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 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.

Measurement of the enriched stable isotope 58Fe in iron related disorders- comparison of INAA and MC-ICP-MS.

As a safer alternative for the use of radioactive tracers, the enriched stable 58Fe isotope has been introduced in studies of iron metabolism. In this study this isotope is measured with instrumental neutron activation analysis (INAA) in blood samples of patients with iron related disorders and controls after oral ingestion of a 58Fe containing pharmaceutical. Results were compared with those derived from MC-ICP-MS, applied on the same samples, and analytical and practical aspects of the two techniques were compared. Both techniques showed an increased absorption and incorporation in red blood cells of the 58Fe isotope in iron deficient patients in contrast to the controls. In all individuals results of INAA measurements were in good agreement with those of MC-ICP-MS (|zeta| < 2). Uncertainties in INAA are substantially higher than those achievable by MC-ICP-MS but the INAA technique offers a high specificity and selectivity for iron close to 100%. In contrast to INAA, sample preparation before measurement is very critical in MC-ICP-MS and interferences with 58Ni and 54Cr may hamper the measurement of 58Fe and 54Fe respectively. Since it takes at least five days after irradiation to reduce the activity of interfering radionuclides (mainly 24Na), INAA is a more time consuming procedure; the need of a nuclear reactor facility makes it also less accessible than MC-ICP-MS. Costs are comparable. Both INAA and MC-ICP-MS are able to adequately measure changes in iron isotope composition in blood when an enriched stable iron isotope is applied in clinical research. Although MC-ICP-MS is more sensitive, is faster and has easier access, in INAA preparative steps before measurement are simpler and there are hardly demands on the kind and size of the samples. This may be relevant working with biomaterials in a clinical setting.

An intensified training schedule in recreational male runners is associated with increases in erythropoiesis and inflammation and a net reduction in plasma hepcidin.

Background: Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. Objective: We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. Design: In a prospective intervention, nonanemic, iron-sufficient men (n = 10) completed a 34-d study consisting of a 16-d control phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Results: Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P < 0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P < 0.05). Training tended to increase geometric mean iron absorption by 24% (P = 0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P < 0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P < 0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. Conclusions: In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.

A 1-h time interval between a meal containing iron and consumption of tea attenuates the inhibitory effects on iron absorption: a controlled trial in a cohort of healthy UK women using a stable iron isotope.

Background: Tea has been shown to be a potent inhibitor of nonheme iron absorption, but it remains unclear whether the timing of tea consumption relative to a meal influences iron bioavailability.Objective: The aim of the study was to investigate the effect of a 1-h time interval of tea consumption on nonheme iron absorption in an iron-containing meal in a cohort of iron-replete, nonanemic female subjects with the use of a stable isotope (57Fe).Design: Twelve women (mean ± SD age: 24.8 ± 6.9 y) were administered a standardized porridge meal extrinsically labeled with 4 mg 57Fe as FeSO4 on 3 separate occasions, with a 14-d time interval between each test meal (TM). The TM was administered with water (TM-1), with tea administered simultaneously (TM-2), and with tea administered 1 h postmeal (TM-3). Fasted venous blood samples were collected for iron isotopic analysis and measurement of iron status biomarkers. Fractional iron absorption was estimated by the erythrocyte iron incorporation method.Results: Iron absorption was 5.7% ± 8.5% (TM-1), 3.6% ± 4.2% (TM-2), and 5.7% ± 5.4% (TM-3). Mean fractional iron absorption was found to be significantly higher (2.2%) when tea was administered 1 h postmeal (TM-3) than when tea was administered simultaneously with the meal (TM-2) (P = 0.046). An ∼50% reduction in the inhibitory effect of tea (relative to water) was observed, from 37.2% (TM-2) to 18.1% (TM-3).Conclusions: This study shows that tea consumed simultaneously with an iron-containing porridge meal leads to decreased nonheme iron absorption and that a 1-h time interval between a meal and tea consumption attenuates the inhibitory effect, resulting in increased nonheme iron absorption. These findings are not only important in relation to the management of iron deficiency but should also inform dietary advice, especially that given to those at risk of deficiency. This trial was registered at clinicaltrials.gov as NCT02365103.

Iron Bioavailability from Ferric Pyrophosphate in Extruded Rice Cofortified with Zinc Sulfate Is Greater than When Cofortified with Zinc Oxide in a Human Stable Isotope Study.

Background: Extruded rice grains are often cofortified with iron and zinc. However, it is uncertain if the addition of zinc to iron-fortified rice affects iron absorption and whether this is zinc-compound specific.Objective: We investigated whether zinc, added as zinc oxide (ZnO) or zinc sulfate (ZnSO4), affects human iron absorption from extruded rice fortified with ferric pyrophosphate (FePP).Methods: In 19 iron-depleted Swiss women (plasma ferritin ≤16.5 µ/L) aged between 20 and 39 y with a normal body mass index (in kg/m2; 18.7-24.8), we compared iron absorption from 4 meals containing fortified extruded rice with 4 mg Fe and 3 mg Zn. Three of the meals contained extruded rice labeled with FePP (57FePP): 1) 1 meal without added zinc (57FePP-Zn), 2) 1 cofortified with ZnO (57FePP+ZnO), and 3) 1 cofortified with ZnSO4 (57FePP+ZnSO4). The fourth meal contained extruded rice without iron or zinc, extrinsically labeled with ferrous sulfate (58FeSO4) added as a solution after cooking. All 4 meals contained citric acid. Iron bioavailability was measured by isotopic iron ratios in red blood cells. We also measured relative in vitro iron solubility from 57FePP-Zn, 57FePP+ZnO, and 57FePP+ZnSO4 expressed as a fraction of FeSO4 solubility.Results: Geometric mean fractional iron absorption (95% CI) from 57FePP+ZnSO4 was 4.5% (3.4%, 5.8%) and differed from 57FePP+ZnO (2.7%; 1.8%, 4.1%) (P < 0.03); both did not differ from 57FePP-Zn: 4.0% (2.8%, 5.6%). Relative iron bioavailabilities compared with 58FeSO4 were 62%, 57%, and 38% from 57FePP+ZnSO4, 57FePP-Zn, and 57FePP+ZnO, respectively. In vitro solubility from 57FePP+ZnSO4 differed from that of 57FePP-Zn (14.3%; P < 0.02) but not from that of 57FePP+ZnO (10.2% compared with 13.1%; P = 0.08).Conclusions: In iron-depleted women, iron absorption from FePP-fortified extruded rice cofortified with ZnSO4 was 1.6-fold (95% CI: 1.4-, 1.9-fold) that of rice cofortified with ZnO. These findings suggest that ZnSO4 may be the preferable zinc cofortificant for optimal iron bioavailability of iron-fortified extruded rice. This trial was registered at clinicaltrials.gov as NCT02255942.

Iron bioavailability from fresh cheese fortified with iron-enriched yeast.

PURPOSE: An iron-enriched yeast able to lyse at body temperature was developed for iron fortification of chilled dairy products. The aim was to evaluate iron (Fe) absorption from iron-enriched yeast or ferrous sulfate added to fresh cheese. METHODS: Two stable isotope studies with a crossover design were conducted in 32 young women. Fe absorption from fresh cheese fortified with iron-enriched yeast (2.5 mg 58Fe) was compared to that from ferrous sulfate (2.5 mg 57Fe) when ingested with fresh cheese alone or with fresh cheese consumed with bread and butter. Iron absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean fractional iron absorption from fresh cheese fortified with iron-enriched yeast consumed alone was significantly lower than from the cheese fortified with FeSO4 (20.5 vs. 28.7 %; p = 0.0007). When the fresh cheese was consumed with bread and butter, iron absorption from both fortificants decreased to 6.9 % from the iron-enriched yeast compared to 8.4 % from ferrous sulfate. The relative bioavailability of the iron-enriched yeast compared to ferrous sulfate was 0.72 for the cheese consumed alone and 0.82 for cheese consumed with bread and butter (p = 0.157). CONCLUSIONS: Iron from iron-enriched yeast was 72-82 % as well absorbed as ferrous sulfate indicating that the yeast lysed during digestion and released its iron.

Iron bioavailability in 8-24-month-old Thai children from a micronutrient-fortified quick-cooking rice containing ferric ammonium citrate or a mixture of ferrous sulphate and ferric sodium ethylenediaminetetraacetic acid.

A quick-cooking rice, produced from broken rice, is a convenient ingredient for complementary foods in Thailand. The rice is fortified with micronutrients including iron during the processing procedure, which can cause unacceptable sensory changes. A quick-cooking rice fortified with ferric ammonium citrate (FAC) or a mixture of ferrous sulphate (FeSO4 ) and ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), with a 2:1 molar ratio of iron from FeSO4 : iron from NaFeEDTA (FeSO4 + NaFeEDTA), gave a product that was organoleptically acceptable. The study compared iron absorption by infants and young children fed with micronutrient-fortified quick-cooking rice containing the test iron compounds or FeSO4 . Micronutrient-fortified quick-cooking rice prepared as a traditional Thai dessert was fed to two groups of 15 8-24-month healthy Thai children. The iron fortificants were isotopically labelled with (57) Fe for the reference FeSO4 or (58) Fe for the tested fortificants, and iron absorption was quantified based on erythrocyte incorporation of the iron isotopes 14 days after feeding. The relative bioavailability of FAC and of the FeSO4 + NaFeEDTA was obtained by comparing their iron absorption with that of FeSO4 . Mean fractional iron absorption was 5.8% [±standard error (SE) 1.9] from FAC and 10.3% (±SE 1.9) from FeSO4 + NaFeEDTA. The relative bioavailability of FAC was 83% (P = 0.02). The relative bioavailability of FeSO4 + NaFeEDTA was 145% (P = 0.001). Iron absorption from the rice containing FAC or FeSO4 + NaFeEDTA was sufficiently high to be used in its formulation, although iron absorption from FeSO4 + NaFeEDTA was significantly higher (P < 0.00001).

Review: The potential of the common bean (Phaseolus vulgaris) as a vehicle for iron biofortification.

Common beans are a staple food and the major source of iron for populations in Eastern Africa and Latin America. Bean iron concentration is high and can be further increased by biofortification. A major constraint to bean iron biofortification is low iron absorption, attributed to inhibitory compounds such as phytic acid (PA) and polyphenol(s) (PP). We have evaluated the usefulness of the common bean as a vehicle for iron biofortification. High iron concentrations and wide genetic variability have enabled plant breeders to develop high iron bean varieties (up to 10 mg/100 g). PA concentrations in beans are high and tend to increase with iron biofortification. Short-term human isotope studies indicate that iron absorption from beans is low, PA is the major inhibitor, and bean PP play a minor role. Multiple composite meal studies indicate that decreasing the PA level in the biofortified varieties substantially increases iron absorption. Fractional iron absorption from composite meals was 4%-7% in iron deficient women; thus the consumption of 100 g biofortified beans/day would provide about 30%-50% of their daily iron requirement. Beans are a good vehicle for iron biofortification, and regular high consumption would be expected to help combat iron deficiency (ID).

Iron uptake and ferrokinetics in healthy male subjects of an iron-based oral phosphate binder (SBR759) labeled with the stable isotope (58)Fe.

SBR759 is a novel polynuclear iron(III) oxide-hydroxide starch·sucrose·carbonate complex being developed for oral use in chronic kidney disease (CKD) patients with hyperphosphatemia on hemodialysis. SBR759 binds inorganic phosphate released by food uptake and digestion in the gastro-intestinal tract increasing the fecal excretion of phosphate with concomitant reduction of serum phosphate concentrations. Considering the high content of ∼20% w/w covalently bound iron in SBR759 and expected chronic administration to patients, absorption of small amounts of iron released from the drug substance could result in potential iron overload and toxicity. In a mechanistic iron uptake study, 12 healthy male subjects (receiving comparable low phosphorus-containing meal typical for CKD patients: ≤1000 mg phosphate per day) were treated with 12 g (divided in 3 × 4 g) of stable (58)Fe isotope-labeled SBR759. The ferrokinetics of [(58)Fe]SBR759-related total iron was followed in blood (over 3 weeks) and in plasma (over 26 hours) by analyzing with high precision the isotope ratios of the natural iron isotopes (58)Fe, (57)Fe, (56)Fe and (54)Fe by multi-collector inductively coupled mass spectrometry (MC-ICP-MS). Three weeks following dosing, the subjects cumulatively absorbed on average 7.8 ± 3.2 mg (3.8-13.9 mg) iron corresponding to 0.30 ± 0.12% (0.15-0.54%) SBR759-related iron which amounts to approx. 5-fold the basal daily iron absorption of 1-2 mg in humans. SBR759 was well-tolerated and there was no serious adverse event and no clinically significant changes in the iron indices hemoglobin, hematocrit, ferritin concentration and transferrin saturation.

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.

Genetic reduction of phytate in common bean (Phaseolus vulgaris L.) seeds increases iron absorption in young women.

Iron bioavailability from common beans is negatively influenced by phytic acid (PA) and polyphenols (PPs). Newly developed low-PA (lpa) beans with 90% less PA and variable PPs might improve iron bioavailability. The aim of this study was to evaluate the influence of lpa beans on iron bioavailability in women (n = 20). We compared iron absorption from 4 different beans using a paired, double meal, crossover design. Iron absorption was measured as erythrocyte incorporation of stable iron isotopes (Fe(57), Fe(58)) from 2 lpa bean lines, one high in PPs (means ± SDs; PA = 124 ± 10 mg/100 g; PPs = 462 ± 25 mg/100 g) and one low in PPs (PA = 70 ± 10 mg/100 g; PPs = 54 ± 2 mg/100 g). The other 2 beans used were their parents with a normal PA concentration, one high in PPs (PA = 1030 ± 30 mg/100 g; PPs = 676 ± 19 mg/100 g) and one low in PPs (PA = 1360 ± 10 mg/100 g; PPs = 58 ± 1 mg/100 g). Fractional iron absorption from the lpa bean high in PPs was 6.1% (95% CI: 2.6, 14.7), which was 60 and 130% higher compared with the parent high in PPs (P < 0.001) and low in PPs (P < 0.001), respectively. The total amount of iron absorbed per test meal from the lpa bean high in PPs (372 µg; 95% CI: 160, 890) was 60 and 163% higher compared with the parent high in PPs (P < 0.001) and low in PPs (P < 0.001), respectively. Fractional iron absorption from the lpa line low in PPs (4%; 95% CI: 1.8, 8.7) was 50% higher and the total amount of iron absorbed per test meal (261 µg; 95% CI: 120, 570) was 85% higher than iron from the parent low in PPs (P < 0.001). There was no difference between the lpa beans high or low in PPs or between the parents high or low in PPs. A 90% reduction in PA leads to an increase in bioavailable iron from beans, independent of the PP concentration. The lpa mutation could be a key tool for improving iron bioavailability from beans.

Effects of dietary factors on the pharmacokinetics of 58Fe-labeled hemin after oral administration in normal rats and the iron-deficient rats.

Hemin, iron (III) protoporphyrin chloride (IX), as a stable form of heme iron, has been used in iron absorption studies. The aim of the present study was to elucidate the influences of body iron status and three dietary factors (green tea extract, ascorbic acid, and calcium) on the pharmacokinetics of hemin using stable isotope labeling methods followed by ICP-MS measurement. In this study, a rapid, sensitive, and specific ICP-MS method for the determination of (58)Fe originating from hemin in rat plasma was developed and a rat model of iron deficiency anemia was established. It was found that hemin iron absorption increased significantly under iron deficiency anemia status, with AUC0-t and AUC0-∞ showing significant increase in anemic rats compared to normal ones. Green tea extract strongly inhibited hemin iron absorption in both normal rats and iron-deficient rats. In normal rats administered with green tea extract, C max resulted significantly reduced, whereas in anemic rats administered with green tea extract both AUC0-t and AUC0-∞ were reduced. On the other hand, ascorbic acid significantly affected hemin iron absorption only in iron-deficient rats, in which C max showed a significant increase. Interestingly, calcium slowed down the hemin iron absorption rate in normal rats, MRT0-t being significantly different in calcium-treated animals compared to untreated ones. This trend also appeared in the iron-deficient group but it did not reach statistical significance. Our data suggest that the mechanism of hemin iron absorption is regulated by body iron status and dietary factors can influence hemin iron absorption to varying degrees. Moreover, these results may also have general implication in the iron deficiency treatment with iron supplements and fortification of foods.

Assessment of iron absorption in mice by ICP-MS measurements of (57)Fe levels.

BACKGROUND: The study of iron metabolism is essential in nutritional sciences as iron deficiency is one of the most common nutritional deficiencies in humans and represents a serious health problem worldwide. The mouse is utilized as a unique and powerful model for the identification and characterization of genes involved in iron metabolism and for studying the pathogenesis of iron disorders. Thus, sophisticated and sensitive techniques have been developed to study iron metabolism in this animal model. In particular, iron absorption has been studied in mice by using the radioisotopes (55)Fe and (59)Fe in tied-off or dissected and everted duodenal segments. Nevertheless, several drawbacks discourage the extended use of these approaches. METHODS AND RESULTS: Here, we report the use of the stable isotope (57)Fe to measure iron absorption in mice. We show that after oral administration of (57)Fe-containing solutions, it is possible to measure both duodenal iron retention and duodenal iron transfer to specific organs, using inductively coupled plasma mass spectrometry (ICP-MS). As (57)Fe is administered orally, no surgical operation is needed before the end of the experiment, thus allowing the measurement of iron absorption under physiologic conditions. Moreover, the use of ICP-MS for (57)Fe detection ensures high sensitivity and provides quantitative data. Finally, the use of a stable isotope enables the measurement of both iron absorption and histologic and/or biochemical analyses in the same animal. CONCLUSIONS: The use of (57)Fe to measure iron absorption in mice, therefore, represents an alternative to radioisotope-based methods, providing a new tool to extend our knowledge on the mechanism of iron absorption.

Effect of calcium on iron absorption in women with marginal iron status.

We measured non-haem Fe absorption with and without added Ca in a short-term feeding study, in thirteen women with marginal Fe status, by the use of a double stable isotope technique. Supplementing 500 mg Ca as calcium carbonate significantly (P = 0.0009) reduced Fe absorption from a single meal from 10.2 % (range 2.2-40.6) to 4.8 % (range 0.7-18.9). A significant inverse correlation in the absence ( - 0.67, P = 0.010) and presence ( - 0.58, P = 0.037) of Ca, respectively, was found between Fe absorption and Fe stores measured by serum ferritin (SF). Wide variation in Fe absorption was observed between individuals in the absence and in the presence of Ca, despite pre-selection of participants within a relatively narrow range of iron stores (SF concentrations). Correction of Fe absorption data based on group mean SF was not found to be useful in reducing the inter-individual variability in iron absorption. It appears that selecting a study group with a narrow initial range of Fe stores does not necessarily reduce the inter-individual variability in Fe bioavailability measurements. These results support the hypothesis that body Fe stores, although an important determinant of dietary Fe absorption, are not the main factor that determines Fe absorption under conditions of identical dietary intake in subjects with low Fe stores.

Nonheme-iron absorption in first-degree relatives is highly correlated: a stable-isotope study in mother-child pairs.

BACKGROUND: Iron absorption in humans is highly variable even after iron status and dietary components that influence iron absorption are controlled for. Inherited factors may help explain this variance. OBJECTIVE: Our objective was to compare nonheme-iron absorption from a noninhibitory, stable-isotope-labeled test meal in preschool-aged children and their mothers. DESIGN: We provided 72 test meals based on degermed maize flour and milk powder and fortified with [(57)Fe]ferrous fumarate or [(58)Fe]ferrous sulfate to healthy Mexican preschool children [n = 18; mean (+/-SD) age: 3.6 +/- 1.0 y] and their mothers [n = 18; mean (+/-SD) age: 28.0 +/- 5.2 y]. Iron absorption was calculated on the basis of incorporation of isotopes into erythrocytes after 14 d and was adjusted for differences in iron status. RESULTS: There was a wide variation in iron absorption from the test meals: in the mothers and children, the median fractional absorption of ferrous sulfate was 22.55% (range: 1.65-54.83%) and 5.51% (range: 2.23-17.20%), respectively (P < 0.0001). After adjustment for serum ferritin, the significant difference in absorption between mothers and their children disappeared. Despite this broad range of iron absorption, corrected fractional iron absorption from the ferrous fumarate-fortified (r(2) = 0.582) and the ferrous sulfate-fortified test meals (r(2) = 0.557) was strongly correlated in mothers and their children (P < 0.0001). There was a striking positive correlation between the mean corrected fractional iron absorption from both test meals in mothers and their children (r(2) = 0.782, P < 0.0001). In regression analyses that included age, sex, and hemoglobin, the only significant predictor of corrected fractional iron absorption in children was corrected fractional iron absorption in their mothers (standardized beta = 0.884, P < 0.001). CONCLUSIONS: Nonheme-iron absorption exhibits a strong familial tendency. After differences in meal matrix and serum ferritin are accounted for, these data suggest that inheritance and/or shared environmental factors explain most of the variance in dietary iron absorption.

Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin.

BACKGROUND: Plasma hepcidin appears to be a major regulator of iron absorption and homeostasis, but there are few data in humans. OBJECTIVES: With the use of iron stable isotopes, we aimed to determine whether circulating hepcidin predicts dietary iron bioavailability, to quantify the amount of absorbed iron after oral iron loading, and to measure the plasma hepcidin response. DESIGN: In the first study, young women (n = 98) with an iron status varying from iron deficiency anemia to iron sufficiency (women with serum ferritin concentrations 25-40 microg/L were not included) were given stable isotope-labeled test meals (n = 196) containing ferrous sulfate, ferrous fumarate, or ferric pyrophosphate, after which plasma hepcidin and iron bioavailability were measured. In the second study, iron-sufficient men (n = 4) were given 3.8- and 60-mg oral doses of labeled ferrous sulfate. The stable isotope appearance curve was determined, and the plasma hepcidin response was measured over 6 h. RESULTS: In study 1, plasma hepcidin and plasma ferritin were strongly correlated (r = 0.79, P < 0.001). Plasma hepcidin significantly, but modestly, predicted iron bioavailability from ferrous sulfate and ferrous fumarate (r = -0.51 and -0.46, respectively; P < 0.0001) but not from ferric pyrophosphate (r = -0.30, P = 0.056, respectively). In study 2, the 3.8-mg dose increased mean circulating absorbed iron to a peak of 0.42 micromol/L at 60 min but did not increase plasma hepcidin, The 60-mg dose increased mean circulating absorbed iron to a peak of 5.9 micromol/L at 120 min and produced an approximately 30% increase in mean plasma hepcidin at 6 h (P < 0.01). CONCLUSIONS: Plasma hepcidin is only a modest predictor of dietary iron bioavailability in humans. Oral iron loading, measured by stable-isotope appearance curves, increases circulating hepcidin.

Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin.

BACKGROUND/AIMS: The dysmetabolic iron overload syndrome (DIOS) is a common disorder but its origin remains unclear. METHODS: A case-control study was conducted to compare intestinal absorption of iron in 16 men with DIOS (age 53 +/- 11 years, serum ferritin 750 +/- 372 microg/l, hepatic iron 78 +/- 25 micromol/g) and in 32 age-matched controls with normal body iron stores (16 overweight subjects and 16 lean subjects). Intestinal absorption was calculated as the area under the curve (AUC) of 58Fe administered orally and correlated with plasma hepcidin and with insulin resistance parameters including HOMA. RESULTS: Intestinal iron absorption was lower in DIOS (AUC = 22.4 +/- 15.9 microg/l/h) compared to both overweight controls (AUC = 40.5 +/- 29.4 microg/l/h, p=0.04) and to lean controls (AUC = 102.5 +/- 113.5 microg/l/h, p < 0.01). There was an inverse correlation between intestinal iron absorption and plasma hepcidin (r = -0.61, p < 0.001), HOMA (r = -0.35, p = 0.01) and C reactive protein (r = -0.52, p < 0.001). CONCLUSIONS: In overweight subjects with normal iron stores, iron absorption is decreased through hepcidin upregulation. In patients with DIOS, this decrease is more pronounced due to an additional effect of iron excess on circulating hepcidin levels.

Iron absorption is more closely related to iron status than to daily iron intake in 12- to 48-mo-old children.

Few studies have evaluated iron absorption in small children after the first year of life. Our objectives were to examine the relations among iron intake, iron absorption, and iron status in a group of healthy children. We studied 28 children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative of their usual daily mineral intake. A multi-tracer stable isotope study was performed to assess iron absorption both from a meal ((58)Fe) and from a reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes. Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and more so to reference dose iron absorption (r(2) = 0.653, P < 0.0001). Iron absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049) but was not correlated with iron intake (P = 0.20). However, zinc intake was not correlated with measures of iron status, including reference dose iron absorption and serum ferritin (r(2) < 0.1, P > 0.25). Total absorbed iron was similar to needs estimated by the Institute of Medicine. We conclude that iron absorption in young children is more closely related to iron status than to iron intake. Reference dose iron absorption may be superior to serum ferritin as a surrogate measure for iron status in this age group. Although zinc intake may affect iron absorption from a meal, it does not appear to have a detectable effect on overall iron status in otherwise well-nourished children.

Iron absorption and oxidant stress during erythropoietin therapy in very low birth weight premature infants: a cohort study.

BACKGROUND: Iron supplementation may be associated with oxidative stress particularly in premature infants. Our purpose was to examine 1) early supplemental iron during treatment with erythropoietin (EPO) and oxidative stress; 2) enhanced iron absorption during EPO in those infants receiving human milk. Therefore, we determined the effect of erythropoietin plus supplemental iron intakes (4 mg/kg/d) on antioxidant status and iron incorporation. METHODS: Ten very-low-birth-weight infants who were enterally fed and receiving either human milk or formula were followed for 4 weeks during erythropoietin therapy; blood and urine were collected at 3 times; baseline, 2 and 4 weeks later. Once oral feeds commenced the study protocol was initiated. After baseline blood collection, a dose of Fe57 was administered. Two weeks later, a dose of Fe58 was administered as ferrous chloride to determine the effect of human-milk or formula on iron incorporation into RBCs. RESULTS: Infants started the study at 35 +/- 13 days. Incorporation of isotope into RBCs did not differ between formula fed for Fe57 (mean incorporation 8 +/- 2.9 n = 3) compared to human-milk fed infants (8.7 +/- 5 n = 7) nor for Fe58 (6 +/- 2.7 n = 3 vs. 8.6 +/- 5 n = 7). Tissue damage measured by malondialdehyde in plasma and F-2--isoprostanes in urine, did not differ by feed or over time. Neither ability to resist oxidative stress/nor RBC superoxide dismutase differed according to feed or over time. CONCLUSION: Data suggest that during erythropoietin therapy antioxidant defence in VLBW infants are capable of dealing with early supplemental iron during treatment with EPO.