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.

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.

Anthropogenic Asian aerosols provide Fe to the North Pacific Ocean.

Fossil-fuel emissions may impact phytoplankton primary productivity and carbon cycling by supplying bioavailable Fe to remote areas of the ocean via atmospheric aerosols. However, this pathway has not been confirmed by field observations of anthropogenic Fe in seawater. Here we present high-resolution trace-metal concentrations across the North Pacific Ocean (158°W from 25°to 42°N). A dissolved Fe maximum was observed around 35°N, coincident with high dissolved Pb and Pb isotope ratios matching Asian industrial sources and confirming recent aerosol deposition. Iron-stable isotopes reveal in situ evidence of anthropogenic Fe in seawater, with low δ56Fe (-0.23‰ > δ56Fe > -0.65‰) observed in the region that is most influenced by aerosol deposition. An isotope mass balance suggests that anthropogenic Fe contributes 21-59% of dissolved Fe measured between 35° and 40°N. Thus, anthropogenic aerosol Fe is likely to be an important Fe source to the North Pacific Ocean.

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.

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.

The TMPRSS6 variant (SNP rs855791) affects iron metabolism and oral iron absorption - a stable iron isotope study in Taiwanese women.

Genome wide studies have associated TMPRSS6 rs855791 (2321 C>T) with iron status and hepcidin. It is unclear whether this polymorphism affects iron absorption. In nonanemic Taiwanese women (n=79, 44 TT variant, 35 CC variant), we administered standardized rice-based test meals containing 4 mg of labeled 57Fe or 58Fe as FeSO4 on alternate days. Fractional iron absorption was measured by erythrocyte incorporation of the tracers 14 days after administration. Compared to the CC variant, in the TT variant serum iron and transferrin saturation were lower (P=0.001; P<0.001, respectively) and serum hepcidin/transferrin saturation and serum hepcidin/serum iron ratios were higher (P=0.042; P=0.088, respectively). Serum hepcidin did not differ between groups (P=0.862). Geometric mean (95% CI) fractional iron absorption, corrected to a serum ferritin of 15 µg/L, was 26.6% (24.0, 29.5) in the CC variant and 18.5% (16.2, 21.1) in the TT variant (P=0.002). Overall, predictors of iron absorption were: serum ferritin (P<0.001); genetic variant (P=0.032); and hepcidin (P<0.001). In the models by variant, in the CC variant the model explained 67-71% of variability in absorption and serum ferritin was the only significant predictor (P<0.001); in the TT variant, the model explained only 35-43% of variability, and hemoglobin (P=0.032), soluble transferrin receptor (P=0.004) and hepcidin (P<0.001) were significant predictors. Women with the TMPRSS6 rs855791 (2321 C>T) polymorphism show altered iron homeostasis which affects oral iron absorption and may increase their risk for iron deficiency. The trial was registered at www.clinicaltrials.gov as NCT03317873, and funded by the Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, (grant CMRPG8F0721) and ETH Zurich, Switzerland.

Consumption of a Single Dose of Prebiotic Galacto-Oligosaccharides Does Not Enhance Iron Absorption from Micronutrient Powders in Kenyan Infants: A Stable Iron Isotope Study.

BACKGROUND: Long-term feeding of prebiotic galacto-oligosaccharides (GOS) increases iron absorption in African infants, but the underlying mechanism and how long GOS need to be fed to infants to achieve an increase in absorption is uncertain. OBJECTIVES: In Kenyan infants, we tested whether the addition of GOS to a single test meal would affect iron absorption from a micronutrient powder (MNP) containing ferrous sulfate (FeSO4) and another MNP containing ferrous fumarate (FeFum) and sodium iron ethylenediaminetetraacetate (NaFeEDTA). METHODS: In a randomized-entry, prospective crossover study, iron deficient (87%) and anemic (70%) Kenyan infants (n  = 23; mean ± SD age, 9.9 ± 2.1 months) consumed 4 stable iron isotope-labeled maize porridge meals fortified with MNPs containing 5 mg iron as FeFum + NaFeEDTA, or FeSO4, either without or with 7.5 g GOS. The primary outcome, fractional iron absorption (FIA), was assessed by erythrocyte incorporation of isotopic labels. Data were analyzed using a 2-way repeated-measures ANOVA. RESULTS: There was no significant interaction between GOS and the iron compounds on FIA, and the addition of GOS did not have a significant effect on FIA. There was a statistically significant difference in FIA between the meals fortified with FeSO4 and with FeFum + NaFeEDTA (P  < 0.001).Given with GOS, FIA from FeSO4 was 40% higher than from FeFum + NaFeEDTA (P  < 0.001); given without GOS, it was 51% higher (P  < 0.01). CONCLUSIONS: The addition of GOS to a single iron-fortified maize porridge test meal in Kenyan infants did not significantly increase iron absorption, suggesting long-term feeding of GOS may be needed to enhance iron absorption at this age. This study was registered at clinicaltrials.gov as NCT02666417.

Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco.

BACKGROUND: Available data suggest that polyphenols from tea can inhibit iron absorption from ferric sodium EDTA (NaFeEDTA), but previous studies were done in small groups of mostly nonanemic adults. Morocco recently introduced national wheat flour fortification with NaFeEDTA, but tea is the national beverage and is consumed with most meals. OBJECTIVES: Our objective was to quantify bioavailability of iron from NaFeEDTA when added to a wheat flour-based meal in both nonanemic women and women with iron deficiency anemia (IDA), when consumed with and without traditional Moroccan green tea. METHODS: We recruited 2 groups of healthy Moroccan women (n = 46): women with IDA (n = 25; hemoglobin <12 g/dL,  serum ferritin <15 µg/L) and nonanemic women (n = 21). Each group received in random order 2 standardized test meals containing 6 mg Fe as isotopically labeled NaFeEDTA and either 300 mL of tea or water. Fractional iron absorption (FIA) was measured by the erythrocyte incorporation of stable iron isotopes after 14 d. We performed linear mixed-model analysis and post hoc sample t tests to assess the effects of group and tea on FIA. RESULTS: The polyphenol content of the tea serving was 492 mg. Tea consumption reduced iron absorption from NaFeEDTA by >85% in both IDA and nonanemic women. There were group (P < 0.001) and tea (P < 0.001) effects on FIA, but no group by tea interaction (P = 0.312). Median (IQR) FIA (%) in women with IDA from test meals consumed without and with tea was 36.7 (24.2-39.8) and 4.1 (2.8-6.1), respectively (P < 0.001). Median (IQR) FIA (%) in nonanemic women from test meals consumed without and with tea was 16.7 (9.2-24.2) and 1.4 (0.8-2.9), respectively (P < 0.001). CONCLUSIONS: FIA from wheat flour-based meals without and with tea was ∼2-fold higher in women with IDA than in nonanemic women. Providing fortificant iron as NaFeEDTA cannot overcome the inhibition of tea polyphenols on iron absorption, even in IDA, where iron absorption is strongly upregulated. This trial was registered at www.clinicaltrials.gov as NCT02175888.

Stable isotope evidence (Fe, Cu) suggests that sex, but not aging is recorded in rhesus macaque (Macaca mulatta) bone.

OBJECTIVES: Here, we examine (1) if the sex-related differences in iron (Fe) and copper (Cu) isotope ratios, represented as δ56 Fe and δ65 Cu values, respectively observed in humans exist in bulk occipital bone and incisors of male and female non-human primates, and (2) if the variation of Fe and Cu isotope ratios, known to vary in human blood as a factor of age are similar in non-human primate bone. MATERIALS AND METHODS: Isotope ratios were measured from the skeletal elements of 20 rhesus macaques (Macaca mulatta) with known life history traits. The metals were purified by column chromatography and their isotope ratios measured by MC-ICP-MS. Data were analyzed using generalized additive models (GAM). RESULTS: When accounting for age and sex independently, we found a significant relationship between δ65 Cu values and occipital bone, but not in incisors. There were no significant relationships observed between δ56 Fe values, occipital bone, or incisors. Similarly, there were no significant relationships observed between δ56 Fe values, δ65 Cu values, and age. DISCUSSION: We suggest that Cu and Fe isotope ratios have the potential to be useful supplementary tools in future research in biological anthropology, but additional studies are needed to further verify the relationship between sex, age, δ65 Cu, and δ56 Fe values in primates.

Prepregnancy Obesity Is Not Associated with Iron Utilization during the Third Trimester.

BACKGROUND: An adequate maternal iron supply is crucial for maternal red blood cell (RBC) expansion, placental and fetal growth, and fetal brain development. Obese women may be at risk for poor iron status in pregnancy due to proinflammatory-driven overexpression of hepcidin leading to decreased iron bioavailability. OBJECTIVE: The objective of this study was to determine the impact of prepregnancy (PP) obesity on third-trimester maternal iron utilization. DESIGN: Using the stable isotope 57Fe, we measured iron utilization in the third trimester in PP obese [BMI (in kg/m2): ≥30] and nonobese (BMI: 18.5-29.9) women. We also assessed iron status, hepcidin, inflammation, erythropoietin, dietary iron intake, and gestational weight gain. Descriptive and inferential statistical tests (e.g., Student t test, Pearson correlation) were used for data analysis. RESULTS: Fifty pregnant women (21 PP obese, 29 PP nonobese) were included. Mean age was 27.6 ± 6.8 y and mean gestational age at time of 57Fe administration was 32.7 ± 0.7 wk. Anemia (hemoglobin <11 g/dL for non-black and <10.2 g/dL for black women) affected 38% of women (43% PP obese compared with 35% PP nonobese; P = 0.55). Women with PP obesity had significantly higher C-reactive protein (8.5 compared with 3.4 mg/L, P = 0.0007) and total body iron corrected for inflammation (6.0 compared with 4.3 mg/kg, P = 0.04) compared with the nonobese women. There was no difference in serum hepcidin or iron utilization between the PP BMI groups. CONCLUSION: This is the first study to assess the impact of PP obesity on maternal iron utilization. We found no difference in iron utilization in the third trimester of pregnancy in women with and without PP obesity. Despite higher frequency of anemia, women with PP obesity had less depleted body iron stores, suggesting some degree of iron sequestration. This finding should be followed up and extended to understand effects on fetal iron bioavailability.

Iron Absorption is Greater from Apo-Lactoferrin and is Similar Between Holo-Lactoferrin and Ferrous Sulfate: Stable Iron Isotope Studies in Kenyan Infants.

BACKGROUND: Whether lactoferrin (Lf) binds iron to facilitate its absorption or to sequester iron from potential enteropathogens remains uncertain. Bovine Lf is added to many infant formulas, but previous studies in infants reported that Lf had no effect on or inhibited iron absorption. The effects of the apo (iron-free) or the holo (iron-loaded) forms of Lf on iron absorption are unclear. OBJECTIVES: Our objective was to compare iron absorption from a maize-based porridge containing: 1) labeled ferrous sulfate (FeSO4) alone; 2) labeled FeSO4 given with bovine apo-Lf; and 3) intrinsically labeled bovine holo-Lf. METHODS: In a crossover study, we measured iron absorption in Kenyan infants (n = 25; mean ± SD age 4.2 ± 0.9 months; mean ± SD hemoglobin 109 ± 11 g/L) from maize-based test meals containing: 1) 1.5 mg of iron as 54Fe-labeled FeSO4; 2) 1.42 mg of iron as 58Fe-labeled FeSO4, given with 1.41 g apo-Lf (containing 0.08 mg iron); and 3) 1.41 g holo-Lf carrying 1.5 mg iron as 57Fe. The iron saturation levels of apo- and holo-Lf were 0.56% and 47.26%, respectively primary outcome was fractional iron absorption (FIA), assessed by erythrocyte incorporation of isotopic labels. RESULTS: The FIA from the meal containing apo-Lf + FeSO4 (geometric mean, 9.8%; -SD and +SD, 5.4% and 17.5%) was higher than from the meals containing FeSO4 (geometric mean, 6.3%; -SD and +SD, 3.2% and 12.6%; P = 0.002) or holo-Lf (geometric mean, 5.0%; -SD and +SD, 2.8% and 8.9%; P <0.0001). There was no significant difference in FIA when comparing the meals containing holo-Lf versus FeSO4 alone (P = 0.24). CONCLUSIONS: The amount of iron absorbed from holo-Lf was comparable to that of FeSO4, and the addition of apo-Lf to a test meal containing FeSO4 significantly increased (+56%) iron absorption. These findings suggest that Lf facilitates iron absorption in young infants. Because Lf binds iron with high affinity, it could be a safe way to provide iron to infants in low-income countries, where iron fortificants can adversely affect the gut microbiome and cause diarrhea. This study was registered at clinicaltrials.gov as NCT03617575.

Acute Consumption of Prebiotic Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate, but not from Ferrous Sulfate and Ferric Pyrophosphate: Stable Iron Isotope Studies in Iron-Depleted Young Women.

BACKGROUND: Although acute consumption of high doses of prebiotic galacto-oligosaccharides (GOS) increases fractional iron absorption (FIA) from ferrous fumarate (FeFum), it is uncertain if low doses of GOS have this effect. Furthermore, whether GOS improve iron absorption from other commonly used iron compounds and whether ascorbic acid (AA) enhances the effect of GOS on iron absorption from FeFum is unclear. OBJECTIVES: In iron-depleted women [serum ferritin (SF) <30 µg/L], we assessed: 1) whether the acute enhancing effect of GOS on FeFum is dose dependent; 2) if GOS would affect FIA from ferrous sulfate (FeSO4) or ferric pyrophosphate (FePP); and 3) if AA and GOS given together enhance FIA from FeFum to a greater extent compared with GOS alone. METHODS: We recruited 46 women (mean age 22.0 y, mean BMI 21.3 kg/m2, median SF 17.1 µg/L), and measured FIA from 14 mg iron labeled with stable isotopes in the following conditions: 1) FIA from FeFum given with 3.5 g, 7 g GOS, and without GOS; 2) FIA from FeSO4 and FePP given with and without 15 g GOS; and 3) FIA from FeFum given with 7 g GOS with and without 93 mg AA. FIA was measured as erythrocyte incorporation of stable isotopes after 14 d. Comparisons were made using paired samples t-test or Wilcoxon rank sum test where appropriate. RESULTS: Giving 7 g of GOS significantly increased FIA from FeFum (+26%; P = 0.039), whereas 3.5 g GOS did not (P = 0.130). GOS did not significantly increase FIA from FeSO4 (P = 0.998) or FePP (P = 0.059). FIA from FeFum given with GOS and AA was significantly higher compared with FeFum given with GOS alone (+30%; P <0.001). CONCLUSIONS: In iron-depleted women, GOS does not increase FIA from FeSO4 or FePP, but it increases FIA from FeFum. Thus, a combination of FeFum and GOS may be a well-absorbed formula for iron supplements. The study was registered at clinicaltrials.gov as NCT03762148.

Addition of Whole Wheat Flour During Injera Fermentation Degrades Phytic Acid and Triples Iron Absorption from Fortified Tef in Young Women.

BACKGROUND: Iron deficiency is a major public health concern in Ethiopia, where the traditional diet is based on tef injera. Iron absorption from injera is low due to its high phytic acid (PA) content. OBJECTIVES: We investigated ways to increase iron absorption from FeSO4-fortified tef injera in normal-weight healthy women (aged 21-29 y). METHODS: Study A (n = 22) investigated the influence on fractional iron absorption (FIA) from FeSO4-fortified injera of 1) replacing 10% tef flour with whole wheat flour (a source of wheat phytase), or 2) adding an isolated phytase from Aspergillus niger. Study B (n = 18) investigated the influence on FIA of replacing FeSO4 in tef injera with different amounts of NaFeEDTA. In both studies, the iron fortificants were labeled with stable isotopes and FIA was calculated from erythrocyte incorporation of stable iron isotopes 14 d after administration. RESULTS: In study A, the median (IQR) FIA from the 100% tef injera meal was 1.5% (0.7-2.8%). This increased significantly (P < 0.05) to 5.3% (2.4-7.1%) on addition of 10% whole wheat flour, and to 3.6% (1.6-6.2%) on addition of A. niger phytase. PA content of the 3 meals was 0.62, 0.20, and 0.02 g/meal, respectively. In study B, the median (IQR) FIA from the 100% tef injera meal was 3.3% (1.1-4.4%) and did not change significantly (P > 0.05) on replacing 50% or 75% of FeSO4 with NaFeEDTA. CONCLUSIONS: FIA from tef injera by young women was very low. NaFeEDTA was ineffective at increasing iron absorption, presumably due to the relatively low EDTA:Fe molar ratios. Phytate degradation, however, greatly increased during tef fermentation on addition of native or isolated phytases. Replacing 10% tef with whole wheat flour during injera fermentation tripled FIA in young women and should be considered as a potential strategy to improve iron status in Ethiopia.

The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women.

PURPOSE: A technological gap exists for the iron (Fe) fortification of difficult-to-fortify products, such as wet and acid food products containing polyphenols, with stable and bioavailable Fe. Fe picolinate, a novel food ingredient, was found to be stable over time in this type of matrix. The objective of this study was to measure the Fe bioavailability of Fe picolinate in a complementary fruit yogurt. METHODS: The bioavailability of Fe picolinate was determined using stable iron isotopes in a double blind, randomized cross-over design in non-anemic Swiss women (n = 19; 25.1 ± 4.6 years). Fractional Fe absorption was measured from Fe picolinate (2.5 mg 57Fe per serving in two servings given morning and afternoon) and from Fe sulfate (2.5 mg 54Fe per serving in two servings given morning and afternoon) in a fortified dairy complementary food (i.e. yogurt containing fruits). Fe absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean (95% CI) fractional iron absorption from Fe picolinate and Fe sulfate were not significantly different: 5.2% (3.8-7.2%) and 5.3% (3.8-7.3%) (N.S.), respectively. Relative bioavailability of Fe picolinate versus Fe sulfate was 0.99 (0.85-1.15). CONCLUSION: Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.

Quantification of dissolved iron sources to the North Atlantic Ocean.

Dissolved iron is an essential micronutrient for marine phytoplankton, and its availability controls patterns of primary productivity and carbon cycling throughout the oceans. The relative importance of different sources of iron to the oceans is not well known, however, and flux estimates from atmospheric dust, hydrothermal vents and oceanic sediments vary by orders of magnitude. Here we present a high-resolution transect of dissolved stable iron isotope ratios (δ(56)Fe) and iron concentrations ([Fe]) along a section of the North Atlantic Ocean. The different iron sources can be identified by their unique δ(56)Fe signatures, which persist throughout the water column. This allows us to calculate the relative contribution from dust, hydrothermal venting and reductive and non-reductive sedimentary release to the dissolved phase. We find that Saharan dust aerosol is the dominant source of dissolved iron along the section, contributing 71-87 per cent of dissolved iron. Additional sources of iron are non-reductive release from oxygenated sediments on the North American margin (10-19 per cent), reductive sedimentary dissolution on the African margin (1-4 per cent) and hydrothermal venting at the Mid-Atlantic Ridge (2-6 per cent). Our data also indicate that hydrothermal vents in the North Atlantic are a source of isotopically light iron, which travels thousands of kilometres from vent sites, potentially influencing surface productivity. Changes in the relative importance of the different iron sources through time may affect interactions between the carbon cycle and climate.

Iron isotope evidence for arsenic mobilization in shallow multi-level alluvial aquifers of Jianghan Plain, central China.

Intake of groundwater with arsenic (As) concentrations exceeding the World Health Organization standard of 10 µg L-1 adversely impacts over 100 million people worldwide. Geogenic As contaminated groundwater within central Yangtze River Basin has recently been reported, but the variations within different depths of aquifers are not commonly observed and the processes controlling As variations have yet to be resolved. Here we report the significant As variations within two different depths (10 m and 25 m) of shallow multi-level alluvial aquifers at Jianghan Plain, a floodplain in the central Yangtze River Basin, which is also a recently discovered geogenic As affected area with cases of waterborne arsenicosis. The multi-year monitoring of aquifer chemistry results show that the As concentrations increase with the Fe(II) concentrations when As contents are relatively lower (<200 µg L-1) in upper phreatic aquitard (at 10 m depth), while decrease with Fe(II) concentrations when As contents are much greater in lower confined aquifer (at 25 m depth), and the highest is up to 1070 µg L-1. Iron isotope analysis were conducive to characterize Fe cycling in the aquifers and thus illustrate geochemical processes controlling As mobilization of shallow groundwaters. Results showed that groundwater is generally enriched in isotopically light Fe with δ56Fe values between - 1.60‰ and + 0.06‰ (median - 0.55‰). In the upper phreatic aquitard, microbial reductive dissolution of As-associated Fe(III) oxides, hydroxides and oxyhydroxides is the major process controlling As concentrations lower than 200 µg L-1. The reduction process could lead to the increasing As concentrations with the gradually increasing δ56Fe values, and a positive correlation between Fe and Î´56Fe, and between dissolved As and δ56Fe values is observed, respectively. In strongly reducing conditions as the lower confined aquifer, jointly microbial reduction of sulfate promotes the As mobilization through HS- abiotic reduction of Fe(III) minerals, resulting in As concentrations greater than 200 µg L-1. These findings could provide new insights for differentiating the major factors controlling As mobilization at different depths of aquifers, and provide better water managements for similar geogenic As-affected shallow alluvial aquifers.

Introducing Specificity to Iron Oxide Nanoparticle Imaging by Combining 57Fe-Based MRI and Mass Spectrometry.

Iron oxide nanoparticles (ION) are highly sensitive probes for magnetic resonance imaging (MRI) that have previously been used for in vivo cell tracking and have enabled implementation of several diagnostic tools to detect and monitor disease. However, the in vivo MRI signal of ION can overlap with the signal from endogenous iron, resulting in a lack of detection specificity. Therefore, the long-term fate of administered ION remains largely unknown, and possible tissue deposition of iron cannot be assessed with established methods. Herein, we combine nonradioactive 57Fe-ION MRI with ex vivo laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging, enabling unambiguous differentiation between endogenous iron (56Fe) and iron originating from applied ION in mice. We establish 57Fe-ION as an in vivo MRI sensor for cell tracking in a mouse model of subcutaneous inflammation and for assessing the long-term fate of 57Fe-ION. Our approach resolves the lack of detection specificity in ION imaging by unambiguously recording a 57Fe signature.

Consumption of Galacto-Oligosaccharides Increases Iron Absorption from Ferrous Fumarate: A Stable Iron Isotope Study in Iron-Depleted Young Women.

BACKGROUND: Animal studies suggest prebiotics can increase iron absorption, but results from human studies are equivocal. OBJECTIVES: In iron-depleted women, before (baseline) and after daily consumption of galacto-oligosaccharides (GOS) for 4 wk, we sought to assess fractional iron absorption (FIA) from an iron supplement given with and without single doses of GOS in test meals or water. METHODS: In all women (n = 34; median serum ferritin concentration = 16.4 µg/L), FIA from doses of 14 mg iron labeled with stable isotopes was measured in the following conditions at baseline: 1) FIA from ferrous fumarate (FeFum) in water given with and without 15 g GOS; 2) FIA from FeFum in a test meal given with and without 15 g GOS; 3) FIA from ferrous sulfate (FeSO4) in a test meal given without 15 g GOS. All subjects then consumed âˆ¼15 g GOS daily for 4 wk. Then the following conditions were tested: 4) FIA from FeFum in a test meal with and without 15 g GOS; and 5) FIA from FeSO4 in a test meal with 15 g GOS. FIA was measured as erythrocyte incorporation of stable isotopes. RESULTS: At baseline, GOS significantly increased FIA from FeFum when given with water (+61%; P < 0.001) and the meal (+28%; P = 0.002). After 4 wk of GOS consumption, GOS again significantly increased FIA from FeFum in the meal (+29%; P = 0.044). However, compared with baseline, consumption of GOS for 4 wk did not significantly enhance absorption from FeFum in the meal given without GOS. FIA from FeSO4 given with GOS in a meal after 4 wk of GOS consumption was not significantly greater than FIA from FeSO4 in a meal without GOS at baseline. CONCLUSIONS: In iron-depleted women, GOS given with FeFum increases FIA, but 4 wk of GOS consumption did not enhance this effect. The study was registered at clinicaltrials.gov as NCT03325270.

High Bioavailability from Ferric Pyrophosphate-Fortified Bouillon Cubes in Meals is Not Increased by Sodium Pyrophosphate: a Stable Iron Isotope Study in Young Nigerian Women.

BACKGROUND: It is challenging to find an iron compound that combines good bioavailability with minimal sensory changes when added to seasonings or condiments. Ferric pyrophosphate (FePP) is currently used to fortify bouillon cubes, but its bioavailability is generally low. Previously, the addition of a stabilizer, sodium pyrophosphate (NaPP), improved iron bioavailability from a bouillon drink. OBJECTIVE: We assessed whether there is a dose-response effect of added NaPP on iron bioavailability from local meals prepared with intrinsically labeled FePP-fortified bouillon cubes in young Nigerian women using iron stable isotope techniques. METHODS: In a double-blind, randomized, cross-over trial, women (n = 24; aged 18-40 y; mean BMI 20.5 kg/m2) consumed a Nigerian breakfast and lunch for 5 d prepared with bouillon cubes containing 2.5 mg 57Fe (as FePP) and 3 different molar ratios of NaPP: 57Fe (0:1, 3:1, and 6:1). Iron bioavailability was assessed by measuring 57Fe incorporation into erythrocytes 16 d after each 5 d NaPP: 57Fe feeding period. Data were analyzed using a linear regression model of log iron absorption on NaPP ratio, with body weight and baseline body iron stores as covariates and subject as a random intercept. RESULTS: Of the women included, 46% were anemic and 26% were iron deficient. Iron bioavailability was 10.8, 9.8, and 11.0% for the 0:1, 3:1, and 6:1 NaPP:57Fe treatments, respectively. There was no dose-response effect of an increasing NaPP:57Fe ratio (ß ± SE: 0.003 ± 0.028, P = 0.45). CONCLUSIONS: In this study, the addition of NaPP did not increase iron bioavailability from FePP-fortified bouillon cubes. However, iron bioavailability from the Nigerian meals prepared with FePP-fortified bouillon cubes was higher than expected. These results are encouraging for the potential of bouillon cubes as a fortification vehicle. Further studies are needed to assess the effect of FePP-fortified bouillon cubes on improving iron status in low-income populations. This trial was registered at clinicaltrials.gov as NCT02815449.