Iron therapy begun concurrently with antimalarial treatment may not be well absorbed because of malaria-induced inflammation. Delaying the start of iron therapy may permit better iron absorption and ...distribution.
We compared erythrocyte iron incorporation in children who started iron supplementation concurrently with antimalarial treatment or 28 d later. We hypothesized that delayed iron supplementation would be associated with greater incorporation and better hematologic recovery.
We enrolled 100 children aged 6-59 mo with malaria and hemoglobin concentrations of 50.0-99.9 g/L who presented to Mulago Hospital, Kampala, into a randomized trial of iron therapy. All children were administered antimalarial treatment. Children with zinc protoporphyrin (ZPP) ≥80 μmol/mol heme were randomly assigned to start iron supplementation concurrently with the antimalarial treatment immediate iron (I) group or 28 d later delayed iron (D) group. All children were administered iron-stable isotope (57)Fe on day 0 and (58)Fe on day 28. We compared the percentage of iron incorporation at the start of supplementation (I group at day 0 compared with D group at day 28, aim 1) and hematologic recovery at day 56 (aim 2).
The percentage of iron incorporation (mean ± SE) was greater at day 28 in the D group (16.5% ± 1.7%) than at day 0 in the I group (7.9% ± 0.5%; P < 0.001). On day 56, concentrations of hemoglobin and ZPP and plasma ferritin, soluble transferrin receptor (sTfR), hepcidin, and C-reactive protein did not differ between the groups. On day 28, the hemoglobin (mean ± SD) and plasma iron markers (geometric mean; 95% CI) reflected poorer iron status in the D group than in the I group at this intervening time as follows: hemoglobin (105 ± 15.9 compared with 112 ± 12.4 g/L; P = 0.04), ferritin (39.3 μg/L; 23.5, 65.7 μg/L compared with 79.9 μg/L; 58.3, 110 μg/L; P = 0.02), sTfR (8.9 mg/L; 7.4, 10.7 mg/L compared with 6.7 mg/L; 6.1, 7.5 mg/L; P = 0.01), and hepcidin (13.3 ng/mL; 8.3, 21.2 ng/mL compared with 38.8 ng/mL; 28.3, 53.3 ng/mL; P < 0.001).
Delaying the start of iron improves incorporation but leads to equivalent hematologic recovery at day 56 in Ugandan children with malaria and anemia. These results do not demonstrate a clear, short-term benefit of delaying iron. This trial was registered at clinicaltrials.gov as NCT01754701.
Objectives
To investigate the link between serum erythroferrone (ERFE) levels and iron status parameters in pediatric patients with iron deficiency anemia.
Methods
The study consisted of 66 children ...(36 with iron deficiency anemia and 30 healthy age‐ and gender‐matched controls) who were investigated for serum levels of iron, total iron‐binding capacity (TIBC) using automated chemistry analyzer, serum ferritin using electrochemiluminescence immunoassay and ERFE by specific enzyme‐linked immunosorbent assay (ELISA) kit.
Results
Serum erythroferrone levels in iron deficiency anemia patients (191.55 ± 83.74 pg/mL) were significantly higher than those in control group (42.22 ± 16.55 pg/mL) (P < .001). In iron deficiency anemia patients, serum erythroferrone concentrations correlated negatively with hemoglobin concentration (r = −.39; P = .01), serum iron (r = −.63; P < .001), transferrin saturation (r = −.66; P < .001), and serum ferritin (r = −.46; P = .004) while positive correlation was observed between serum erythroferrone concentrations and TIBC (r = .62; P < .001)
Conclusion
The newly identified erythroferrone hormone may act as physiological hepcidin suppressor in cases with iron deficiency anemia, and so it may serve as a specific promising target of therapy in such cases.
Even though iron supplementation can be effective, it is necessary to be cautious of toxicity and aim to do no harm, therefore, it is important to examine the length of time the benefits of iron ...supplementation can be maintained following its cessation. The main purpose of this study was to analyze if iron stores and strength performance were maintained in elite female volleyball players for the final 18 weeks of a competitive season following the cessation of 11 weeks of iron supplementation.
Twenty-two volleyballers (age: 27.0 ± 5.6 years.) were assigned to two groups (iron treatment group-ITG,
= 11 or control gropu-CG,
= 11) at the beginning of a previous trial (T0) and ITG consumed 325mg/d of ferrous sulphate for 11 weeks (T11). Then, in the present study iron status and strength were measured again 10 (T21) and 18 weeks later (T29) after the cessation of supplementation.
At the end of the previous trial (T11), ITG maintained iron status as measured by hematological parameters (serum iron-sFE, serum ferritin-FER, transferrin saturation index-TSI, and hemogloblin-Hb), however, CG showed a decrease in these markers at T11. Further, from T0 to T11 ITG experienced greater (
< 0.05) changes in clean and jerk, power clean, and total mean strength (TMS-sum of all strength tests) than CG. In the present, follow-up investigation, there was a group-by-time interaction in favor of CG vs. ITG from T11 to T21 for FER (
= 0.028) and Hb (
= 0.042). Further, there was an increase for CG (
< 0.001) in power clean for CG from T11 (38.4 ± 1.7 kg) to T21 (41.3 ± 1.9 kg) and T29 (41.8 ± 1.7 kg), but no change for power clean in ITG (
> 0.05). A group-by-time interaction from T11 to T29 occurred in favor of CG for half-squat (
= 0.049) and TMS (
= 0.049).
Our findings suggest that the benefits of iron supplementation are not sustained in elite female volleyballers if supplementation is ceased for 18 weeks.
Copper is an essential mineral nutrient that provides the cofactors for some key enzymes. However, excess copper is paradoxically cytotoxic. Wilson’s disease is an autosomal recessive hereditary ...disease characterized by pathological copper accumulation in many organs, with high mortality and disability. Nevertheless, many questions about the molecular mechanism in Wilson’s disease remain unknown and there is an imperative need to address these questions to better exploit therapeutic strategy. In this study, we constructed the mouse model of Wilson’s disease, ATP7A−/− immortalized lymphocyte cell line and ATP7B knockdown cells to explore whether copper could impair iron-sulfur cluster biogenesis in eukaryotic mitochondria. Through a series of cellular, molecular, and pharmacological analyses, we demonstrated that copper could suppress the assembly of Fe–S cluster, decrease the activity of the Fe–S enzyme and disorder the mitochondrial function both in vivo and in vitro. Mechanistically, we found that human ISCA1, ISCA2 and ISCU proteins have a strong copper-binding activity, which would hinder the process of iron-sulfur assembly. Of note, we proposed a novel mechanism of action to explain the toxicity of copper by providing evidence that iron-sulfur cluster biogenesis may be a primary target of copper toxicity both in cells and mouse models. In summary, the current work provides an in-depth study on the mechanism of copper intoxication and describes a framework for the further understanding of impaired Fe–S assembly in the pathological processes of Wilson’s diseases, which helps to develop latent therapeutic strategies for the management of copper toxicity.
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•Copper could suppress the assembly of Fe–S cluster and decrease the activity of the Fe–S enzyme.•ISCA1, ISCA2 and ISCU have a copper-binding activity, which would hinder the process of iron-sulfur assembly.•Iron-sulfur cluster biogenesis is an important target of copper toxicity both in cells and mouse models.
Iron–sulfur (Fe–S) cluster-containing proteins are essential components of cells. In eukaryotes, Fe–S clusters are synthesized by the mitochondrial iron–sulfur cluster (ISC) machinery and the ...cytosolic iron–sulfur assembly (CIA) system. In the mammalian ISC machinery, preassembly of the Fe–S cluster on the scaffold protein (ISCU) involves a cysteine desulfurase complex (NFS1/ISD11) and frataxin (FXN), the protein deficient in Friedreich’s ataxia. Here, by comparing the biochemical and spectroscopic properties of quaternary (ISCU/NFS1/ISD11/FXN) and ternary (ISCU/NFS1/ISD11) complexes, we show that FXN stabilizes the quaternary complex and controls iron entry to the complex through activation of cysteine desulfurization. Furthermore, we show for the first time that in the presence of iron and l-cysteine, an Fe4S4 cluster is formed within the quaternary complex that can be transferred to mammalian aconitase (mACO2) to generate an active enzyme. In the absence of FXN, although the ternary complex can assemble an Fe–S cluster, the cluster is inefficiently transferred to ACO2. Taken together, these data help to unravel further the Fe–S cluster assembly process and the molecular basis of Friedreich’s ataxia.
In iron-depleted women without anemia, oral iron supplements induce an increase in serum hepcidin (SHep) that persists for 24 hours, decreasing iron absorption from supplements given later on the ...same or next day. Consequently, iron absorption from supplements is highest if iron is given on alternate days. Whether this dosing schedule is also beneficial in women with iron-deficiency anemia (IDA) given high-dose iron supplements is uncertain. The primary objective of this study was to assess whether, in women with IDA, alternate-day administration of 100 and 200 mg iron increases iron absorption compared to consecutive-day iron administration. Secondary objectives were to correlate iron absorption with SHep and iron status parameters. We performed a cross-over iron absorption study in women with IDA (n=19; median hemoglobin 11.5 mg/dL; mean serum ferritin 10 mg/L) who received either 100 or 200 mg iron as ferrous sulfate given at 8 AM on days 2, 3 and 5 labeled with stable iron isotopes 57Fe, 58Fe and 54Fe; after a 16-day incorporation period, the other labeled dose was given at 8 AM on days 23, 24 and 26 (days 2, 3 and 5 of the second period). Iron absorption on days 2 and 3 (consecutive) and day 5 (alternate) was assessed by measuring erythrocyte isotope incorporation. For both doses, SHep was higher on day 3 than on day 2 (
<0.001) or day 5 (
<0.01) with no significant difference between days 2 and 5. Similarly, for both doses, fractional iron absorption (FIA) on days 2 and 5 was 40-50% higher than on day 3 (
<0.001), while absorption on day 2 did not differ significantly from day 5. There was no significant difference in the incidence of gastrointestinal side effects comparing the two iron doses (
=0.105). Alternate day dosing of oral iron supplements in anemic women may be preferable because it sharply increases FIA. If needed, to provide the same total amount of iron with alternate day dosing, twice the daily target dose should be given on alternate days, as total iron absorption from a single dose of 200 mg given on alternate days was approximately twice that from 100 mg given on consecutive days (
<0.001). In IDA, even if hepatic hepcidin expression is strongly suppressed by iron deficiency and erythropoietic drive, the intake of oral iron supplements leads to an acute hepcidin increase for 24 hours. The study was funded by ETH Zürich, Switzerland. This study has been registered at
.
Iron oxide nanoparticles (IONPs) have been proposed as targeted carriers to deliver therapeutic molecules in the central nervous system (CNS). However, IONPs may damage neural tissue via free iron ...accumulation, protein aggregation, and oxidative stress. Neuroprotective effects of quercetin (QC) have been proven due to its antioxidant and anti-inflammatory properties. However, poor solubility and low bioavailability of QC have also led researchers to make various QC-involved nanoparticles to overcome these limitations. We wondered how high doses or prolonged treatment with quercetin conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) could improve cognitive dysfunction and promote neurogenesis without any toxicity. It can be explained that the QC inhibits protein aggregation and acts against iron overload via iron-chelating activity, iron homeostasis genes regulation, radical scavenging, and attenuation of Fenton/Haber-Weiss reaction. In this review, first, we present brain iron homeostasis, molecular mechanisms of iron overload that induced neurotoxicity, and the role of iron in dementia-associated diseases. Then by providing evidence of IONPs neurotoxicity, we discuss how QC neutralizes IONPs neurotoxicity, and finally, we make a brief comparison between QC and conventional iron chelators. In this review, we highlight that QC as supplementation and especially in conjugated form reduces iron oxide nanoparticles neurotoxicity in clinical application.
Iron is a micronutrient essential for cellular energy and metabolism, necessary for maintaining body homoeostasis. Iron deficiency is an important co-morbidity in patients with heart failure (HF). A ...major factor in the pathogenesis of anaemia, it is also a separate condition with serious clinical consequences (e.g. impaired exercise capacity) and poor prognosis in HF patients. Experimental evidence suggests that iron therapy in iron-deficient animals may activate molecular pathways that can be cardio-protective. Clinical studies have demonstrated favourable effects of i.v. iron on the functional status, quality of life, and exercise capacity in HF patients. It is hypothesized that i.v. iron supplementation may become a novel therapy in HF patients with iron deficiency.
Daily administration of oral iron is considered the current treatment standard for treating iron deficiency anemia due to availability and reduced cost compared to intravenous iron therapy. But ...adverse effects like epigastric pain, heartburn, and constipation reduce compliance to daily oral iron. There is scanty evidence regarding compliance and efficacy with alternate-day iron therapy. As per our knowledge, this is the first systematic review to compare daily with alternate-day oral iron therapy. Six electronic databases including PubMed and EMBASE were searched for randomized controlled trials, quasi-experimental studies published between January 2000 to March 2023 that compared daily with alternate day iron therapy in individuals diagnosed with iron deficiency anemia. The primary outcome analyzed was a change in hemoglobin. The other hematological parameters were assessed as secondary outcomes. Risk of bias was assessed regarding randomization process, deviation from intended intervention, missing outcome data, measurement of the outcome, and selection of the reported result. Out of the 9 full-text articles, 2 were not included as one was an ongoing trial and the second one had a different study design. The reviewed trials involved 594 participants, and the study participants ranged from 19 to 200. The mean age of the participants in the reported trials was 21 ± 2 to 49 ± 16 years. There is no significant increase in hemoglobin level and also the iron indices namely ferritin, hepcidin, total iron binding capacity, and reticulocyte count between daily and alternate-day dosing of iron. However, the frequency of adverse effects especially nausea, metallic taste, and altered bowel habits are reduced with alternate-day dosing. Oral iron given daily or on alternate days did not have a significant difference in the hemoglobin levels though iron absorption may be affected in the initial few days.
Trial registration: The review protocol was registered with PROSPERO (Prospero2023CRD42023393095).
This article examines the association of iron deficiency (ID) and iron deficiency anemia (IDA) with children's development and behavior, with the goal of providing recommendations to prevent the ...developmental loss associated with these conditions. Children's risk for ID and IDA is particularly high during the second 6 months of life when prenatal stores are depleted. Longitudinal studies from infancy through adolescence and early adulthood suggest that socioemotional development is uniquely vulnerable to ID and IDA, perhaps being associated with shared neural pathways, and the effects of early iron deficiencies may be irreversible. In addition to direct effects on brain function, ID and IDA may also affect child development indirectly through non‐responsive mother‐child interactions. Maternal ID is a global problem that may contribute to high rates of maternal depression and non‐responsive caregiving. Intervention trials illustrate that children benefit from both nutritional intervention and early learning interventions that promote responsive mother‐child interactions. Recommendations to reduce the developmental loss associated with ID and IDA are to reduce the incidence of these conditions by efforts to prevent premature birth, delay cord clamping, ensure adequate maternal iron status, provide iron‐rich complementary foods, and ensure access to postnatal interventions that promote responsive mother‐infant interaction patterns and early learning opportunities for infants.
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