Oral Iron Supplementation Research Articles

This study aims to investigate the effect of 8 weeks of ferrous sulfate supplementation (160 mg elemental iron/day) on fatigue and physical performance in young women with iron deficiency anemia (IDA). In this uncontrolled pilot clinical trial, twenty-three women with IDA aged between 18 and 30 years participated in this study. Aerobic fitness, muscle strength and muscle endurance were performed to evaluate physical capacities. Moreover, the multidimensional fatigue inventory (MFI-20) was used to assess general, physical, and mental fatigue, reduced activity and motivation. Due to multiple comparisons, the level of significance was set at 0.00625. The results of this study revealed that muscle endurance values increased significantly (P < 0.001) after 8 weeks of iron supplementation compared to pre-intervention values. In addition, scores of general (P < 0.001), physical (P < 0.001) and mental (P < 0.001) fatigue, and reduced activity (P < 0.001) and motivation (P = 0.006) decreased significantly in post- intervention compared to pre- intervention. However, there were no improvements in aerobic fitness (P = 0.008) and muscle strength (P = 0.086). In women of reproductive age with IDA, 8 weeks of iron supplementation improve muscle endurance, but not aerobic fitness or muscle strength. These improvements could be explained by the increase in hemoglobin (Hb) (by 17.62%) and serum ferritin (by 63.2%) concentrations and the decrease in fatigue scores after the supplementation period.

Iron deficiency anemia (IDA) is the most common nutritional deficiency in the world, particularly affecting children and women. The first-line treatment for IDA is oral iron supplementation, preferred for its cost-effectiveness and convenience of administration but is often accompanied by side effects like oxidative stress, infections, and low-solubility/precipitation. This study explores the use of ferritins-self-assembled nanocage proteins serving as soluble cellular-iron reservoirs-as a safer alternative for oral iron intervention. Ideal oral iron supplements must withstand gastric conditions, not trigger oxidative stress, and reach the absorption site intact. DNA protection assays and microbial growth studies demonstrate the antioxidative properties of ferritin, contrary to ferrous salts, underscoring its potential as a safer iron supplement. While ferritin shows commendable gastric tolerance, prolonged exposure can hamper its structural integrity/mineral retention. To further enhance its stability, ferritin is fabricated with gelatins, which preserved its structure/iron content under simulated gastric conditions. The combination of inherent antioxidant and controlled iron release properties of ferritin with gelatin's protective effect could help overcome the limitations of the commercial supplements. The findings of this study could pave the way for the development of "gelatin-coated iron-loaded ferritin"-based oral formulations as a safer option for IDA management.

Haemophilia A and B are hereditary bleeding disorders that require multidisciplinary perioperative management. Data on orthopaedic surgery outcomes with extended-half-life (EHL) recombinant Fc-fusion factor VIII (rFVIIIFc) and factor IX (rFIXFc) products remain limited. To evaluate the efficacy of EHL rFVIIIFc or rFIXFc in major orthopaedic surgery, focusing on haemostasis, safety and factor consumption. This prospective study involved persons with haemophilia A or B treated with rFVIIIFc or rFIXFc undergoing orthopaedic surgery. Twenty major orthopaedic surgeries (2018-2023) were included in 19 persons with severe or moderate haemophilia A (n=14) or B (n=5), median age 46 years (range 26-60). Procedures included arthroplasty, arthrodesis, arthroscopic synovectomy, prosthetic revision of the knee or ankle, and removal of a femur fracture fixation device. Median hospital stay was 7 days (range 2-18). Median cumulative factor consumption was 300 and 388IU/kg for haemophilia A and B, respectively. Haemostatic efficacy was rated as 'good' in 95% (n=18) of cases, 'poor' in 5% (n=1), and not documented in one case. Median haemoglobin (Hb) change was -2.0g/dL (range -4.6 to +0.5); no transfusions were required. Complications were reported in 45% (n=9) of cases (anaemia 40%; blood loss 5%) and managed with oral supplementation of iron and folates. No adverse events related to rFVIIIFc or rFIXFc administration were observed. RFVIIIFc and rFIXFc provide effective haemostasis during orthopaedic surgery in patients with haemophilia A and B, with a favourable safety profile. Further multicentre studies are warranted to confirm these results and refine perioperative management guidelines.

Iron is an essential trace element that is important for the development, structure, and functioning of the brain. Iron has been both favorably and unfavorably implicated in neuropsychiatric disorders. For example, iron adequacy in pregnancy and early childhood has been suggested to reduce the risk of neurodevelopmental disorders and schizophrenia, but iron mechanisms have been implicated in neurodegenerative disorders, multiple sclerosis, and stroke. Supplemental iron may be indicated to treat restless legs syndrome, akathisia, and pica, but more commonly to treat iron deficiency associated with poor nutrition in major mental illness. Supplemental iron is commonly orally administered but is poorly absorbed by this route. It is therefore necessary to know what improves and what impairs iron absorption. This article explains that, for best absorption, oral iron supplements are ideally dosed as ferrous salts. The dose should be administered in the morning, on a fasting stomach, along with about 100 mg of vitamin C in the form of a tablet, or with a glass of orange or other citrus juice. If neither vitamin C nor citrus juice is available, as a poorer option, iron should be dosed with plain water. Absorption is markedly reduced if iron is administered in the afternoon, or with food such as cereals and other grains, or with beverages such as milk, tea, and coffee. Calcium supplements, antacids, H2 inhibitors, and proton pump inhibitors also reduce the absorption of orally administered iron. Some data suggest that alternate day dosing improves fractional iron absorption as well as reduces adverse effects of treatment. Finally, to reduce the risk of pill esophagitis, iron should be dosed with a full glass of liquid, and the patient should not recline or lie down for at least the next 30-60 min.

BackgroundAnaemia and iron deficiency are a global healthcare burden affecting almost 25% of the population. Many anaemia cases are caused by depletion of iron stores which can be treated by oral iron supplementation. However, anaemia may also result from functional iron deficiency, where chronic inflammation prevents utilisation of stored iron. Anaemia and iron deficiency are rarely profiled in general populations; however, they can have significant healthcare implications.MethodsData from n = 33,029 serum samples were retrospectively analysed from individuals undertaking private health checks within Randox Health (UK). Samples were measured to detect anaemia, iron and vitamin deficiencies, based on established guidelines.ResultsThe overall prevalence of anaemia in the study was 6.0% (n = 1,917/31,803). The prevalence of anaemia was higher in females, with almost 1 in 10 (9.9%; n = 1,558/15,715) classified as anaemic; anaemia prevalence was highest in females aged 18–50 years. Similarly, absolute iron deficiency was also higher in females, with almost 1 in 3 (31.6%; n = 4,633/14,677) impacted. Functional iron deficiency was high in the study individuals across all age groups and sexes.ConclusionThe study identified that anaemia and iron deficiency are common underlying conditions in a health-conscious UK population. Despite the high prevalence of anaemia and iron deficiency burden on females of menstruating age, demonstrated in this study, and reported in the literature, screening for these conditions is not widespread. Should there be a national screening programme for anaemia and iron deficiency in females?

Preventive Oral Iron Supplementation with Sucrosomial® Iron to Maintain Hemoglobin Level During Chemotherapy in Cancer Patients: A Prospective Observational Study

ObjectivesThis study has two primary objectives: (a) to conduct a comparative cost-effectiveness analysis of four commonly used oral iron supplements for treating iron-deficiency anemia during pregnancy in China, including ferrous succinate sustained-release tablets, polysaccharide-iron complex capsules, iron protein succinylate oral solution, and iron dextran oral solution; and (b) to assess the budget impact of including ferrous succinate sustained-release tablets in the National Reimbursement Drug List (NRDL) on national medical insurance expenditures.MethodsA decision tree model was developed to analyze the cost-effectiveness based on treatment efficacy derived from a network meta-analysis. A sensitivity analysis was conducted to address uncertainties in the parameters. Subsequently, a budget impact analysis model was utilized to calculate the effect of including ferrous succinate sustained-release tablets in the NRDL on the expenditures of employee medical insurance funds, resident medical insurance funds, and the total medical insurance fund expenditures.ResultsThe cost-effectiveness analysis showed that ferrous succinate sustained-release tablets are a cost-effective treatment option. When compared to polysaccharide-iron complex capsules, the additional cost per effect of the ferrous succinate sustained-release tablets is $3.23. If these tablets are included in the NRDL, the total medical insurance expenditure on oral iron preparations for treating iron-deficiency anemia in pregnant women is expected to decrease from $160.14 million to $156.82 million between 2025 and 2027.ConclusionFerrous succinate sustained-release tablets are a cost-effective treatment option for iron-deficiency anemia during pregnancy in China.

Inflammation-Driven Differential Response to Intravenous vs. Oral Iron Supplementation in Patients on Hemodialysis: Post Hoc Analysis of the IHOPE Trial

Iron Supplementation with Ferrous Sulfate or Ferrous Bisglycinate for 12 Weeks Does Not Influence Group B Streptococcus Colonization in Cambodian Women: A Secondary Analysis of a Randomized Controlled Trial.

Iron deficiency anemia in children is commonly managed with oral iron supplements, but liquid formulations are often associated with undesirable tooth staining. This in vitro study evaluated enamel discoloration on primary teeth after exposure to ferrous sulfate and iron polymaltose complex. Sixty extracted primary anterior teeth were divided into three groups and immersed daily for 21 days; with color change measured using a spectrophotometer and stereomicroscopy. Ferrous sulfate caused the highest degree of staining (ΔE = 12.6), followed by iron polymaltose (ΔE = 6.3), while controls showed minimal change (ΔE = 1.2). Ferrous sulfate was associated with significantly greater enamel staining, highlighting the need to prefer low-staining formulations to improve pediatric compliance and aesthetics.

Background/Objectives: The objective is to study the trajectories of hematologic and biochemical markers in moderately anemic pregnant women receiving oral iron supplementation throughout pregnancy. Methods: This prospective cohort study was conducted from August 2021 to September 2023 involving 315 pregnant women from rural areas of Belgaum, Karnataka, India, with hemoglobin levels between 7.0 and 9.9 g/dL and serum ferritin < 30 ng/mL and/or TSAT < 20%. Participants received iron-folic acid supplementation (IFAS) as per Anaemia Mukt Bharat guidelines. Blood samples were collected to measure various hematologic and iron markers and compared across each visits. Results: We report a complete adherence rate of 95.3% for iron and 97.8% for folic acid supplementation throughout pregnancy and also observed significant improvements in hemoglobin (9.36 (8.55, 9.74) to 12.03 (11.49, 12.72)) g/dL, hematocrit (29.93 ± 2.87 to 33.71 ± 3.69) %, MCV (72.16 ± 7.90 to 83.47 ± 7.65) fL, MCH (22.44 ± 3.01 to 26.77 ± 3.08) pg levels from the early second to the early third trimester of pregnancy with significant difference (<0.001). Increased erythropoiesis was reported by a higher reticulocyte hemoglobin (23.30 ± 3.03 to 27.84 ± 3.83) pg and immature reticulocyte fractions (6.90 (4.30, 9.50) to 7.30 (4.3, 11.0)) %. Initially, iron, ferritin and TSAT levels increased but later stabilized or slightly declined towards the end of pregnancy. Conclusions: Daily IFAS in moderately anemic pregnant women improved the trajectory of iron parameters, with peak gains in early third trimester. High adherence via counselling supports targeted monitoring and trimester-specific strategies to reduce maternal anemia and may improve outcomes.

The oral iron supplementation leads to gut dysbiosis, further activating intestinal inflammatory response leading to inflammatory bowel syndrome. Iron salt supplementation combined with synbiotics has become an effective strategy to tackle gut health with iron-deficiency anaemia. Progressing toward targeted and sustained release of oral drug delivery, in this work, we have developed thiolated-hyaluronic acid encapsulated synbiotic hydrogel (HASH + BIDF) comprising iron dextran (ID), soluble millet dietary fiber (DF), and probiotic Lactobacillus rhamnosus (LR). The consumption of developed HASH + BIDF was able to recover the hemoglobin (Hb) levels among diet-induced anemic mice (Hb ∼ 9.5) in a treatment period of 2 weeks (Hb ∼ 14.4). In vivo conditions marked recovery of iron marker mRNA levels. DMT-1 from ∼11.13-fold change in anemic to 0.25-fold change after HASH + BIDF treatment, and DcytB expression change from ∼50.96-fold expression under anemic conditions to ∼0.3-fold in the HASH + BIDF supplemented group were observed. Estimating the ferritin protein expression provided significant enhancement in HASH + BIDF indicating replenishment of metabolic iron stores with oral formulation. Lowered expression of TNF-α and IL-6 in intestinal tissues in both Western blotting and immunofluorescence after treatment with HASH + BIDF indicated the anti-inflammatory response of the prepared formulation. The findings suggested a step toward the development of an integrated oral iron supplementation medium with improved bioavailability and reduced gut inflammation.

Oral administration of polysaccharide-iron complexes (UCP-Fe(III)) is limited by their degradation in the gastric environment, which reduces bioavailability. We developed core-shell sodium alginate/chitosan hydrogel microsphere for pH-responsive UCP-Fe(III) delivery. High sodium alginate (SA) concentrations increased viscosity and storage modulus, enhancing mechanical stability. The encapsulation efficiency of UCP-Fe(III) reached 94.41% using 2.0% SA. Noncovalent interactions between UCP-Fe(III) and SA contributed to enhanced hardness and chewiness of the microspheres, while higher SA concentrations promoted a denser cross-linked network. The hydrogel microspheres showed low swelling in simulated gastric fluid (SGF, pH 2.0; swelling ratio: 467.33-588.50%) but rapid swelling in simulated intestinal fluid (SIF, pH 7.4; swelling ratio: 800-962.17%), indicating significant pH responsiveness. They effectively prevented premature release (only 12.14-23.48% in SGF after 2 h) while enabling sustained release (87.60-95.16% in SIF after 6 h). This study provides a new strategy for developing oral iron supplements with pH-responsive sustained-release properties.

Introduction: Anemia is common in hemodialysis patients, and iron supplementation is essential for its management. However, the impact of baseline inflammation on the efficacy of oral versus intravenous iron remains unclear. Methods: This post hoc analysis of the IHOPE trial included 193 maintenance hemodialysis patients stratified by median baseline high-sensitivity C-reactive protein (hsCRP). Patients were randomized to receive intravenous iron sucrose (100 mg once biweekly) or oral polysaccharide-iron complex (150 mg twice daily) for 24 weeks. The primary outcome was hemoglobin level at 24 weeks. Secondary outcomes included hsCRP, oxidative stress markers, and iron parameters. Results: At 24 weeks, patients with high baseline hsCRP had lower hemoglobin levels than those with low hsCRP (113.82 ± 12.04 vs. 118.05 ± 13.50 g/L, p = 0.038), despite similar baseline hemoglobin values. Among patients receiving intravenous iron sucrose, those with high hsCRP had significantly lower hemoglobin (112.90 ± 13.19 vs. 121.32 ± 13.46 g/L; p = 0.005) and higher hsCRP and superoxide dismutase levels, suggesting persistent inflammation and oxidative stress. In contrast, hemoglobin levels were similar between high and low hsCRP subgroups in the oral polysaccharide-iron complex group (p = 0.913). Iron parameters and adverse events were comparable across groups. Conclusion: This post hoc analysis suggests baseline inflammation significantly modifies responses to specific iron formulations in hemodialysis patients. Patients with elevated hsCRP showed poorer hemoglobin responses to intravenous iron sucrose, while oral polysaccharide-iron complex maintained consistent efficacy across inflammatory states. These findings warrant prospective studies on inflammation-guided personalization of iron therapy.

This review article discusses multifactorial pathophysiology, the relationship between clinical characteristics, functional and absolute ID, and the advantages of medicinal intervention in chronic heart failure (CHF). It also covers how iron shortage affects other body parts. The most recent publications that included substantial scientific data on the connection between CHF and ID, with or without anaemia, were selected. Complex physiopathological interactions, including higher hepcidin levels, systemic inflammation, and activation of the renin-angiotensin-aldosterone system, have been identified in these patients. These mechanisms exacerbate the outcomes for patients by amplifying the severity of anemia, chronic heart failure (CHF), and Chronic kidney disease (CKD). Research in this area has been limited and has shown inconsistent findings. Still, it has also examined evidence-based treatment approaches and diagnostic guidelines, especially in relation to iron supplements and erythropoietin-stimulating medications. Anemia is a frequent chronic heart failure consequence and a poor prognostic factor. We still don't completely understand the many complex causes of anemia. Iron deficiency screening is highly recommended for people with cardiac ailments because of its significance for their prognoses. Due to the paucity of research proving its effectiveness, the high incidence of unfavourable gastrointestinal side effects, and the prolonged length of time required for treatment to boost haemoglobin levels, an oral iron supplement is not advised for people with chronic heart failure. An insufficient amount of iron not only impacts the heart but also various other body components.

Ferritin-guided iron supplementation as an alternative or complement to prolonged blood donation intervals (FORTE): a double-blind, randomised, controlled trial.

Anaemia in cancer patients: Advances and challenges in the era of precision oncology.

ABSTRACTObjectives:To explore whether uniform supplementation causes iron overload among a cohort of South Indian non-anemic pregnant women with diabetes-in-pregnancy (DIP).Methods:The study took place between May 2022 and May 2024 and consisted of 120 participants from 2 groups: healthy pregnant women (HP) and pregnant women with DIP. Levels of Hb and the serum indices of iron homeostasis-iron, unsaturated iron-binding capacity, total iron-binding capacity, transferrin saturation, ferritin, hepcidin, soluble transferrin receptor (sTfR), and sTfR index, were estimated. The levels of high-sensitivity C-reactive protein, indices of oxidative stress, malondialdehyde, total antioxidant status (TAS), and oxidative stress index (OSI; ratio of MDA/TAS), and inflammatory markers, interleukin-10 (IL-10) and interleukin-18 (IL-18), were also estimated. The perinatal outcomes between the 2 groups were compared.Results:The serum iron and ferritin levels were lower, and HbA1c levels were higher in the DIP than in HP. The indices of iron homeostasis and Hb were comparable between the 2 groups. While the levels of OSI were higher in the DIP, the pro-inflammatory markers were comparable between the 2 groups. The perinatal outcome of DIP was inferior in comparison to HP.Conclusion:The current uniform daily oral iron supplementation dose in non-anemic South Indian women with DIP did not show evidence of iron overload in our cohort, contrary to expectations.

Estimated unit costs of anaemia interventions for women of reproductive age in 193 UN member states: a costing study

Abstract BackgroundIron‐deficiency anemia (IDA) affects over one‐third of pregnant patients globally, contributing to severe maternal morbidity and adverse neonatal outcomes. Oral iron supplementation, while cost‐effective, is limited by poor absorption, significant gastrointestinal side effects, and poor adherence. The use of intravenous (IV) iron addresses many of these concerns, including eliminating GI side effects and the need for daily therapy. However, administration of IV iron in pregnant patients is typically restricted to specialized infusion centers or hospitals due to concerns about acute side effects, cost, resource utilization, the need for fetal heart rate monitoring, and extended infusion times.MethodsThis descriptive study evaluated the implementation, safety, and feasibility of outpatient IV iron infusions for pregnant patients with IDA, with maternal hemoglobin response and outcomes reported as secondary findings. Patients received a single or series of doses of IV iron spaced weekly, with hemoglobin levels monitored before and after treatment. No fetal heart tracing was performed. Antepartum patients treated with IV iron at our outpatient obstetric clinic from 2017 to 2024 were identified retrospectively, and their charts were reviewed.ResultsA total of 417 pregnant patients received IV iron (87.3% iron sucrose; 12.7% Ferric Carboxymaltose); 65.9% received ≥600 mg total dose (2–3 dose protocol), while 34.1% received lower cumulative doses (1–2 infusions). Therapy was well‐tolerated with no anaphylactic reactions reported. Side effects were experienced in only 11.5% of patients and were relatively minor, with dizziness (6.2%), headache (1.9%), and hypotension (1.7%) being the most common. Adverse maternal outcomes (PPH, ICU admission, blood transfusions, and re‐admissions) were low, particularly in patients who received the last infusion more than 10 days before delivery. Neonatal outcomes included a 7.4% NICU admission rate and a 3.5% rate of infants weighing less than 2500 g. Mean hemoglobin increased by 1.5 g/dL, consistent with prior studies.ConclusionThis study demonstrates that IV iron therapy can be safely given in obstetrical clinics without significant maternal or fetal safety concerns. This obviates the need for more resource‐intensive and costly settings such as infusion or hospital‐based centers.