Search

Background: Iron deficiency without anaemia is a common health problem, especially in young menstruating women. The efficacy of the usually recommended oral iron supplementation is limited due to increased plasma hepcidin concentration, which reduces iron absorption and leads to side effects such as intestinal irritation. This observation raises the question of how low-dose iron therapy may affect plasma hepcidin levels and whether oral iron intake dose-dependently affects plasma hepcidin production., Methods: Fifteen non-anaemic women with iron deficiency (serum ferritin ≤30 ng/ml) received a single dose of 0, 6, 30, or 60 mg of elemental oral iron as ferrous sulfate on different days. Plasma hepcidin was measured before and seven hours after each dose., Results: Subjects had an average age of 23 (standard deviation = 3.0) years and serum ferritin of 24 ng/ml (interquartile range = 16-27). The highest mean change in plasma hepcidin levels was measured after ingesting 60 mg of iron, increasing from 2.1 ng/ml (interquartile range = 1.6-2.9) to 4.1 ng/ml (interquartile range = 2.5-6.9; p < 0.001). Iron had a significant dose-dependent effect on the absolute change in plasma hepcidin (p = 0.008), where lower iron dose supplementation resulted in lower plasma hepcidin levels. Serum ferritin levels were significantly correlated with fasting plasma hepcidin levels (R2 = 0.504, p = 0.003) and the change in plasma hepcidin concentration after iron intake (R2 = 0.529, p = 0.002)., Conclusion: We found a dose-dependent effect of iron supplementation on plasma hepcidin levels. Lower iron dosage results in a smaller increase in hepcidin and might thus lead to more efficient intestinal iron absorption and fewer side effects. The effectiveness and side effects of low-dose iron treatment in women with iron deficiency should be further investigated. This study was registered at the Swiss National Clinical Trials Portal (2021-00312) and ClinicalTrials.gov (NCT04735848).

Background: Roxadustat is an oral hypoxia inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) that regulates iron metabolism in patients with chronic kidney disease (CKD) primarily by reducing hepcidin levels and mobilizing internal iron stores. More data are needed to demonstrate the efficacy of roxadustat in regulating iron metabolism in patients with peritoneal dialysis (PD) compared with erythropoiesis stimulating agents (ESAs)., Methods: This prospective cohort study enrolled PD patients with a mean hemoglobin level of 60-100 g/L. All subjects were randomized into two groups at a ratio of 2:1 the roxadustat group (106 cases), and the ESA group (53 cases). The primary endpoint was the change in the iron biomarker levels and the proportion of patients with absolute iron deficiency and functional iron deficiency., Results: Compared with ESAs, roxadustat significantly decreased hepcidin level (difference, - 20.09 ng/mL; 95% CI, - 30.26 to - 9.92), attenuated the increase in serum soluble transferrin receptor (sTFR) level (difference, - 7.87 nmol/L; 95% CI, - 12.11 to - 3.64), and reduced the proportion of patients with functional iron deficiency (roxadustat, 11.43%; ESA, 33.33%). There was no significant difference in safety of the two groups over the duration of the study., Conclusions: Compared with ESA group, roxadustat group showed significant differences in all iron biomarker levels except serum ferritin (sFt) and transferrin saturation (TSAT). These results suggest that roxadustat was superior to ESAs as a therapy for iron metabolism in PD patients., Trial Registration: This study completed Chinese Clinical Trial Registration on March 4, 2022 (registration number: ChiCTR2200057231)., (© 2023. The Author(s).)

The study evaluated the safety and effectiveness of the generic intravenous (IV) iron treatment (Feriv®), in a Spanish cohort with absolute iron deficiency (ID) (serum ferritin <50 ng/ml, with or without anaemia) (n = 122; 91% women; median age of 44 years [IQR: 33.7-54]). Iron-related biomarkers were measured before treatment (baseline), 2 weeks after beginning the protocol (intermediate control, IC) and between 7 and 10 days after treatment completion (final time-point). Primary efficacy endpoints were ferritin levels ≥ 50 ng/ml, anaemia restoration or an increase in haemoglobin (Hb) of at least one point in patients without baseline anaemia. After treatment, iron-related biomarkers improved, including ferritin, Hb, sideremia, transferrin, transferrin saturation index, soluble transferrin receptor (sTfR), and hepcidin. Baseline ferritin concentration (13.5 ng/ml [IQR: 8-24.2]) increased at the IC and continued rising at the final time-point, reaching a median ferritin of 222 ng/ml and 97.3% of patients ≥ 50 ng/ml. At the final time-point, anaemia prevalence decreased from 26.2% to 5%, while the 34.1% without baseline anaemia showed an increase in Hb of at least one point. Headache was the only drug-adverse event recorded in 2.3% of patients. At a late time-point (27.5 median weeks after ending therapy [IQR: 22-40]), evaluated in a subgroup of 66 patients, 18% had ferritin levels < 50 ng/ml. Multivariate analysis showed that low baseline ferritin and high sTfR/hepcidin ratio tended to be independently associated with ID recurrence. Feriv® is a safe, effective first-line treatment for absolute ID, with improvement of serum ferritin and Hb. ID recurrence was associated with the baseline degree of iron stores depletion, indicated by serum ferritin, and sTfR/hepcidin ratio., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Iron is an essential nutrient for oxygen supply and aerobic metabolism. Iron deficiency impacts cellular respiration and mitochondrial energy metabolism, which can lead to reduced skeletal muscle function and muscle mass, causing sarcopenia. Intravenous iron offers the ability to rapidly correct iron deficiency, but the functional impact on patient mental and physical health is unclear. We assessed the effects of intravenous iron therapy on physical function and quality of life in the treatment of adults with non-anaemic iron deficiency. An update and reanalysis of a previously published Cochrane systematic review was performed to assess randomized controlled trials that compared any intravenous iron preparation with placebo in adults. The primary functional outcome measure was physical performance as defined by the trial authors. Secondary outcome measures included fatigue and quality-of-life scores, and adverse effects at the end of follow-up. Biochemical efficacy was assessed by change in serum ferritin and haemoglobin concentration levels. Twenty-one randomized controlled trials, comprising 3514 participants, were included. Intravenous iron compared with placebo resulted in significantly increased physical function measured by mean peak oxygen consumption (mean difference [MD] 1.77 mL/kg/min, 95% confidence interval [CI] 0.57 to 2.97). An overall improvement in fatigue was seen (standardized MD 0.30, 95% CI -0.52 to -0.09) but no overall difference in quality of life (MD 0.15, 95% CI -0.01 to 0.31). Biochemically, intravenous iron resulted in improved serum ferritin (MD 245.52 μg/L, 95% CI 152.1 to 338.9) and haemoglobin levels (MD 4.65 g/L, 95% CI 2.53 to 6.78). There was a higher risk of developing mild adverse events in the intravenous iron group compared with the placebo group (risk ratio 1.77, 95% CI 1.10 to 2.83); however, no differences were seen in serious adverse events (risk difference 0, 95% CI -0.01 to 0.01). The quality of evidence was rated 'low' and 'very low' for all outcome variables, except for fatigue, mainly due to most studies being judged as having a high risk of bias. In non-anaemic iron-deficient adults, the use of intravenous iron compared with placebo improved physical function and reduced fatigue scores. However, we remain uncertain about the efficacy in this population due to low-quality evidence, and there is a need for further studies to address potential impact on overall quality of life., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Iron deficiency is frequent in patients with chronic heart failure (CHF) with a prevalence of 50%, and its frequency varies depending on the study groups. The presence of iron deficiency limits erythropoiesis, leading to the development of anemia over time in patients with CHF, regardless of gender, race, and left ventricular ejection fraction (LVEF). Observational studies demonstrate a higher prevalence of iron deficiency in women and in patients with higher NYHA (New York Heart Association) functional class, decreased LVEF, increased brain natriuretic peptide (NT-proBNP), or increased high-sensitivity C-reactive protein. Iron deficiency and anemia in patients with CHF are independently associated with a decreased exercise capacity, hospitalizations for CHF, an increase in overall mortality and mortality from cardiovascular diseases. The clinical significance of iron deficiency requires the need to diagnose iron metabolism in all patients with CHF. Current guidelines for the diagnosis and treatment of CHF indicate the need to determine the level of ferritin and saturation of transferrin in all patients with a suspected diagnosis of heart failure. The use of oral iron therapy in patients with CHF demonstrates its low efficacy in correcting this condition according to the clinical trials. At the same time the use of intravenous iron therapy is safe and improves symptoms, exercise capacity and quality of life in patients with heart failure with reduced ejection fraction and iron deficiency, which has been shown both in international placebo-controlled trials and meta-analyses. The use of iron carboxymaltose should improve CHF symptoms, exercise capacity and quality of life in patients with CHF and LVEF45%. Intravenous iron therapy has also been shown to reduce readmissions for CHF in patients with an LVEF50% who have recently been hospitalized for worsening CHF.

Background: Although some studies have described the association between serum ferritin levels and specific disorders in child and adolescent psychiatry, few have focused on mental status per se with low serum ferritin levels in children and adolescents. This study examined the effects of iron administration on psychological status of children and adolescents with reduced serum ferritin concentration., Methods: This prospective study evaluated 19 participants aged 6-15 years with serum ferritin levels <30 ng/mL who visited a mental health clinic and received oral iron administration for 12 weeks. The participants were assessed using the Clinical Global Impression Severity (CGI-S), Profile of Mood States 2nd Edition Youth-Short (POMS), Center for Epidemiologic Studies Depression Scale (CES-D), and Pittsburgh Sleep Quality Index (PSQI). In addition to serum ferritin, blood biochemical values such as hemoglobin (Hb) and mean corpuscular volume (MCV) were examined. School attendance was recorded., Results: The most prevalent physical symptoms were fatigability and insomnia. The CGI-S, PSQI, and CES-D scores decreased significantly following iron supplementation, whereas the scores of almost all POMS subscales improved significantly at week 12. No participant had hemoglobin levels <12 g/dL. Serum ferritin concentration increased significantly, whereas Hb and MCV remained unchanged. At baseline, 74% of the participants did not attend school regularly; this number improved to varying degrees by week 12., Conclusions: Serum ferritin levels would be preferable to be measured in children and adolescents with insomnia and/or fatigability regardless of psychiatric diagnoses or gender. Iron supplementation can improve the hypoferritinemia-related psychological symptoms of children and adolescents, such as poor concentration, anxiety, depression, low energy and/or irritability.

Iron deficiency in pregnancy is a major public health problem that causes maternal complications. The objective of this randomized, controlled trial was to examine the bioavailability, efficacy, and safety of oral ferrous bisglycinate plus folinic acid supplementation in pregnant women with iron deficiency. Subjects (12−16 weeks of gestation, n = 120) were randomly allocated to receive oral iron as ferrous bisglycinate (equiv. iron 24 mg) in supplement form with folinic acid and multivitamins (test group, n = 60) or as ferrous fumarate (equiv. iron 66 mg iron, control group, n = 60) after breakfast daily. Iron absorption was assessed by measuring fasted serum iron levels at 1 and 2 h immediately after supplementation. Hematological biomarkers and iron status were assessed before intervention, and at 3 and 6 months. Side effects were monitored throughout the intervention. A significant increase in serum iron was seen in both groups (p < 0.001) during the bioavailability assessment; however, the test group increases were comparatively higher than the control values at each timepoint (p < 0.001). Similarly, both test and control groups demonstrated a statistically significant increases in hemoglobin (Hb) (p < 0.001), erythrocytes (p < 0.001), reticulocytes (p < 0.001), mean corpuscular volume (MCV) (p < 0.001), mean corpuscular hemoglobin (MCH) (p < 0.001), mean corpuscular hemoglobin concentration (MCHC) (p < 0.001), % transferrin saturation (p < 0.001), and ferritin (p < 0.001) at 3 and 6 months after supplementation. However, in all cases, the test group increases were numerically larger than the control group increases at each timepoint. The test intervention was also associated with significantly fewer reports of nausea, abdominal pain, bloating, constipation, or metallic taste (p < 0.001). In conclusion, ferrous bisglycinate with folinic acid as a multivitamin nutraceutical format is comparable to standard ferrous fumarate for the clinical management of iron deficiency during pregnancy, with comparatively better absorption, tolerability, and efficacy and with a lower elemental iron dosage.

Background: Over the last decade, preoperative anemia has become recognized as a clinical condition in need of management. Although the etiology of preoperative anemia can be multifactorial, two thirds of anemic elective surgical patients have iron deficiency anemia. At the same time, one third of nonanemic elective surgical patients are also iron deficient., Methods: Modified RAND Delphi methodology was used to identify areas of consensus among an expert panel regarding the management of iron deficiency in patients undergoing cardiac surgery. A list of statements was sent to panel members to respond to using a five-point Likert scale. All panel members subsequently attended a face-to-face meeting. The initial survey was presented and discussed, and panel members responded to each statement on the Likert scale again. Based on the second survey, the panel came to a consensus on recommendations., Results: The panel recommended all patients undergoing cardiac surgery be evaluated for iron deficiency, whether or not anemia is present. Evaluation should include iron studies and reticulocyte hemoglobin content. If iron deficiency is present, with or without anemia, patients should receive parenteral iron. Erythropoietin-stimulating agents may be appropriate for some patients., Conclusions: Consensus of an expert panel resulted in a standardized approach to diagnosing and managing iron deficiency in patients undergoing cardiac surgery., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Patients suffering from heart failure (HF) and iron deficiency (ID) have worse outcomes. Treatment with intra-venous (IV) ferric carboxymaltose has been shown to reduce HF rehospitalizations and to improve functional capacity and symptoms in patients with HF and reduced ejection fraction (HFrEF). However, IV ferric carboxymaltose is significantly more expensive than IV sodium ferric gluconate complex (SFGC) limiting its availability to most HF patients around the globe. Methods: A retrospective analysis comparing patients admitted to internal medicine or cardiology departments between January 2013 to December 2018 due to acute decompensated HF (ADHF) and treated with or without IV SFGC on top of standard medical therapy. Results: During the study period, a total of 1863 patients were hospitalized due to ADHF with either HFrEF or HF with preserved ejection fraction (HFpEF). Among them, 840 patients had laboratory evidence of iron deficiency (absolute or functional) and met the inclusion criteria. One hundred twenty-two of them (14.5%) were treated with IV SFGC during the index hospitalization. Patients treated with IV iron were more likely to have history of ischemic heart disease, atrial fibrillation, and chronic kidney disease. The rate of readmissions due to ADHF was similar between the groups at 30 days, 3 months, and 1 year. Conclusion: High risk patient hospitalized to ADHF and treated with IV SFGC showed comparable ADHF readmission rates, compared to those who did not receive iron supplementation.

Ferumoxytol is an intravenous iron oxide nanoparticle formulation that has been approved by the U.S. Food and Drug Administration (FDA) for treating anemia in patients with chronic kidney disease. In recent years, ferumoxytol has also been demonstrated to have potential for many additional biomedical applications due to its excellent inherent physical properties, such as superparamagnetism, biocatalytic activity, and immunomodulatory behavior. With good safety and clearance profiles, ferumoxytol has been extensively utilized in both preclinical and clinical studies. Here, we first introduce the medical needs and the value of current iron oxide nanoparticle formulations in the market. We then focus on ferumoxytol nanoparticles and their physicochemical, diagnostic, and therapeutic properties. We include examples describing their use in various biomedical applications, including magnetic resonance imaging (MRI), multimodality imaging, iron deficiency treatment, immunotherapy, microbial biofilm treatment and drug delivery. Finally, we provide a brief conclusion and offer our perspectives on the current limitations and emerging applications of ferumoxytol in biomedicine. Overall, this review provides a comprehensive summary of the developments of ferumoxytol as an agent with diagnostic, therapeutic, and theranostic functionalities., Competing Interests: Competing Interests: DC and HK are named as inventors of a patent on the use of iron oxide nanoparticles as anti-biofilm agents., (© The author(s).)

Background: Iron deficiency (ID) is common in patients with chronic kidney disease (CKD). Intravenous (IV) iron in heart failure leads to improvement in exercise capacity and improvement in quality-of-life measurements; however, data in patients with CKD are lacking., Methods: The Iron and the Heart Study was a prospective double blinded randomised study in non-anaemic CKD stages 3b-5 patients with ID which investigated whether 1000 mg of IV iron (ferric derisomaltose (FDI)) could improve exercise capacity in comparison to placebo measured at 1 and 3 months post infusion. Secondary objectives included effects on haematinic profiles and haemoglobin, safety analysis and quality of life questionnaires (QoL)., Results: We randomly assigned 54 patients mean (SD) age for FDI (n = 26) 61.6 (10.1) years vs placebo (n = 28; 57.8 (12.9) years) and mean eGFR (33.2 (9.3) vs. 29.1 (9.6) ml/min/1.73m 2 ) at baseline, respectively. Adjusting for baseline measurements, six-minute walk test (6MWT) showed no statistically significant difference between arms at 1 month (p = 0.736), or 3 months (p = 0.741). There were non-significant increases in 6MWT from baseline to 1 and 3 months in the FDI arm. Haemoglobin (Hb) at 1 and 3 months remained stable. There were statistically significant increases in ferritin (SF) and transferrin saturation (TSAT) at 1 and 3 months (p < 0.001). There was a modest numerical improvement in QoL parameters. There were no adverse events attributable to IV iron., Conclusion: This study demonstrated a short-term beneficial effect of FDI on exercise capacity, but it was not significant despite improvements in parameters of iron status, maintenance of Hb concentration, and numerical increases in functional capacity and quality of life scores. A larger study will be required to confirm if intravenous iron is beneficial in iron deficient non-anaemic non-dialysis CKD patients without heart failure to improve the 6MWT., Trial Registration: European Clinical Trials Database (EudraCT) No: 2014-004133-16 REC no: 14/YH/1209 Date First Registered: 2015-02-17 and date of end of trail 2015-05-23 Sponsor ref R1766 and Protocol No: IHI 141.