Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

Cross-sectional and longitudinal associations of Iron biomarkers and cardiovascular risk factors in pre- and postmenopausal women: leveraging repeated measurements to address natural variability.

BACKGROUND: The association between iron biomarkers and cardiovascular disease risk factors (CVD-RFs) remains unclear. We aimed to (1) evaluate the cross-sectional and longitudinal associations between iron biomarkers (serum ferritin, transferrin saturation (TSAT), transferrin) and CVD-RFs among women, and (2) explore if these associations were modified by menopausal status. METHOD: Cross-sectional and longitudinal analyses including 2542 and 1482 women from CoLaus cohort, respectively. Multiple linear regression and multilevel mixed models were used to analyse the associations between Iron biomarkers and CVD-RFs. Variability of outcomes and iron markers between surveys was accessed using intraclass correlation (ICC). RESULTS: After multivariable adjustment, elevated serum ferritin levels were associated with increased insulin and glucose levels, while higher transferrin levels were linked to elevated glucose, insulin and total cholesterol, and systolic and diastolic blood pressure (p < 0.05). No association was observed between CVD-RFs and TSAT (p > 0.05). Iron biomarkers demonstrated low reliability across reproductive stages but exhibited stronger associations in the perimenopausal group. In longitudinal analysis, we found association only for transferrin with lower glucose levels [ß = - 0.59, 95% CI (- 1.10, - 0.08), p = 0.02] and lower diastolic blood pressure [ß = - 7.81, 95% CI (- 15.9, - 0.56), p = 0.04]. CONCLUSION: In cross-sectional analysis, transferrin was associated with several CVD-RFs, and the associations did not change according to menopausal status. Conversely, in the longitudinal analyses, changes in transferrin were associated only with lower glucose and diastolic blood pressure levels. These differences might stem from the substantial longitudinal variation of iron biomarkers, underscoring the need for multiple iron measurements in longitudinal analyses.

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

INTRODUCTION: Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. METHODS: We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. RESULTS: The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). CONCLUSIONS: The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Diagnosing aceruloplasminemia: navigating through red herrings.

A 58-year-old female was found to have hyperferritinemia (Serum ferritin:1683 ng/mL) during work-up for mild normocytic anemia. Transferrin saturation(TSAT) was low-normal. Magnetic resonance imaging (MRI) abdomen showed evidence of hepatic iron deposition. Liver biopsy showed 4 + hepatic iron deposition without any evidence of steatosis or fibrosis. Quantitative liver iron was elevated at 348.3 µmol/g dry liver weight [Reference range(RR): 3-33 µmol/g dry liver weight]. She was presumptively diagnosed with tissue iron overload, cause uncertain. A diagnosis of ferroportin disease (FD) was considered, but the pattern of iron distribution in the liver, mainly within the hepatic parenchyma (rather than in the hepatic Kupffer cells seen in FD), and the presence of anemia (uncommon in FD) made this less likely. She was treated with intermittent phlebotomy for over a decade with poor tolerance due to worsening normocytic to microcytic anemia. A trial of deferasirox was done but it was discontinued after a month due to significant side effects. During the course of treatment, her ferritin level decreased. Over the past 1.5 years, she developed progressively worsening neurocognitive decline. MRI brain showed areas of susceptibility involving basal ganglia, midbrain and cerebellum raising suspicion for metabolic deposition disease. Neuroimaging findings led to testing for serum copper and ceruloplasmin levels which were both found to be severely low. Low serum copper, ceruloplasmin levels and neuroimaging findings led us to consider Wilson disease however prior liver biopsy showing elevated hepatic iron rather than hepatic copper excluded the diagnosis of Wilson disease. After shared decision making, ceruloplasmin gene analysis was not pursued due to patient's preference and prohibitive cost of testing. The diagnosis of aceruloplasminemia was ultimately made. The biochemical triad of hyperferritinemia, low-normal TSAT and microcytic anemia should raise the possibility of aceruloplasminemia. Since neurological manifestations are rare in most inherited iron overload syndromes, neurological symptoms in a patient with tissue iron overload should prompt consideration of aceruloplasminemia as a differential diagnosis.

Imbalance of Iron Availability and Demand in Patients With Acute and Chronic Heart Failure.

BACKGROUND: Iron deficiency (ID) is a frequent comorbidity in patients with acute (AHF) and chronic heart failure (CHF) associated with morbidity and death. We aimed to better characterize iron homeostasis in patients with heart failure applying different biomarkers and to evaluate the accuracy of current ID definition by the European Society of Cardiology/American College of Cardiology/American Heart Association to indicate tissue iron availability and demand. METHODS AND RESULTS: We performed a retrospective cohort study investigating 277 patients with AHF and 476 patients with CHF between February 2021 and May 2022. Patients with AHF had more advanced ID than patients with CHF, reflected by increased soluble transferrin receptor and soluble transferrin receptor-ferritin index, and lower ferritin, serum iron, transferrin saturation, hepcidin, and reticulocyte hemoglobin. Decreased iron availability or increased tissue iron demand, reflected by increased soluble transferrin receptor-ferritin index and decreased reticulocyte hemoglobin, was found in 84.1% (AHF) and 28.0% (CHF) with absolute ID and in 50.0% (AHF) and 10.5% (CHF) with combined ID according to the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition. Low hepcidin expression as an indicator of systemic ID was found in 91.1% (AHF) and 80.4% (CHF) of patients with absolute ID and in 32.3% (AHF) and 18.8% (CHF) of patients with combined ID. ID definitions with higher specificity reduce the need for iron supplementation by 25.5% in patients with AHF and by 65.6% in patients with CHF. CONCLUSIONS: Our results suggest that the current European Society of Cardiology/American College of Cardiology/American Heart Association-based ID definition might overestimate true ID, particularly in CHF. More stringent thresholds for ID could more accurately identify patients with heart failure with reduced tissue iron availability who benefit from intravenous iron supplementation.

Iron status and sarcopenia-related traits: a bi-directional Mendelian randomization study.

Although serum iron status and sarcopenia are closely linked, the presence of comprehensive evidence to establish a causal relationship between them remains insufficient. The objective of this study is to employ Mendelian randomization techniques to clarify the association between serum iron status and sarcopenia. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the potential causal relationship between iron status and sarcopenia. MR analyses were performed using inverse variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were conducted to verify the reliability of the causal association results. Then, we harvested a combination of SNPs as an integrated proxy for iron status to perform a MVMR analysis based on IVW MVMR model. UVMR analyses based on IVW method identified causal effect of ferritin on appendicular lean mass (ALM, ß = - 0.051, 95% CI - 0.072, - 0.031, p = 7.325 × 10-07). Sensitivity analyses did not detect pleiotropic effects or result fluctuation by outlying SNPs in the effect estimates of four iron status on sarcopenia-related traits. After adjusting for PA, the analysis still revealed that each standard deviation higher genetically predicted ferritin was associated with lower ALM (ß = - 0.054, 95% CI - 0.092, - 0.015, p = 0.006). Further, MVMR analyses determined a predominant role of ferritin (ß = - 0.068, 95% CI - 0.12, - 0.017, p = 9.658 × 10-03) in the associations of iron status with ALM. Our study revealed a causal association between serum iron status and sarcopenia, with ferritin playing a key role in this relationship. These findings contribute to our understanding of the complex interplay between iron metabolism and muscle health.

Determination of calcium, iron, and selenium in human serum by isotope dilution analysis using nitrogen microwave inductively coupled atmospheric pressure plasma mass spectrometry (MICAP-MS).

In this study, we demonstrate the applicability of nitrogen microwave inductively coupled atmospheric pressure mass spectrometry (MICAP-MS) for Ca, Fe, and Se quantification in human serum using isotope dilution (ID) analysis. The matrix tolerance of MICAP-MS in Na matrix was investigated, revealing that high Na levels can suppress the signal intensity. This suppression is likely due to the plasma loading and the space charge effect. Moreover, 40Ca and 44Ca isotopic fractionation was noted at elevated Na concentration. Nine certified serum samples were analyzed using both external calibration and ID analysis. Overestimation of Cr, Zn, As, and Se was found in the results of external calibration, which might result from C-induced polyatomic interference and signal enhancement, respectively. Further investigations performed with methanol showed a similar enhancement effect for Zn, As, and Se, potentially supporting this assumption. The mass concentrations determined with ID analysis show metrological compatibility with the reference values, indicating that MICAP-MS combined with ID analysis can be a promising method for precise Ca, Fe, and Se determination. Moreover, this combination reduces the influence of matrix effects, broadening the applicability of MICAP-MS for samples with complex matrixes.

Serum and tissue metallome of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) patients have late presentation at the time of diagnosis and a poor prognosis. Metal dyshomeostasis is known to play a role in cancer progression. However, the blood and tissue metallome of PDAC patients has not been assessed. This study aimed to determine the levels of essential and toxic metals in the serum and pancreatic tissue from PDAC patients. Serum samples were obtained from PDAC patients before surgical resection. Tissue (tumor and adjacent normal pancreas) were obtained from the surgically resected specimen. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis was performed to quantify the levels of 10 essential and 3 toxic metals in these samples. Statistical analysis was performed to identify dysregulated metals in PDAC and their role as potential diagnostic and prognostic biomarkers. Significantly decreased serum levels of magnesium, potassium, calcium, iron, zinc, selenium, arsenic, and mercury and increased levels of molybdenum were shown to be associated with PDAC. There were significantly decreased levels of zinc, manganese and molybdenum, and increased levels of calcium and selenium in the pancreatic tumor tissue compared with the adjacent normal pancreas. Notably, lower serum levels of calcium, iron, and selenium, and higher levels of manganese, were significantly associated with a poor prognosis (i.e., overall survival) in PDAC patients. In conclusion, this is the first study to comprehensively assess the serum and tissue metallome of PDAC patients. It identified the association of metals with PDAC diagnosis and prognosis.

Value of serum iron and urine neutrophil gelatinase-associated lipocalin in predicting the mortality of critically ill patients with sepsis.

INTRODUCTION: We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis. METHODS: Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters. RESULTS: Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 µmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85. DISCUSSION: These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Demographic Characteristics and Low Iron Status Markers Are Associated with Hemoglobin Levels and Anemia among Children Living at High Elevation in Cusco, Peru.

Anemia is a complex condition associated with diet, chronic infections, and blood loss. Children living at high altitudes have higher absolute hemoglobin levels due to hypoxemia. However, they are exposed to repeated infections and dietary limitations. We conducted a cross-sectional study to identify factors affecting the hemoglobin concentration in children living in high-altitude rural communities in the Anta province of Peru. All children 3-16 years of age attending public schools were invited to participate. We enrolled children 3-16 years old in schools and visited their homes to collect demographic, socioeconomic, medical history, and anthropometric data. Children provided blood and stool samples for complete blood counts, iron status markers, and helminth infection testing. Among the 2,000 children enrolled, the mean age was 9.9 (±3.4) years, 1,004 (50.2%) were female, and the median residence altitude was 3,398 (interquartile range 3,35-3,497) meters. The mean hemoglobin level was 15 (±1.15) mg/dL; 320 (16%) had anemia as defined by WHO. Children with anemia were more likely to have lower serum iron levels (odds ratio [OR] 2.8 [95% CI 2.2-3.6], P <0.001) and serum transferrin saturation (OR 2.8 [95% CI 2-3.9], P <0.001). Younger age (OR 0.85 [95% CI 0.82-0.89], P <0.001), stunting (OR 0.68 [95% CI 0.59-0.79], P <0.001), education of the mother (OR 0.94 [95% CI 0.91-0.98], P <0.005), and low eosinophils (OR 0.49 [95% CI 0.26-0.9], P = 0.022) were associated with anemia. Helminth infections were not associated with anemia. Anemia among children at high altitude is multifactorial, but iron deficiency is a contributing factor. Further studies are needed to evaluate iron status and anemia in children living at high altitudes.

Serum iron concentration and leptin inversely relate, partially mediated by body mass index in American adults.

Iron metabolism and leptin are interconnected, and both link with obesity. In this cross-sectional study, we hypothesized that serum iron markers associate with leptin, with body mass index (BMI) acting as a mediator, confounder, and effect modifier in this relationship. We analyzed data from the National Health and Nutrition Examination Survey III, with a focus on serum iron markers and leptin. The relationship between serum iron markers and leptin was determined by multiple linear regression. The bootstrap method was used to investigate the mediating effect of BMI on this association. Among 3888 American adults, serum iron and transferrin saturation showed a negative association with leptin (log2-transformed) (ß: -0.010, 95% confidence interval [CI], -0.013 to -0.006, P < .001; ß: -0.006, 95% CI, -0.008 to -0.004, P < .001). Total iron-binding capacity was positively associated with the serum concentration of leptin (log2-transformed) (ß: 0.002, 95% CI, 0-0.004, P = .0292). Sex, BMI, and body fat percentage significantly influenced these associations. Notably, the association between the iron markers and leptin diminished in individuals with a BMI ≥30 kg/m2. There was no observable relationship between leptin and serum ferritin concentrations. BMI mediated 4.81% of the serum iron-leptin association, with no mediation of body fat percentage. Our study identified a link between serum iron and leptin, with BMI as a mediating factor. In clinical settings, it is vital to understand how treatments targeting iron metabolism can directly impact serum leptin concentration and the subsequent physiological changes.

Increased erythroferrone levels in malarial anaemia.

We assessed the diagnostic potential of erythroferrone as a biomarker for iron homeostasis comparing iron deficiency cases with anaemia of inflammation and controls. The dysregulation of the hepcidin axis was observed by Latour et al. in a mouse model of malarial anaemia induced by prolonged Plasmodium infection leading to increased erythroferrone concentrations. In line with that, we found significantly higher erythroferrone levels in cases with malaria and anaemia in an African population, compared to asymptomatic controls. Therefore, our findings extend the previous ones of the mouse model, suggesting also a dysregulation of the hepcidin axis in humans, which should be further corroborated in prospective studies and may lay the basis for the development of improved treatment strategies according to ERFE concentrations in such patients.

The association between growth differentiation factor-15, erythroferrone, and iron status in thalassemic patients.

BACKGROUND: Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin. METHODS: This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin. RESULTS: The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin. CONCLUSIONS: High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity. IMPACT: Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients.

Iron status and obesity-related traits: A two-sample bidirectional Mendelian randomization study.

Background: The association between iron status and obesity-related traits is well established by observational studies, but the causality is uncertain. In this study, we performed a two-sample bidirectional Mendelian randomization analysis to investigate the causal link between iron status and obesity-related traits. Methods: The genetic instruments strongly associated with body mass index (BMI), waist-hip ratio (WHR), serum ferritin, serum iron, transferrin saturation (TSAT), and total iron-binding capacity (TIBC) were obtained through a series of screening processes from summary data of genome-wide association studies (GWAS) of European individuals. We used numerous MR analytical methods, such as inverse-variance weighting (IVW), MR-Egger, weighted median, and maximum likelihood to make the conclusions more robust and credible, and alternate methods, including the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis to evaluate the horizontal pleiotropy and heterogeneities. In addition, the MR-PRESSO and RadialMR methods were utilized to identify and remove outliers, eventually achieving reduced heterogeneity and horizontal pleiotropy. Results: The results of IVW analysis indicated that genetically predicted BMI was associated with increased levels of serum ferritin (ß: 0.077, 95% CI: 0.038, 0.116, P=1.18E-04) and decreased levels of serum iron (ß: -0.066, 95% CI: -0.106, -0.026, P=0.001) and TSAT (ß: -0.080, 95% CI: -0.124, -0.037, P=3.08E-04), but not associated with the levels of TIBC. However, the genetically predicted WHR was not associated with iron status. Genetically predicted iron status were not associated with BMI and WHR. Conclusions: In European individuals, BMI may be the causative factor of serum ferritin, serum iron, and TSAT, but the iron status does not cause changes in BMI or WHR.

The clinical relevance of detectable plasma iron species in iron overload states and subsequent to intravenous iron-carbohydrate administration.

Many disorders of iron homeostasis (e.g., iron overload) are associated with the dynamic kinetic profiles of multiple non-transferrin bound iron (NTBI) species, chronic exposure to which is associated with deleterious end-organ effects. Here we discuss the chemical nature of NTBI species, challenges with measuring NTBI in plasma, and the clinical relevance of NTBI exposure based on source (iron overload disorder vs. intravenous iron-carbohydrate complex administration). NTBI is not a single entity but consists of multiple, often poorly characterized species, some of which are kinetically non-exchangeable while others are relatively exchangeable. Prolonged presence of plasma NTBI is associated with excessive tissue iron accumulation in susceptible tissues, with consequences, such as endocrinopathy and heart failure. In contrast, intravenous iron-carbohydrate nanomedicines administration leads only to transient NTBI appearance and lacks evidence for association with adverse clinical outcomes. Assays to measure plasma NTBI are typically technically complex and remain chiefly a research tool. There have been two general approaches to estimating NTBI: capture assays and redox-activity assays. Early assays could not avoid capturing some iron from transferrin, thus overestimating NTBI. By contrast, some later assays may have promoted the donation of NTBI species to transferrin during the assay procedure, potentially underestimating NTBI levels. The levels of transferrin saturation at which NTBI species have been detectable have varied between different methodologies and between patient populations studied.

Serum iron availability, but not iron stores, is lower in naturally menstruating than in oral contraceptive athletes.

This study measured serum markers of iron status in naturally menstruating and oral contraceptive (OC) athletes during the main hormonal milieus of these two profiles to identify potential differences confounding the diagnosis of iron deficiency in female athletes. Resting blood samples were collected from 36 naturally menstruating athletes during the early-follicular phase (EFP), mid- late-follicular phase (MLFP) and mid-luteal phase (MLP) of the menstrual cycle. Simultaneously, blood samples were collected from 24 OC athletes during the withdrawal and active-pill phase of the OC cycle. Serum iron, ferritin, transferrin, transferrin saturation (TSAT), C-reactive protein (CRP), interleukin-6 and sex hormones were analyzed. Naturally menstruating athletes showed lower levels of TSAT, iron and transferrin than OC athletes when comparing the bleeding phase of both profiles (p<0.05) as well as when comparing all analyzed phases of the menstrual cycle to the active pill phase of the OC cycle (p<0.05). Interestingly, only lower transferrin was found during MLFP and MLP compared to the withdrawal phase of the OC cycle (p>0.05), with all other iron markers showing no differences (p>0.05). Intracycle variations were also found within both types of cycle, presenting reduced TSAT and iron during menstrual bleeding phases (p<0.05). In conclusion, in OC athletes, serum iron availability, but not serum ferritin, seems higher than in naturally menstruating ones. However, such differences are lost when comparing the MLFP and MLP of the menstrual cycle with the withdrawal phase of the OC cycle. This should be considered in the assessment of iron status in female athletes.Highlights Naturally menstruating athletes present lower TSAT, iron and transferrin in all analyzed phases of the menstrual cycle compared to OC athletes during their active pill phase. However, both the mid-late follicular and mid-luteal phases of the menstrual cycle do not differ from the withdrawal phase of the oral contraceptive cycle.Intracycle variations are found for TSAT and iron in both naturally menstruating and oral contraceptive athletes, which are mainly driven by a reduction in TSAT and iron during menstrual bleeding phases.As serum iron availability changes significantly as a function of the athlete's hormonal status, it should be considered in the assessment of the athlete's iron status as well as standardise the phase of the menstrual cycle in which to assess iron markers to avoid misdiagnosis or misleading results.In contrast, the assessment of iron stores through serum ferritin is substantially stable and the athlete's hormonal status does not seem to be of relevance for this purpose.

EFFECT OF IRON ON BONE TISSUE METABOLISM AND THYROID FUNCTION IN CHILDREN LIVING ON RADIOLOGICALLY CONTAMINATED TERRITORIES SINCE THE ChNPP ACCIDENT. / VPLYV ZALIZA NA PROTsESY METABOLIZMU V KISTKOVII TKANYNI TA FUNKTsIIu ShchYTOPODIBNOÏ ZALOZY UDITEI, IaKI ZhYVUT' NA RADIOAKTYVNO ZABRUDNENYKh TERYTORIIaKh PISLIa AVARIÏ NA ChAES.

OBJECTIVE: To assess the metabolic processes in bone tissue and state of thyroid gland depending on iron metabolism parameters in children of pre-pubertal, pubertal and post-pubertal age, living on radiologically contaminated territories after the ChNPP accident. MATERIALS AND METHODS: Children (n = 119) aged 6 to 18 years were examined and the 4 study groups were formed, featuring the childhood, pre-pubertal, pubertal and post-pubertal life periods. Clinical symptoms, iron metabolism parameters (serum iron (SI) and ferritin (SF) content, transferrin saturation coefficient), parameters of bone tissue metabolism (serum creatinine and alkaline phosphatase (APh)), and amino acid content in urine were taken into account. Functional state of thyroid, titers of antibodies to thyroperoxidase (TPOAb) and thyroglobulin (TgAb) were assayed. Results and their discussion are presented depending on the age of children, biochemical parameters of blood, iron metabolism findings, thyroid gland function and individualized radiation doses. RESULTS: In 13.4 % of pubertal and post-pubertal children an elevated content of SI and SF was observed. APh levels were increased in 20.2 % of children (758.9 ± 16.3 U/l) being directly correlated with SI levels (rs = 0.50; р < 0.01). In 16.3 % of children of pubertal and post-pubertal age, in whom the level of SI was above 27 µmol/l, a direct correlation with serum thyroid-stimulating hormone (TSH) level was established in case of the hormone content above 2.5 mU/l (rs = 0.50; р < 0.05). Serum creatinine level directly correlated with glycine content in urine (rs = 0.70), which is a part of collagen, and inversely correlated with serum APh (rs = -0.47), (р < 0.05). Under the levels of SI higher than (15.1 ± 1.2) µmol/l and SF higher than (87.5 ± 6.4) ng/ml, the TPOAb titer was higher than at lower iron concentrations (U-test = 64.5, р < 0.05). The TgAb titer directly correlated with SI (rs = 0.39) and TSH (rs = 0.81) levels (р < 0.01). The average effective radiation dose in children was (0.75 ± 0.10) mSv. A direct correlation was established between the child's radiation dose and age (rs = 0.33; р < 0.05). CONCLUSIONS: Bone metabolism depends on the age of children, characteristics of pubertal period, excess of iron in the body, and functional state of thyroid system, which is involved in collagen formation and protein metabolism.

Iron status of blood donors.

PURPOSE OF REVIEW: This review examines recent research on the prevalence and importance of iron deficiency in blood donors, and on efforts to mitigate it. RECENT FINDINGS: Premenopausal females, teenagers, and high-frequency donors are at the highest risk for donation-induced iron deficiency, in both high-resource and low-resource settings. The physiology relating iron stores to hemoglobin levels and low hemoglobin deferral is well elucidated in blood donor populations, yet the clinical effects attributable to iron loss in the absence of anemia are challenging to identify. Expanded adoption of ferritin testing is improving donor management but may cause decreases in the blood supply from temporary donor loss. The potential for personalized donor management is emerging with development of computational models that predict individual interdonation intervals that aim to optimize blood collected from each donor while minimizing low hemoglobin deferrals. SUMMARY: Measures to reduce iron deficiency are available that can be deployed on a standardized or, increasingly, personalized basis. Blood centers, regulators, and donors should continue to evaluate different tactics for addressing this problem, to obtain a balanced approach that is optimal for maintaining adequate collections while safeguarding donor health.

Relationship between Oxidative Stress and the Blood Iron Concentration and Antioxidant Status in Major ß-thalassemia in Iraq.

Reduction or total lack of beta-globin chains caused by a congenital disease called ß-thalassemia major is one of the lives threatening diseases. Patients who suffer from ß-thalassemia need a repeated blood transfusion for survival. The repeated blood transfusion in ß-thalassemia patients may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The current study aimed to investigate the correlation of oxidative stress with serum trace element levels and antioxidant enzyme status in ß-thalassemia major patients. A total of 130 serum samples were obtained from ß-thalassemia major patients (n=100; 50 males and 50 females) and healthy individuals (n=30; 15 males and 15 females). Hematological parameters were measured on both groups by a comprehensive blood test that included the amount of hemoglobin Hb, packed cells volume, number of red blood cells, mean corpuscular volume ratio, mean corpuscular hemoglobin ratio, mean corpuscular hemoglobin concentration, red cell distribution width, white blood cells, and platelets counts. All of these blood parameters showed a clear decrease in thalassemia patients, except for red blood cells and platelets counts, which demonstrated a significant increase. The highest significant mean for iron in males and females were 233.768 and 219.150 µgm\dL in patients, respectively, while the mean level of iron significantly reduced in the control group (113.40 and 103.33 µgm\dL in males and females, respectively). The results indicated a significant decrease in uric acid in males and females in the patient group (41.042 and 40.582 mg\L in males and females, respectively), compared to the control group (53.866 and 43.60 mg\L in males and females, respectively). Allantoin concentration was detected by high-performance liquid chromatography technique, the results of which showed that the highest values in patients were 62.822 and 25.480 mg\L in males and females, respectively, compared to the control group 2.342 and 1.481 mg\L in males and females, respectively. Superoxide dismutase concentration decreased in patients (129.635 and 111.848 U\mL in males and females, respectively), compared to the control group (208.623 and 190.413 U\ml in males and females, respectively).