Efficacy Of Iron Supplementation Research Articles

Efficacy of iron supplementation on physical capacity in non-anaemic iron-deficient individuals: protocol for an individual patient data meta-analysis

BackgroundA deficiency in iron stores is associated with various adverse health complications, which, if left untreated, can progress to states of anaemia, whereby there is significant detriment to an individual’s work capacity and quality of life due to compromised erythropoiesis. The most common methods employed to treat an iron deficiency include oral iron supplementation and, in persistent and/or unresponsive cases, intravenous iron therapy. The efficacy of these treatments, particularly in states of iron deficiency without anaemia, is equivocal. Indeed, both randomised control trials and aggregate data meta-analyses have produced conflicting evidence. Therefore, this study aims to assess the efficacy of both oral and intravenous iron supplementation on physical capacity, quality of life, and fatigue scores in iron-deficient non-anaemic individuals using individual patient data (IPD) meta-analysis techniques.MethodsAll potential studies, irrespective of design, will be sourced through systematic searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, Web of Science: Science Citation Index Expanded, Web of Science: Conference Proceedings Citation Index-Science, ClinicalTrials.gov, and World Health Organization (WHO) International Clinical Trials Registry Platform. Individual patient data from all available trials will be included and subsequently analysed in a two-stage approach. Predetermined subgroup and sensitivity analyses will be employed to further explain results.DiscussionThe significance of this IPD meta-analysis is one of consolidating a clear consensus to better inform iron-deficient individuals of the physiological response associated with iron supplementation. The IPD approach, to the best of our knowledge, is novel for this research topic. As such, the findings will significantly contribute to the current body of evidence.Systematic review registrationPROSPERO CRD42020191739.

Intestinal microbiota composition and efficacy of iron supplementation in Peruvian children.

Despite repeated public health interventions, anemia prevalence among children remains a concern. We use an evolutionary medicine perspective to examine the intestinal microbiome as a pathway underlying the efficacy of iron-sulfate treatment. This study explores whether gut microbiota composition differs between anemic children who respond and do not respond to treatment at baseline and posttreatment and if specific microbiota taxa remain associated with response to iron supplementation after controlling for relevant inflammatory and pathogenic variables. Data come from 49 pre-school-aged anemic children living in San Juan de Lurigancho, Lima, Peru. We tested for differences in alpha and beta diversity using QIIME 2 and performed differential abundance testing in DESeq2 in R. We ran multivariate regression models to assess associations between abundance of specific taxa and response while controlling for relevant variables in Stata 17. While we found no evidence for gut microbiota diversity associated with child response to iron treatment, we observed several differential abundance patterns between responders and non-responders at both timepoints. Additionally, we present support for a nonzero relationship between lower relative abundance of Barnesiellaceae and response to iron supplementation in samples collected before and after treatment. While larger studies and more specific approaches are needed to understand the relationship between microbes and anemia in an epidemiological context, this study suggests that investigating nutritional status and pathogen exposure is key to better understanding the gut microbiome and impact of iron fortification.

Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial

IntroductionApproximately 40% of children aged 6–59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of...

Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss.

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with a low-iron diet (LID) also showed iron deposition in the decidua and adverse pregnancy outcomes. Decreased ferroportin (cellular iron exporter) expression that inhibited the iron export from decidual stromal cells (DSCs) might be the reason for local iron deposition in DSCs from low-serum-iron RPL patients and LID-fed mice. Iron supplementation reduced iron deposition in the decidua of spontaneous abortion models and improved pregnancy outcomes. Local iron overload caused ferroptosis of DSCs by downregulating glutathione (GSH) and glutathione peroxidase 4 levels. Both GSH and cystine (for the synthesis of GSH) supplementation reduced iron-induced lipid reactive oxygen species (ROS) and cell death in DSCs. Ferroptosis inhibitor, cysteine, and GSH supplementation all effectively attenuated DSC ferroptosis and reversed embryo loss in the spontaneous abortion model and LPS-induced abortion model, making ferroptosis mitigation a potential therapeutic target for RPL patients. Further study that improves our understanding of low-serum-iron-induced DSC ferroptosis is needed to inform further clinical evaluations of the safety and efficacy of iron supplementation in women during pregnancy.

Regulation of Iron Transport Is Required for Terminal Erythroid Differentiation Even Under Iron-Replete Conditions Sufficient for Hemoglobinization

Developing erythroid cells are the main consumer of iron in vertebrates, as their main function is to oxygenate tissues via hemoglobin. Iron metabolism is a key driver of erythroid development and hemoglobin synthesis. When iron deficient, or when iron metabolism is dysregulated, erythroid cells are both lacking in hemoglobin and exhibit differentiation defects. Currently, the efficacy of iron supplementation in patients is monitored by quantitating hemoglobin levels. However, the effect of iron supplementation on erythroid differentiation is less clear. As hemoglobinization and erythroid differentiation are inextricably intertwined with erythroid function, we sought to understand whether and how iron supplementation functions to restore erythroid differentiation during iron deficiency. Tackling this problem in vivo has been fraught with technical challenges as vertebrates with mutations in iron metabolism genes often die from anemia in utero. To circumvent this problem, we used zebrafish with genetic iron metabolism defects to determine if iron supplementation could rescue erythropoietic defects at both the cellular and systemic level. Zebrafish are tractable in vivo models for such studies as they develop externally and can easily be treated by exogenous iron in their water. To carry out this study, we designed a system to sort Tg(globin lcr:eGFP) erythrocytes from single zebrafish embryos onto slides for imaging, while keeping sufficient numbers of cells for genotyping of the same embryo. We used two zebrafish lines which carry loss of function mutations in the mfrn1 (carrying a mitochondrial iron trafficking defect) and fpn1 (carrying a defect in iron export from intestinal and yolk syncytial epithelium-a model of dietary iron deficiency). Both lines had decreased erythroid cell numbers. In addition, the erythroid cells were hemoglobin deficient and had erythroid differentiation defects which included enlarge nuclei. We showed that exogenous iron supplementation (labeled as "rescue) in mfrn1 mutant zebrafish restored hemoglobinization (benzidine staining) but not erythroid cell number (% lcr:eGFP) or terminal differentiation. However, iron supplementation in fpn1 mutant zebrafish, restored erythroid cell number but not terminal differentiation defects. The main difference in the 2 mutants is that the mfrn1 mutant has a defect in intracellular iron trafficking leading to defective iron metabolism, while the fpn1 mutant has defective iron export to erythroid cells but their erythroid cells have intact intracellular iron trafficking. mfrn1 mutants had defects in cell cycle progression and increased apoptosis in their erythroid cells which likely is a cause for decreased erythroid cell numbers. Our data suggests that in addition to adequate iron levels, correct regulation of iron trafficking is required for optimal erythroid iron utilization, terminal erythropoiesis and potentially, proliferation and differentiation of erythroid progenitors. This may indicate a role for iron transporters in directing iron fate, as well as signaling to developmental pathways. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Safety and efficacy of iron supplementation after myocardial infarction in mice with moderate blood loss anaemia.

AimsIron deficiency is frequently observed in patients with acute coronary syndrome and associates with poor prognosis after acute myocardial infarction (AMI). Anaemia is linked to dysregulation of iron metabolism, red blood cell dysfunction, and increased reactive oxygen species generation. Iron supplementation in chronic heart failure is safe and improves cardiac exercise capacity. Increases in iron during ischaemia or immediately after reperfusion are associated with detrimental effects on left ventricular (LV) function. The safety and applicability of iron during or immediately after reperfusion of AMI in anaemia are not known. We aimed to study the safety and efficacy of iron supplementation within 1 h or deferred to 24 h after reperfusion of AMI by analysing LV function and infarct size.Methods and resultsIn a mouse model of moderate blood loss anaemia (n = 6–8 mice/group), the effects of iron supplementation (20 mg iron as ferric carboxymaltose per kg body weight) within 1 h and deferred to 24 h after ischaemia/reperfusion were assessed. Cardiac function was analysed in vivo by echocardiography at baseline (Day 3) with and without anaemia, after AMI (24 h), and after administration of intravenous iron. Anaemia was characterized by iron deficiency and a trend towards increased haemolysis, which was supported by increased plasma free‐haemoglobin [sham vs. anaemia (n = 8/group): P < 0.05]. Anaemia increased heart rate, LV end‐diastolic volume, stroke volume, and cardiac output, while LV end‐systolic volume remained unchanged at baseline. Superimposition of AMI deteriorated global LV function, whereas infarct sizes remained unaffected [sham vs. anaemia (n = 6/group): P = 0.9]. Deferred iron supplementation 24 h after ischaemia/reperfusion resulted in reversal of end‐systolic volume increase and reduced infarct size [% of area at risk: sham vs. anaemia + iron after 24 h; (n = 6/group); 48 ± 7 vs. 38 ± 7; P < 0.05], whereas administration within 1 h after reperfusion was neutral [sham vs. anaemia + iron; (n = 6/group); 48 ± 7 vs. 42 ± 8; P = 0.56]. Moreover, iron application after reperfused AMI showed unaltered mortality compared with sham.ConclusionsIron supplementation 24 h after reperfusion of AMI is safe and reversed enlargement of end‐systolic volume after AMI resulting in increased stroke volume and cardiac output. This highlights its potential as adjunctive treatment in anaemia with ID after reperfused AMI. Time point of iron application after reperfusion appears critical.

Efficacy of iron supplementation in patients with inflammatory bowel disease treated with anti-tumor necrosis factor-alpha agents.

Background:Anemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, data on the influence of anti-tumor necrosis factor-alpha (anti-TNF-α) agents and iron supplementation on anemia in patients with IBD are sparse. We assessed the effect of iron supplementation in patients with IBD initially treated with an anti-TNF-α agent.Methods:Data from 79 IBD patients who started anti-TNF-α treatment at a tertiary hospital were analyzed. The patients were divided into the anti-TNF-α (n = 52) and anti-TNF-α with iron supplementation (n = 27) groups. Effects on laboratory parameters, the prevalence of anemia, and disease activity were evaluated at baseline (year 0) and 1 year later.Results:The hemoglobin (Hb) level significantly increased between years 0 and 1 in both groups [12.0 ± 1.8–13.3 ± 2.0 g/dL in the anti-TNF-α group (p < 0.001) and 9.8 ± 2.4–11.7 ± 2.3 g/dL in the anti-TNF-α and iron supplementation group (p = 0.004)]. In a subgroup analysis of severely anemic patients with IBD, iron supplementation increased the magnitude of the improvement in Hb level (8.5 ± 1.5–11.4 ± 2.1 g/dL; p = 0.001) compared with the anti-TNF-α group (9.3 ± 0.8–11.4 ± 2.7 g/dL; p = 0.081). Disease activity was significantly improved in both groups at year 1 compared with year 0. Persistent anemia was significantly correlated with severe anemia at baseline (p = 0.017).Conclusion:In anemic patients with IBD, anti-TNF-α agents led to clinically meaningful improvements in anemia independent of iron supplementation. Also, iron supplementation could be helpful in severely anemic patients with IBD.

Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials

ObjectiveIron supplementation in iron-deficiency anaemia is standard practice, but the benefits of iron supplementation in iron-deficient non-anaemic (IDNA) individuals remains controversial. Our objective is to identify the effects of iron...

Efficacy of iron supplementation may be misinterpreted using conventional measures of iron status in iron-depleted, nonanemic women undergoing aerobic exercise training

Background: Despite its known detrimental effects, iron deficiency remains the most common micronutrient deficiency in the world. Many interventions that aim to improve iron status involve physically active populations. Intense aerobic exercise training negatively affects iron status; however, the impact of regular moderate aerobic exercise on the effectiveness of iron supplementation remains unclear.Objective: This study aimed to determine whether aerobic training modifies the assessment of the effectiveness of iron supplementation in improving conventional iron status measures.Design: Seventy-two iron-depleted, nonanemic Chinese women [serum ferritin (sFer) <25 μg/L and hemoglobin >110 g/L] were included in an 8-wk, partially blinded, randomized controlled trial with a 2 × 2 factorial design including iron supplements (42 mg elemental Fe/d) or placebo and aerobic training (five 25-min sessions/wk at 75-85% of maximum heart rate) or no training. Linear mixed models were used to evaluate the relation between supplement type, training, and changes in iron status over time, measured by sFer, hemoglobin, soluble transferrin receptor (sTfR), and estimated total body iron.Results: After treatment, both the iron-supplemented trained and untrained groups showed significantly improved sFer, sTfR, and body iron values compared with either of the placebo groups. Similarly, trained participants had significantly higher aerobic fitness measures than untrained participants. Training modified the sFer response to supplementation (training by supplement interaction, P = 0.07), with the iron-supplemented trained group having significantly lower sFer than the iron-supplemented untrained group at week 8 (mean ± SD: 31.8 ± 13.5 and 47.6 ± 15.7 μg/L, respectively; P = 0.042), whereas there was no significant difference between the placebo trained and untrained groups (21.3 ± 12.2 and 20.3 ± 7.0 μg/L, respectively; P = 1.00).Conclusions: Regular aerobic training reduces the apparent effectiveness of iron supplementation in improving sFer and calls into question whether conventional measures of iron status accurately reflect iron metabolism in physically active, nonanemic women. This trial was registered at clinicaltrials.gov as NCT03002090.

Iron Supplementation in Iron-Replete and Nonanemic Pregnant Women in Tanzania: A Randomized Clinical Trial.

Anemia is common in pregnancy and increases the risk of adverse outcomes. Iron deficiency is a leading cause of anemia in sub-Saharan Africa, and iron supplementation is the standard of care during pregnancy; however, recent trials among children have raised concerns regarding the safety of iron supplementation in malaria-endemic regions. There is limited evidence on the safety of iron supplementation during pregnancy in these areas. To evaluate the safety and efficacy of iron supplementation during pregnancy in a malaria-endemic region. We conducted a randomized, double-blind, placebo-controlled clinical trial among pregnant women presenting for antenatal care in Dar es Salaam, Tanzania, from September 28, 2010, through October 4, 2012. Iron-replete, nonanemic women were eligible if they were uninfected with human immunodeficiency virus, primigravidae or secundigravidae, and at or before 27 weeks of gestation. Screening of 21,316 women continued until the target enrollment of 1500 was reached. Analyses followed the intent-to-treat principle and included all randomized participants. Participants were randomized to receive 60 mg of iron or placebo, returning every 4 weeks for standard prenatal care, including malaria screening, prophylaxis with the combination of sulfadoxine and pyrimethamine, and treatment, as needed. The primary outcomes were placental malaria, maternal hemoglobin level at delivery, and birth weight. Among 1500 study participants (750 randomized for each group), 731 in iron group and 738 in placebo group had known birth outcomes and 493 in iron group and 510 in placebo group had placental samples included in the analysis. Maternal characteristics were similar at baseline in the iron and placebo groups, and 1354 (91.7%) used malaria control measures. The risk of placental malaria was not increased by maternal iron supplementation (relative risk [RR], 1.03; 95% CI, 0.65-1.65), and iron supplementation did not significantly affect birth weight (3155 vs 3137 g, P = .89). Compared with placebo, iron supplementation significantly improved the mean increase from baseline to delivery for hemoglobin (0.1 vs -0.7 g/dL, P < .001) and serum ferritin (41.3 vs 11.3 µg/L, P < .001). Iron supplementation significantly decreased the risk of anemia at delivery by 40% (RR, 0.60; 95% CI, 0.51-0.71) but not severe anemia (RR, 0.68; 95% CI, 0.41-1.14). Iron supplementation significantly reduced the risk of maternal iron deficiency at delivery by 52% (RR, 0.48; 95% CI, 0.32-0.70) and the risk of iron deficiency anemia by 66% (RR, 0.34; 95% CI, 0.19-0.62). Prenatal iron supplementation among iron-replete, nonanemic women was not associated with an increased risk of placental malaria or other adverse events in the context of good malaria control. Participants receiving supplementation had improved hematologic and iron status at delivery compared with the placebo group. These findings provide support for continued administration of iron during pregnancy in malaria-endemic regions. clinicaltrials.gov Identifier: NCT01119612.

Effect of an iron-deficient diet on rat tongue with special reference to the efficacy of iron supplementation

Effect of an iron-deficient diet on rat tongue with special reference to the efficacy of iron supplementation

Effect of zinc on efficacy of iron supplementation in improving iron and zinc status in women.

Iron and zinc may interact in micronutrient supplements and thereby decrease efficacy. We investigated interactive effects of combined zinc and iron supplementation in a randomized controlled trial conducted in 459 Guatemalan women. Four groups were supplemented for 12 weeks: (1) weekly iron and folic acid (IFA); (2) weekly IFA and 30 mg zinc; (3) daily IFA; (4) daily IFA and 15 mg zinc. Effects were assessed by generalized linear regression. Baseline hemoglobin (Hb) concentration was 137.4 ± 15.5 g/L, 13% were anemic and 54% had zinc deficiency. Hb cconcentrations were similar by supplement type, but Hb concentrations improved significantly in anemic women at baseline (increase of 21.8 g/L). Mean percentage changes in serum ferritin were significantly higher in daily compared to weekly supplemented groups (86% versus 32%). The addition of zinc to IFA supplements had no significant impact on iron or zinc status. In conclusion, adding zinc to IFA supplements did not modify efficacy on iron status or improve zinc status, but daily supplementation was more efficacious than weekly in improving iron stores.

Safety and Efficacy of Iron Supplements in Malaria-Endemic Areas

Where malaria surveillance and health care is inadequate, iron supplements given without food can increase the severity of malarial infections. The likely explanation is that the rate of iron influx into the plasma from high-dose oral supplements exceeds the rate of iron binding to transferrin and a quantity of non-transferrin-bound iron (NTBI) is formed. It is proposed that NTBI increases the intensity of malarial infections by increasing the sequestration of malaria-infected red cells in the capillaries of the brain and intestine, causing more cerebral malaria and further increasing the permeability of the intestinal barrier to the passage of pathogens. Bacteremia is frequently reported in children with severe malaria. At the same time, high iron doses stimulate the growth of pathogenic bacteria in the stool, further increasing the potential for bacteremia. The normal immune response to malaria, as well as other infections and inflammatory disorders, is to prevent further microbial growth by stimulating hepcidin synthesis and preventing the passage of iron into the plasma. Iron absorption is decreased and the efficacy of the iron interventions would be expected to be lower in the presence of infections.

Anemia, Iron and Pregnancy Outcome

When maternal anemia is diagnosed before midpregnancy, it has been associated with an increased risk of preterm delivery. Maternal anemia detected during the later stages of pregnancy, especially the third trimester, often reflects the expected (and necessary) expansion of maternal plasma volume. Third-trimester anemia usually is not associated with increased risk of preterm delivery. High hemoglobin concentration, elevated hematocrit and increased levels of serum ferritin late in pregnancy, however, all have been associated with increased preterm delivery. This increased risk may reflect in part the failure to expand maternal plasma volume adequately, thus diminishing appropriate placental perfusion. Although controlled trials of iron supplementation during pregnancy have consistently demonstrated positive effects on maternal iron status at delivery, they have not demonstrated reductions in factors that are associated with maternal anemia, i.e., increased risk of preterm delivery and infant low birth weight. One reason for discordant findings may be the exclusion of many gravidas with iron deficiency from these trials or the data concerning gravidas with pregnancy outcomes such as preterm delivery from the analysis. Finally, recent concerns have been voiced about harmful effects of iron supplementation during pregnancy. No adverse effects of iron supplementation on pregnancy outcome have been demonstrated to date. Questions about the efficacy of iron supplementation during pregnancy for reducing adverse outcomes such as preterm delivery and side effects from iron supplementation, including the potential for oxidation of lipids and DNA, require further research in iron-deficient women.