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Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

ABSTRACT: Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO₄-NP; specific surface area [SSA] 98 m²g^-1) compared to to ferrous sulfate (FeSO₄), the reference compound. We show that absorption of iron from FePO₄-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO₄, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two ⁵⁷Fe-labeled FePO₄-NP with SSAs of 98 m²g^-1 and 188 m²g^-1 was 2.8-fold and 5.4-fold higher than from bulk FePO₄ with an SSA of 25 m²g^-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO₄-NP 188 m²g^-1 achieved 72% relative bioavailability compared to FeSO₄. These data suggest FePO₄-NPs may be useful for nutritional applications.

SUBMITTER: Baumgartner J

PROVIDER: S-EPMC8857185 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Baumgartner Jeannine J Winkler Hans Christian HC Zandberg Lizelle L Tuntipopipat Siriporn S Mankong Phatchari P Bester Cor C Hilty Florentine F Zeevaart Jan Rijn JR Gowachirapant Sueppong S Zimmermann Michael B MB

Scientific reports 20220218 1

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO<sub>4 ...[more]

PMID: 35181698

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Project description:In iron-depleted women without anemia, oral iron supplements induce an increase in serum hepcidin (SHep) that persists for 24 hours, decreasing iron absorption from supplements given later on the same or next day. Consequently, iron absorption from supplements is highest if iron is given on alternate days. Whether this dosing schedule is also beneficial in women with iron-deficiency anemia (IDA) given high-dose iron supplements is uncertain. The primary objective of this study was to assess whether, in women with IDA, alternate-day administration of 100 and 200 mg iron increases iron absorption compared to consecutive-day iron administration. Secondary objectives were to correlate iron absorption with SHep and iron status parameters. We performed a cross-over iron absorption study in women with IDA (n=19; median hemoglobin 11.5 mg/dL; mean serum ferritin 10 mg/L) who received either 100 or 200 mg iron as ferrous sulfate given at 8 AM on days 2, 3 and 5 labeled with stable iron isotopes 57Fe, 58Fe and 54Fe; after a 16-day incorporation period, the other labeled dose was given at 8 AM on days 23, 24 and 26 (days 2, 3 and 5 of the second period). Iron absorption on days 2 and 3 (consecutive) and day 5 (alternate) was assessed by measuring erythrocyte isotope incorporation. For both doses, SHep was higher on day 3 than on day 2 (P<0.001) or day 5 (P<0.01) with no significant difference between days 2 and 5. Similarly, for both doses, fractional iron absorption (FIA) on days 2 and 5 was 40-50% higher than on day 3 (P<0.001), while absorption on day 2 did not differ significantly from day 5. There was no significant difference in the incidence of gastrointestinal side effects comparing the two iron doses (P=0.105). Alternate day dosing of oral iron supplements in anemic women may be preferable because it sharply increases FIA. If needed, to provide the same total amount of iron with alternate day dosing, twice the daily target dose should be given on alternate days, as total iron absorption from a single dose of 200 mg given on alternate days was approximately twice that from 100 mg given on consecutive days (P<0.001). In IDA, even if hepatic hepcidin expression is strongly suppressed by iron deficiency and erythropoietic drive, the intake of oral iron supplements leads to an acute hepcidin increase for 24 hours. The study was funded by ETH Zürich, Switzerland. This study has been registered at www.clinicaltrials.gov as #NCT03623997.

Project description:BackgroundBouillon cubes are a potential vehicle for iron fortification. They are currently fortified with ferric pyrophosphate (FePP), which is known to be poorly absorbed. The objective of this study was to assess the iron absorption of Aspergillus oryzae grown in FePP (ASP-p) and compare it with FePP and ferrous sulfate (FeSO4)-fortified bouillon cubes.MethodsIn 2 single-blinded, crossover studies, healthy women with serum ferritin concentrations <40 μg/L were randomly assigned to consume a rice-vegetable meal with iron-fortified chicken bouillon. Subjects in study I (n = 17, 18-26 y) consumed iron from both iron sources as 57FePP and 58ASP-p (intrinsically labeled with 58FePP) with a meal containing 4.2 mg of total iron provided for 3 d. Study II (n = 18, 18-29 y) was similar except that subjects consumed 57FeSO4 and 58ASP-p. Whole-blood stable isotope enrichment after 14 d was used to measure fractional iron absorption. Hemoglobin, hematocrit, serum ferritin, hepcidin, and serum C-reactive protein were analyzed at baseline and at 14 d. A t test was used to compare the mean differences in fractional absorptions within each study and baseline characteristics between studies.ResultsGeometric mean (95% CI) fractional iron absorption of FePP [0.94% (0.63%, 1.40%)] was lower than ASP-p [2.20% (1.47%, 3.30%)] (P < 0.0001) in study I. In study II, ASP-p fractional absorption [2.98% (2.03%, 4.38%)] was lower than that of FeSO4 [9.88% (6.70%, 14.59%)] (P < 0.0001). Both ferritin (r = -0.41, P = 0.014) and hepcidin (r = -0.42, P = 0.01) concentrations were inversely correlated with ASP-p iron absorption. Fractional absorption of ASP-p was also positively correlated with FePP (r = 0.92, P < 0.0001) and FeSO4 (r = 0.52, P < 0.02) absorption.ConclusionsASP-p-fortified bouillon provided 2.3-fold higher absorbable iron than the currently used FePP. Bouillon fortified with ASP-p may contribute sufficient bioavailable iron to meet the daily iron requirements in young women only if consumed with other iron-fortified staple foods. This trial was registered at clinicaltrials.gov as NCT03586245.

Project description:BackgroundIron-deficiency anemia (IDA) is associated with alterations in infant behavior and development that may not be corrected with iron therapy.ObjectiveTo determine if a home-based intervention to foster child development improves behavior and development of infants with IDA.MethodsInfants with IDA and nonanemic infants aged 6 and 12 months were treated with oral iron and randomly assigned to a year of surveillance or intervention. Infants in the surveillance group were visited weekly, and information on iron intake, feeding, and health were recorded. Infants in the intervention were visited weekly, and the home visits included an hour-long program to foster child development by providing support to the mother-infant relationship. The number of infants enrolled was 128 (66 who received intervention) and 149 (70 intervention) at 6 and 12 months, respectively. Psychologists who were unaware of iron status and intervention assignment assessed infants' cognitive, motor, and social-emotional development (Bayley Scales) at the beginning, midpoint, and end of the year; 116 6-month-olds and 134 12-month-olds had at least 2 assessments. Hierarchical linear modeling was used to analyze change over time.ResultsInfants with IDA, regardless of enrollment age, were rated as less positive in social-emotional behavior at baseline. There were significant interactions between iron status and intervention associated with change in cognitive performance and positive social-emotional behavior. Infants with IDA who received intervention had developmental trajectories comparable to those of nonanemic infants in the intervention and surveillance groups, but these infants did not catch up in social-emotional behavior. Infants with IDA who received surveillance showed less increase in cognitive scores and had declines in positive social-emotional ratings.ConclusionsHome-based intervention to foster child development improved cognitive and social-emotional scores in infants with IDA, but social-emotional differences remained between infants with IDA and those without IDA.

Project description:Abstract Objectives Iron deficiency is estimated to affect up to 1.5–2 billion people worldwide. Edible insects can be a rich source of iron and may have a smaller environmental food print than other animal source foods. Mealworm (Tenebrio molitor) larvae are recognized as an edible insect, but iron bioavailability in humans has not been investigated. Chitin, a major component of insect biomass, is a known iron binder. Our primary objective was to measure fractional iron absorption (FIA) from T.molitor with and without chitin in young women. Secondly, we aimed to assess the effect of the presence of mealworm biomass on iron absorption from iron present in low-phytate maize porridge. Methods Non-anemic females (18–45 years, body weight < 65 kg) were recruited and FIA was measured as erythrocyte incorporation of stable isotopes tracers in red blood cells 14 days after test meal administration. Using a randomized cross over design, three different meals were administered to each subject, consisting of A) a low phytate refined maize porridge with 54FeSO4; B) intrinsically labelled (57Fe) T.molitor with native chitin and extrinsic 58FeSO4; C) intrinsically labelled (57Fe) T.molitor with reduced chitin and extrinsic 58FeSO4. Results Median serum ferritin concentration in the participating subjects (n = 21) was 22.7 µg/L. Iron content in T.molitor larvae was FIA from meals B (58Fe, 5.28%) and C (58Fe, 4.55%) in which mealworm biomass was given in combination with maize porridge did not significantly differ to FIA from maize porridge fed alone (5.84%). In case of intrinsic labelling, FIA from meals B (57Fe, 4.11%) and C (57Fe, 4.03%) were significantly lower compared to maize meal A (P < 0.001). Conclusions FIA from T.molitor was similar to low-phytate containing maize. Presence of mealworm biomass did not enhance or inhibit the FIA of iron present in the maize meal. Furthermore, a chitin reduction process did not show any discernible effect on FIA. T.molitor larvae could be a viable source of iron in the human diet, but iron absorption may be similar to plant-based foods. The study was registered at clinicaltrials.gov as NCT04510831. Funding Sources Coop Research Program, World Food System Center, ETH Zurich, Switzerland.

Project description:BackgroundCo-extrusion of ferric pyrophosphate (FePP) with solubilizers, citric acid/trisodium citrate (CA/TSC), or ethylenediaminetetraacetic acid (EDTA) sharply increases iron absorption. Whether this can protect against the inhibition of iron absorption by phytic acid (PA) is unclear. Sodium pyrophosphate (NaPP) may be a new enhancer of iron absorption from FePP.ObjectivesOur objectives were to 1) investigate the ligand coordination of iron, zinc, and solubilizers in extruded rice and test associations with iron solubility and absorption, 2) assess whether co-extrusion of FePP + CA/TSC rice can protect against inhibition of iron absorption by PA; 3) determine the effect of zinc oxide (ZnO) compared with zinc sulfate (ZnSO4), and 4) quantify iron absorption from FePP + NaPP rice.MethodsWe produced labeled 57FePP rice cofortified with ZnSO4 and EDTA, CA/TSC or NaPP, and FePP + EDTA rice with ZnO. We used electron paramagnetic resonance (EPR) to characterize iron-ligand complexes. We measured in vitro iron solubility and fractional iron absorption (FIA) in young women (n = 21, age: 22 ± 2 y, BMI: 21.3 ± 1.5 kg/m2 geometric mean plasma ferritin, 28.5 μg/L) compared with ferrous sulfate (58FeSO4). FIA was compared by linear mixed-effect model analysis.ResultsThe addition of zinc and solubilizers created new iron coordination complexes of Fe(III) species with a weak ligand field at a high-spin state that correlated with solubility (r2 = 0.50, P = 0.02) and absorption (r2 = 0.72, P = 0.02). Phytic acid reduced FIA from FePP + CA/TSC rice by 50% (P < 0.001), to the same extent as FeSO4. FIA from FePP + EDTA + ZnO and FePP + EDTA + ZnSO4 rice did not significantly differ. Mean FIAs from FePP + EDTA + ZnSO4, FePP + CA/TSC + ZnSO4, and FePP + NaPP + ZnSO4 rice were 9% to 11% and did not significantly differ from each other or from FeSO4.ConclusionRice extrusion of FePP with solubilizers resulted in bioavailable iron coordination complexes. In the case of FePP + CA/TSC, PA exerted similar inhibition of FIA as with FeSO4. FePP + NaPP could be a further viable solubilizing agent for rice fortification. This study was registered at clinicaltrials.gov as NCT03703739.

Dataset Information

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

Publications

Iron from nanostructured ferric phosphate: absorption and biodistribution in mice and bioavailability in iron deficient anemic women.

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