary agricultural, food, and health sector collaborations along city-specific value chains. Adopting a transdiciplinary systems approach, the main interventions of NICE are (i) advocacy and policy dialogue, (ii) building of decentralized institutional capacity in multi-sectoral collaborations, (iii) support of data-driven planning, coordination and resource mobilization, (iv) anchoring of innovations and new approaches in city-level partnerships, (v) capacity building in the agricultural, retail, health and education sectors, as well as (vi) evidence generation from putting policies into practice at the local level. NICE is coordinated by in-country partners and local offices of the Swiss public-private consortium partners.DiscussionThe NICE project seeks to contribute to urban food system resilience and enhanced sustainable nutrition for city populations by (A) strengthening urban governance structures involving key stakeholders including women and youth, (B) generating income for producers along the supply chain, (C) triggering change in producers' and consumers' behavior such that nutritious and agroecologically produced foods are both in demand as well as available and affordable in urban markets, and (D) allowing a scale up of successful approaches to other national and international cities and city networks.

Secondary cities (SC) link rural food production with urban populations. SC are rapidly growing, lack of infrastructure and face changes in dietary patterns. Across women of reproductive age (WRA) all forms of malnutrition have been identified. SC offer an opportunity for food systems transformation. We argue to uncover the demand-related determinants of purchasing, preparing, consuming, and feeding practices among WRA with low socioeconomic status living SC in Rwanda to identify possible interventions to enhance the demand of agroecological produced food. Thematic analysis is conducted among WRA with low socioeconomic status living in SC -Rubavu, and Rusizi- in Rwanda. Eighteen face-to-face, in-home observations were conducted in the manner of compact ethnographic research. These observations covered the participants' way of living, home environment, shopping and cooking observation, a pantry/kitchen audit. Transcripts from the interviews are being coded with NVIVO software. Ethical consent was provided by the Rwanda National Ethics Committee. Preliminary findings show that most WRA involved in the interviews prepare two meals per day. The most commonly food items consumed are irish potatoes, bananas, rice, and flour, with women indicating little to no intention of trying out new dishes or new preparation type. The most common cooking method is boiling, salt and garlic being the primary spieces used. WRA do not consume special food items based on their current life stage (pregnancy or lactation). The household budget for purchasing food is provided and decided mainly by men; however, women make the purchase and cooking decisions. The purchase of foods is determined by price, owing to minimal purchase power. Health care professionals and social workers are the trusted source of information. Final results will be available by May 2022. Our findings will help design a social marketing campaign to promote the purchasing, consumption, and cooking practices of locally produced agroecological foods that is specifically targeted to WRA of low socioeconomic status living in those SC. The NICE project is supported by the Swiss Agency for Development and Cooperation and implemented by the Swiss Tropical and Public Health Institute, ETH Zürich, Sight and Life, and the Syngenta Foundation for Sustainable Agriculture.

Introduction: Increased iron losses may reduce the effectiveness of iron supplementation. The objectives of our study were (i) to determine if daily oral doses of iron increase iron losses in Kenyan infants, measured using long-term labelling with a stable isotope of iron (58Fe), (ii) to detect increases in gastrointestinal bleeding, and (iii) to compare the results in Kenyan infants with iron dose, absorption, and loss from other long-term isotopic studies. Long-term studies of iron absorption and loss require an equilibration period of one year or more to allow the isotopic tracer to uniformly label body iron. Thereafter, an increase in body iron from absorption is proportional to the rate of decrease in the concentration of the isotopic tracer in circulating blood. A loss of endogenous body iron is proportional to the rate of decrease in the amount of the isotopic tracer. Conventional use of biomarkers to evaluate the effect of iron supplementation programs do not separately determine iron absorption and loss and can estimate only net changes in body iron. Single meal or short-term studies using stable iron isotopes do not assess loss and evaluate only acute iron absorption. Methods: We enrolled 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron had equilibrated with 58Fe tracer given at least one year earlier. The toddlers received 6 mg elemental iron/kg body weight (BW) daily for 91 days as an oral ferric ammonium citrate iron syrup. We estimated iron absorption and loss from the shift in stable iron isotopic ratios in blood over the study period. We measured occult blood in fecal samples with an HemoQuant fluorometric assay by determining hemoglobin and porphyrin concentrations. We measured fecal calprotectin to assess enterocyte damage and fecal pH to evaluate gut inflammation. We then examined the relationship of iron dose, absorption, and loss in Kenyan infants with the results from all published investigations using the long-term stable isotope methodology. We compared the 6 mg/kg BW dose in the Kenyan toddlers with doses of 0.8-1.2 mg/kg BW in Gambian toddlers (Br J Haematol. 2021;192:179-89) and women in Benin and Switzerland (Am J Clin Nutr. 2021;113:1657-1669), and with dietary iron alone in Malawian children (Am J Clin Nutr. 2021;114:986-996) and U.S. toddlers (J Nutr. 2005;135:771-777). Results: In Kenyan infants, after 3 months of daily iron supplementation with 6 mg iron/kg BW, the median (interquartile range) iron absorption was 1.07 (0.98; 1.27) mg/day. During supplementation, 0.61 (0.26, 0.79) mg/day, or 57% of the amount of absorbed iron, was lost (Figure 1). For comparison, WHO estimates basal iron loss for 1-3-year-old children as 0.19 mg/day. The net gain in iron was 0.65 (0.21; 0.68) mg/day, and was associated with an increase in hemoglobin from 10.7 (10.2; 11.2) to 11.5 (11.1; 12.1) g/dL and in plasma ferritin from 12.9 (8.3; 16.1) to 26.2 (20.5; 29.9) μg/L, and a decrease in soluble transferrin receptor from 13.2 (9.6; 15.7) to 7.4 (6.4; 8.6) mg/L (for all, P < 0.001). Supplementation did not increase heme/porphyrin fecal losses or calprotectin and did not decrease fecal pH. The comparison of the iron dose, absorption, and loss in Kenyan infants with those of published studies using the long-term stable isotope methodology (Figure 2) found that daily iron loss was strongly correlated with iron absorption (Pearson r=0.95, p<0.005) but had no significant relationship with iron dose (p=0.24). Conclusions: The source of the iron losses with supplementation remains to be determined. Because humans have no regulated means to eliminate iron, increased iron excretion cannot account for the greater iron loss observed during supplementation. Our results provide evidence that the amounts of iron lost increase with the amount of iron absorbed rather than the dose of iron given during iron supplementation. In general, limited net iron gains with iron supplementation have been attributed to internal influences, such as inflammatory increases in hepcidin, or to external effects, such as poor adherence or inhibition from dietary phytates, polyphenols or other components. The results of these long-term stable iron isotopic measurements suggest a potential alternative explanation, that increased iron losses during iron supplementation reduce the effectiveness of iron interventions. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

BACKGROUNDPrevention 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.OBJECTIVESIn this study, we aimed to quantify iron absorption, loss, and balance in apparently healthy 5- to 7-y-old children living in rural Africa.METHODSWe 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.RESULTSOf 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).CONCLUSIONSOur 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.

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.

SummaryWe report the first measurements of long‐term iron absorption and loss during iron supplementation in African children using a stable isotope of iron (57Fe). After uniform labelling of body iron with 57Fe, iron absorption is proportional to the rate of decrease in the 57Fe tracer concentration, while iron loss is proportional to the rate of decrease in the 57Fe tracer amount. Anaemic Gambian toddlers were given 2 mg 57Fe 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 3·8‐fold during the iron supplementation period compared to the control period [median (interquartile range, IQR): 1·00 (0·82; 1·28) mg/day vs. 0·26 (0·22; 0·35) mg/day; P = 0·001]. Unexpectedly, during the supplementation period, daily iron loss also increased by 3·4‐fold [0·75 (0·55; 0·87) mg/day vs. 0·22 (0·19; 0·29) mg/day; P = 0·005]. 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: 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: 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.Objective: Using fortified rice produced by coating or hot or cold extrusion, we compared 1) iron and zinc absorption with the use of stable isotopes, 2) iron and zinc retention during cooking, and 3) starch microstructure.Methods: We conducted 2 studies in young women: in study 1 [n = 19; mean ± SD age: 26.2 ± 3.4 y; body mass index (BMI; in kg/m2): 21.3 ± 1.6], we compared the fractional iron absorption (FAFe) from rice meals containing isotopically labeled ferric prophosphate (57FePP), zinc oxide (ZnO), citric acid, and micronutrients fortified through hot extrusion (HER1) with rice meals fortified through cold extrusion containing 57FePP, ZnO, citric acid, and micronutrients (CER); in study 2 (n = 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 57FePP, 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.Results: FAFe (95% CI) was greater from CER [2.2% (1.4%, 3.4%)] than from HER1 [1.2% (0.7%, 2.0%)] (P = 0.036). There was no difference in FAFe between HER2 [5.1% (3.7%, 7.1%)] and COR [4.0% (2.9%, 5.4%)] (P = 0.14), but FAFe from COR was lower than that from the reference meal [6.6% (4.9%, 9.0%)] (P = 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%)] (P = 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.Conclusions: 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 ( 54 FePP, 57 FePP, 58 FePP) in a cross‐over multiple meal absorption study. Fortified extruded rice meals either contained: zinc oxide (ZnO; 54 FePP+ZnO), zinc sulphate (ZnSO 4 ; 57 FePP+ZnSO 4 ), alone or in combination with a citrate buffer CA/TSC ( 54 FePP+ZnO+CA/TSC or 57 FePP+ZnSO 4 +CA/TSC) or ZnO, CA and edetate (EDTA; 58 FePP+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 54 FePP+ZnO, 57 FePP+ZnSO 4 , 54 FePP+ZnO+CA/TSC, 57 FePP+ZnSO 4 +CA/TSC, 58 FePP+ZnO+CA+EDTA versus non‐fortified extruded rice with 58 FeSO 4 (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 54 FePP+ZnSO 4 +CA/TSC (6.3%; 5.3,7.4) and 58 FePP+ZnO+CA+EDTA (6.5%; 5.3,8.1) did not differ from the reference (6.6%; 5.4,8.1). FAFe between 57 FePP+ZnSO 4 (3.5%; 2.7,4.5) and 54 FePP+ZnO+CA/TSC (4.4%; 3.6,5.5) was not different, but both differed from 54 FePP+ZnSO 4 +CA/TSC, 58 FePP+ZnO+CA+EDTA and the reference (P<0.038), however, 54 FePP+ZnO (2.3%; 1.9,2.8) showed the lowest FAFe and significantly differed from all other meals (P<.035). Conclusions Iron absorption from FePP‐fortified rice is affected by both the zinc source (ZnO or ZnSO 4 ) and absorption enhancers (CA/TSC and CA+EDTA). For maximal iron absorption, rice fortification should be implemented using ZnSO 4 as the zinc fortificant and CA/TSC or CA+EDTA as iron absorption enhancers. Support or Funding Information This study was funded by the Laboratory of Human Nutrition, DSM Nutritional Products, USAID and Abbott Nutrition.

Global efforts to reduce iron deficiency anemia are hindered by the unreliability of current iron status biomarkers in the presence of infection and inflammation. We developed and evaluated a novel stable iron isotope method based on the dilution of labelled body iron to measure and quantify the efficacy of an iron intervention and to quantify iron balance in rural Gambian toddlers.To label total body iron, we orally administered 2 mg 57Fe as FeSO4 to anemic infants (mean(SD) age: 16.7(1.6) months; Hb < 11.0 g/dl) and waited 41(4.9) weeks for equilibration of the 57Fe in body iron. We then randomly allocated the toddlers to 12 weeks of directly supervised feeding with: A) a micronutrient powder (MNP) containing 12 mg Fe given every day; B) a MNP containing 12 mg Fe given for seven days when hepdicin < 5.5 ng/ml at weekly screening; C) a MNP containing 6 mg Fe given for seven days when hepdicin < 5.5 ng/ml at weekly screening. We quantified the rate of change of body iron (RCFe), iron absorption (FeAbs), as well as the change in Hb (ΔHb), soluble transferrin receptor (ΔsTfR) and plasma ferritin (ΔPF). These markers were assessed in all toddlers in blood samples on day 49 and 84 of the intervention, and after a 12‐week control period post‐intervention.Complete data from 41 subjects was available for analysis. Time elapsed from isotopic administration to intervention start was not correlated with RCFe, suggesting complete isotopic label equilibration. RCFe significantly differed between the intervention and control period (P < 0.01), as did ΔHb (P < 0.01) and ΔsTfR (P < 0.01) but not ΔPF (P = 0.17). Compared to conventional iron biomarkers, RCFe had the strongest association with total administered iron dose (R2 = 0.44, P < 0.01). RCFe was also associated with ΔHb, ΔsTfR and ΔPF (R2 = 0.37, P < 0.01; R2 = 0.49, P < 0.01 and R2 = 0.11, P < 0.05, respectively). Across the three groups, FeAbs during the intervention (0.36 ± 0.13 mg Fe/d) was significantly higher than during the control period (0.13 ± 0.07 mg Fe/d, P < 0.01). During the intervention, FeAbs was significantly higher in group A (0.47 ± 0.18 mg Fe/d) than in groups B or C (0.30 ± 0.10 mg Fe/d and 0.33 ± 0.12 mg Fe/d, P = 0.01). Daily iron losses were significantly higher during the intervention (0.25 ± 0.11 mg Fe/d) than during the control period (0.11 ± 0.12 mg Fe/d, P < 0.01); there were no significant differences in daily iron losses between the three groups.ConclusionsRCFe measured with this technique is superior to conventional iron biomarkers in prediction of the administered iron dose. It may allow to quantify iron absorption, losses and overall iron balance over the long term, and is a promising tool to evaluate iron interventions with high precision entirely free from confounding by inflammation.Support or Funding InformationThis study was funded by ETH Zurich and Bill & Melinda Gates Foundation.