Serum pro-hepcidin concentrations and their responses to oral iron supplementation in healthy subjects manifest considerable inter-individual variation

Author(s):  
Susanna Luukkonen ◽  
Kari Punnonen

AbstractHepcidin participates in the regulation of iron homeostasis and its precursor pro-hepcidin can be measured in serum. We evaluated pro-hepcidin serum concentrations in healthy subjects and the possible effects of iron supplementation on the results. The results suggest extensive physiological variation in serum pro-hepcidin concentrations between healthy subjects with no symptoms or signs of anaemia, infections, inflammations, chronic disease or other interpretative factors. Before pro-hepcidin measurements can be used in clinical practise, further investigations are required to identify the physiological factors affecting normal serum pro-hepcidin variations in healthy subjects. The responses of serum pro-hepcidin to a 100-mg oral dose of iron also showed considerable inter-individual variation. In male subjects, no systematic changes in serum pro-hepcidin concentrations were found and the increase in serum iron was fairly modest. In nine out of the ten female subjects who had rather low amounts of storage iron, iron supplementation was followed by an increase in both serum iron and serum pro-hepcidin concentrations. There were considerable inter-individual differences in the timing and magnitude of the response. We also evaluated the conceivable influences of sample storage and freeze-thaw cycles on the results of serum pro-hepcidin ELISA. We did not observe any changes in the results after serum samples were frozen and thawed up to four times and/or stored at room temperature for up to 6h.Clin Chem Lab Med 2006;44:1361–2.

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. SCI-27-SCI-27
Author(s):  
Tracey Rouault

Ferroportin (FPN), the only known vertebrate iron exporter, transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues and cells in vivo. Most of the circulating iron is consumed by erythroid cells to synthesize hemoglobin. Recently, we found that erythroid cells not only consume large amounts of iron, but also return significant amounts of iron to the blood. Erythroblast-specific Fpn knockout (Fpn KO) mice developed lower serum iron levels in conjunction with tissue iron overload and increased FPN expression in spleen and liver without changing hepcidin levels. Our results also showed that Fpn KO mice, which suffer from mild hemolytic anemia, were sensitive to phenylhydrazine-induced oxidative stress but were able to tolerate iron deficiency upon exposure to a low-iron diet and phlebotomy, supporting that the anemia of Fpn KO mice resulted from erythrocytic iron overload and resulting oxidative injury rather than a red blood cell (RBC) production defect. Moreover, we found that the mean corpuscular volume (MCV) values of gain-of-function FPN mutation patients were positively associated with serum transferrin saturations, whereas MCVs of loss-of-function FPN mutation patients were not, supporting that erythroblasts donate iron to blood through FPN in response to serum iron levels. Our results indicate that FPN of erythroid cells has an unexpectedly essential role in maintaining systemic iron homeostasis and protecting RBCs from oxidative stress, providing insight into the pathophysiology of FPN diseases. When malaria parasites invade red blood cells (RBCs), they consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. We recently found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation,Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPNQ248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. Zhang DL, Wu J, Shah BN et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359 (6383):1520-1523. Zhang DL, Ghosh MC, Ollivierre H, Li Y, Rouault TA. Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress. Blood. 2018;132 (19):2078-2087. Zhang DL, Rouault TA. How does hepcidin hinder ferroportin activity. Blood. 2018;131 (8):840-842. Disclosures No relevant conflicts of interest to declare.


Author(s):  
Sridevi Sivarama Krishnan ◽  
Vignesh Vikram ◽  
Bhagavatham Meenakshi ◽  
Chitraa R Chandran

Introduction: Gingival Crevicular Fluid (GCF) has been referred to as a promising medium for detection of markers for periodontal disease activity. Analysis of GCF shows minute changes in biomarker levels well before the onset of clinical signs and symptoms; which helps to even predict a person’s predisposition towards periodontal disease occurrence. The elemental analysis of human blood serum is noteworthy in routine clinical practice as well as in medical research. Aim: This study was done to determine the changes in calcium and iron levels in GCF and serum in human subjects with normal periodontal health and those with disease. Materials and Methods: This was a cross-sectional study conducted from March 2019 to December 2019. Eight study subjects (4 healthy subjects and 4 periodontitis cases) were selected from the patients reporting to the Department of Periodontics at Tagore Dental College and Hospital, Chennai. The subjects were chosen based on inclusion and exclusion criteria and all patients were subjected to a clinical examination wherein the Probing Depth (PD) and Clinical Attachment Level (CAL) were recorded by a single examiner using William’s Periodontal probe. The GCF samples were collected by Capillary Tubing method. Blood was collected by venipuncture and centrifuged to provide serum samples. Dual viewing Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES) was used to estimate Calcium and Iron in GCF and serum. SPSS version 21.0 was used for statistical analysis. Mann Whitney U test was used for comparing the groups. p-value less than 0.05 was considered statistically significant. Results: Serum iron levels were significantly less in periodontitis patients than healthy subjects (p-value 0.043). GCF iron level (p-value 0.386), GCF calcium level (p-value 0.149) and serum calcium level (p-value 0.564) did not show any major variation among subjects with normal periodontal health and those with disease. Conclusion: The findings of this study showed that iron and calcium are present in GCF and serum samples of healthy persons and patients with chronic periodontitis which can be detected using ICP-OES. A significant difference in serum iron levels between health and disease could indicate a patient’s predisposition towards developing periodontitis. Calcium levels in GCF and serum do not point towards periodontal disease activity.


2021 ◽  
Vol 9 ◽  
Author(s):  
Mingyan Li ◽  
Ying Lv ◽  
Jionghuan Ying ◽  
Lin Xu ◽  
Weijun Chen ◽  
...  

Objective: The aim of this study was to investigate the effects of unified iron supplementation and identify the factors related to the iron homeostasis among preterm infants.Method: A total of 250 preterm infants were divided into neonatal anemic (NA, n = 154) and non-neonatal anemic group (NNA, n = 96). Iron supplements at a dose of 2 mg/kg per day were given from 40 weeks' gestational age to 6 months. Iron status parameters were measured at 3 and 6 months, respectively. Prevalence of iron deficiency (ID) and iron deficiency anemia (IDA), and the correlated factors were analyzed. Growth and side-effects were monitored.Results: There were no significant differences for the prevalence of ID or IDA between the two groups. Multivariate regression analyses showed that higher Hb at birth and early treatment of blood transfusion reduced the risk of ID/IDA at 3 months (all p < 0.05); while higher level of Hb at 3 months (p = 0.004) and formula feeding reduced the occurrence of ID/IDA at 6 months (p < 0.05); males had a 3.35 times higher risk to develop ID/IDA than girls (p = 0.021). No differences in growth and side effects were found.Conclusion: A daily dose of 2 mg/kg iron supplement is beneficial to maintain iron homeostasis in majority preterm infants within 6 months regardless of their neonatal anemia history. Under the routine iron supplementation, Hb level at birth and at 3 months, early treatment of blood transfusion, gender and feeding patterns are the major factors affecting the prevalence of ID/IDA among preterm infants in infancy.


2015 ◽  
Vol 100 (9) ◽  
pp. 3388-3392 ◽  
Author(s):  
Klaus Kapelari ◽  
Julia Köhle ◽  
Dieter Kotzot ◽  
Wolfgang Högler

Context: Autosomal dominant hypophosphatemic rickets (ADHR) is the only hereditary disorder of renal phosphate wasting in which patients may regain the ability to conserve phosphate. Low iron status plays a role in the pathophysiology of ADHR. Objective: This study reports of a girl with ADHR, iron deficiency, and a paternal history of hypophosphatemic rickets that resolved without treatment. The girl's biochemical phenotype resolved with iron supplementation. Subjects: A 26-month-old girl presented with typical features of hypophosphatemic rickets, short stature (79 cm; −2.82 SDS), and iron deficiency. Treatment with elemental phosphorus and calcitriol improved her biochemical profile and resolved the rickets. The girl's father had presented with rickets at age 11 months but never received medication. His final height was reduced (154.3 cm; −3.51 SDS), he had undergone corrective leg surgery and had an adult normal phosphate, fibroblast growth factor 23, and iron status. Father and daughter were found to have a heterozygous mutation in exon 3 of the FGF23 gene (c.536G>A, p.Arg179Gln), confirming ADHR. Intervention: Withdrawal of rickets medication was attempted off and on iron supplementation. Results: Withdrawal of rickets medication in the girl was unsuccessful in the presence of low-normal serum iron levels at age 5.6 years but was later successful in the presence of high-normal serum iron levels following high-dose iron supplementation. Conclusions: We report an association between iron supplementation and a complete loss of biochemical ADHR phenotype, allowing withdrawal of rickets medication. Experience from this case suggests that reduction and withdrawal of rickets medication should be attempted only after iron status has been optimized.


BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e046865
Author(s):  
Gorkem Sezgin ◽  
Ling Li ◽  
Johanna Westbrook ◽  
Elisabeth Wearne ◽  
Denise Azar ◽  
...  

Background and objectiveSerum iron results are not indicative of iron deficiency yet may be incorrectly used to diagnose iron deficiency instead of serum ferritin results. Our objective was to determine the association between serum iron test results and iron-deficiency diagnosis in children by general practitioners.Design, setting, patients and main outcome measuresA retrospective observational study of 14 187 children aged 1–18 years with serum ferritin and serum iron test results from 137 general practices in Victoria, Australia, between 2008 and 2018. Generalised estimating equation models calculating ORs were used to determine the association between serum iron test results (main exposure measure) and iron-deficiency diagnosis (outcome measure) in the following two population groups: (1) iron-deplete population, defined as having a serum ferritin <12 µg/L if aged <5 years and <15 µg/L if aged ≥5 years and (2) iron-replete population, defined as having a serum ferritin >30 µg/L.Results3484 tests were iron deplete and 15 528 were iron replete. Iron-deplete children were less likely to be diagnosed with iron deficiency if they had normal serum iron levels (adjusted OR (AOR): 0.73; 95% CI 0.57 to 0.96). Iron-replete children had greater odds of an iron-deficiency diagnosis if they had low serum iron results (AOR: 2.59; 95% CI 1.72 to 3.89). Other contributors to an iron-deficiency diagnosis were female sex and having anaemia.ConclusionSerum ferritin alone remains the best means of diagnosing iron deficiency. Reliance on serum iron test results by general practitioners is leading to significant overdiagnosis and underdiagnosis of iron deficiency in children.


2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 289-291
Author(s):  
L Russell ◽  
R Mangat ◽  
J Plant ◽  
S Hansen ◽  
D Armstrong ◽  
...  

Abstract Background Iron deficiency (ID) is common in patients receiving parenteral nutrition (PN), likely due to a lack of iron in the PN formula. There is no clear consensus on how often serum iron should be tested or iron supplementation should be given, at which dose or route, in patients on long-term PN. Within the Hamilton Health Sciences (HHS) home PN (HPN) program, the prevalence of ID or iron deficiency anemia (IDA) is unknown. This knowledge will contribute to better iron prescribing practices with ultimate benefit on patient’s health. Aims To assess the prevalence of ID and IDA in patients enrolled in the HHS HPN Program. The secondary aim was to assess supplementation practices for patients enrolled in the HPN program according to gastrointestinal(GI) diagnosis and duration on PN. Methods We conducted a retrospective study including consecutive adult patients enrolled in the HHS-HPN program from January 2015 to November 2020. We collected data on demographics (age, sex, and GI diagnosis), iron supplementation (dose, duration, and route), and information related to iron-deficiency (hemoglobin, serum iron, ferritin, TIBC, and folate) at pre-set intervals (enrollment, 3, 6, 12, 18, 24, 30, 36, 48, 60 months) and last measured. ID was defined as ferritin ≤45μg/L or serum iron ≤9μmol/L. IDA was defined as hemoglobin &lt;130g/L in men or &lt;120g/L in women in the context of ID. Data were expressed as median (IQR) for continuous variables and n/N(%) for categorical variables. Chi2 was performed to assess differences between groups and logistic regression to assess predictors of ID and IDA. The analysis was conducted using SPSS software(v26). Results The analysis included 125 HPN patients (50 males, median age of 55 (40–65) years). Patients received PN for a median of 195 (83–521) days. The most common diagnoses were malignancy (36.8%) and inflammatory bowel disease (23.2%); the most common indications for HPN was short bowel (29.6%) and bowel obstruction (27.2%). Iron profiles were measured in 77% of patients. At enrollment, 42.2% of patients had ID and 38.9% had IDA. Only 13% of patients with ID and 22.8% with IDA had iron supplementation (Figure 1). A total of 38 patients received iron either oral or IV (oral=44.7% vs IV=55.3%; p=0.66). There was no correlation between low levels of serum iron or ferritin with iron supplementation (p=0.23, 0.45 respectively). Age, sex, diagnosis, or reason for PN did not correlate with ID or IDA at any time point. Conclusions Iron-deficiency and IDA are common in patients enrolled in the HHS HPN program independently of age, sex, diagnosis and reason for PN. Prospective studies are needed to implement the most effective way to ensure proper monitoring and treatment of iron deficiency in this population. Funding Agencies None


The Auk ◽  
2006 ◽  
Vol 123 (2) ◽  
pp. 405-418 ◽  
Author(s):  
Jón Einar Jónsson ◽  
Alan D. Afton ◽  
Ray T. Alisauskas ◽  
Cynthia K. Bluhm ◽  
Mohamed E. El Halawani

AbstractWe investigated effects of ecological and physiological factors on brood patch area and prolactin levels in free-ranging Lesser Snow Geese (Chen caerulescens caerulescens; hereafter “Snow Geese”) and Ross's Geese (C. rossii). On the basis of the body-size hypothesis, we predicted that the relationships between prolactin levels, brood patch area, and body condition would be stronger in Ross's Geese than in the larger Snow Geese. We found that brood patch area was positively related to clutch volume and inversely related to prolactin levels in Ross's Geese, but not in Snow Geese. Nest size, nest habitat, and first egg date did not affect brood patch area in either species. Prolactin levels increased as incubation progressed in female Snow Geese, but this relationship was not significant in Ross's Geese. Prolactin levels and body condition (as indexed by size-adjusted body mass) were inversely related in Ross's Geese, but not in Snow Geese. Our findings are consistent with the prediction that relationships between prolactin levels, brood patch area, and body condition are relatively stronger in Ross's Geese, because they mobilize endogenous reserves at faster rates than Snow Geese.Factores Ecológicos y Fisiológicos que Afectan el Área del Parche de Incubación y los Niveles de Prolactina en Gansos Nidificantes del Ártico


2005 ◽  
Vol 11 (3) ◽  
pp. 353-360 ◽  
Author(s):  
Roberta Seraglia ◽  
Susanna Vogliardi ◽  
Graziella Allegri ◽  
Stefano Comai ◽  
Mario Lise ◽  
...  

Fourteen blood samples from patients with melanomas and 11 blood samples from healthy subjects were analyzed by matrix-assisted laser desorption/ionization mass spectrometry. The study focussed on species of low molecular weight, in the 800–5000 Da range, present in plasma and sera. While for healthy subjects plasma samples lead to the production of a higher number of ionic species, for melanoma patients a high number of diagnostic ions, present with high frequency and with quite high relative abundance, are present, in particular, in serum samples and, to a lesser extent, also in plasma. Since plasma samples are obtained more easily in comparison to sera, it is possible to suggest that plasma can also be used for these studies.


2016 ◽  
Vol 22 ◽  
pp. 7 ◽  
Author(s):  
Leif Inge Tjelta ◽  
Shaher A. I. Shalfawi

Running distances from 3000 m to the marathon (42 195 m) are events dominated by energy contribution of the aerobic energy system. The physiological factors that underlie success in these running events are maximal oxygen uptake (VO2max), running economy (RE), the utilization of the maximum oxygen uptake (%VO2max) and velocity at the anaerobic threshold (vAT). VO2max for distance runners competing on an international level has been between 70 and 87 ml/kg/min in men, and between 60 and 78.7 ml/kg/min in women, respectively. Due to lack of air resistance, laboratory testing of RE and vAT are recommended to be conducted on treadmill with 1% slope. %VO2max are in most studies expressed as the average fractional utilization of VO2max at vAT. Much of the current understanding regarding the response to exercise is based on studies of untrained and moderately trained individuals. To use this knowledge to give training recommendations to elite runners is hardly valid. Researchers should therefore exercise caution when giving training recommendations to coaches and elite distance runners based on limited available research.


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