Absorption of iron from edible house crickets: a randomized crossover stable-isotope study in humans.

BACKGROUND: Edible insects are a novel source of animal protein. Moreover, edible insects contain iron concentrations similar to meat, potentially making them a valuable iron source for human consumers. Yet, it is unknown to what extent iron from insects is absorbed in humans. OBJECTIVES: In this exploratory study, we assessed fractional iron absorption from house crickets (Acheta domesticus) consumed with refined (low-phytate, noninhibiting) or nonrefined (high-phytate, inhibiting) meals. METHODS: Intrinsically [57Fe]-labeled and control crickets were reared. Six iron-balanced experimental meals were randomly administered crossover to 20 iron-depleted females (serum ferritin <25 µg/L; 18-30 y old), in 2 time-blocks of 3 consecutive days, 2 wk apart. Three meals consisted of refined maize flour porridge with either [57Fe]-labeled crickets, [58Fe]SO4 (reference meal), or unlabeled crickets plus [54Fe]SO4. The other 3 meals consisted of nonrefined maize flour porridge with the same respective additions. Blood samples were drawn to assess the 14-d isotope enrichment in erythrocytes, and meal-specific fractional iron absorption was calculated. In vitro digestion was used to explore possible explanations for unexpected findings. RESULTS: Mean fractional iron absorption from 57Fe-labeled house crickets with refined maize porridge (3.06%) and from refined maize porridge with unlabeled crickets (4.92%) was lower than from the reference meal (14.2%), with respective mean differences of -11.1% (95% CI: -12.6%, -9.68%) and -9.29% (95% CI: -10.8%, -7.77%). Iron absorption from all meals based on unrefined maize porridge was low (<3%), and did not differ for the 2 meals with crickets compared with the reference meal. In vitro digestion showed that chitin, chitosan, and calcium limited iron bioaccessibility to a large extent. CONCLUSIONS: Iron absorption from house crickets and fortified maize porridge with crickets is low, which may be explained by the presence of chitin and other inhibitors in the cricket biomass.This trial was registered at https://www.trialregister.nl as NL6821.

Term infant formula supplemented with milk-derived oligosaccharides shifts the gut microbiota closer to that of human milk-fed infants and improves intestinal immune defense: a randomized controlled trial.

BACKGROUND: Bovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent concentrations of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile. OBJECTIVE: To investigate the effects of an MOS-supplemented infant formula on gut microbiota and intestinal immunity. METHODS: In a double-blind, randomized, controlled trial, healthy term formula-fed infants aged 21-26 d either received an intact protein cow milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until the age of 6 mo. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as the reference. Fecal samples collected at baseline, and the ages of 2.5 and 4 mo were assessed for microbiota (16S ribosomal RNA-based approaches), metabolites, and biomarkers of gut health and immune response. RESULTS: Aged 2.5 and 4 mo, redundancy analysis (P = 0.002) and average phylogenetic distance (P < 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally born infants and approaching HFI vaginally born infants. Relative bifidobacteria abundance was higher in EG compared with CG (P < 0.05) approaching HFI. At the age of 4 mo, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P < 0.001) and ∼65% (P < 0.01) lower in EG compared with CG, respectively. Geometric LS mean (95% CI) fecal secretory IgA in EG was twice that of CG [70 (57, 85) compared with 34 (28, 42) mg/g, P < 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG compared with CG (P = 0.065). Compared with CG, EG and HFI had lower fecal calcium excretion (by ∼30%, P < 0.005) and fecal pH (P < 0.001), and higher lactate concentration (P < 0.001). CONCLUSIONS: Infant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves the intestinal immune response.

Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis.

Anemia of inflammation is a hallmark of tuberculosis. Factors controlling iron metabolism during anemia of inflammation and its resolution are uncertain. Whether iron supplements should be given during antituberculosis treatment to support hemoglobin (Hb) recovery is unclear. Before and during treatment of tuberculosis, we assessed iron kinetics, as well as changes in inflammation and iron metabolism indices. In a 26-week prospective study, Tanzanian adults with tuberculosis (N = 18) were studied before treatment and then every 2 weeks during treatment; oral and intravenous iron tracers were administered before treatment and after intensive phase (8/12 weeks) and complete treatment (24 weeks). No iron supplements were given. Before treatment, hepcidin and erythroferrone (ERFE) were greatly elevated, erythrocyte iron utilization was high (∼80%), and iron absorption was negligible (<1%). During treatment, hepcidin and interleukin-6 levels decreased ∼70% after only 2 weeks (P< .001); in contrast, ERFE did not significantly decrease until 8 weeks (P< .05). ERFE and interleukin-6 were the main opposing determinants of hepcidin (P< .05), and greater ERFE was associated with reticulocytosis and Hb repletion (P< .01). Dilution of baseline tracer concentration was 2.6-fold higher during intensive phase treatment (P< .01), indicating enhanced erythropoiesis. After treatment completion, iron absorption increased ∼20-fold (P< .001), and Hb increased ∼25% (P< .001). In tuberculosis-associated anemia of inflammation, our findings suggest that elevated ERFE is unable to suppress hepcidin, and iron absorption is negligible. During treatment, as inflammation resolves, ERFE may remain elevated, contributing to hepcidin suppression and Hb repletion. Iron is well absorbed only after tuberculosis treatment, and supplementation should be reserved for patients remaining anemic after treatment. This trial was registered at www.clinicaltrials.gov as #NCT02176772.

Direct assessment of body iron balance in women with and without iron supplementation using a long-term isotope dilution method in Benin and Switzerland.

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.

Measurement of long-term iron absorption and loss during iron supplementation using a stable isotope of iron (57 Fe).

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 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.

Micronutrient-fortified infant cereal improves Hb status and reduces iron-deficiency anaemia in Indian infants: an effectiveness study.

Anaemia affects approximately 69 % of Indian children aged 6-12 months, with Fe deficiency (ID) being a common cause. The effectiveness of micronutrient-fortified infant cereal in improving Fe status and neurodevelopment was evaluated in non-anaemic and mildly anaemic Indian infants. An intervention group (IC) enrolled at age 6 months consumed 50 g/d of rice-based cereal providing 3·75 mg Fe/d as ferrous fumarate for 6 months (n 80) and was compared with a matched static cross-sectional control group (CG) without intervention enrolled at age 12 months (n 80). Mean Hb was higher in IC (118·1 (sd 10·2) g/l) v. CG (109·5 (sd 16·4) g/l) at age 12 months (adjusted mean difference: 9·7 g/l; 95 % CI 5·1, 14·3; P < 0·001), while geometric mean serum ferritin tended to be higher (27·0 (-1 sd 13·4, +1 sd 54·4) v. 20·3 (-1 sd 7·5, +1 sd 55·0) ng/ml); P = 0·085) and soluble transferrin receptor was lower (1·70 (-1 sd 1·19, +1 sd 2·43) v. 2·07 (-1 sd 1·29, +1 sd 3·33) mg/l; P = 0·014). Anaemia (23 v. 45 %; P = 0·007) and ID (17 v. 40 %; P = 0·003) were lower in IC v. CG. Bayley Scales of Infant and Toddler Development Third Edition scores for language (P = 0·003), motor development (P = 0·018), social-emotional (P = 0·004) and adaptive behaviour (P < 0·001), but not cognitive development (P = 0·980), were higher in IC v. CG. No significant difference in anthropometric Z-scores was observed between the groups. Consuming a micronutrient-fortified infant cereal daily for 6 months during complementary feeding promoted better Fe status while reducing the risk for anaemia and ID and was associated with superior neurodevelopmental scores.

Asymptomatic Helicobacter Pylori Infection in Preschool Children and Young Women Does Not Predict Iron Bioavailability from Iron-Fortified Foods.

Helicobacter pylori infection is common in low-income countries. It has been associated with iron deficiency and reduced efficacy of iron supplementation. Whether H. pylori infection affects iron absorption from fortified and biofortified foods is unclear. Our objective was to assess whether asymptomatic H. pylori infection predicts dietary iron bioavailability in women and children, two main target groups of iron fortification programs. We did a pooled analysis of studies in women of reproductive age and preschool children that were conducted in Benin, Senegal and Haiti using stable iron isotope tracers to measure erythrocyte iron incorporation. We used mixed models to assess whether asymptomatic H. pylori infection predicted fractional iron absorption from ferrous sulfate, ferrous fumarate or NaFeEDTA, controlling for age, hemoglobin, iron status (serum ferritin), inflammation (C-reactive protein), and test meal. The analysis included 213 iron bioavailability measurements from 80 women and 235 measurements from 90 children; 51.3% of women and 54.4% of children were seropositive for H. pylori. In both women and children, hemoglobin (Hb), serum ferritin (SF), and C-reactive protein (CRP) did not differ between the seropositive and seronegative groups. Geometric mean (95% CI) fractional iron absorption (%), adjusted for SF, was 8.97% (7.64, 10.54) and 6.06% (4.80, 7.67) in H. pylori positive and negative women (p = 0.274), and 9.02% (7.68, 10.59) and 7.44% (6.01, 9.20) in H. pylori positive and negative children (p = 0.479). Our data suggest asymptomatic H. pylori infection does not predict fractional iron absorption from iron fortificants given to preschool children or young women in low-income settings.

Anemia in tuberculosis cases and household controls from Tanzania: Contribution of disease, coinfections, and the role of hepcidin.

BACKGROUND: Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts. METHODS: We analyzed serum samples from 102 TB cases and 98 controls without TB, matched by age/sex, for hepcidin, iron, and inflammation parameters. Five controls developed TB within 12 months. We used linear regression to assess associations. RESULTS: Anemia of chronic disease (ACD) was more frequent among cases than controls (59.8% vs. 26.1%), but iron-deficiency anemia more frequent in controls (10% vs. 1%). The median hepcidin level was higher in cases than controls (63.7 vs. 14.2 ng/mL), but coinfections with HIV, helminths, and respiratory pathogens did not show cumulative effects. Hepcidin was associated with more severe TB symptom scoring (coefficient 0.8, 95% confidence interval [CI] 0.5-1.2) and higher mycobacterial load (0.7, 95% CI 0.4-1.0). Hepcidin was higher in TB cases and controls who developed TB compared to controls without TB (p<0.001), even when restricting to HIV-negative study participants. CONCLUSIONS: ACD was the predominate etiology in TB patients suggesting limited benefit from iron supplementation. Increased hepcidin levels long before active disease, indicating altered iron metabolism, may be a marker for developing disease among TB-exposed individuals. Clinical management of anemia and nutrition interventions in TB patients need to be considered to improve the clinical course and outcomes.

Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials.

BACKGROUND: Current guidelines to treat iron deficiency recommend daily provision of ferrous iron divided through the day to increase absorption. However, daily dosing and split dosing might increase serum hepcidin and decrease iron absorption from subsequent doses. Our study aim was to compare iron absorption from oral iron supplements given on consecutive versus alternate days and given as single morning doses versus twice-daily split dosing. METHODS: We did two prospective, open-label, randomised controlled trials assessing iron absorption using (54Fe)-labelled, (57Fe)-labelled, or (58Fe)-labelled ferrous sulfate in iron-depleted (serum ferritin ≤25 µg/L) women aged 18-40 years recruited from ETH Zurich and the University of Zurich, Switzerland. In study 1, women were randomly assigned (1:1) to two groups. One group was given 60 mg iron at 0800 h (±1 h) on consecutive days for 14 days, and the other group was given the same doses on alternate days for 28 days. In study 2, women were assigned to two groups, stratified by serum ferritin so that two groups with similar iron statuses could be formed. One group was given 120 mg iron at 0800 h (±1 h) and the other was given the dose split into two divided doses of 60 mg at 0800 h (±1 h) and 1700 h (±1 h) for three consecutive days. 14 days after the final dose, the groups were each crossed over to the other regimen. Within-individual comparisons were done. The co-primary outcomes in both studies were iron bioavailability (total and fractional iron absorption), assessed by measuring the isotopic label abundance in erythrocytes 14 days after administration, and serum hepcidin. Group allocations in both studies were not masked and primary and safety analyses were done on an intention-to-treat basis. The studies were registered at ClinicalTrials.gov, numbers NCT02175888 (study 1) and NCT02177851 (study 2) and are complete. FINDINGS: For study 1, 40 women were enrolled on Oct 15-29, 2015. 21 women were assigned to the consecutive-day group and 19 to the alternate-day group. At the end of treatment (14 days for the consecutive-day group and 28 days for the alternate-day group), geometric mean (-SD, +SD) cumulative fractional iron absorptions were 16·3% (9·3, 28·8) in the consecutive-day group versus 21·8% (13·7, 34·6) in the alternate-day group (p=0·0013), and cumulative total iron absorption was 131·0 mg (71·4, 240·5) versus 175·3 mg (110·3, 278·5; p=0·0010). During the first 14 days of supplementation in both groups, serum hepcidin was higher in the consecutive-day group than the alternate-day group (p=0·0031). In study 2, 20 women were enrolled between Aug 13 and 18, 2015. Ten women were assigned to receive once-daily dosing and ten were assigned to receive twice-daily divided dosing. No significant differences were seen in fractional (day 1-3 geometric mean: 11·8% [7·1, 19·4] once daily vs 13·1% [8·2, 20·7] twice daily; p=0·33) or total iron absorption (day 1-3: 44·3 mg [29·4, 66·7] once daily vs 49·4 [35·2, 69·4] twice daily; p=0·33) between the two dosing regimens. Twice-daily divided doses resulted in a higher serum hepcidin concentration than once-daily dosing (p=0·013). No grade 3 or 4 adverse events were reported in either study. INTERPRETATION: In iron-depleted women, providing iron supplements daily as divided doses increases serum hepcidin and reduces iron absorption. Providing iron supplements on alternate days and in single doses optimises iron absorption and might be a preferable dosing regimen. These findings should be confirmed in iron-deficient anaemic patients. FUNDING: Swiss National Science Foundation, Bern, Switzerland.

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants.

Background: Whether consumption of prebiotics increases iron absorption in infants is unclear.Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+NaFeEDTA) in Kenyan infants.Design: Infants (n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57FeFum+Na58FeEDTA or ferrous sulfate (54FeSO4). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixed-effects models.Results: There was a significant group-by-compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, (P < 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3-37.5%) and 25.5% (IQR: 15.1-37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO4 (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P < 0.001) and positively correlated with Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.001).Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417.

Duration of exclusive breastfeeding is a positive predictor of iron status in 6- to 10-month-old infants in rural Kenya.

The prevalence of iron-deficiency anemia (IDA) is high in infants in Sub-Saharan Africa. Exclusive breastfeeding of infants to 6 months of age is recommended by the World Health Organization, but breast milk is low in iron. Some studies suggest exclusive breastfeeding, although beneficial for the infant, may increase risk for IDA in resource-limited settings. The objective of this study was to determine if duration of exclusive breastfeeding is associated with anemia and iron deficiency in rural Kenyan infants. This was a cross-sectional study of 6-10-month-old infants (n = 134) in southern coastal Kenya. Anthropometrics, hemoglobin (Hb), plasma ferritin (PF), soluble transferrin receptor (sTfR), and C-reactive protein were measured. Body iron stores were calculated from the sTfR/PF ratio. Socioeconomic factors, duration of exclusive breastfeeding, nature of complementary diet, and demographic characteristics were determined using a questionnaire. Mean ± SD age of the infants was 7.7 ± 0.8 months. Prevalence of anemia, ID, and IDA were 74.6%, 82.1%, and 64.9%, respectively. Months of exclusive breastfeeding correlated positively with Hb (r = 0.187; p < .05) and negatively with sTfR (r = -0.246; p < .05). sTfR concentrations were lower in infants exclusively breastfed at least 6 months compared with those exclusively breastfed for less than 6 months (7.6 (6.3, 9) vs. 8.9 (6.7, 13.4); p < .05). Controlling for gender, birth weight, and inflammation, months spent exclusively breastfeeding was a significant negative predictor of sTfR and a positive predictor of Hb (p < .05). The IDA prevalence in rural Kenyan infants is high, and greater duration of exclusive breastfeeding predicts better iron status and higher Hb in this age group.

Sodium pyrophosphate enhances iron bioavailability from bouillon cubes fortified with ferric pyrophosphate.

Fe fortification of centrally manufactured and frequently consumed condiments such as bouillon cubes could help prevent Fe deficiency in developing countries. However, Fe compounds that do not cause sensory changes in the fortified product, such as ferric pyrophosphate (FePP), exhibit low absorption in humans. Tetra sodium pyrophosphate (NaPP) can form soluble complexes with Fe, which could increase Fe bioavailability. Therefore, the aim of this study was to investigate Fe bioavailability from bouillon cubes fortified with either FePP only, FePP+NaPP, ferrous sulphate (FeSO4) only, or FeSO4+NaPP. We first conducted in vitro studies using a protocol of simulated digestion to assess the dialysable and ionic Fe, and the cellular ferritin response in a Caco-2 cell model. Second, Fe absorption from bouillon prepared from intrinsically labelled cubes (2·5 mg stable Fe isotopes/cube) was assessed in twenty-four Fe-deficient women, by measuring Fe incorporation into erythrocytes 2 weeks after consumption. Fe bioavailability in humans increased by 46 % (P<0·005) when comparing bouillons fortified with FePP only (4·4 %) and bouillons fortified with FePP+NaPP (6·4 %). Fe absorption from bouillons fortified with FeSO4 only and with FeSO4+NaPP was 33·8 and 27·8 %, respectively (NS). The outcome from the human study is in agreement with the dialysable Fe from the in vitro experiments. Our findings suggest that the addition of NaPP could be a promising strategy to increase Fe absorption from FePP-fortified bouillon cubes, and if confirmed by further research, for other fortified foods with complex food matrices as well.

Cofortification of ferric pyrophosphate and citric acid/trisodium citrate into extruded rice grains doubles iron bioavailability through in situ generation of soluble ferric pyrophosphate citrate complexes.

BACKGROUND: Iron fortification of rice is a promising strategy for improving iron nutrition. However, it is technically challenging because rice is consumed as intact grains, and ferric pyrophosphate (FePP), which is usually used for rice fortification, has low bioavailability. OBJECTIVE: We investigated whether the addition of a citric acid/trisodium citrate (CA/TSC) mixture before extrusion increases iron absorption in humans from FePP-fortified extruded rice grains. DESIGN: We conducted an iron absorption study in iron-sufficient young women (n = 20), in which each participant consumed 4 different meals (4 mg Fe/meal): 1) extruded FePP-fortified rice (No CA/TSC); 2) extruded FePP-fortified rice with CA/TSC added before extrusion (CA/TSC extruded); 3) extruded FePP-fortified rice with CA/TSC solution added after cooking and before consumption (CA/TSC solution); and 4) nonextruded rice fortified with a FeSO4 solution added after cooking and before consumption (reference). Iron absorption was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. In in vitro experiments, we assessed the soluble and dialyzable iron from rice meals in which CA/TSC was added at different preparation stages and from meals with different iron:CA:TSC ratios. RESULTS: Fractional iron absorption was significantly higher from CA/TSC-extruded meals (3.2%) than from No CA/TSC (1.7%) and CA/TSC solution (1.7%; all P < 0.05) and was not different from the FeSO4 reference meal (3.4%). In vitro solubility and dialyzability were higher in CA/TSC-extruded rice than in rice with No CA/TSC and CA/TSC solution, and solubility increased with higher amounts of added CA and TSC in extruded rice. CONCLUSIONS: Iron bioavailability nearly doubled when CA/TSC was extruded with FePP into fortified rice, resulting in iron bioavailability comparable to that of FeSO4 We attribute this effect to an in situ generation of soluble FePP citrate moieties during extrusion and/or cooking because of the close physical proximity of FePP and CA/TSC in the extruded rice matrix. This trial was registered at clinicaltrials.gov as NCT02176759.

A higher proportion of iron-rich leafy vegetables in a typical Burkinabe maize meal does not increase the amount of iron absorbed in young women.

Food-to-food fortification can be a promising approach to improve the low dietary iron intake and bioavailability from monotonous diets based on a small number of staple plant foods. In Burkina Faso, the common diet consists of a thick, cereal-based paste consumed with sauces composed of mainly green leaves, such as amaranth and jute leaves. Increasing the quantity of leaves in the sauces substantially increases their iron concentration. To evaluate whether increasing the quantity of leaves in sauces would provide additional bioavailable iron, an iron absorption study in 18 young women was conducted in Zurich, Switzerland. Burkinabe composite test meals consisting of the maize paste tô accompanied by an iron-improved amaranth sauce, an iron-improved jute sauce, or a traditional amaranth sauce were provided as multiple meals twice a day for 2 consecutive days. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes. Mean fractional iron absorption from maize paste consumed with an iron-improved amaranth sauce (4.9%) did not differ from the same meal consumed with an iron-improved jute sauce (4.9%; P = 0.9), resulting in a similar quantity of total iron absorbed (679 vs. 578 µg; P = 0.3). Mean fractional iron absorption from maize paste accompanied by a traditional amaranth sauce (7.4%) was significantly higher than that from the other 2 meal types (P < 0.05), but the quantity of total iron absorbed was similar (591 µg; P = 0.4 and 0.7, respectively). A food-to-food fortification approach based on an increase in leafy vegetables does not provide additional bioavailable iron, presumably due to the high phenolic compound concentration of the leaves tested. Alternative measures, such as adding iron absorption enhancers to the sauces, need to be investigated to improve iron nutrition from Burkinabe maize meals.

Sodium iron EDTA and ascorbic acid, but not polyphenol oxidase treatment, counteract the strong inhibitory effect of polyphenols from brown sorghum on the absorption of fortification iron in young women.

In addition to phytate, polyphenols (PP) might contribute to low Fe bioavailability from sorghum-based foods. To investigate the inhibitory effects of sorghum PP on Fe absorption and the potential enhancing effects of ascorbic acid (AA), NaFeEDTA and the PP oxidase enzyme laccase, we carried out three Fe absorption studies in fifty young women consuming dephytinised Fe-fortified test meals based on white and brown sorghum varieties with different PP concentrations. Fe absorption was measured as the incorporation of stable Fe isotopes into erythrocytes. In study 1, Fe absorption from meals with 17 mg PP (8·5%) was higher than that from meals with 73 mg PP (3·2%) and 167 mg PP (2·7%; P< 0·001). Fe absorption from meals containing 73 and 167 mg PP did not differ (P= 0·9). In study 2, Fe absorption from NaFeEDTA-fortified meals (167 mg PP) was higher than that from the same meals fortified with FeSO4 (4·6 v. 2·7%; P< 0·001), but still it was lower than that from FeSO4-fortified meals with 17 mg PP (10·7%; P< 0·001). In study 3, laccase treatment decreased the levels of PP from 167 to 42 mg, but it did not improve absorption compared with that from meals with 167 mg PP (4·8 v. 4·6%; P= 0·4), whereas adding AA increased absorption to 13·6% (P< 0·001). These findings suggest that PP from brown sorghum contribute to low Fe bioavailability from sorghum foods and that AA and, to a lesser extent, NaFeEDTA, but not laccase, have the potential to overcome the inhibitory effect of PP and improve Fe absorption from sorghum foods.

Total iron absorption by young women from iron-biofortified pearl millet composite meals is double that from regular millet meals but less than that from post-harvest iron-fortified millet meals.

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.

Iron bioavailability from a lipid-based complementary food fortificant mixed with millet porridge can be optimized by adding phytase and ascorbic acid but not by using a mixture of ferrous sulfate and sodium iron EDTA.

Home fortification with lipid-based nutrient supplements (LNSs) is a promising approach to improve bioavailable iron and energy intake of young children in developing countries. To optimize iron bioavailability from an LNS named complementary food fortificant (CFF), 3 stable isotope studies were conducted in 52 young Beninese children. Test meals consisted of millet porridge mixed with CFF and ascorbic acid (AA). Study 1 compared iron absorption from FeSO4-fortifed meals with meals fortified with a mixture of FeSO4 and NaFeEDTA. Study 2 compared iron absorption from FeSO4-fortifed meals without or with extra AA. Study 3 compared iron absorption from FeSO4-fortified meals with meals containing phytase added prior to consumption, once without or once with extra AA. Iron absorption was measured as erythrocyte incorporation of stable isotopes. In study 1, iron absorption from FeSO4 (8.4%) was higher than that from the mixture of NaFeEDTA and FeSO4 (5.9%; P < 0.05). In study 2, the extra AA increased absorption (11.6%) compared with the standard AA concentration (7.3%; P < 0.001). In study 3, absorption from meals containing phytase without or with extra AA (15.8 and 19.9%, respectively) increased compared with meals without phytase (8.0%; P < 0.001). The addition of extra AA to meals containing phytase increased absorption compared with the test meals containing phytase without extra AA (P < 0.05). These findings suggest that phytase and AA, and especially a combination of the two, but not a mixture of FeSO4 and NaFeEDTA would be useful strategies to increase iron bioavailability from a CFF mixed with cereal porridge.

Afebrile Plasmodium falciparum parasitemia decreases absorption of fortification iron but does not affect systemic iron utilization: a double stable-isotope study in young Beninese women.

BACKGROUND: Iron deficiency anemia (IDA) affects many young women in sub-Saharan Africa. Its etiology is multifactorial, but the major cause is low dietary iron bioavailability exacerbated by parasitic infections such as malaria. OBJECTIVE: We investigated whether asymptomatic Plasmodium falciparum parasitemia in Beninese women would impair absorption of dietary iron or utilization of circulating iron. DESIGN: Iron absorption and utilization from an iron-fortified sorghum-based meal were estimated by using oral and intravenous isotope labels in 23 afebrile women with a positive malaria smear (asexual P. falciparum parasitemia; > 500 parasites/µL blood). The women were studied while infected, treated, and then restudied 10 d after treatment. Iron status, hepcidin, and inflammation indexes were measured before and after treatment. RESULTS: Treatment reduced low-grade inflammation, as reflected by decreases in serum ferritin, C-reactive protein, interleukin-6, interleukin-8, and interleukin-10 (P < 0.05); this was accompanied by a reduction in median serum hepcidin of ≈ 50%, from 2.7 to 1.4 nmol/L (P < 0.005). Treatment decreased serum erythropoietin and growth differentiation factor 15 (P < 0.05). Clearance of parasitemia increased geometric mean dietary iron absorption (from 10.2% to 17.6%; P = 0.008) but did not affect systemic iron utilization (85.0% compared with 83.1%; NS). CONCLUSIONS: 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.