Serum Ferritin Concentration Research Articles

Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}

BackgroundThe World Health Organization recommends universal iron supplementation for children aged 6–23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation.MethodsThis will be a two-arm, randomised controlled trial. Gambian children aged 6–12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor).DiscussionThis study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6–12 months.Trial registrationPan African Clinical Trial Registry PACTR202210523178727

Iron overload syndrome. Ethiopatogenesis. magnetic resonance imaging techniques for quantitative assessment of iron overload status: a review

INTRODUCTION: The development of iron overload syndrome may be due to both hereditary and acquired factors. The danger of this condition is manifested in the irreversible loss of parenchymatous pool as a result of cirrhotic transformation and marked fibrosis, caused by the consequent accumulation of iron complexes, of such important internal organs as the liver and heart. The amount of iron in the body is assessed by detecting serum ferritin concentration or by measuring liver and heart iron concentration by biopsy (LIC — liver iron concentration; HIC — heart iron concentration). Insufficient diagnostic significance of the serum ferritin concentration criterion, as well as the invasiveness and traumatization of biopsies, are limitations to the widespread use of these methods.OBJECTIVE: The purpose of this review is to present the main etio-pathogenetic factors of iron overload, the impact of this metabolic disorder on the body, and to reflect the basic principles of diagnosis and the leading role of quantitative MRI in the assessment of iron overload of vital internal organs.MATERIALS AND METHODS: Performed literature search in Russian and English languages for the period from 2001 to 2022 years in Medline/PubMed, RINC/Elibrary, CyberLeninka, Google Scholar databases by keywords: iron overload syndrome, liver, liver cirrhosis, ferritin, hemosiderin, MR diagnostics iron overload, MR relaxometry, R2*/T2*, thesaurismoses, magnetic resonance tomography, SIR (signal intensity ratio), LIC (liver iron concentration), biopsy, chronic diffuse liver diseases, DIOS.RESULTS: The final analysis included 27 publications devoted to various etio-pathogenetic aspects of iron overload syndrome. The forms of iron complexes residence in liver parenchymatous tissue are presented. Characteristics of MR-signal behavior depending on the severity of inhomogeneity of the magnetic field created by iron complexes are characterized. The areas of application of magnetic resonance imaging scanning modes for detection and quantitative diagnostics of iron overload are reflected.CONCLUSION: The ferritin-iron complex, also called ferrihydride, has high paramagnetic properties that provide high contrast MR images in the state of tissue iron overload. The leading methods for quantitative assessment of iron overload are the signal intensity ratio (SIR) method and T2*/R2*-relaxometry. Advantages and disadvantages of these methods, consisting in the limits of determining the degree of overload, make it possible to cover a wide range of overload values by complementing each other. Also the influence of parenchyma architectonics disturbances and concomitant accumulation diseases contribute to the formation of diagnostic inaccuracies. Therefore, the development of complex qualitative-quantitative MR diagnostics in order to isolate highly selective biomarkers will play an important role in MR diagnostics of iron overload syndrome.

The heavy subunit of ferritin stimulates NLRP3 inflammasomes in hepatic stellate cells through ICAM-1 to drive hepatic inflammation.

Serum ferritin concentrations increase during hepatic inflammation and correlate with the severity of chronic liver disease. Here, we report a molecular mechanism whereby the heavy subunit of ferritin (FTH) contributes to hepatic inflammation. We found that FTH induced activation of the NLRP3 inflammasome and secretion of the proinflammatory cytokine interleukin-1β (IL-1β) in primary rat hepatic stellate cells (HSCs) through intercellular adhesion molecule-1 (ICAM-1). FTH-ICAM-1 stimulated the expression of Il1b, NLRP3 inflammasome activation, and the processing and secretion of IL-1β in a manner that depended on plasma membrane remodeling, clathrin-mediated endocytosis, and lysosomal destabilization. FTH-ICAM-1 signaling at early endosomes stimulated Il1b expression, implying that this endosomal signaling primed inflammasome activation in HSCs. In contrast, lysosomal destabilization was required for FTH-induced IL-1β secretion, suggesting that lysosomal damage activated inflammasomes. FTH induced IL-1β production in liver slices from wild-type mice but not in those from Icam1-/- or Nlrp3-/- mice. Thus, FTH signals through its receptor ICAM-1 on HSCs to activate the NLRP3 inflammasome. We speculate that this pathway contributes to hepatic inflammation, a key process that stimulates hepatic fibrogenesis associated with chronic liver disease.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 μg/L, or ferritin concentration between 100 and 300 μg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Correlation of serum ferritin and thyroid hormone levels: A matched case–control study

Introduction: Hypothyroidism is a common disorder of the endocrine system caused by insufficient biologically active hormones at the tissue level or the inability of the tissue to utilize thyroid hormones. Iron plays a crucial role in the synthesis and metabolism of thyroid hormones, and it is stored in the body as ferritin. We aimed to evaluate the correlation between serum ferritin (SF) levels and thyroid hormone panel levels in both hypothyroid and euthyroid subjects. Methods: In 2022, a matched case–control study was conducted. The study involved participants with hypothyroidism and a control group (n = 53). The levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and SF were measured using the chemiluminescence immunoassay on a Mindray Cl 900-i analyzer (Shenzhen Mindray Bio-Medical Electronics Co., China). Results: The hypothyroid group had TSH levels that were significantly higher (10.76 [8.54-18.76] vs. 1.76 [1.26-2.58]; p &lt; 0.001) and SF concentrations that were significantly lower (39.08 [21.15-45.70] vs. 54.09 [41.41-71.82]; p &lt; 0.001) compared to the control group. In both male and female subjects of the hypothyroid group, a strong negative correlation was found between SF concentration and TSH levels ([Rho = −0.855,p &lt; 0.01]; [Rho = −0.747; p &lt; 0.01]). In female subjects of the hypothyroid group, a weak positive correlation was found between SF concentration and fT3 (Rho = 0.488; p &lt; 0.05). In the euthyroid group, a correlation of the same strength and direction was found for fT4 (Rho = 0.366; p &lt; 0.05). Conclusion: Research results indicate a correlation between lower SF concentrations and hypothyroidism, which is of particular importance for understanding the etiopathogenesis, diagnosis, monitoring, and treatment modalities of patients with hypothyroidism.

An 8-Week Vitamin D3–Fortified Fruit Drink Supplementation Increases Serum Ferritin Concentration: A Randomized Controlled Trial in Malaysian Women With Low Iron Stores

BackgroundThere is limited randomized controlled trial evidence to support the association between vitamin D deficiency and anemia risk, highlighting the necessity for further investigations into the role of vitamin D in influencing iron status. ObjectiveThe aim of this study was to determine the effect of vitamin D3–fortified fruit drink consumption (4,000 IU) on vitamin D and iron status biomarkers among iron-deficient women (serum ferritin of <20 μg/L [to convert μg/L ferritin to ng/mL, multiply by 1]). DesignAn 8-week double-blind randomized controlled trial was conducted. Subjects/settingA total of 45 healthy, nonpregnant, nonlactating subjects aged 18 through 40 years (mean [SD] 25.3 [4.6] years) were included in the study, excluding those who donated blood 6 months prior, regularly consumed nutritional supplements, or had gastrointestinal or iron metabolic disorders. InterventionSubjects were randomly assigned to receive either vitamin D3–fortified fruit drink or a placebo. Main outcome measuresMeasurements of 25-hydroxyvitamin D (25[OH]D), serum ferritin, high-sensitivity C-reactive protein, and full blood count concentrations were obtained at baseline, interim, and post intervention. Statistical analysesA mixed model, repeated measures analysis of variance was used to analyze the intervention effect. ResultsAttrition rate for the study was 13%, with 6 dropouts, and 39 subjects completed the study. Daily consumption of vitamin D3–fortified fruit drink in the intervention group resulted in significant increases in 25(OH)D and serum ferritin concentrations compared with the placebo group. The intervention group showed significantly higher mean (SD) changes (Δ) in both 25(OH)D (Δ 76.4 [30.2] nmol/L [to convert nmol/L 25(OH)D to ng/mL, multiply by .4] vs Δ –1.3 [10.7] nmol/L; P = .001) and serum ferritin concentrations (Δ 2.2 [4.2] μg/L vs Δ –0.3 [3.4] μg/L; P = .048) between baseline and post intervention. The other iron status biomarkers were not affected by the intervention. ConclusionsOur study found that daily vitamin D3–fortified fruit drink supplementation for 8 weeks effectively improved 25(OH)D and iron stores, indicated by increased serum ferritin concentrations, in iron-deficient women. Further research is needed to evaluate its safety, efficacy, feasibility, and optimal food fortification in diverse populations.

The iron status of rural Nigerian women in the second and third trimesters of pregnancy: implications for the iron endowment and subsequent dietary iron needs of their babies.

The aim of the study was to determine the iron status of rural-dwelling pregnant Nigerian women in the second and third trimesters, and to predict their risk of giving birth to babies with suboptimal iron endowment. This was a prospective cohort study conducted between April and August 2021. A total of 174 consecutive and consenting pregnant rural dwellers, who met the inclusion criteria, were recruited by convenience sampling from the antenatal clinic of a public hospital in Nsukka, a semirural town in south-east Nigeria. The study participants were aged 21-40 years, and their iron status was determined by measuring blood haemoglobin (Hb) and serum ferritin (SF) concentration. Hb concentration was determined by the cyanmethemoglobin method and the SF concentration was determined by enzyme immunoassay method. Almost half (47.7%) of the participants had Hb concentrations below 11 g/dL, while about two out of every five (40.8%) had SF concentrations less than 15 &micro;g/L. The prevalence of iron deficiency, iron deficiency anaemia (IDA) and non-iron deficiency anaemia were 40.8%, 23.6% and 24.7%, respectively. The mean SF levels varied with maternal age, gestation stage, pregnancy intervals and the intake of iron supplements. The mean SF concentration was higher in the second trimester than in the third. The mean SF concentration &plusmn; standard deviation (37.10&plusmn;3.02 &micro;g/L) was higher in the group that took iron supplements than in the group that did not (20.76&plusmn;2.11 &micro;g/L). However, two out of five participants in both groups had SF concentrations less than 15.0 &micro;g/L. The prevalence of IDA was quite high among the participants in both trimesters even with the widespread intake of the recommended oral iron supplements. About four out of 10 of the participants had SF concentrations of less than 15 &micro;g/L and were thus judged at risk of giving birth to babies with poor iron deposits. Therefore, more effective strategies are needed to monitor and prevent IDA among pregnant women in rural populations of Nigeria and, by inference, other parts of tropical Africa.

Correlation between iron metabolism indicators and programmed death ligand 1 expression in advanced non-small cell lung cancer.

The dysregulation of iron metabolism is closely linked to the onset and progression of lung cancer. This study aimed to explore the association between iron metabolism indicators (serum iron, transferrin, ferritin) and the expression level of programmed death factor ligand 1 in primary lesions of advanced non-small cell lung cancer. A cohort of 62 patients, including 42 men and 20 women, was recruited from October 2022 to July 2023, all diagnosed with advanced non-small cell lung cancer, confirmed through radiographic imaging and histopathological analysis. Comprehensive clinical data (such as gender, age, familial lung cancer history, smoking history, pathological classification, clinical stage, etc.) and concentrations of fasting serum iron, transferrin, and ferritin were collected. Patients were categorized into PD-L1 negative (<1% expression) and programmed death ligand 1 (PD-L1) positive (≥1% expression) groups based on PD-L1 expression levels in tumor tissues. Subsequently, the correlation between levels of serum iron, transferrin, ferritin, and PD-L1 expression in advanced non-small cell lung cancer were examined. Patients in the PD-L1 positive group exhibited lower levels of peripheral serum iron and transferrin compared to those in the PD-L1 negative group (P<0.05). For patients exhibiting positive PD-L1 expression, a negative correlation was observed between PD-L1 expression and both serum iron and transferrin levels (r = -0.465, P=0.003; r = -0.447, P=0.005), and a positive correlation was noted between PD-L1 expression and ferritin levels (r=0.393, P=0.015). We conclude that in In patients with advanced non-small cell lung cancer, serum iron and transferrin levels can serve as partial predictors of PD-L1 expression; among those positive for PD-L1, a significant association exists between indicators of iron metabolism and PD-L1 expression.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case–control study

PurposeDepression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status.MethodsThis is a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13–17 years. We assessed depression severity using the Children’s Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire.ResultsSF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) μg/L) and controls (32.5 (22.6, 48.3) μg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls.ConclusionCases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

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) (β: –0.010, 95% confidence interval [CI], –0.013 to –0.006, P < .001; β: –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) (β: 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.

Anemia and Iron Deficiency Predict All-Cause Mortality in Patients with Heart Failure and Preserved Ejection Fraction: 6-Year Follow-Up Study.

The aim of this study was to assess the prevalence of anemia and iron deficiency in patients with heart failure with preserved ejection fraction (HFpEF) and its impact on clinical outcomes. We retrospectively analyzed 212 patients with HFpEF and identified anemia as a serum hemoglobin level of less than 13 g/dL in men and less than 12 g/dL in women. Additionally, ID was defined as a serum ferritin concentration < 100 ng/mL or 100-299 ng/mL with transferrin saturation < 20%. Patients were followed up for an average of 66.2 ± 12.1 months, with the endpoint being all-cause mortality among patients with HFpEF, both with and without anemia and iron deficiency. Furthermore, we explored other predictors of all-cause mortality. The average age of the entire group was 70.6 ± 10.5 years, with females comprising 55% of the patients. Anemia was present in 81 (38.2%) patients, while 108 (50.9%) had iron deficiency. At the end of the follow-up period, 60 (28.3%) of the patients had passed away. Patients with anemia displayed more heart failure (HF) symptoms, diastolic dysfunction, higher NT-pro-BNP levels, and worse baseline functional capacity than those without. Similarly, patients with iron deficiency showed more pronounced HF symptoms and worse functional capacity than those without. The results from the multivariable analyses revealed that anemia (hazard ratio [HR]: 5.401, 95% confidence interval [CI]: 4.303-6.209, log-rank p = 0.001), advanced age, iron deficiency (HR: 3.502, 95% CI: 2.204-6.701, log-rank p = 0.015), decreased left ventricular ejection fraction, chronic kidney disease, and paroxysmal nocturnal dyspnea were all independently associated with all-cause mortality. It is essential to consider anemia and iron deficiency as common comorbidities in managing and prognosis HFpEF, as they significantly increase mortality risk.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Prevalence of Iron Deficiency Anaemia and the Diagnostic Utility of Soluble Transferrin Receptor and sTfR/Log Ferritin Index among Pregnant Women: A Cross-sectional Study

Introduction: Anaemia is a significant global health concern, particularly among pregnant women. This condition, primarily caused by Iron Deficiency (ID), poses risks to both maternal and foetal health. However, interpreting iron status through biochemical tests faces challenges. While serum ferritin concentration is a specific indicator of ID, its accuracy can be compromised by factors like inflammation. Serum Soluble Transferrin Receptor (sTfR) has shown promise in accurately diagnosing anaemia, especially in pregnant women, as it remains unaffected by pregnancy-related changes. Nonetheless, studies on its efficiency have yielded mixed results. Aim: To study the prevalence of Iron Deficiency Anaemia (IDA) among pregnant women and also to evaluate the accuracy of sTfR levels and the sTfR/Log Ferritin Index as diagnostic markers in predicting IDA among pregnant women. Materials and Methods: This cross-sectional study was conducted at NEIGRIHMS, Shillong, Meghalaya, India, between April 2021 and November 2022. A total of 92 pregnant women in their first trimester were included in the study. An automated clinical chemistry analyser measured serum iron and highsensitivity C-Reactive Protein (hsCRP). Serum ferritin and sTfR levels were assessed via chemiluminescence assay. Sensitivity and specificity of sTfR levels and the sTfR/Log Ferritin Index in predicting IDA were determined utilising the Receiver Operating Characteristic (ROC) curve. Results: Most participants, 38 individuals (41.3%), were aged 20 to 25 years. The prevalence of anaemia was observed in eight individuals, comprising 8.7%, with sTfR proving highly sensitive (87.5%) and specific (75%) for IDA at 25.24 nmol/L. Both sTfR (r=-0.360) and sTfR-ferritin Index (r=-0.344) had significant negative correlations with Haemoglobin (Hb) (p-value&lt;0.001), while ferritin (r=0.156) didn’t correlate significantly with Hb (p-value=0.136). Notably, CRP didn’t affect sTfR levels, enhancing its reliability. Conclusion: sTfR levels and the sTfR-Ferritin index were significantly higher in pregnant women with IDA. They exhibited greater sensitivity and specificity compared to serum ferritin in detecting IDA.

Association between overweight/obesity and iron deficiency anaemia among women of reproductive age: a systematic review.

Numerous studies have examined the relationship between overweight/obesity and iron deficiency anaemia (IDA) across diverse population groups, but a definitive link has not been clearly determined. This systematic review examined the association between overweight/obesity and IDA in women of reproductive age (WRA). The initial search was performed in the CINAHL, Embase, MEDLINE, SCOPUS and Web of Science databases. The studies included should report at least one Fe status with/without an inflammatory marker, using the BMI to define overweight/obesity. Only baseline data were extracted for longitudinal studies. Global. Pregnant or non-pregnant women aged 18-50 years. In total, twenty-seven papers were included (twelve addressing pregnant women and fifteen addressing non-pregnant women). Overall, most of the studies reported no association between overweight/obesity and Hb concentration. However, a positive association was reported more frequently in pregnant women. The association between overweight/obesity and serum ferritin concentrations was mixed. Most of the studies on non-pregnant women reported a positive association. Only a few studies measured hepcidin and inflammatory markers, and the majority revealed an increased level among overweight/obese WRA. Among pregnant women, overweight/obesity was positively associated with anaemia and IDA but negatively associated with iron deficiency (ID). Meanwhile, overweight/obese non-pregnant women were positively associated with anaemia, ID and IDA. Overweight/obesity was associated with a decreased prevalence of anaemia and IDA but an increased prevalence of ID, while its association with several Fe markers was inconclusive. Further studies integrating the assessment of various Fe markers, inflammatory markers and hepcidin are needed.

Markers of oxidative stress in children with iron deficiency anemia

BackgroundOxidative stress can occur in iron deficiency anemia (IDA), causing cellular injury. The primary objective of the study was to assess serum malondialdehyde (MDA), protein carbonyl as oxidants and glutathione reductase catalase, superoxide dismutase (SOD), and vitamin C levels as antioxidants in patients with IDA and healthy controls; and secondary objectives were to observe the levels among the mild, moderate and severe category of IDA and their correlations with serum iron and ferritin. Material and methodsFifty-five patients of IDA and 50 healthy controls were enrolled. Diagnosis of IDA was made based on the cut-off values of low hemoglobin as per age, serum iron <30 μg/dL, ferritin <12 ng/mL, and transferrin saturation <16 %. Serum levels of MDA, protein carbonyl, glutathione reductase, catalase, SOD, and vitamin C were estimated. ResultsThe median age of patients and controls was 6 years. IDA patients had significantly raised mean levels of MDA (p < 0.001) and protein carbonyl (p < 0.001) and decreased glutathione reductase (p < 0.001), catalase (p < 0.001), SOD (p = 0.014) and vitamin C (p = 0.010) than controls. Parameters were comparable among mild, moderate, and severe degrees of IDA. Significantly negative correlations of MDA (r = −0. 713, p < 0.001, −0.683 p < 0.001) and protein carbonyl (r = −0.500, p < 0.001, - 0.519, p < 0.001) and positive correlations of glutathione reductase (r = 0.607, p < 0.001, 0.629, p < 0.001), catalase (r = 0.447, p < 0.001, 0.436, p < 0.001), SOD (r = 0.209, p = 0.032, 0.175, p = 0.075) and vitamin C (r = 0.233,p = 0.017, 0.197, p = 0.044) were observed with serum iron and ferritin, respectively. ConclusionOxidative stress exists in patients with IDA, unaffected by the severity of anemia, and has significant correlations with serum iron and ferritin concentrations.

RESULTS OF IRON SUPPLEMENTATION FOR REGULAR VOLUNTARY NON-REMUNERATED BLOOD DONORS AT NATIONAL INSTITUTE OF HEMATOLOGY AND BLOOD TRANSFUSION

Objective: To evaluate the results of iron supplementation for RRVBD at the National Institute of Hematology and Blood Transfusion (NIHBT). Subjects and methods: Including 279 RRVBD with serum ferritin below 26 ng/ml taking iron tablets containing 35 mg of elemental iron. Methods: Cross-sectional description, prospective study. Results: The average age of RRVBD taking iron tablets is 27.8 years old, the average number of blood donations is 11 times, the average time of re-testing is 169.5 days. The proportion of RRVBD taking iron tablets and testing on time is 43.4%, the proportion of RRVBD not taking iron tablets or not taking enough iron tablets is 18.3%, the proportion of RRVBD taking enough iron tablets and not coming to the test on time is 18.6%. The proportion of RRVBD dropping out of the study is 19.7%. Hematological parameters (red blood cell count, hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean serum iron concentration) of RRVBD taking iron tablets are within the normal range, the serum ferritin concentration of RRVBD recovered after taking iron tablets is: in the group of blood donors taking enough iron tablets and testing on time, the mean serum ferritin concentration before taking iron tablets is 15.8 ± 5.5 ng/ml and after taking iron tablets is 24.7 ± 14.9 ng/ml, the proportion of blood donors with ferritin returning to normal range after taking iron tablets is 39.7%. In group of blood donors not taking iron tablets or not taking enough iron tablets, serum ferritin before iron intake is 18.1 ± 5.3 ng/ml and after iron intake is 14.2 ± 10.9 ng/ml, the proportion of blood donors having serum ferritin returning to normal range after iron intake is 7.8%. In group of RRVBD taking enough iron tablets and not coming to the test on time, the mean serum ferritin concentration before iron intake is 16.5 ± 5.9 ng/ml and after iron intake is 28.8 ± 17.1 ng/ml, the proportion of blood donors with serum ferritin concentration returning to normal range after blood donation is 51.9%. Conclusion: The proportion of regularly repeated voluntary blood donors taking enough iron tablets and testing on time is 43.4%, the proportion of regularly repeated voluntary blood donors not taking iron tablets or not taking enough iron tablets is 18.3%, the proportion of regularly repeated voluntary blood donors taking enough iron tablets and not coming to the test on time is 18.6%, the proportion of regularly repeated voluntary blood donors not taking iron tablets and not testing is 19.7%. Hematological parameters (red blood cell count, Hb, MCV, MCH and mean serum iron concentration) of regularly repeated voluntary blood donors taking iron tablets before and after iron intake are within the normal range. The proportion of blood donors with serum ferritin concentration after iron intake returning to the normal range: blood donors taking enough iron tablets and testing on time is 39.7%, blood donors not taking iron tablets or not taking enough iron tablets is 7.8% and blood donors taking enough iron tablets and not coming to the test on time is 51.9%.

Cohort-Based Reference Values for Serum Ferritin and Transferrin and Longitudinal Determinants of Iron Status in European Children Aged 3–15 Years

BackgroundReference values of ferritin and transferrin for European children do not exist. ObjectiveWe aimed to provide sex-, age-, and body mass index (BMI)-specific serum ferritin and transferrin reference percentiles of 3–15-y-old children based on cohort data and to investigate determinants of iron status. MethodsA total of 3390 ferritin and 3416 transferrin measurements from children residing in 8 European countries participating in the IDEFICS/I.Family cohort (https://www.isrctn.com/ISRCTN62310987) at baseline (W0) and 6 y later (W3) were used to estimate percentiles using the generalized additive model for location, scale and shape. Associations of serum ferritin and transferrin concentrations with total iron intake, total iron intake additionally adjusted for vitamin C intake, and iron from heme sources were investigated separately with adjustment for sex, age, country of residence, parental education, usual energy intake and BMI z-score in regression models using cross-sectional and longitudinal data. ResultsThe age-specific ferritin and transferrin 5th and 95th reference percentiles ranged from 10.9 to 81.1 μg/L and 2.23 to 3.56 g/L, respectively. A deficient iron status was observed in 3% of children at W0 and 7% of children and adolescents at W3, respectively. At both waves, a higher iron intake from heme sources was positively associated with serum ferritin {W0: β = 3.21 [95% confidence interval (CI): 0.71, 5.71]; W3: β = 4.48 [95% CI: 2.09, 6.87]}, that is, children consuming one mg more heme iron had a 3.21 and 4.48 μg/L higher ferritin concentration. Adherence to a mainly vegetarian diet was associated with a lower chance for sufficient serum ferritin cross-sectionally at W3 [odds ratio (OR) 0.40 (95% CI: 0.21, 0.81)] and longitudinally [OR 0.35 (95% CI: 0.15, 0.93)]. ConclusionsAge-, sex-, and BMI-specific reference percentiles of serum ferritin and transferrin concentrations based on cohort data are provided for European children aged 3–15 y and may be used in clinical practice.

Serum Iron, Ferritin, Erythroferrone and their Inter-Correlation In Adult Cigarette Smokers: A Case-Control study

Cigarette smoking is one of the leading causes of lung and blood cancers worldwide. A higher risk of pulmonary injury is associated with elevated lung iron and ferritin levels. Erythroferrone (ERFE) is a newly discovered tumor necrosis factor (TNF) superfamily member produced by erythroblasts during erythropoiesis. Eventually, it suppresses hepcidin during enhanced erythropoietic activity. The current study investigated the relationship between serum ferritin, iron, and erythroferrone concentrations among adult smokers. This study included 76 selected adult cigarette smokers and 48 healthy individuals (non-smokers) as a control group. The enzyme-linked immunosorbent assay (ELISA) and chemiluminescent immunoassay (CLIA) biochemical techniques were used to accurately measure serum iron, ferritin, and erythroferrone. Cigarette smokers (CS) had a mean age of 42.75±2.92 years, while healthy control (HC) subjects had a mean age of 37.36±2.7 years. The findings have shown a significant increase in serum iron, ferritin, and EREF levels in CS (119± 4.30, 131.1±6.58, and 75.02±2.09) compared with HC (98.67±7.84, 85.50±4.12, and 65.74±2.25) respectively. This study has shown a significant positive correlation between serum EREF (P=0.0072, r=0.4089) and the duration of smoking &lt;20 years and a moderate association between serum iron (P=0.1907, r=0.4511) and the duration of smoking &lt;40 years. For the first time, this outcome shows increased serum EREF and overexpression by erythroblasts in subjects associated with smoking habits, along with increased serum iron and ferritin levels. An indicative correlation is found between EREF overexpression, iron overload, and hyperferritinemia with reference to the duration of smoking. The study also illustrates the interconnection between iron metabolism perturbations and ERFE overexpression induced by cigarette smoking.

Manganese and Sleep Outcomes in United States Adults: Results from the 2017–2020 National Health and Nutrition Examination Survey (NHANES)

BackgroundManganese (Mn) is an essential micronutrient, but inadequate or excess Mn intake can have a detrimental impact on human health. Despite the essentiality, little is known about the relationship between Mn and sleep. ObjectiveThis study aimed to examine the relationship between blood Mn concentrations and sleep outcomes in US adults. MethodsThis cross-sectional study used data on blood Mn and sleep from the 2017–2020 National Health and Nutrition Examination Survey (NHANES) (n = 8356, age ≥18 y). Multivariable logistic regression was used to examine associations between quintiles of blood Mn concentrations and subjective sleep outcomes (short sleep duration, late sleep midpoint, trouble sleeping, and obstructive sleep apnea [OSA] symptoms), adjusting for age, gender, body mass index, race/ethnicity, income, smoking, inflammation-adjusted serum ferritin concentration (iron status), caffeine, and alcohol intake. Gender-stratified models were used due to interactions with gender. ResultsThe mean (SE) blood Mn concentration was 9.7 (0.1) μg/L in US adults. In males, a nonlinear association was noted in the relationship between blood Mn levels and short sleep duration on weekdays and weekends. The third Mn quintile (Q3) group had lower odds of short sleep duration (<7 h) on weekdays (odds ratio [OR]=0.6, 95% confidence interval [CI]: 0.4, 0.9) than the lowest Mn quintile (Q1, reference) after adjusting for covariates in males. The second Mn quintile (Q2) group had lower odds of late sleep midpoint on weekdays than Q1 (OR=0.6, 95% CI: 0.4, 0.8). In females, Q2 group had lower odds of OSA symptoms than Q1 (OR: 0.6, 95% CI: 0.4, 0.9). No relationship was noted between Mn and trouble sleeping. ConclusionsGender differences exist in the association between Mn and sleep in adults. Q1 group had the poorest sleep outcomes, including higher odds of short sleep duration (in males), late sleep midpoint (in males), and OSA symptoms (in females).

Prognostic value of three iron deficiency definitions in patients with advanced heart failure

Abstract Background Iron deficiency (ID) is a common co-morbidity in patients with chronic heart failure (HF) and is an independent predictor of adverse prognosis including quality of life and exercise capacity (1-3). Intravenous iron replacement improves outcomes in HF patients including exercise capacity, quality of life, rate of HF hospitalisation and possibly mortality (1-4). Different definitions of ID are used in clinical practice. European HF guidelines define ID as a serum ferritin concentration of &amp;lt; 100 ng/ml, or a serum ferritin of concentration of 100-299 ng/ml with a transferrin saturation (TSAT) &amp;lt; 20% (5) because this definition was used in most trials of iron replacement in HF (1-3). However, other criteria to diagnose ID have been proposed based on comparison to the gold standard of bone marrow biopsy including serum iron ≤ 13 µmol/L and TSAT &amp;lt; 20% (6). Serum ferritin concentrations to diagnose ID has been criticised because inflammation can lead to increased serum ferritin concentrations even in patients who would fulfil ID criteria based on alternative definitions (7). Purpose The prognostic value of ID in patients with advanced HF, assessed for heart transplantation, is currently not well established. This patient population is characterised by relatively young age, single-organ pathology and prognosis is largely determined by the severity of heart disease rather than co-morbidities. In this study we investigated the prognostic value of various ID definitions in this patient cohort. Methods and Results Consecutive patients assessed for heart transplantation at a single UK centre between January 2010 and May 2022 were included. ID was defined as 1) serum ferritin concentration of &amp;lt; 100 ng/ml, or 100-299 ng/ml with transferrin saturation &amp;lt; 20% (guideline definition), 2) serum iron concentration ≤ 13 µmol/L, or 3) transferrin saturation &amp;lt; 20%. The primary outcome measure was a composite of all-cause mortality, urgent heart transplantation or need for mechanical circulatory support. 801 patients were included, and the prevalence of ID was 39-55% depending on definition used. ID, defined by either serum iron or transferrin saturation, was an independent predictor of the primary outcome measure [HR 1.532 (95% CI 1.264 - 1.944) and HR 1.595 (95% CI 1.323 - 2.033), respectively], but the same association was not seen with the guideline definition of ID [HR 1.085 (95% CI 0.8827 - 1.333)]. These findings were robust in multivariable cox regression analysis. ID, by all definitions, was associated with lower six-minute walk distance, lower peak oxygen consumption, higher intra-cardiac filling pressures and lower cardiac output. Conclusions ID, when defined by serum iron concentration or transferrin saturation was associated with increased frequency of adverse clinical outcomes in patients with advanced HF. The same association was not seen with guideline definition of ID.