Measurement of iron absorption and iron gains from birth to 6 months in breastfed and formula-fed infants using iron isotope dilution.

Little is known about iron kinetics in early infancy. We administered stable iron isotopes to pregnant women and used maternal-fetal iron transfer to enrich newborn body iron. Dilution of enriched body iron by dietary iron with natural isotopic composition was used to assess iron kinetics from birth to 6 months. In breastfed (BF, n = 8), formula-fed (FF, n = 7), or mixed feeding (MF, n = 8) infants, median (interquartile range) iron intake was 0.27, 11.19 (10.46-15.55), and 4.13 (2.33-6.95) mg/day; iron absorbed was 0.128 (0.095-0.180), 0.457 (0.374-0.617), and 0.391 (0.283-0.473) mg/day (BF versus FF, P < 0.01); and total iron gains were 0.027 (-0.002-0.055), 0.349 (0.260-0.498), and 0.276 (0.175-0.368) mg/day (BF versus FF, P < 0.001; BF versus MF, P < 0.05). Isotope dilution can quantify long-term iron absorption and describe the trajectory of iron depletion during early infancy.

A Large Proportion of the Neonatal Iron Pool Is Acquired from the Gestational Diet in a Murine Model.

BACKGROUND: Iron is crucial for growth and development, but excess iron is harmful. Neonatal mice have elevated concentrations of circulating iron, but the source of this iron is unclear. This lack of understanding makes it difficult to optimize early life iron balance. OBJECTIVES: Identify the origins of neonatal tissue-specific iron pools using dietary manipulation and cross-fostering murine models. METHODS: To determine whether tissue-specific neonatal iron was primarily acquired during gestation or after birth, pups born to iron-sufficient or iron-deficient dams were cross-fostered, and tissues were harvested at postnatal days 3-5 to measure iron content. A separate set of female mice were fed a diet enriched with the stable iron isotope 57 (57Fe) for 4 generations to replace naturally abundant liver iron isotope 56 (56Fe) stores with 57Fe. To quantify the proportions of neonatal iron acquired during gestation, pups born to dams with 56Fe or 57Fe stores were cross-fostered, and tissues were harvested at postnatal day 3-5 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. Finally, to quantify the proportion of neonatal iron acquired from the maternal diet, female mice with 56Fe or 57Fe stores switched diets upon mating, and pup tissues were harvested on P0 to determine 56Fe:57Fe ratios by inductively coupled plasma mass spectrometry. RESULTS: Perinatal iron deficiency resulted in smaller pups, and gestational iron deficiency resulted in lower neonatal serum and liver iron. Cross-fostering between dams with 56Fe and 57Fe stores demonstrated that ≤70% of neonatal serum, liver, and brain iron were acquired during gestation. Dietary manipulation experiments using dams with 56Fe and 57Fe stores showed that over half of neonatal serum, liver, and brain iron were from the dam's gestational diet rather than preconception iron stores. CONCLUSIONS: This study provides quantitative values for the sources of neonatal iron, which may inform approaches to optimize neonatal iron status.

Precise measurement of Fe isotopes in marine and biological samples by pseudo-high-resolution multi-collector inductively coupled plasma mass spectrometry (MC-ICPMS).

This paper introduces an enhanced technique for analyzing iron isotopes in complex marine and biological samples. A dedicated iron purification method for biological marine matrices, utilizing three ion exchange columns, is validated. The MC-ICPMS in pseudo-high-resolution mode determines precise iron isotopic ratios, with sensitivity improved through the DSN-100 desolvating nebulizer system and Apex-IR. Only 2 µg of iron on DSN versus 1 µg on Apex is needed for six replicates (30-60 times improvement) while 10 to 20 µg is required for a single measurement on a wet system considering the resolution power (Rp) is maintained at 11,000-13,000. The Ni-doping method with a Fe/Ni ratio of 1 yields more accurate isotopic ratios than standard-sample bracketing alone. Measurement reproducibility of triplicate samples from marine biological experiments on MC-ICPMS is ± 0.03‰ (2SD) for δ56Fe and ± 0.07‰ for δ57Fe (2SD). This study introduces a novel iron purification process specifically designed for marine and biological samples, enhancing sensitivity and enabling more reliable measurements with smaller sample sizes and reduced uncertainties. It proposes iron isotopic compositions for biological reference materials, offering a valuable reference dataset in diverse scientific disciplines.

Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased 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.

Impact of Flooding-Drainage Alternation on Fe Uptake and Transport in Rice: Novel Insights from Iron Isotopes.

Iron (Fe) isotopes were utilized to provide insights into the temporal changes underlying Fe uptake and translocation during rice growth (tillering, jointing, flowering, and maturity stages) in soil-rice systems under typical flooding-drainage alternation. Fe isotopic composition (δ56Fe values) of the soil solution generally decreased at vegetative stages in flooding regimes but increased during grain-filling. Fe plaques were the prevalent source of Fe uptake, as indicated by the concurrent increase in the δ56Fe values of Fe plaques and rice plants during rice growth. The increasing fractionation magnitude from stem/nodes I to flag leaves can be attributed to the preferred phloem transport of light isotopes toward grains, particularly during grain-filling. This study demonstrates that rice plants take up heavy Fe isotopes from Fe plaque and soil solution via strategy II during flooding and the subsequent drainage period, respectively, thereby providing valuable insights into improving the nutritional quality during rice production.

Prebiotics increase iron absorption and reduce the adverse effects of iron on the gut microbiome and inflammation: a randomized controlled trial using iron stable isotopes in Kenyan infants.

BACKGROUND: Iron fortificants tend to be poorly absorbed and may adversely affect the gut, especially in African children. OBJECTIVE: We assessed the effects of prebiotic galacto-oligosaccharides/fructo-oligosaccharides (GOS/FOS) on iron absorption and gut health when added to iron-fortified infant cereal. METHODS: We randomly assigned Kenyan infants (n = 191) to receive daily for 3 wk a cereal containing iron and 7.5 g GOS/FOS (7.5 g+iron group), 3 g (3-g+iron group) GOS/FOS, or no prebiotics (iron group). A subset of infants in the 2 prebiotic+iron groups (n = 66) consumed 4 stable iron isotope-labeled test meals without and with prebiotics, both before and after the intervention. Primary outcome was fractional iron absorption (FIA) from the cereal with or without prebiotics regardless of dose, before and after 3 wk of consumption. Secondary outcomes included fecal gut microbiota, iron and inflammation status, and effects of prebiotic dose. RESULTS: Median (25th-75th percentiles) FIAs from meals before intervention were as follows: 16.3% (8.0%-27.6%) without prebiotics compared with 20.5% (10.4%-33.4%) with prebiotics (Cohen d = 0.53; P < 0.001). FIA from the meal consumed without prebiotics after intervention was 22.9% (8.5%-32.4%), 41% higher than from the meal without prebiotics before intervention (Cohen d = 0.36; P = 0.002). FIA from the meal consumed with prebiotics after intervention was 26.0% (12.2%-36.1%), 60% higher than from the meal without prebiotics before intervention (Cohen d = 0.45; P = 0.007). After 3 wk, compared with the iron group, the following results were observed: 1) Lactobacillus sp. abundances were higher in both prebiotic+iron groups (P < 0.05); 2) Enterobacteriaceae sp. abundances (P = 0.022) and the sum of pathogens (P < 0.001) were lower in the 7.5-g+iron group; 3) the abundance of bacterial toxin-encoding genes was lower in the 3-g+iron group (false discovery rate < 0.05); 4) fecal pH (P < 0.001) and calprotectin (P = 0.033) were lower in the 7.5-g+iron group. CONCLUSIONS: Adding prebiotics to iron-fortified infant cereal increases iron absorption and reduces the adverse effects of iron on the gut microbiome and inflammation in Kenyan infants. This trial was registered at clinicaltrials.gov as NCT03894358.

Novel bioanalytical strategy using isotope pattern deconvolution and ICP-QMS for the study of iron incorporation in erythrocytes: An insight to better assessment.

Iron is an essential element for human life and its nutritional status in the human body is directly linked to human health. More than 1015 atoms of iron per second are necessary for the maintenance of haemoglobin formation. To predict iron bioavailability three approaches are normally employed: (a) faecal recovery; (b) plasma appearance; and (c) erythrocyte incorporation (the most used). Isotope Pattern Deconvolution (IPD) is a mathematical tool that allows the isolation of distinct isotope signatures from mixtures of natural abundance and enriched tracers. In this work we propose a novel strategy to assess erythrocyte iron incorporation, based on the use of an iron stable isotope (57Fe) and the IPD concept. This strategy allows direct calculation of the exogenous concentration of 57Fe incorporated into RBCs after supplementation. In this way, to determine the mass of iron incorporated into erythrocytes, the unique prediction that must be made is the blood volume, estimate to reproduce the natural dilution of the tracer (57Fe) in the blood. This novel bioanalytical approach was applied for the measurements of iron incorporation and further iron absorption studies in humans, using a group of twelve healthy participants, that should be further evaluated for the assessment of other chemical elements that could be of health concerns and directly impact society.

Uniquely low stable iron isotopic signatures in deep marine sediments caused by Rayleigh distillation.

Dissimilatory iron reduction (DIR) is suggested to be one of the earliest forms of microbial respiration. It plays an important role in the biogeochemical cycling of iron in modern and ancient sediments. Since microbial iron cycling is typically accompanied by iron isotope fractionation, stable iron isotopes are used as tracer for biological activity. Here we present iron isotope data for dissolved and sequentially extracted sedimentary iron pools from deep and hot subseafloor sediments retrieved in the Nankai Trough off Japan. Dissolved iron (Fe(II)aq) is isotopically light throughout the ferruginous sediment interval but some samples have exceptionally light isotope values. Such light values have never been reported in natural marine environments and cannot be solely attributed to DIR. We show that the light isotope values are best explained by a Rayleigh distillation model where Fe(II)aq is continuously removed from the pore water by adsorption onto iron (oxyhydr)oxide surfaces. While the microbially mediated Fe(II)aq release has ceased due to an increase in temperature beyond the threshold of mesophilic microorganisms, the abiotic adsorptive Fe(II)aq removal continued, leading to uniquely light isotope values. These findings have important implications for the interpretation of dissolved iron isotope data especially in deep subseafloor sediments.

Total Iron Absorbed from Iron-Biofortified Potatoes Is Higher than that from Nonbiofortified Potatoes: A Randomized Trial Using Stable Iron Isotopes in Women from the Peruvian Highlands.

BACKGROUND: Yellow-fleshed potatoes biofortified with iron have been developed through conventional breeding, but the bioavailability of iron is unknown. OBJECTIVES: Our objective was to measure iron absorption from an iron-biofortified yellow-fleshed potato clone in comparison with a nonbiofortified yellow-fleshed potato variety. METHODS: We conducted a single-blinded, randomized, crossover, multiple-meal intervention study. Women (n = 28; mean ± SD plasma ferritin 21.3 ± 3.3 µg/L) consumed 10 meals (460 g) of both potatoes, each meal extrinsically labeled with either 58Fe sulfate (biofortified) or 57Fe sulfate (nonfortified), on consecutive days. Iron absorption was estimated from iron isotopic composition in erythrocytes 14 d after administration of the final meal. RESULTS: Mean ± SD iron, phytic acid, and ascorbic acid concentrations in iron-biofortified and the nonfortified potato meals (mg/per 100 mg) were 0.63 ± 0.01 and 0.31 ± 0.01, 39.34 ± 3.04 and 3.10 ± 1.72, and 7.65 ± 0.34 and 3.74 ± 0.39, respectively (P < 0.01), whereas chlorogenic acid concentrations were 15.14 ± 1.72 and 22.52 ± 3.98, respectively (P < 0.05). Geometric mean (95% CI) fractional iron absorption from the iron-biofortified clone and the nonbiofortified variety were 12.1% (10.3%-14.2%) and 16.6% (14.0%-19.6%), respectively (P < 0.001). Total iron absorption from the iron-biofortified clone and the nonbiofortified variety were 0.35 mg (0.30-0.41 mg) and 0.24 mg (0.20-0.28 mg) per 460 g meal, respectively (P < 0.001). CONCLUSIONS: TIA from iron-biofortified potato meals was 45.8% higher than that from nonbiofortified potato meals, suggesting that iron biofortification of potatoes through conventional breeding is a promising approach to improve iron intake in iron-deficient women. The study was registered at www. CLINICALTRIALS: gov as Identifier number NCT05154500.

Tissue-variation of iron stable isotopes in marine fish coupled with speciation analysis using X-ray absorption fine structure.

The Fe stable isotope ratio (δ56Fe) in tissues is a potential parameter for examining the Fe metabolism in marine fish. Although the effect of ferritin storage has been proposed as a possible cause of heavy isotope (56Fe) enrichment in the liver, no speciation and stable isotope ratio coupling data are available. Here, we report the δ56Fe values measured by multicollector ICP-MS and the result of Fe K-edge X-ray absorption near-edge structure (XANES) analysis of multiple tissues obtained from a skipjack tuna (Katsuwonus pelamis) and a chub mackerel (Scomber japonicus). Apparent isotopic fractionation between the liver and the muscle samples (Δ56FeL-M = Î´56Feliver - Î´56Femuscle) from these species was observed (0.85 ‰ and 0.57 ‰, respectively). The dominant Fe species in the muscle was heme Fe (the sum of methemoglobin, oxyhemoglobin, and deoxyhemoglobin), while ferritin was not detected according to the linear combination fitting of the XANES spectra. In the liver, ferritin contribution was ca. 28 %-54 % of the total Fe content. The apparent difference in δ56Fe between heme Fe and ferritin was estimated to range from 1.41 ‰ to 1.52 ‰ based on the tissue-specific δ56Fe values and the XANES results. These results indicate that the Fe storage as ferritin does not induce the lowering of δ56Fe in the muscle, considering the low contribution of the liver Fe to the total Fe content in the body.

Iron isotopic fractionation driven by low-temperature biogeochemical processes.

Iron is geologically important and biochemically crucial for all microorganisms, plants and animals due to its redox exchange, the involvement in electron transport and metabolic processes. Despite the abundance of iron in the earth crust, its bioavailability is very limited in nature due to its occurrence as ferrihydrite, goethite, and hematite where they are thermodynamically stable with low dissolution kinetics in neutral or alkaline environments. Organisms such as bacteria, fungi, and plants have evolved iron acquisition mechanisms to increase its bioavailability in such environments, thereby, contributing largely to the iron cycle in the environment. Biogeochemical cycling of metals including Fe in natural systems usually results in stable isotope fractionation; the extent of fractionation depends on processes involved. Our review suggests that significant fractionation of iron isotopes occurs in low-temperature environments, where the extent of fractionation is greatly governed by several biogeochemical processes such as redox reaction, alteration, complexation, adsorption, oxidation and reduction, with or without the influence of microorganisms. This paper includes relevant data sets on the theoretical calculations, experimental prediction, as well as laboratory studies on stable iron isotopes fractionation induced by different biogeochemical processes.

Novel Insights into Marine Iron Biogeochemistry from Iron Isotopes.

The micronutrient iron plays a major role in setting the magnitude and distribution of primary production across the global ocean. As such, an understanding of the sources, sinks, and internal cycling processes that drive the oceanic distribution of iron is key to unlocking iron's role in the global carbon cycle and climate, both today and in the geologic past. Iron isotopic analyses of seawater have emerged as a transformative tool for diagnosing iron sources to the ocean and tracing biogeochemical processes. In this review, we summarize the end-member isotope signatures of different iron source fluxes and highlight the novel insights into iron provenance gained using this tracer. We also review ways in which iron isotope fractionation might be used to understand internal oceanic cycling of iron, including speciation changes, biological uptake, and particle scavenging. We conclude with an overview of future research needed to expand the utilization of this cutting-edge tracer.

Iron Isotopes in Acid Mine Drainage: Extreme and Divergent Fractionation between Solid (Schwertmannite, Jarosite, and Ferric Arsenate) and Aqueous Species.

Examination of stable Fe isotopes is a powerful tool to explore Fe cycling in a range of environments. However, the isotopic fractionation of Fe in acid mine drainage (AMD) has received little attention and is poorly understood. Here, we analyze Fe isotopes in waters and Fe(III)-rich solids along an AMD flow-path. Aqueous Fe spanned a concentration and δ56Fe range of ∼420 mg L-1 and + 0.04‰ at the AMD source to ∼100 mg L-1 and -0.81‰ at ∼450 m downstream. Aqueous As (up to ∼33 mg L-1) and SO42- (up to ∼2000 mg L-1), like aqueous Fe, decreased in concentration down the flow-path. X-ray absorption spectroscopy indicated that downstream attenuation in aqueous Fe, As, and SO42- was due to the precipitation of amorphous ferric arsenate (AFA), schwertmannite, and jarosite. The Fe(III) in these solids displayed extreme variability in δ56Fe, spanning +3.95‰ in AFA near the AMD source to -1.34‰ in schwertmannite at ∼450 m downstream. Similarly, the isotopic contrast between solid Fe(III) precipitates and aqueous Fe (Δ56Feppt-aq) dropped along the flow-path from about +4.1 to -1.1‰. The shift from positive to negative Δ56Feppt-aq reflects divergence between competing equilibrium versus kinetic fractionation processes.

Large Fractionation in Iron Isotopes Implicates Metabolic Pathways for Iron Cycling in Boreal Shield Lakes.

Stable Fe isotopes have only recently been measured in freshwater systems, mainly in meromictic lakes. Here we report the δ56Fe of dissolved, particulate, and sediment Fe in two small dimictic boreal shield headwater lakes: manipulated eutrophic Lake 227, with annual cyanobacterial blooms, and unmanipulated oligotrophic Lake 442. Within the lakes, the range in δ56Fe is large (ca. -0.9 to +1.8‰), spanning more than half the entire range of natural Earth surface samples. Two layers in the water column with distinctive δ56Fe of dissolved (dis) and particulate (spm) Fe were observed, despite differences in trophic states. In the epilimnia of both lakes, a large Δ56Fedis-spm fractionation of 0.4-1‰ between dissolved and particulate Fe was only observed during cyanobacterial blooms in Lake 227, possibly regulated by selective biological uptake of isotopically light Fe by cyanobacteria. In the anoxic layers in both lakes, upward flux from sediments dominates the dissolved Fe pool with an apparent Δ56Fedis-spm fractionation of -2.2 to -0.6‰. Large Δ56Fedis-spm and previously published metagenome sequence data suggest active Fe cycling processes in anoxic layers, such as microaerophilic Fe(II) oxidation or photoferrotrophy, could regulate biogeochemical cycling. Large fractionation of stable Fe isotopes in these lakes provides a potential tool to probe Fe cycling and the acquisition of Fe by cyanobacteria, with relevance for understanding biogeochemical cycling of Earth's early ferruginous oceans.

Quantitating Iron Transport across the Mouse Placenta In Vivo using Nonradioactive Iron Isotopes.

Iron is essential for maternal and fetal health during pregnancy, with approximately 1 g of iron needed in humans to sustain a healthy pregnancy. Fetal iron endowment is entirely dependent on iron transfer across the placenta, and perturbations of this transfer can lead to adverse pregnancy outcomes. In mice, measurement of iron fluxes across the placenta traditionally relied on radioactive iron isotopes, a highly sensitive but burdensome approach. Stable iron isotopes (57Fe and 58Fe) offer a nonradioactive alternative for use in human pregnancy studies. Under physiological conditions, transferrin-bound iron is the predominant form of iron taken up by the placenta. Thus, 58Fe-transferrin was prepared and injected intravenously in pregnant dams to directly assess placental iron transport and bypass maternal intestinal iron absorption as a confounding variable. Isotopic iron was quantitated in the placenta and mouse embryonic tissues by inductively coupled plasma mass spectrometry (ICP-MS). These methods can also be employed in other animal model systems of physiology or disease to quantify in vivo iron dynamics.

Iron Bioavailability from Ferrous Ammonium Phosphate, Ferrous Sulfate, and Ferric Pyrophosphate in an Instant Milk Drink-A Stable Isotope Study in Children.

Ferrous ammonium phosphate (FAP) is an iron salt that has been developed for the fortification of food matrices sensitive to color and flavor changes. The objective of the study was to measure iron absorption from FAP in young children and compare it to a previous evaluation of FAP in young women. A double-blind randomized crossover study with two parallel arms was used to evaluate the iron absorption from FAP added to reconstituted milk powder in comparison to that from ferrous sulfate (FeSO4) and ferric pyrophosphate (FePP). Iron absorption was measured in 39 children aged 3- to 6-years-old using erythrocyte incorporation of stable Fe isotopes (57Fe, 58Fe). The geometric mean iron absorption in iron replete children from FAP, FeSO4 and FePP from milk was 8.3%, 7.6% and 2.1%, respectively. Iron absorption from FAP and FeSO4 fortified milk was not significantly different (p = 0.199); however, it was significantly higher than from FePP fortified milk (p < 0.001). Iron bioavailability from FAP and FePP relative to FeSO4 (relative bioavailability (RBV)) was 110% and 33%, respectively. The RBV of FAP (110%) in iron replete children was higher than previously reported RBV (71%) in mainly iron deficient women. The difference in iron status between the children and women in the respective studies may explain the different RBV values and is discussed.

Laboratory study of iron isotope fractionation during dissolution of mineral dust and industrial ash in simulated cloud water.

Atmospheric deposition is a key mode of iron (Fe) input to ocean regions where low concentrations of this micronutrient limit marine primary production. Various natural particles (e.g., mineral dust, volcanic ash) and anthropogenic particles (e.g., from industrial processes, biomass burning) can deliver Fe to the ocean, and assessment of their relative importance in supplying Fe to seawater requires knowledge of both their deposition flux and their Fe solubility (a proxy for Fe bioavailability). Iron isotope (54Fe, 56Fe, 57Fe, 58Fe) analysis is a potential tool for tracing natural and anthropogenic Fe inputs to the ocean. However, it remains uncertain how the distinct Fe isotopic signatures (δ56Fe) of these particles may be modified by physicochemical processes (e.g., acidification, photochemistry, condensation-evaporation cycles) that are known to enhance Fe solubility during atmospheric transport. In this experimental study, we measure changes over time in both Fe solubility and δ56Fe of a Tunisian soil dust and an Fe-Mn alloy factory industrial ash exposed under irradiation to a pH 2 solution containing oxalic acid, the most widespread organic complexing agent in cloud- and rainwater. The Fe released per unit surface area of the ash (∼1460 µg Fe m-2) is ∼40 times higher than that released by the dust after 60 min in solution. Isotopic fractionation is also observed, to a greater extent in the dust than the ash, in parallel with dissolution of the solid particles and driven by preferential release of 54Fe into solution. After the initial release of 54Fe, the re-adsorption of A-type Fe-oxalate ternary complexes on the most stable surface sites of the solid particles seems to impair the release of the heavier Fe isotopes, maintaining a relative enrichment in the light Fe isotope in solution over time. These findings provide new insights on Fe mobilisation and isotopic fractionation in mineral dust and industrial ash during atmospheric processing, with potential implications for ultimately improving the tracing of natural versus anthropogenic contributions of soluble Fe to the ocean.

Fetal iron uptake from recent maternal diet and the maternal RBC iron pool.

BACKGROUND: During pregnancy iron can be obtained from the diet, body iron stores, or iron released from RBC catabolism. Little is known about the relative use of these sources to support fetal iron acquisition. OBJECTIVES: To describe longitudinal change in iron absorption and enrichment across gestation and partitioning of RBC iron to the fetus. METHODS: Fifteen pregnant women ingested an oral stable iron isotope (57Fe) in the second trimester (T2) of pregnancy (weeks 14-16) to label the RBC pool, and a second oral stable isotope (58Fe) in the third trimester (T3) (weeks 32-35). Absorption was measured at T2 and T3. Change in RBC 57Fe enrichment was monitored (18.8-26.6 wk) to quantify net iron loss from this pool. Iron transfer to the fetus was determined based on RBC 57Fe and 58Fe enrichment in umbilical cord blood at delivery. RESULTS: Iron absorption averaged 9% at T2 and increased significantly to 20% (P = 0.01) by T3. The net increase in iron absorption from T2 to T3 was strongly associated with net loss in maternal total body iron (TBI) from T2 to T3 (P = 0.01). Mean time for the labeled RBC 57Fe turnover based on change in RBC enrichment was 94.9 d (95% CI: 43.5, 207.1 d), and a greater decrease in RBC 57Fe enrichment was associated with higher iron absorption in T2 (P = 0.001). Women with a greater decrease in RBC 57Fe enrichment transferred more RBC-derived iron to their fetus (P < 0.05). CONCLUSIONS: Iron absorption doubled from T2 to T3 as maternal TBI declined. Women with low TBI had a greater decrease in RBC iron enrichment and transferred more RBC-derived iron to their neonate. These findings suggest maternal RBC iron serves as a significant source of iron for the fetus, particularly in women with depleted body iron stores.

Zinc regulation of iron uptake and translocation in rice (Oryza sativa L.): Implication from stable iron isotopes and transporter genes.

Iron (Fe) is an essential nutrient for living organisms and Fe deficiency is a worldwide problem for the health of both rice and humans. Zinc (Zn) contamination in agricultural soils is frequently observed. Here, we studied Fe isotope compositions and transcript levels of Fe transporter genes in rice growing in nutrient solutions having a range of Zn concentrations. Our results show Zn stress reduces Fe uptake by rice and drives its δ56Fe value to that of the nutrient solution. These observations can be explained by the weakened Fe(II) uptake through Strategy I but enhanced Fe(III) uptake through Strategy II due to the competition between Zn and Fe(II) combining with OsIRT1 (Fe(II) transporter) in root, which is supported by the downregulated expression of OsIRT1 and upregulated expression of OsYSL15 (Fe(III) transporter). Using a mass balance box model, we also show excess Zn reduces Fe(II) translocation in phloem and its remobilization from senescent leaf, indicating a competition of binding sites on nicotianamine between Zn and Fe(II). This study provides direct evidence that how Zn regulates Fe uptake and translocation in rice and is of practical significance to design strategies to treat Fe deficiency in rice grown in Zn-contaminated soils.

A test to measure oral iron absorption and glucose tolerance simultaneously in 18 to 55 year old premenopausal women.

BACKGROUND & AIMS: Several methods are available to measure iron absorption (IA). The oral iron absorption test (OIAT) measures IA based on a change in serum iron (ΔSeFe) concentration after an oral iron dose. The objective of this study was to validate the OIAT by comparing it to the reference method of fractional iron absorption (FIA) using red blood cell incorporation of stable iron isotopes from a labeled iron dose. A second objective was to assess whether the OIAT could be done simultaneously with an oral glucose tolerance test (OGTT), since iron deficiency and glucose intolerance may coexist, especially among overweight individuals with low-grade inflammation. METHODS: In this prospective experimental study, 116 women were enrolled and IA was measured using two different approaches 1) FIA from a labeled test meal containing 6 mg of 57Fe and 2) the OIAT assessing ΔSeFe at 2 h after the intake of 100 mg oral iron, done simultaneously with an OGTT. Markers of iron status, glycaemia and inflammation, and serum hepcidin, were measured. RESULTS: Prevalence of anemia and iron deficiency (defined as low serum ferritin) were 21% and 14%, respectively. ΔSeFe during the OIAT-OGTT was positively associated with FIA (r = 0.578, p < 0.001). ΔSeFe was not significantly correlated with markers of glucose and insulin metabolism during the OIAT-OGTT. CONCLUSIONS: The combined OIAT and OGTT method described here correlates well with FIA measured by stable iron isotopes, and could provide information on both IA and glucose tolerance in a single 2-h test, decreasing the burden on patients. clinicaltrials.gov (NCT03642223).