Iron Supplementation Research Articles

Anemia is a serious heath concern due to its high prevalence in the global population. Its occurrence in surgical patients varies greatly and correlates with worse outcomes. Higher costs and severe complications could also result from insufficient iron status. An effective way to mitigate the burden of iron deficiency could be the adoption of national patient blood management (PBM) programs. This study aimed to quantify the potential health economic benefits of implementing preoperative anemia management (the first pillar of PBM) with ferric carboxymaltose (FCM) in Romanian hospitals. An already published decision-tree-based health economic model was adapted and populated with Romanian cost and epidemiological data from 2019. Cardiac (coronary artery bypass grafting) and non-cardiac (hip and knee arthroplasty) elective surgery cases were analyzed. Costs of complications per discharged case were assessed on the basis of data from ten local hospitals. A total of 14,641 cases met the inclusion criteria. On the basis of our sample of ten hospitals, the complication costs per case ranged from €1067.43 (for stroke) to €2896.14 (for sepsis with pneumonia). The health economic model simulated two scenarios. In the first scenario, all cases with anemia received FCM treatment. The total savings at the national level total were at least €1,500,875. In the second scenario half of the cases with anemia received treatment, resulting in savings of €363,779. Our results suggest that introducing iron deficiency anemia treatment with FCM in case of elective surgical interventions results in considerable cost reduction for the healthcare system.

Blood transfusion is common in patients with infectious endocarditis (IE) treated surgically. Limited literature on RBC transfusion outcomes in surgical IE. We aimed to clarify impacts of red blood cell (RBC) transfusion on long-term results of IE patients with surgical intervention. We conducted a retrospective study on the medical records of patients with IE undergoing cardiac surgery from 2006 to 2022 in our hospital. In our investigation, 814 IE patients were enrolled into RBC ≥ 2 units group (n = 305) and RBC < 2 units group (n = 509). There were 305 RBC ≥ 2 units patients (37.5%, 305/814). Compared with RBC < 2 units group, all-time mortality (26.2% vs 10.4%, P <.001) significantly increased in RBC ≥ 2 units group. We found vegetation diameter ≥ 10 mm, cardiopulmonary bypass length ≥ 120 minutes, aortic occlusion length ≥ 90 minutes, preoperative aortic regurgitation ≥ 4 cm2, postoperative left ventricular end diastolic diameter ≥ 70 mm, ventilation length ≥ 72 hours, ang intensive care unit stay ≥ 3 days to be related to RBC ≥ 2 units. RBC ≥ 2 units is significantly related to 1- and 5-year mortality after cardiac operation and all-time mortality. The presence of RBC ≥ 2 units in IE is a risk factor of long-term survival. In our investigation, the presence of RBC ≥ 2 units has adverse impact on long-term results of IE patients with surgical intervention. The management strategies for IE anemia may not be limited to blood transfusions, but also include drug treatments such as iron supplements and red blood cell stimulants. This study provides valuable information for clinical practice of blood transfusion in cardiac surgery.

To evaluate the comparative effectiveness of four pharmacologic regimens-oxytocin, carbetocin, oxytocin plus tranexamic acid (TXA), and carbetocin plus TXA-for postpartum hemorrhage (PPH) prophylaxis in cesarean deliveries. This prospective cohort study was conducted at a tertiary center in Istanbul, Turkey, between March 2024 and January 2025. A total of 400 women undergoing cesarean delivery at 34+0-39+6weeks of gestation were sequentially assigned to one of four prophylactic intervention groups (n=100 each): oxytocin, oxytocin+TXA, carbetocin, or carbetocin+TXA. Medications were administered post-placental delivery. Third-stage labor management was standardized. Primary outcomes included estimated blood loss (EBL), 24-h hemoglobin change (ΔHb), and need for transfusion or intravenous iron. Baseline neonatal characteristics, including birthweight and Apgar scores, were recorded to ensure comparability across groups. Baseline characteristics were similar across groups. Hemoglobin decline differed significantly (p=0.015), being lowest in the carbetocin+TXA group (7.73±6.68 %) and highest in the oxytocin group (10.70±7.23 %). Although mean EBL was lowest in the carbetocin+TXA group, the difference was not statistically significant (p=0.172). Transfusion and iron supplementation rates were low and comparable. No adverse neonatal outcomes were observed. Carbetocin combined with TXA was associated with the most favorable hematologic profile. These findings support the use of multimodal pharmacologic strategies for PPH prevention in cesarean births and may inform future protocol development.

Background Chronic kidney disease (CKD) is a serious, long-term illness that damages kidneys and lowers glomerular filtration rate. CKD often causes anemia. Iron deficiency (ID) is common in these patients and worsens illness symptoms. Modern hematology analysers can measure reticulocyte mean cell hemoglobin (MCHr), which directly measures iron integration into erythrocyte hemoglobin. MCHr can improve iron deficiency detection in CKD patients, who have aberrant iron indicators due to chronic inflammation. This research aims to evaluate the effectiveness of MCHr as a marker for ID in patients with CKD. Method To obtain data for this study, CBC, reticulocyte profile, and iron biomarkers were collected from King Khalid National Guard Hospital (Ref No. IRB/1861/23). Transferring saturation was calculated using (Serum iron/TIBC) × 100. GraphPad Prism 9 software was used to analyze the data, and Mann-Whitney, Spearman correlation, and ROC plots were used to determine MCHr's diagnostic performance. A p - value &amp;lt; 0.05 was considered significant. Result The study compared 190 individuals undergoing hemodialysis (HD) with 165 healthy blood donors. The HD group showed lower levels of RBC, Hb, MCHr, serum iron, and total iron-binding capacity (TIBC). Despite anemia, the HD group had higher levels of ferritin and transferrin saturation (TSAT). MCHr demonstrated excellent diagnostic performance in identifying iron deficiency anemia (IDA), particularly in functional iron deficiency. When TSAT was &amp;lt; 20%, MCHr showed an AUC of 0.98, with 100% specificity and 72.41% sensitivity, significantly outperforming ferritin and TSAT in inflammatory settings. In the HD group with ferritin levels &amp;lt; 200 ng/mL, the MCHr cut-off value of &amp;lt; 31.20 pg had a sensitivity and specificity of 89.47% and an AUC of 0.89. When TSAT was &amp;lt; 20%, the MCHr cut-off value of &amp;lt; 23.95 pg had a sensitivity of 72.41%, specificity of 100%, and AUC of 0.98. Conclusions Based on the findings, MCHr is more effective than ferritin and TSAT in detecting iron deficiency in hemodialysis patients. Future research should use MCH to investigate the impact of iron therapy with or without rHuEPO.

Iron deficiency anaemia (IDA) affects 25% of the global population, with detrimental effects on the health of women and children. Treatments with iron supplements offer temporary relief but often yield adverse effects, hindering patient adherence. Additionally, IDA is associated with oxidative stress, which becomes significantly exacerbated during iron supplementation. Our study aimed to address this challenge by developing a plant-based nutritional formula rich in bioavailable iron and antioxidants devoid of adverse effects. Chemical analysis of edible plants, focused on the content of iron and iron absorption inhibitors, guided formula development. In vivo studies on rats with IDA evaluated iron bioavailability from the formulated plant-based nutraceuticals. Results of animal studies showed significant improvements in IDA-associated blood parameters after 28 days of oral administration of the nutraceuticals. Additionally, the nutraceuticals did not impede the benefits of iron supplementation. These findings strongly indicate that plant-based nutraceuticals can serve as an effective source of bioavailable iron, potentially improving treatment adherence and at the same time aligning with ongoing WHO and UNICEF initiatives to enhance IDA management.

Anemia remains a global public health problem and continues to pose a significant burden in many developing countries. Several national and regional studies have reported that the prevalence of anemia among adolescent girls ranges from 14% to 50%, depending on location and survey methods, with many studies showing rates exceeding 30% in certain populations. Female students (santriwati) living in Islamic boarding schools (pondok pesantren) are particularly vulnerable to anemia. Common contributing factors include inadequate iron intake, irregular communal eating practices, limited nutritional knowledge, excessive menstrual bleeding, and restricted access to health services. The implementation of the community engagement program consisted of three main stages: (1) Socialization and initial hemoglobin (Hb) screening to obtain a preliminary overview of anemia status; (2) Health education and interactive discussions delivered through lectures, question-and-answer sessions, and educational video presentations; and (3) Evaluation and post-activity monitoring through joint reflections involving both the boarding school administrators and the participants. The combination of Hb screening, interactive counseling sessions, leaflet-based educational media, and institutional support from the boarding schools proved effective in creating a conducive environment for promoting healthy behaviors. However, challenges such as limited availability of Hb testing equipment and negative perceptions toward iron supplementation still need to be addressed through continuous approaches and cross-sectoral collaboration.

Patients with heart failure with reduced ejection fraction are at high risk for iron deficiency (ID) due to low intake and high losses. Randomized controlled trials show intravenous (IV) iron improves quality of life and lowers readmissions. Suboptimal ID screening may stem from limited awareness of ID thresholds and guidelines in heart failure. We hypothesized that implementing provider education and optimized EHR notification would improve ID screening and IV iron infusion rates over 6 months among inpatients at a community hospital. Presentations were delivered to the Internal Medicine Residents, Hospitalists, and Cardiologists, reviewing key trials and recommendations for ID in CHF from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), and the American Heart Association (AHA). A flyer summarizing diagnostic criteria and IV iron treatment was then posted in high-traffic provider areas. A Best Practice Alert (BPA) was also implemented, which triggered if a patient had heart failure and no iron studies in the past 6 months, automatically adding iron study orders unless removed. IV iron was recommended through education via presentations and flyers, using criteria of ferritin &lt;100 ng/mL or 100–299 ng/mL with TSAT &lt;20%. Pre-intervention data (PRE) were collected from 10/1/2024 - 2/13/2025, and post-intervention (POST) from 2/14 - 5/20/2025. Exclusions included previous iron studies or iron supplementation within 6 months. A chi-square test of independence was performed to measure if there was a statistically significant difference between PRE and POST for ID screening, IV infusion, and oral iron rates. 2,461 encounters met inclusion criteria (PRE: 1,507, POST: 954). Prior to the intervention, 12.8% were screened for ID compared to 24.1% after intervention with an Absolute Benefit Increase of 11.3% (p &lt; 0.001). The rate of IV iron repletion increased significantly (PRE: 4.8% vs. POST: 6.8%, p &lt; 0.05). Oral iron repletion rates were not significantly different in PRE vs. POST (4.5% to 4.8%, p &gt; 0.05). ID screening improved with minimal burden via provider education and BPAs. IV iron use rose modestly, limited by reliance on education alone and brief hospital stays with competing clinical priorities. Future efforts should target education on oral iron absorption limitations, investigate barriers to IV iron infusion, and optimize the outpatient transition for continued ID management.

Background: Randomized trials, including AFFIRM-AHF, show that intravenous (IV) iron improves functional status and reduces hospitalizations in patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency. However, real-world evidence remains limited. We aimed to assess these outcomes in a large, multicenter electronic health record network. Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network. Adults with HFrEF and iron deficiency or anemia (ferritin ≤100 ng/mL or hemoglobin ≤11 g/dL) were included. Patients with prior malignancy, ESRD, erythropoietin exposure, or blood transfusion were excluded. IV iron exposure included iron sucrose, ferric carboxymaltose, ferric gluconate, ferumoxytol, iron dextran, and ferric derisomaltose. Matching was 1:1 on demographics, comorbidities, and therapies, yielding two balanced cohorts (n=62,318 each). Outcomes were assessed over two years. Results: IV iron therapy was associated with a modestly increased risk of supraventricular tachycardia (HR 1.15, 95% CI 1.08–1.22, p&lt;0.001) and ventricular tachycardia (HR 1.11, 95% CI 1.05–1.17, p&lt;0.001), but not atrial fibrillation/flutter (HR 0.98, 95% CI 0.93–1.03, p=0.985). No significant differences were observed in blood transfusion, PCI, or CABG rates. The IV iron group had significantly lower rates of elevated high-sensitivity C-reactive protein (hs-CRP ≥3 mg/L; HR 0.82, 95% CI 0.74–0.91, p&lt;0.001), with no difference in NT-proBNP elevations. Cardiac outcomes—including cardiac arrest, acute heart failure, myocardial infarction, cardiomyopathy, and new-onset ejection fraction &lt;20%—did not differ significantly. IV iron therapy was associated with reduced all-cause hospitalization (HR 0.74, 95% CI 0.71–0.78, p&lt;0.001), while emergency and outpatient visit rates were similar. All-cause mortality was not significantly different (HR 1.02, 95% CI 1.00–1.04, p=0.120). Conclusion: In this large, real-world cohort of HFrEF patients with iron deficiency, IV iron therapy reduced hospitalizations and inflammation (hs-CRP), with no effect on mortality or most cardiac outcomes. A modest increase in SVT and VT was observed. These findings support guideline recommendations for IV iron in HFrEF and highlight the need for arrhythmia monitoring.

Background and Aim: Iron deficiency (ID) is a common condition worldwide, affecting about one-third of the population, and is particularly prevalent in heart failure (HF) patients. In HF, ID worsens symptoms such as fatigue and shortness of breath, contributing to higher hospitalization rates and mortality. Intravenous (IV) iron therapies like Ferric Carboxymaltose (FCM) and Ferric Derisomaltose (FDI) have effectively enhanced symptoms and improved quality of life. This meta-analysis examines the safety and efficacy of these iron treatments. Methods: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to May 2024 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. Our protocol was registered with PROSPERO (CRD#CRD42023469246). Our study included Randomized Controlled Trials (RCTs). The primary outcomes of our study includes major adverse events such as Cardiovascular Mortality, All-Cause Death, heart failure hospitalization rate, KCCQ, LVEF, MLHFQ3, and Peak Oxygen Consumption (pVO2). Results: Twenty-four RCTs with 11,333 participants were analyzed. The pooled analysis indicated that All-cause mortality risk reduction was observed with FCM [RR=0.89; 95% CI: 0.75–1.04] and FDI [RR=0.95; 95% CI: 0.81–1.12]. FCM significantly reduced composite outcomes of hospitalization for HF or cardiovascular mortality [HR=0.74; 95% CI: 0.59–0.93], while FDI showed modest effects [HR=0.86; 95% CI: 0.56–1.26]. Kansas City Cardiomyopathy Questionnaire scores improved notably with FCM [MD=5.21; 95% CI: 2.22–8.19]. Left Ventricular Ejection Fraction improvement was highest with Iron Sucrose [MD=2.92; 95% CI: 1.61–4.21]. For the Minnesota Living with Heart Failure Questionnaire (MLHFQ), Iron Sucrose also showed the most improvement [MD = -18.00; 95% CI: -38.52 to 2.52], followed by FCM and FDI. In peak oxygen consumption (pVO2), FCM exhibited modest benefits [MD = 1.25; 95% CI: -2.34 to 4.84]. The six-minute walk test (6MWT) results identified Ferrous Sulphate as the most effective [MD = 53; 95% CI: -18.85 to 124.85], followed by FCM. Conclusion: This highlights Ferric Carboxymaltose as a promising iron therapy for heart failure patients with iron deficiency. However, clinical decisions should consider patient factors, tolerability, and cost-effectiveness. Further long-term studies are needed to optimize treatment and prevent hospitalization.

Background: On Apr. 1, 2022, the AHA/ACC/HFSA released guidelines recommending intravenous (IV) iron for patients with heart failure with reduced ejection fraction (HFrEF) and iron deficiency (ID) based on evidence from randomized trials suggesting improved patient outcomes. However, adherence to this Class 2a recommendation remains understudied. Methods: Using TriNetX’s US Collaborative Network, an aggregation of ~125 million de-identified patient electronic health records, we identified HFrEF patients with ID across eight 6-month time blocks relative to Apr. 1, 2022: one before and seven after, ending on May 16, 2025—the date of data extraction. For each time block, we applied a standardized cohort selection workflow to identify adults with HFrEF (ICD-10-CM: I50.2) and ID, defined as ferritin &lt;100 μg/L or 100–300 μg/L with transferrin saturation &lt;20%. We then searched for orders for oral, injectable, or unspecified iron placed after the diagnosis of ID and extracted relevant data. Chi-square tests were used to assess trends. Results: The sample of HFrEF patients with ID in each time block ranged from 1,753 to 35,810. In the 6 months prior to guideline release, the treatment rate was 25.4%. Post-guidelines, we observed a consistent increase in the treatment rates (p&lt;0.001), peaking at 42.4% between Oct. 2024 and Mar. 2025 before decreasing between Apr. 2025 and May 16, 2025. Additionally, the percentage of treated patients prescribed oral and unspecified iron decreased (p&lt;0.001 for both), whileinjectable formulations remained relatively consistent at approximately 48% with a slight overall increase across time blocks (p&lt;0.001). Conclusions: Despite updated national guidelines endorsing IV iron therapy for HFrEF patients with ID, treatment remains suboptimal across U.S. clinical settings. A marked increase in treatment rates was observed following guideline publication, suggesting growing clinician awareness and evolving practice patterns. Notably, even when accounting for all forms of iron, treatment rates remained below 50%, highlighting a significant gap relative to guideline intent, which specifically recommends IV iron. The shift away from oral and unspecified formulations toward consistent use of injectable iron likely reflects increased alignment with evidence-based care and improved documentation. These findings highlight the need for targeted interventions to promote consistent adoption of guideline-directed therapies in this high-risk population.

Background: Iron deficiency (ID) is common among patients with heart failure (HF), and it is associated with poor functional outcomes, increased hospitalizations, and higher mortality. This meta-analysis evaluates the efficacy of intravenous ferric carboxymaltose (FCM) in HF patients with ID. Methods: We conducted a literature search of major bibliographic databases up to April 15, 2025, to identify randomized controlled trials (RCTs) comparing FCM with placebo or standard care in HF patients with ID. The primary outcome was a composite of recurrent hospitalizations for heart failure (HHF) or cardiovascular (CV) death assessed at 1-year and complete follow-up. Risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) were estimated using a random-effects model. Results: Eleven RCTs (6,493 patients) were included in the review. FCM significantly reduced the composite of recurrent HHF or CV death at 1-year (RR 0.73, 95% CI 0.62–0.85) and over maximum follow-up (RR 0.80, 95% CI 0.68–0.94) compared to control. Recurrent HHF was significantly reduced with FCM administration (1-year RR 0.69, 95% CI 0.57–0.84; complete follow-up RR 0.75, 95% CI 0.60–0.94). FCM demonstrated a trend toward reduced all-cause (RR: 0.86, 95% CI: 0.74–1.00) and CV mortality at 1-year (RR: 0.86, 95% CI: 0.72–1.02), but this effect was attenuated over longer follow-up. FCM significantly improved 6-minute walk test performance (MD 29.19 m, 95% CI 11.95–46.43). The trial sequential analysis confirmed robust evidence for the primary outcome. Conclusion: Intravenous FCM in HF patients is associated with reduced risk of adverse cardiovascular events and improved functional capacity. Further trials are needed to clarify its long-term survival impact.

Background: Iron deficiency is a common comorbidity in patients with pulmonary hypertension (PH), affecting approximately 43–60% of this population. Iron plays a crucial role in oxygen transport and cellular energy metabolism, and its deficiency has been associated with impaired exercise tolerance and worse clinical outcomes. While intravenous iron supplementation, has shown promise in improving functional parameters in heart failure, its role in PH remains less well defined. A systematic synthesis of the evidence is warranted to better understand the potential therapeutic value of iron supplementation in this high-risk population. Hypothesis: Our hypothesis proposes that iron supplementation may significantly improve functional outcomes in PH patients with documented iron deficiency. Methods: We conducted a systematic review and meta-analysis to evaluate the effect of iron supplementation on the functional capacity in adults with PH. We used PubMed, MEDLINE and EMBASE for our systematic search of relevant studies published between 2014-2024. The studies reported a change in functional capacity with a 6-minute walk test (6MWT) distance. To assess study quality, we used the Newcastle- Ottawa Scale for observational studies and Jadad score for randomized controlled trials (RCTs). Using random-effects models, we calculated the mean differences with a 95% confidence interval. Results: From the collected studies, nine studies met the inclusion criteria (Figure 1). The pooled effect showed a significant improvement in 6MWT distance following iron supplementation (28.64 meters; 95% CI: 16.64 to 40.64; p &lt; 0.01) with a substantial heterogeneity (78.5%) (Figure 2) . Of the studies considered, high-quality RCTs displayed smaller, non-significant changes (10.65 meters; 95% CI: -10.81 to 32.11) and non-randomized studies showed larger effects on functional capacity (31.68 meters; 95% CI: 21.90 to 41.45) (Figure 3). Improvements were more evident in patients with anemia at baseline. Conclusions: Iron supplementation may improve functional capacity in patients with pulmonary hypertension, particularly those with anemia. However, heterogeneity, potential bias, and differences between randomized and non-randomized studies limit the strength of current evidence. Well-designed, adequately powered trials are needed to clarify the clinical benefits and underlying mechanisms. Until then, iron therapy should be considered on a case-by-case basis.

BackgroundEvidence on antenatal care (ANC) and emergency service utilization during pregnancy in Latin America remains limited. Understanding these patterns is critical given the substantial benefits of ANC and emergency services in improving maternal and neonatal outcomes, preventing and managing pregnancy complications, and reducing maternal and infant mortality. This study examined ANC and emergency service utilization among pregnant women affiliated with the Mexican Institute of Social Security (IMSS) and identified factors associated with their use.MethodsWe conducted an observational eCohort study through telephone interviews with 1,390 pregnant women aged 18–49 who initiated ANC at IMSS. Outcomes included the number of ANC visits, emergency room use, perceived quality of ANC, and provider competence assessed through 12 recommended ANC activities: blood pressure and weight measurement, blood and urine tests, ultrasound, and counseling on nutrition, warning signs, birth preparedness, newborn care, psychological health, and folic acid and iron supplementation. Multivariable negative binomial regression models were used to identify factors associated with ANC attendance and emergency service use.ResultsOf the full cohort, 3.7% exited due to miscarriage, 12.4% dropped out after baseline, and 11.8% dropped out during follow-up. One-third of women who left rated the quality of their first ANC visit as poor or fair. In addition, 30% of women who remained in the cohort reported poor or fair ANC quality. On average, participants reported six ANC visits, with 64.8% receiving at least 80% of the 12 recommended ANC activities. Nearly 30% sought emergency services during pregnancy. Higher ANC attendance was associated with hypertension, urinary infections, anemia, early ANC initiation, consultations with obstetricians, and hospital-based ANC follow-ups. Use of emergency services was more common among women with chronic diseases, hypertensive disorders of pregnancy, urinary tract infections, risk of miscarriage, or risk of depression.ConclusionsSubstantial improvements in ANC are needed to strengthen women’s care experiences and promote consistent utilization of ANC services.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-025-08301-9.

Background A plateau hypoxic environment can increase the physiological burden on athletes. Although nutritional interventions have been recognized as a potential strategy to improve plateau acclimatization, evidence in support of specific dietary patterns is still lacking. This study compared the effects of different dietary interventions on cardiopulmonary fitness during plateau exercise through systematic evaluation and network meta-analysis methods. Methods This study systematically reviewed relevant literature up to June 2025 and included 20 randomized controlled trials (RCTs) conducted at altitudes above 1,500 meters involving healthy participants aged 16 years and above who engaged in physical activities. The primary outcomes included cardiopulmonary indicators [maximal oxygen uptake (VO 2max ), heart rate (HR)], blood biomarkers [peripheral oxygen saturation (SpO 2 ), hematocrit (HCT)], and subjective perception indicators [rating of perceived exertion (RPE)]. For each outcome, the pooled effects of each intervention compared to others were estimated. Mean difference (MD) or standardized mean difference (SMD) with 95% Credible Intervals (95% CrI) were calculated. The Surface Under the Cumulative Ranking Curve (SUCRA) was used to rank the dietary interventions and quantify their relative effectiveness. In addition, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was applied to assess the quality of evidence. Results A total of 20 randomized controlled trials involving 329 participants were included, evaluating eight dietary interventions. Moderate-quality evidence indicated that carbohydrate supplementation significantly improved the percentage of maximal oxygen uptake (VO 2max ) compared to placebo (SMD = 1.13, 95% CrI: 0.25 to 2.05) and reduced RPE scores (MD = −0.77, 95% CrI: −1.83 to −0.09). Moderate-quality evidence indicated that carbohydrate supplementation combined with glutamine ranked highest in improving SpO 2 (SUCRA 84.54%) and RPE (SUCRA 69.37%), while iron supplementation showed the highest SUCRA rankings for HR (56.54%) and HCT (66.67%). However, these interventions did not demonstrate statistically significant advantages. Notably, the observed increase in VO 2max exceeded the minimally clinically important difference (MCID) of 1.0 ml/kg/min reported in previous studies, suggesting that the effect of carbohydrate supplementation on VO 2max may have clinical relevance. Conclusions Differences exist in the effects of different dietary interventions on cardiopulmonary fitness during altitude exercise. The current network meta-analysis indicates that carbohydrate-based strategies show beneficial effects, with carbohydrate plus glutamine supplementation demonstrating greater advantages in SpO 2 and RPE, while carbohydrate alone is more supported in improving VO 2max. Therefore, carbohydrate-based strategies may serve as effective options to promote altitude acclimatization, whereas iron supplementation may have potential benefits in improving HCT and HR. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD420251069629 , identifier: CRD420251069629.

Renal anemia, a major complication of chronic kidney disease, contributes to increased cardiovascular risk, mortality, and accelerated progression to kidney failure. However, comprehensive bibliometric analyses evaluating global trends, knowledge gaps, and emerging research hotspots in this field remain lacking. This study retrieved publications related to renal anemia from the Web of Science Core Collection (January 1965–November 2024) and conducted data analysis and visualization using VOSviewer, CiteSpace, Pajek, and Origin. The final dataset included 1,664 publications authored by 7,534 researchers from 2,287 institutions across 72 countries, with Japan, the United States, and China accounting for 45.8% of total publications. Top institutions were Showa University, the University of Tokyo, and King’s College Hospital; Iain C. Macdougall was the most prolific author, while Masaomi Nangaku demonstrated the highest citation impact and centrality. Keyword analysis revealed a growing focus on clinical trials and pathophysiology, highlighting three core therapeutic strategies: erythropoiesis-stimulating agents, iron supplementation, and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), along with several emerging research topics targeting sodium-glucose cotransporter 2 (SGLT2), hepcidin, fibroblast growth factor 23 (FGF23), gut microbiota, zinc, and stem cells. Our conclusions indicate that the field has evolved from erythropoietin replacement therapy to HIF-PHI-centered physiological modulation. Current hotspots center on HIF-PHI clinical translation, with potential therapeutic avenues including SGLT2 inhibitors, hepcidin antagonists, FGF23 signaling modulation, gut microbiota regulation, zinc supplementation, and stem cell-based therapeutics.

Introduction: Iron deficiency (ID) is common in HF and is associated with adverse CV outcomes. There is a paucity of literature on efficacy of intravenous iron replacement (FeIV) in children with HF. Methods: Single-center observational analysis of 244 children (≤ 21 years old) with HF or post-heart transplant (HTX) who received IV iron sucrose (IS, 46%) from 2010-2018 or IV ferric carboxymaltose (FCM, 54%) from 2019-2024. Anemia was defined by World Health Organization age-specific hemoglobin cutoffs; ID was defined as iron saturation (TSAT) &lt;20% or ferritin &lt;100 ng/mL. Primary outcome was change in iron profile and hematological indices. Secondary outcome was change in LVEF and BNP. Exploratory outcome included baseline risk factors for anemia and composite event of HTX listing, need for MCS, or death by latest follow-up. Results: Median age at first FeIV infusion was 3.6 years (IQR 0.8-13.2); 43% were female. Diagnoses included CDM (49%), congenital heart disease (43%), and s/p HTX (8%). Total of 812 FeIV infusions were administered (67% IS; 33% FCM). Median number of infusions per patient was 4 (IQR 3–6) for IS and 1 (IQR 1–2) for FCM (p&lt;0.01). Despite fewer infusions, the median cumulative dose was higher with FCM (19.9 vs 13.1 mg/kg; p&lt;0.01). At baseline, 82% had TSAT &lt;20%, 70% had ferritin &lt;100 ng/mL, 38% had serum iron &lt;40 mcg/dL, and 50% were anemic. Only 56% had TSAT &lt;20% with ferritin &lt;100 ng/mL. Mean follow-up was 255 days (SD±144). Significant increases in TSAT, ferritin, serum iron, hemoglobin, and LVEF, and decreases in BNP, were observed at most follow-up points (Table 1) (all p&lt;0.05). Following FeIV, 81% achieved TSAT ≥20% and 80% ferritin ≥100 ng/mL. Composite event occurred in 28% at median 28 days (IQR 8-102) following first FeIV infusion; time to event occurred significantly earlier in IS vs FCM cohorts (18 vs 32 days, respectively, p=0.04). Multivariable analysis identified ferritin &lt;100 ng/mL was independently associated with decreased risk of anemia and serum iron &lt;40 mcg/dL as increased risk (Table 2). Older era (2010-2018), lower cumulative FeIV dose, ferritin &lt;100 ng/mL, lower TSAT, and higher BNP were all independently associated with higher risk of composite event (Table 3). Conclusion: FeIV effectively corrects ID in children with HF and may be linked with improvements in clinical outcomes. Further studies are needed to confirm safety and clinical benefits of FeIV in pediatric HF.

Iron-deficiency anemia (IDA) is a prevalent global health concern, with nonheme iron salts being the most commonly used iron supplementation therapies. However, these therapies are associated with significant side effects and poor efficacy due to interactions with dietary components. Heme iron, which is less susceptible to such interactions, holds promise as an alternative, but suffers from high individual variability in clinical efficacy. This study systematically investigates the biopharmaceutical properties of hemin and identifies its poor solubility and permeability, classifying it as a Class IV drug with low oral bioavailability, which may explain its suboptimal clinical performance. To overcome this limitation, we developed a hemin-loaded nanoparticle formulation (HNP) to enhance the oral bioavailability and therapeutic efficacy of hemin. The formulation is simple to produce, with a high drug loading capacity (30%), and significantly improves the solubility and permeability of hemin. In rats, the HNP increased the relative bioavailability of hemin by 6.5 times. In vivo studies in an IDA mouse model demonstrated that HNP effectively improved anemia-related indicators, such as the red blood cell count, hemoglobin levels, and hematocrit while also alleviating gastrointestinal inflammation. Additionally, HNP administration restored the diversity and abundance of gut microbiota, which is often impaired in IDA. With excellent safety and biocompatibility, HNP represents a promising oral formulation for the treatment of IDA, offering a potential strategy to enhance heme iron bioavailability and reduce individual variability in therapeutic outcomes.

Introduction: Iron deficiency (ID), affecting up to 50% of Chronic Heart Failure (CHF) patients, is associated with higher mortality, worse symptoms, poorer quality of life and impaired exercise capacity. Chronic inflammation in CHF promotes functional ID through elevated hepcidin levels, impairing iron availability and worsening anemia. The stabilized bivalent liposomal iron (SBLI) bypasses the absorption channel blocked by hepcidin and is directly absorbed by enterocyte cells, allowing immediate and high bioavailability. In previous trials, oral iron therapy has never demonstrated, unlike intravenous administration, an improvement in functional capacity and quality of life in these patients. The aim of our study was to evaluate the efficacy of SBLI in increasing the availability of circulating iron, in patients with CHF, as well as its effects on quality of life. Methods: 59 patients (mean age 68±12 years) with CHF and reduced or mildly reduced ejection fraction and confirmed ID were enrolled in the study. ID was defined as ferritin levels &lt;100 μg/L or ferritin levels of 100 to 299 μg/L along with Transferrin Saturation (TSAT)&lt;20%. Patients were randomized in a double-blind manner to receive SBLI (30 mg twice daily for 1 month, then once daily for an additional 2 months) or placebo. Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were acquired at baseline and after three months of therapy. Results: Baseline characteristics and blood parameters were similar in both groups and all patients were on optimal medical therapy. Blood parameters are reported in Table 1. KCCQ Overall Summary Score significantly improved, in the treatment arm, from 48.9±18.50 to 62.1±13.8 (p&lt;0.001), but not in the placebo arm (from 48.1±16.9 to 50.2±12.2, p=0.06). Conclusions: The positive impact of oral SBLI on iron balance and quality of life underscores its potential as a therapeutic intervention for CHF patients with ID. Its ability to bypass the hepcidin-mediated absorption block allows for a more effective increase in iron balance compared to other formulations. It increases iron bioavailability instead than quick iron storage, avoiding elevated risk of oxidative stress, membrane damage and ferroptotic cell death. It also represents an excellent therapeutic choice in terms of cost-effectiveness. This clinical trial is the first to show that oral SBLI therapy improves quality of life in CHF patients as well as iron bioavailability. Future research can validate these findings.

Nutrition education plays a crucial role in improving the nutritional status of pregnant women, yet evidence of its impact in low-income settings like Ethiopia is limited. This study evaluated the effectiveness of facility-based nutrition education and counseling on pregnant women's knowledge, dietary practices, and iron-folic acid supplement use. A cluster randomized controlled trial was conducted in Addis Ababa, Ethiopia, involving 683 pregnant women across 20 health centers assigned to intervention or control groups. Antenatal care providers in the intervention group received training on pregnancy nutrition and counseling, while the control group continued standard care per national guidelines. A total of 683 pregnant women were enrolled during their first and second ANC visits. Mixed-effects linear regression was used to evaluate outcomes. The study was conducted in Addis Ababa, Ethiopia, from August to December 2017. Pregnant women attending ANC follow-ups and healthcare providers working in ANC units. The intervention group demonstrated significant improvements in knowledge, including iodized salt use (difference-in-differences [DID] 23%), correct iron-folic acid supplementation duration (DID 68%), and the need for additional meals during pregnancy (DID 49.9%). Dietary practices improved with higher dietary diversity (DID 32.3%), increased dairy consumption (MD 1.2 vs. -0.1; DID 1.2 per week), and higher iron-folic acid supplementation (MD 4.9 vs. 1.6; DID 3.2 per week). Nutrition education and counseling during ANC visits significantly improved pregnant women's knowledge and dietary practices. Integrating and strengthening these interventions into routine ANC services could effectively enhance dietary intake and health outcomes.

Cardiorenal disease is commonly complicated by iron deficiency, which worsens clinical outcomes regardless of haemoglobin levels. This review evaluates recent evidence on intravenous iron therapy in this setting. Recent randomized trials demonstrate the important role of intravenous iron in improving functional status and quality of life as well as reducing hospitalizations in patients with heart failure and iron deficiency. In chronic kidney disease, intravenous iron showed potential cardiovascular benefits beyond anaemia correction and is now recommended in updated guidelines. Although historically there were concerns regarding adverse reactions, recent trial data using modern high-dose intravenous irons have demonstrated an acceptable safety profile. Intravenous iron offers clinical benefits in cardiorenal disease, supporting its expanded use even in the absence of anaemia. Broader adoption in clinical practice remains limited despite updated guidelines. Whilst safety data are generally reassuring, further studies will help define long-term safety and optimal use in non-dialysis, non-anaemic populations.