Effects of environmental and occupational lead toxicity and its association with iron metabolism.

BACKGROUND: Discrepancies are present in the findings from clinical trials evaluating a physiological role of iron status in the lead-exposed population. OBJECTIVE: The purpose of this article was to summarize the current understanding of cellular mechanisms of lead toxicity and present a comprehensive review of existing clinical trials related to associations of lead poisoning and iron status. Although an association of iron metabolism pathways that are affected by lead intoxication has been studied, there are still aspects that remain to be elucidated. The existence of additional Pb uptake pathways besides DMT1 transporter-mediated is postulated to non-specifically regulate lead absorption. METHODS: Authors performed a systematic search of PubMed, EMBASE® and Web of Science databases to identify studies that reported an association between health risks of non-organic lead that are associated with iron status markers as possible effect modifier. RESULTS: There were 58 studies that met the pre-defined inclusion criteria for the systematic review. There is a strong body of evidence supporting the hypothesis that alleviated blood lead level can be correlated with a reduced body iron store and increasing the risk of anemia. This association is of a high significance in cases of a young adolescent, weaker in groups of older children and often without a statistical significance in adults. DISCUSSION: Discrepancies in the observations may result from different specificities of lead absorption pathways in children and adults, as well as the power of the statistical tests in varying population sizes. It may be assumed that the extent of iron deficits coupled together with source, timing, and severity of lead exposure, significantly influence the correlation between these factors. Some of the intervention programs of counteracting lead poisoning by iron supplementation proved to be effective and may be a promising prevention strategy for the exposed population.

Renal Clearable Ultrasmall Single-Crystal Fe Nanoparticles for Highly Selective and Effective Ferroptosis Therapy and Immunotherapy.

Iron-based nanoparticles have attracted much attention because of their ability to induce ferroptosis via a catalyzing Fenton reaction and to further potentiate immunotherapy. However, current iron-based nanoparticles need to be used in cooperation with other treatments or be applied in a high dose for effective therapy because of their low reactive oxygen species production efficacy. Here, we synthesized ultrasmall single-crystal Fe nanoparticles (bcc-USINPs) that stayed stable in a normal physiological environment but were highly active in a tumor microenvironment because of the selective acidic etching of an Fe3O4 shell and the exposure of the Fe(0) core. The bcc-USINPs could efficiently induce tumor cell ferroptosis and immunogenetic cell death at a very low concentration. Intravenous injection of iRGD-bcc-USINPs at three doses of 1 mg/kg could effectively suppress the tumor growth, promote the maturation of dendritic cells, and trigger the adaptive T cell response. Combined with programmed death-ligand 1 (PD-L1) immune checkpoint blockade immunotherapy, the iRGD-bcc-USINP-mediated ferroptosis therapy greatly potentiated the immune response and developed strong immune memory. In addition, these USINPs were quickly renal excreted with no side effects in normal tissues. These iRGD-bcc-USINPs provide a simple, safe, effective, and selectively tumor-responsive Fe(0) delivery system for ferroptosis-based immunotherapy.

Evaluating the spectrum-effect profiling and pharmacokinetics of Tieshuang Anshen Prescription with better sedative-hypnotic effect based on Fe2+ than Hg2.

Although Zhusha Anshen Pill (ZSASP) is a commonly used traditional prescription for insomnia, the safety of cinnabar in the formula has always been controversial since its initial application in medical fields. Here, we developed a new prescription, Tieshuang Anshen Prescription (TSASP), by improving ZSASP with Fe2+ instead of Hg2+. Besides, TSASP was further optimized by establishing and testing the HPLC fingerprint and its sedative-hypnotic effect of formulas with different compatibility ratios and performing correlation spectrum analysis. The safety of TSASP was also evaluated by HE staining of liver and kidney. In addition, a validated and robust UHPLC-MS/MS method was established to demonstrate the pharmacokinetic characteristics of berberine, palmatine, jatrorrhizine, ligustilide, catalpol, loganin, liquiritin and liquiritigenin after oral administration of TSASP. Our study originally provides a new non-toxic prescription, TSASP, with better sedative-hypnotic effect in comparison with ZSASP, revealing that Fe2+ could replace Hg2+ to eliminate its toxicity and play a sedative role. Meanwhile, we believe that our pharmacokinetics results may contribute valuable reference to both TSASP's specific mechanism of action and its further clinical efficacy and effectiveness research.

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.

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.

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.

Persistent Iron Deficiency Anemia in Patients with Celiac Disease Despite a Gluten-Free Diet.

Celiac disease (CD) is an autoimmune disorder characterized by intolerance to dietary gluten in genetically predisposed subjects. Iron deficiency anemia (IDA) is a common sign in CD, being the only abnormality in approximately 40% of celiac patients. A multifactorial etiology leads to IDA in CD. The two main causes are the villous atrophy of the mucosa at the site of iron absorption (the duodenum) and the resulting inflammation, which triggers the mechanism that leads to the anemia of chronic disease. Until now, it has been unclear why some patients with CD continue to have IDA despite a careful gluten-free diet (GFD) and the normalization of villous atrophy. Furthermore, some celiac patients are refractory to oral iron supplementation despite the healing of the mucosa, and they thus require periodic intravenous iron administration. The Marsh classification evaluates the degree of inflammation and villous atrophy, but it does not assess the possible persistence of ultrastructural and molecular alterations in enterocytes. The latter was found in CD in remission after adopting a GFD and could be responsible for the persistently reduced absorption of iron and IDA. Even in non-celiac gluten sensitivity, anemia is present in 18.5-22% of patients and appears to be related to ultrastructural and molecular alterations in intestinal microvilli. It is possible that a genetic component may also play a role in IDA. In this review, we evaluate and discuss the main mechanisms of IDA in CD and the possible causes of its persistence after adopting a GFD, as well as their therapeutic implications.

The effect of iron dosing schedules on plasma hepcidin and iron absorption in Kenyan infants.

BACKGROUND: In adults, oral iron doses increase plasma hepcidin (PHep) for 24 h, but not for 48 h, and there is a circadian increase in PHep over the day. Because high PHep decreases fractional iron absorption (FIA), alternate day iron dosing in the morning may be preferable to consecutive day dosing. Whether these effects occur in infants is uncertain. OBJECTIVE: Using stable iron isotopes in Kenyan infants, we compared FIA from morning and afternoon doses and from consecutive, alternate (every second day) and every third day iron doses. METHODS: In prospective studies, we measured and compared FIA and the PHep response from 1) meals fortified with a 12-mg iron micronutrient powder given in the morning or afternoon (n = 22); 2) the same given on consecutive or alternate days (n = 21); and 3) a 12-mg iron supplement given on alternate days or every third day (n = 24). RESULTS: In total, 65.7% of infants were anemic. In study 1, PHep did not differ between morning and afternoon (P = 0.072), and geometric mean FIA[-SD, +SD](%) did not differ between the morning and afternoon doses [15.9 (8.9, 28.6) and 16.1 (8.7, 29.8), P = 0.877]. In study 2, PHep was increased 24 h after oral iron (P = 0.014), and mean FIA [±SD](%) from the baseline dose [23.3 (10.9)] was greater than that from the consecutive day dose (at 24 h) [20.1 (10.4); P = 0.042] but did not differ from the alternate day dose (at 48 h) [20.9 (13.4); P = 0.145]. In study 3, PHep was not increased 48 and 72 h after oral iron (P = 0.384), and the geometric mean FIA[-SD, +SD](%) from doses given at baseline, alternate days, and every third day did not differ [12.7 (7.3, 21.9), 13.8 (7.8, 24.2), and 14.8 (8.8, 24.8), respectively; P = 0.080]. CONCLUSIONS: In Kenyan infants given 12 mg oral iron, morning and afternoon doses are comparably absorbed, dosing on consecutive days increases PHep and modestly decreases iron absorption compared with alternate day dosing, and dosing on alternate days or every third day does not increase PHep or decrease absorption. This trial was registered at clinicaltrials.gov as NCT02989311 and NCT03617575.

Iron Supplementation Influence on the Gut Microbiota and Probiotic Intake Effect in Iron Deficiency-A Literature-Based Review.

Iron deficiency in the human body is a global issue with an impact on more than two billion individuals worldwide. The most important functions ensured by adequate amounts of iron in the body are related to transport and storage of oxygen, electron transfer, mediation of oxidation-reduction reactions, synthesis of hormones, the replication of DNA, cell cycle restoration and control, fixation of nitrogen, and antioxidant effects. In the case of iron deficiency, even marginal insufficiencies may impair the proper functionality of the human body. On the other hand, an excess in iron concentration has a major impact on the gut microbiota composition. There are several non-genetic causes that lead to iron deficiencies, and thus, several approaches in their treatment. The most common methods are related to food fortifications and supplements. In this review, following a summary of iron metabolism and its health implications, we analyzed the scientific literature for the influence of iron fortification and supplementation on the gut microbiome and the effect of probiotics, prebiotics, and/or synbiotics in iron absorption and availability for the organism.

Iron and Physical Activity: Bioavailability Enhancers, Properties of Black Pepper (Bioperine®) and Potential Applications.

Black pepper (Piper nigrum L.) has been employed in medicine (epilepsy, headaches, and diabetes), where its effects are mainly attributed to a nitrogen alkaloid called piperidine (1-(1-[1,3-benzodioxol-5-yl]-1-oxo-2,4 pentenyl) piperidine). Piperine co-administered with vitamins and minerals has improved its absorption. Therefore, this study aimed to describe the impact of the joint administration of iron (Fe) plus black pepper in physically active healthy individuals. Fe is a micronutrient that aids athletic performance by influencing the physiological functions involved in endurance sports by improving the transport, storage, and utilization of oxygen. Consequently, athletes have risk factors for Fe depletion, Fe deficiency, and eventually, anemia, mainly from mechanical hemolysis, gastrointestinal disturbances, and loss of Fe through excessive sweating. Declines in Fe stores have been reported to negatively alter physical capacities such as aerobic capacity, strength, and skeletal muscle recovery in elite athletes. Thus, there is a need to maintain Fe storage, even if Fe intake meets the recommended daily allowance (RDA), and Fe supplementation may be justified in physically active individuals, in states of Fe deficiency, with or without anemia. Females, in particular, should monitor their Fe hematological profile. The recommended oral Fe supplements are ferrous or ferric salts, sulfate, fumarate, and gluconate. These preparations constitute the first line of treatment; however, the high doses administered have gastrointestinal side effects that reduce tolerance and adherence to treatment. Thus, a strategy to counteract these adverse effects is to improve the bioavailability of Fe. Therefore, piperine may benefit the absorption of Fe through its bioavailability enhancement properties. Three research studies of Fe associated with black pepper have reported improvements in parameters related to the metabolism of Fe, without adverse effects. Although more research is needed, this could represent an advance in oral Fe supplementation for physically active individuals.

Molecular Aspects and Treatment of Iron Deficiency in the Elderly.

Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration <12 g/dL in women and <13 g/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease.

[New insights on a long-known element - iron, hepcidin and inflammation]. / Neuer Blick auf ein altes Element ­ Eisen, Hepcidin und Entzündung.

Iron (Fe) is an essential trace element. In daily veterinary practice, it plays a pivotal role e. g. due to its role in Fe deficiency anaemia. The bioavailability of Fe, for example for heme and hemoglobin synthesis, sets high demands on Fe homeostasis. The discovery of hepcidin as being an important regulative protein made a hormone-like regulation of the Fe metabolism evident. Hepcidin is synthesized by the liver and regulates the trans-membranous Fe-transporter ferroportin. An increase of hepcidin leads to a decrease of Fe export from the cell into the extracellular space, the consequence being an internalisation of Fe in the reticuloendothelial system as well as in mononuclear cells. Additionally, enteral Fe uptake decreases. The induction of hepatic hepcidin synthesis seems to be caused by high Fe- and transferrin concentrations in plasma. In addition to this, an increase of cytokines during inflammation similarly triggers hepatic hepcidin synthesis. This finding offers an explanation for the frequently observed decrease of Fe in serum/plasma during acute inflammation, the mechanism thus being termed as cytokine-hepcidin-link. Based on the fact that numerous pathogens require Fe for their own metabolism, internalisation of Fe into the intracellular compartment during inflammation has hence been categorised as being a part of the innate immunity. Iron supplementation, initiated by the veterinarian or the farmer, interferes with this regulation. Currently however, there is a lack of knowledge regarding the clinical and metabolic impacts of parenteral or oral Fe supplementation to farm animals. Therefore, the acquisition of added scientific data via prospective studies is warranted. In consequence, novel findings may lead to a reassessment of Fe supplementation strategies for ruminants, pigs and/or horses.

Iron kinetics following treatment with sucroferric oxyhydroxide or ferric citrate in healthy rats and models of anaemia, iron overload or inflammation.

BACKGROUND: The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models. METHODS: Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs. RESULTS: In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups. CONCLUSIONS: Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

Iron bioavailability from bouillon fortified with a novel ferric phytate compound: a stable iron isotope study in healthy women (part II).

Bouillon cubes are widely consumed and when fortified with iron could contribute in preventing iron deficiency. We report the development (part I) and evaluation (current part II) of a novel ferric phytate compound to be used as iron fortificant in condiments such as bouillon. Ferric pyrophosphate (FePP), is the compound of choice due to its high stability in foods, but has a modest absorption in humans. Our objective was to assess iron bioavailability from a novel iron fortificant consisting of ferric iron complexed with phytic acid and hydrolyzed corn protein (Fe-PA-HCP), used in bouillon with and without an inhibitory food matrix. In a randomised single blind, cross-over study, we measured iron absorption in healthy adult women (n = 22). In vitro iron bioaccessibility was assessed using a Caco-2 cell model. Iron absorption from Fe-PA-HCP was 1.5% and 4.1% in bouillon with and without inhibitory matrix, respectively. Relative iron bioavailability to FeSO4 was 2.4 times higher than from FePP in bouillon (17% vs 7%) and 5.2 times higher when consumed with the inhibitory meal (41% vs 8%). Similar results were found in vitro. Fe-PA-HCP has a higher relative bioavailability versus FePP, especially when bouillon is served with an inhibitory food matrix.

Iron Absorption from Bouillon Fortified with Iron-Enriched Aspergillus oryzae Is Higher Than That Fortified with Ferric Pyrophosphate in Young Women.

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

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.

Folic Acid Affects Iron Status in Female Rats with Deficiency of These Micronutrients.

Although simultaneous supplementation with iron and folic acid is justified, the potential interactions between these micronutrients are unknown. The aim of this study was to determine the effects of oral iron and folic acid, administered together or separately, on iron concentration in tissues in rats with a deficiency of both these micronutrients. In the first stage of the experiment (28 days), 150 8-week-old female Wistar rats were randomly assigned to a control group (C; n = 30) fed the standard diet and to a study group (n = 120) fed a diet deficit in iron and folate. The study group was then randomly divided to four groups: D group fed a deficit diet, FE group fed a deficit diet with iron gluconate, the FOL group fed a deficit diet with folate acid, and the FEFOL group fed a deficit diet with iron gluconate and folate acid. After 2, 10, and 21 days of supplementation, ten animals from each group were killed. Morphological parameters were measured in whole blood. Iron concentration was assayed in serum, liver, spleen, pancreas, heart, and kidneys. Folic acid supplementation more significantly decreased iron concentrations in the pancreas and spleen than in the D group after 10 and 21 days of supplementation. Moreover, the combination of iron with folic acid markedly decreased iron levels in the liver and spleen, in comparison with iron alone, after 10 and 21 days of the experiment. In conclusion, folic acid affects iron status in female rats deficient in these micronutrients in moderate and long-term supplementation.

Iron Fortification and Bioavailability of Chickpea (Cicer arietinum L.) Seeds and Flour.

Iron (Fe) deficiency is one of the most common nutritional disorders, and is mainly due to insufficient intake of bioavailable Fe. Chickpea (Cicer arietinum L.) was examined as a potential vehicle for Fe fortification. Fortificants (FeSO4·7H2O (ferrous sulfate hepta-hydrate), FeSO4·H2O (ferrous sulfate mono-hydrate) and NaFeEDTA (ethylenediaminetetraacetic acid iron (iii) sodium salt)) were applied by a spraying and drying method. At 2000 µg g-1 iron fortificant, the fortified split desi seeds (dal), desi flour and kabuli flour supplied 18-19 mg, 16-20 mg and 11-19 mg Fe per 100 g, respectively. The overall consumer acceptability using a nine-point hedonic scale for sensory evaluation demonstrated that NaFeEDTA-fortified cooked chickpea (soup and chapatti) scored the highest among the three fortificants. Lightness (L*), redness (a*) and yellowness (b*) of Fe-fortified products changed over time. However, no organoleptic changes occurred. Fe bioavailability was increased by 5.8-10.5, 15.3-25.0 and 4.8-9.0 ng ferritin mg-1 protein for cooked split desi seeds (soup), desi chapatti and kabuli chapatti, respectively, when prepared using Fe-fortified chickpea. Desi chapatti showed significantly higher Fe bioavailability than the other two. The increase in Fe concentration and bioavailability in fortified chickpea products demonstrated that these products could provide a significant proportion of the recommended daily Fe requirement.

Asymptomatic Helicobacter Pylori Infection in Preschool Children and Young Women Does Not Predict Iron Bioavailability from Iron-Fortified Foods.

Helicobacter pylori infection is common in low-income countries. It has been associated with iron deficiency and reduced efficacy of iron supplementation. Whether H. pylori infection affects iron absorption from fortified and biofortified foods is unclear. Our objective was to assess whether asymptomatic H. pylori infection predicts dietary iron bioavailability in women and children, two main target groups of iron fortification programs. We did a pooled analysis of studies in women of reproductive age and preschool children that were conducted in Benin, Senegal and Haiti using stable iron isotope tracers to measure erythrocyte iron incorporation. We used mixed models to assess whether asymptomatic H. pylori infection predicted fractional iron absorption from ferrous sulfate, ferrous fumarate or NaFeEDTA, controlling for age, hemoglobin, iron status (serum ferritin), inflammation (C-reactive protein), and test meal. The analysis included 213 iron bioavailability measurements from 80 women and 235 measurements from 90 children; 51.3% of women and 54.4% of children were seropositive for H. pylori. In both women and children, hemoglobin (Hb), serum ferritin (SF), and C-reactive protein (CRP) did not differ between the seropositive and seronegative groups. Geometric mean (95% CI) fractional iron absorption (%), adjusted for SF, was 8.97% (7.64, 10.54) and 6.06% (4.80, 7.67) in H. pylori positive and negative women (p = 0.274), and 9.02% (7.68, 10.59) and 7.44% (6.01, 9.20) in H. pylori positive and negative children (p = 0.479). Our data suggest asymptomatic H. pylori infection does not predict fractional iron absorption from iron fortificants given to preschool children or young women in low-income settings.