Effect of ascorbic acid and citric acid on bioavailability of iron from Tegillarca granosa via an in vitro digestion/Caco-2 cell culture system.

Iron deficiency anaemia (IDA) has been receiving worldwide attention. Developing safe and effective iron supplements is of great significance for IDA treatment. Tegillarca granosa (T. granosa), a traditional aquaculture bivalve species in China, is considered to be an excellent source of micronutrients, but the distribution and bioavailability of these minerals have yet to be investigated. The present research was conducted to determine the contents and in vitro enzymatic digestibility of minerals in T. granosa, using beef and wheat flour as reference foods. Meanwhile, two iron-binding proteins, hemoglobin and ferritin, were extracted from T. granosa, and their structures, iron accessibility and bioavailability were investigated. Moreover, the effects of ascorbic acid (AA) and citric acid (CA), two commonly applied dietary factors, on these parameters were evaluated. Our results indicated that the mineral levels varied significantly among different food matrices, with T. granosa showing the highest contents of the tested elements. Comparison of iron absorption of meat versus wheat flour and hemoglobin versus ferritin confirmed that heme iron exhibited higher bioavailability than non-heme iron. The addition of the two organic acids notably enhanced the cellular iron uptake of T. granosa-derived proteins. This could be because AA/CA weakened hydrogen bonds within proteins and caused disordered secondary structures, thereby improving their enzymatic digestibility and releasing more soluble iron to be available for absorption. The results of this study provided a basis for the development of T. granosa-derived protein-based iron supplements, promoting the diverse utilization of marine aquatic resources.

Iron Fortification Practices and Implications for Iron Addition to Salt.

This introductory article provides an in-depth technical background for iron fortification, and thus introduces a series of articles in this supplement designed to present the current evidence on the fortification of salt with both iodine and iron, that is, double-fortified salt (DFS). This article reviews our current knowledge of the causes and consequences of iron deficiency and anemia and then, with the aim of assisting the comparison between DFS and other common iron-fortified staple foods, discusses the factors influencing the efficacy of iron-fortified foods. This includes the dietary and physiological factors influencing iron absorption; the choice of an iron compound and the fortification technology that will ensure the necessary iron absorption with no sensory changes; encapsulation of iron fortification compounds to prevent unacceptable sensory changes; the addition of iron absorption enhancers; the estimation of the iron fortification level for each vehicle based on iron requirements and consumption patterns; and the iron status biomarkers that are needed to demonstrate improved iron status in populations regularly consuming the iron-fortified food. The supplement is designed to provide a summary of evidence to date that can help advise policy makers considering DFS as an intervention to address the difficult public health issue of iron deficiency anemia, while at the same time using DFS to target iodine deficiency.

In vitro bioaccessibility and bioavailability of iron from fenugreek, baobab and moringa.

Iron deficiency anaemia (IDA) is a common nutritional disorder worldwide. Sustainable food-based approaches are being advocated to use high and bioavailable dietary iron sources to prevent iron deficiency. The study investigated the bioaccessibility and bioavailability of iron from some plant products. Total iron levels in the samples were measured by inductively coupled plasma optical emission spectrometry (ICP-OES). Fractionation of the iron from the digested extracts was carried out by centrifugation and ultrafiltration. Iron bioavailability was determined using an in vitro simulated peptic-pancreatic digestion, followed by measurement of ferritin in Caco-2 cells. The highest amount of bioaccessible iron was obtained from moringa leaves (9.88% ± 0.45 and 8.44 ± 0.01 mg/100 g), but the highest percentage bioavailability was from baobab fruit pulp (99.7% ± 0.13 and 1.74 ± 0.01 mg/100 g) respectively. All the plant products, except for baobab, significantly inhibited iron uptake from FeSO4 and FAC, with fenugreek sprout being the most inhibitory.

Supplemental Microalgal Iron Helps Replete Blood Hemoglobin in Moderately Anemic Mice Fed a Rice-Based Diet.

Iron deficiency anemia affects 1.2 billion people globally. Our objectives were to determine if (1) supplemental iron extracted from defatted microalgae (Nannochloropsis oceanica, DGM) and (2) a combination of minute amount of plant phytase and inulin could help replete hemoglobin in anemic mice. Mice (7 weeks old) were fed a control diet (6 mg Fe/kg). After 10 weeks, the mice were assigned to three treatments: control, control + DGM iron (Fe-DGM, 39 mg Fe/kg), or control + 1% inulin + 250 units of phytase/kg (INU-PHY, 6 mg Fe/kg). The mice had free access to diets and water for 6 weeks. The Fe-DGM group had elevated blood hemoglobin (p < 0.01) and a two-fold greater (p < 0.0001) liver non-heme iron over the control. Strikingly, the INU-PHY group had 34% greater non-heme iron than the control, despite the same concentrations of iron in their diets. Fe-DGM group had altered (p < 0.05) mRNA levels of hepcidin, divalent metal transporter 1, transferrin and transferrin receptor 1. Iron extracted from defatted microalgae seemed to be effective in alleviating moderate anemia, and INU-PHY enhanced utilization of intrinsic iron present in the rice diet. Our findings may lead to a novel formulation of these ingredients to develop safer and bioavailable iron supplements for iron-deficient populations.

Dietary Iron Bioavailability: A Simple Model That Can Be Used to Derive Country-Specific Values for Adult Men and Women.

BACKGROUND: Reference intakes for iron are derived from physiological requirements, with an assumed value for dietary iron absorption. A new approach to estimate iron bioavailability, calculated from iron intake, status, and requirements was used to set European dietary reference values, but the values obtained cannot be used for low- and middle-income countries where diets are very different. OBJECTIVE: We aimed to test the feasibility of using the model developed from United Kingdom and Irish data to derive a value for dietary iron bioavailability in an African country, using data collected from women of child-bearing age in Benin. We also compared the effect of using estimates of iron losses made in the 1960s with more recent data for whole body iron losses. METHODS: Dietary iron intake and serum ferritin (SF), together with physiological requirements of iron, were entered into the predictive model to estimate percentage iron absorption from the diet at different levels of iron status. RESULTS: The results obtained from the 2 different methods for calculating physiological iron requirements were similar, except at low SF concentrations. At a SF value of 30 µg/L predicted iron absorption from the African maize-based diet was 6%, compared with 18% from a Western diet, and it remained low until the SF fell below 25 µg/L. CONCLUSIONS: We used the model to estimate percentage dietary iron absorption in 30 Beninese women. The predicted values agreed with results from earlier single meal isotope studies; therefore, we conclude that the model has potential for estimating dietary iron bioavailability in men and nonpregnant women consuming different diets in other countries.

The Chemical Forms of Iron in Commercial Prenatal Supplements Are Not Always the Same as Those Tested in Clinical Trials.

In the US, 70% of pregnant women use an iron-containing prenatal supplement product; however, only 2.6% of pregnant women have iron-deficiency anemia and 16.3% are iron deficient. Yet, published data on the amounts and chemical forms of iron used in formulating these products are not available, although they are known to affect bioavailability. This information is especially important in comparing commercially available products with those that were tested in clinical trials. Our examination of nonprescription and prescription iron-containing prenatal supplement products in NIH's Dietary Supplement Label Database (DSLD) and DailyMed found the labeled amount of elemental iron ranged between 9 and 60 mg/serving in 148 nonprescription supplements and between 4.5 and 106 mg/serving in 101 prescription supplements. Ferrous fumarate was the preferred chemical form used in these products. In contrast, ferrous sulfate was the preferred chemical form of iron reported in the clinical trials summarized in a 2015 Cochrane Systematic review assessing the effects of daily oral iron supplements for pregnant women. Ferrous sulfate was not found on any prenatal supplement product label in the DSLD or DailyMed. The chemical forms of products on the market and those tested in clinical trials are dissimilar, and we believe this may have clinical implications. The findings raise several questions. Do outcomes in clinical trials correlate with the benefits and risks that might adhere to iron supplements with different iron formulations? Should the differences in chemical forms, their bioavailability, and safety profiles, be considered in greater depth when evaluating the effect of the various formulations on maternal iron nutriture? Should new clinical trials for pregnant and lactating women in the US use a form of iron not found in prenatal supplements sold in the US or should a more common form be used?

Micronutrient-fortified rice can be a significant source of dietary bioavailable iron in schoolchildren from rural Ghana.

Iron deficiency and anemia are prominent contributors to the preventable disease burden worldwide. A substantial proportion of people with inadequate dietary iron rely on rice as a staple food, but fortification efforts are limited by low iron bioavailability. Furthermore, using high iron fortification dosages may not always be prudent in tropical regions. To identify alternative fortification formulations with enhanced absorption, we screened different iron compounds for their suitability as rice fortificants, measured in vitro gastric solubility, and assessed dietary iron bioavailability using stable isotopic labels in rural Ghanaian children. Isotopic incorporation in red blood cells indicates that in the two age groups of children investigated (4 to 6 and 7 to 10 years), formulations provided 36 and 51% of the median daily requirement in absorbed iron, respectively. We describe approaches to enhancing iron bioavailability from fortified rice, which can substantially contribute to the prevention of iron deficiency in rice-eating populations.

A Green-Mediterranean Diet, Supplemented with Mankai Duckweed, Preserves Iron-Homeostasis in Humans and Is Efficient in Reversal of Anemia in Rats.

BACKGROUND: Decreased dietary meat may deplete iron stores, as plant-derived iron bioavailability is typically limited. OBJECTIVES: We explored the effect of a low-meat Mediterranean (green-MED) diet, supplemented with Wolffia globosa duckweed (Mankai: rich in protein and iron) as a food source for humans, on iron status. We further examined the iron bioavailability of Mankai in rats. METHODS: Two hundred and ninety-four abdominally obese/dyslipidemic [mean age = 51.1 y; body mass index (kg/m2) = 31.3; 88% men] nonanemic participants were randomly assigned to physical activity (PA), PA + MED diet, or PA + green-MED diet. Both isocaloric MED groups consumed 28 g walnuts/d and the low-meat green-MED group further consumed green tea (800 mL/d) and Mankai (100 g green shake/d). In a complementary animal experiment, after 44 d of an iron deficiency anemia-inducing diet, 50 female rats (age = 3 wk; Sprague Dawley strain) were randomly assigned into: iron-deficient diet (vehicle), or vehicle + iso-iron: ferrous gluconate (FG) 14, Mankai 50, and Mankai 80 versions (1.7 mg · kg-1 · d-1 elemental iron), or FG9.5 and Mankai 50-C version (1.15 mg · kg-1 · d-1 elemental iron). The specific primary aim for both studies was changes in iron homeostasis parameters. RESULTS: After 6 mo of intervention, iron status trajectory did not differ between the PA and PA + MED groups. Hemoglobin modestly increased in the PA + green-MED group (0.23 g/dL) compared with PA (-0.1 g/dL; P < 0.001) and PA + MED (-0.1 g/dL; P < 0.001). Serum iron and serum transferrin saturation increased in the PA + green-MED group compared with the PA group (8.21 µg/dL compared with -5.23 µg/dL and 2.39% compared with -1.15%, respectively; P < 0.05 for both comparisons), as did folic acid (P = 0.011). In rats, hemoglobin decreased from 15.7 to 9.4 mg/dL after 44 d of diet-induced anemia. After depletion treatment, the vehicle-treated group had a further decrease of 1.3 mg/dL, whereas hemoglobin concentrations in both FG and Mankai iso-iron treatments similarly rebounded (FG14: +10.8 mg/dL, Mankai 50: +6.4 mg/dL, Mankai 80: +7.3 mg/dL; FG9.5: +5.1 mg/dL, Mankai 50-C: +7.1 mg/dL; P < 0.05 for all vs. the vehicle group). CONCLUSIONS: In humans, a green-MED low-meat diet does not impair iron homeostasis. In rats, iron derived from Mankai (a green-plant protein source) is bioavailable and efficient in reversal of anemia. This trial was registered at clinicaltrials.gov as NCT03020186.

Iron bioavailability of four iron sources used to fortify infant cereals, using anemic weaning pigs as a model.

PURPOSE: Iron (Fe) deficiency anemia in young children is a global health concern which can be reduced by Fe fortification of foods. Cereal is often one of the first foods given to infants, providing adequate quantities of Fe during weaning. In this work, we have compared iron bioavailability and iron status of four iron sources used to fortify infant cereals, employing piglets as an animal model. METHOD: The study was conducted on 36 piglets, 30 of them with induced anemia. From day 28 of life, the weaned piglets were fed with four experimental diets (n = 6) each fortified with 120 mg Fe/kg by ferrous sulfate heptahydrate (FSH), electrolytic iron (EI), ferrous fumarate (FF), or micronized dispersible ferric pyrophosphate (MDFP) for another 21 days. In addition, one group of six anemic piglets fed with the basal diet with no iron added (Control-) and a Control+ group of non-anemic piglets (n = 6) were also studied. Blood indicators of iron status were measured after depletion and during the repletion period. The Fe content in organs, hemoglobin regeneration efficiency, and relative bioavailability (RBV) was also determined. RESULTS: The Fe salts adequately treated anemia in the piglets, allowing the animals to recover from the anemic state, although EI was less efficient with regard to replenishing Fe stores giving lower concentrations of plasma ferritin and iron in the spleen, liver, lung, and kidney. In addition, the RBV of EI was 88.27% with respect to the reference iron salt (FSH). CONCLUSIONS: Ferrous fumarate and MDFP were equally as bioavailable as the reference salt, and were used significantly better than EI in piglets. These results contribute to extend the evidence-based results for recommending the most suitable fortificant for infant cereals.

Iron (II) Citrate Complex as a Food Supplement: Synthesis, Characterization and Complex Stability.

Iron deficiency represents a widespread problem for a large part of the population, especially for women, and has received increasing attention in food/supplement research. The contraindications of the iron supplements commercially available (e.g., imbalances in the levels of other essential nutrients, low bioavailability, etc.) led us to search for a possible alternative. In the present work, a rapid and easy method to synthetize a solid iron (II) citrate complex from iron filings and citric acid was developed to serve, eventually, as a food supplement or additive. In order to state its atomic composition and purity, an assortment of analytical techniques was employed (e.g., combustion analysis, thermogravimetry, X-ray diffractometry, UV/Vis spectrophotometry, etc.). Results demonstrate that the synthesized crystalline solid corresponds to the formula FeC6H6O7∙H2O and, by consequence, contains exclusively iron (II), which is an advantage with respect to existing commercial products, because iron (II) is better absorbed than iron (III) (high bioavailability of iron).

Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies.

Plant-based diets in low-income countries (LICs) have a high content of phytic acid (myo-inositol hexaphosphate [InsP6]) and associated magnesium, potassium, and calcium salts. Together, InsP6 acid and its salts are termed "phytate" and are potent inhibitors of iron and zinc absorption. Traditional food processing can reduce the InsP6 content through loss of water-soluble phytate or through phytase hydrolysis to lower myo-inositol phosphate forms that no longer inhibit iron and zinc absorption. Hence, some processing practices can reduce the need for high-dose iron fortificants in plant-based diets and alleviate safety concerns. Dietary phytate-to-iron and phytate-to-zinc molar ratios are used to estimate iron and zinc bioavailability and to identify dietary iron and zinc requirements according to diet type. The European Food Safety Authority has set adult dietary zinc requirements for 4 levels of phytate intake, highlighting the urgent need for phytate food composition data. Such data will improve the ability to estimate the prevalence of inadequate zinc intakes in vulnerable groups in LICs, which will facilitate implementation of targeted policies to alleviate zinc deficiency.

Comparative assessment and suitability of iron and the nutritional composition of fortified foods for young children.

AIM: To assess the suitability of iron content and the nutritional benefits of selected fortified food products marketed for 4-8 year old children in Oman. METHODS: Forty-five fortified foods, which are available in Omani markets, were classified into four groups based on food type and composition: ready-to-eat (RTE) breakfast cereals (two groups), malted milk drinks and milk powder formulas. The nutrition panel displayed on the products' outer package was used as a source of content values for iron and other nutrients. RESULTS: Among the selected products, malted milk drinks contain a significant ( p < 0.001) amount of iron that is 6.2±3.1 mg per 30 g serving (recommended daily intake for children 4-8 years old is 10 mg). The way selected products are served, with milk or water, could have a significant impact on the iron absorption and bioavailability, which is influenced by the presence of calcium and vitamin C. The values recorded from malted milk drinks and milk powder formulas were shown to have vitamin C to iron ratios of 3:1 and 8:1, respectively. Such ratios are reportedly effective in reversing the negative effect of calcium on iron absorption. Iron-fortified foods contain low to moderate amount of iron per serving and are considered more nutritious when compared to iron supplements. CONCLUSION: Iron-fortified foods can be conditionally useful to prevent or restore iron deficiency but not be relied on as an only source of iron. Hence these products must be consumed as a part of a healthy diet plan.

High Dietary Iron Differentially Influences the Iron Distribution in the Livers and the Spleens of Laying Hens After Salmonella Typhimurium Infection.

Salmonella and the host battle for iron (Fe), due to its importance for fundamental cellular processes. To investigate Fe redistribution of Salmonella-infected hens and the effects of high dietary Fe on it, Salmonella-free hens were randomly assigned to 1 of 4 treatments in 2 (two dietary Fe level) × 2 (Salmonella-inoculation or -noninoculation) factorial assignment. After feeding a basal diet supplemented with 60 (adequate, control) or 300 mg Fe/kg (high-Fe) for 4 weeks, 59-week-old Salmonella-free hens were orally inoculated with 5 × 107 colony-forming units of Salmonella Typhimurium (infection) or PBS (vehicle). Blood, spleen, and liver samples (n = 8) were collected at 14 days post-inoculation to determine Fe concentration and Fe transporters expression. Salmonella infection decreased (P < 0.05) hematocrit, serum Fe concentration, and splenic Fe concentration regardless of high-Fe or control hens, whereas increased (P < 0.05) Fe centration in the livers of high-Fe-treated hens. High dietary Fe increased hematocrit and serum Fe concentration, but did not affect (P = 0.11) splenic Fe concentration in Salmonella-infected hens. Salmonella infection did not influence (P = 0.31) liver Fe centration in control hens, but increased (P = 0.04) it in high-Fe-treated hens. High dietary Fe decreased (P < 0.01) the mRNA abundance of divalent metal transporter 1 and transferrin receptor, but increased (P < 0.02) ferroportin-1 (FPN1) mRNA and protein in the spleens and the livers regardless of Salmonella-infected or vehicle hens. Salmonella infection increased (P < 0.02) FPN1 mRNA and protein expression in the spleens, but did not influence its expression in the livers. These results suggested Salmonella infection and high dietary Fe differently influence the Fe distribution in the spleen and the liver of Salmonella-infected hens.

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease.

We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1 year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P = .001), whereas H63D and A736V allele frequencies were similar among patients and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P < .001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

Response to oral sucrosomial iron supplementation in patients undergoing bariatric surgery. The BARI-FER study.

BACKGROUND: Chronic intravenous iron administration is often required after bariatric surgery. Oral sucrosomial iron has a particular form of absorption and may represent an alternative treatment. OBJECTIVE: To assess the effect of switching to oral sucrosomial iron in patients receiving intravenous iron supplementation after bariatric surgery. PATIENTS AND METHODS: A case-control study was conducted on 40 women of childbearing age, of whom 20 were switched to oral sucrosomial iron, while 20 patients continued on intravenous iron sucrose every three months. RESULTS: No significant differences were seen in Hb, ferritin, and TSI levels before and after three months of treatment with sucrosomial iron. CONCLUSION: Oral sucrosomial iron could be an alternative in patients who require parenteral treatment with iron after bariatric surgery.

Dietary iron intake and availability are related to maternal education level in overweight/obese adolescents.

PURPOSE: To compare intakes of dietary iron and enhancers and inhibitors of iron absorption between overweight/obese (OW/OB) adolescents and their normal weight (NW) peers, and between parental education levels stratified by weight status. METHODS: This was a comparative cross-sectional study of adolescents (n 121 OW/OB and n 102 NW) aged 12-14 years, attending a secondary school in Nonthaburi province, Thailand. Socio-demographic data were obtained from participants' parents using a questionnaire. Participants recorded their intakes for 3 non-consecutive days, using a prospective food record. RESULTS: Compared with NW adolescents, OW/OB adolescents consumed more total protein and animal protein after adjustment for energy intake (both p = 0.047). OW/OB adolescents whose mothers were less educated consumed more total iron and available iron after adjustment for energy intake, compared with their OW/OB peers whose mothers were more educated (p = 0.045 and p = 0.040). NW adolescents with more highly educated mothers had higher absolute and energy-adjusted fibre intakes (both p = 0.047). However, NW adolescents of mothers with a high-intermediate level of education consumed less calcium, after adjustment for energy intake (p = 0.028). CONCLUSIONS: OW/OB adolescents with less educated mothers had higher energy-adjusted intakes of iron and available iron. Dietary differences in OW/OB adolescents relative to maternal education, and other socioeconomic indicators, should be explored in a nationally representative data set.

Iron homeostasis during pregnancy.

During pregnancy, iron needs to increase substantially to support fetoplacental development and maternal adaptation to pregnancy. To meet these iron requirements, both dietary iron absorption and the mobilization of iron from stores increase, a mechanism that is in large part dependent on the iron-regulatory hormone hepcidin. In healthy human pregnancies, maternal hepcidin concentrations are suppressed in the second and third trimesters, thereby facilitating an increased supply of iron into the circulation. The mechanism of maternal hepcidin suppression in pregnancy is unknown, but hepcidin regulation by the known stimuli (i.e., iron, erythropoietic activity, and inflammation) appears to be preserved during pregnancy. Inappropriately increased maternal hepcidin during pregnancy can compromise the iron availability for placental transfer and impair the efficacy of iron supplementation. The role of fetal hepcidin in the regulation of placental iron transfer still remains to be characterized. This review summarizes the current understanding and addresses the gaps in knowledge about gestational changes in hematologic and iron variables and regulatory aspects of maternal, fetal, and placental iron homeostasis.

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.

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

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

Iron metabolism: State of the art.

Iron homeostasis relies on the amount of its absorption by the intestine and its release from storage sites, the macrophages. Iron homeostasis is also dependent on the amount of iron used for the erythropoiesis. Hepcidin, which is synthesized predominantly by the liver, is the main regulator of iron metabolism. Hepcidin reduces serum iron by inhibiting the iron exporter, ferroportin expressed both tissues, the intestine and the macrophages. In addition, in the enterocytes, hepcidin inhibits the iron influx by acting on the apical transporter, DMT1. A defect of hepcidin expression leading to the appearance of a parenchymal iron overload may be genetic or secondary to dyserythropoiesis. The exploration of genetic hemochromatosis has revealed the involvement of several genes, including the recently described BMP6. Non-transfusional secondary hemochromatosis is due to hepcidin repression by cytokines, in particular the erythroferone factor that is produced directly by the erythroid precursors. Iron overload is correlated with the appearance of a free form of iron called NTBI. The influx of NTBI seems to be mediated by ZIP14 transporter in the liver and by calcium channels in the cardiomyocytes. Beside the liver, hepcidin is expressed at lesser extent in several extrahepatic tissues where it plays its ancestral role of antimicrobial peptide. In the kidney, hepcidin modulates defense barriers against urinary tract infections. In the heart, hepcidin maintains tissue iron homeostasis by an autocrine regulation of ferroprotine expression on the surface of cardiomyocytes. In conclusion, hepcidin remains a promising therapeutic tool in various iron pathologies.