The opposing effects of acute inflammation and iron deficiency anemia on serum hepcidin and iron absorption in young women

Background:Anemia of inflammation (AI) and iron deficiency anemia (IDA) are the two most prevalent forms of anemia in patients with rheumatoid arthritis (RA). Diagnosis becomes challenging if AI is associated with true ID (AI/ID), as there is still a lack of a gold standard for differentiation between AI and AI/ID. However, as therapies to overcome anemia differ, proper diagnosis and understanding of underlying pathophysiological regulations are necessary.Objectives:The aim of the study was to evaluate the clinical efficiency of hepcidin, a key regulator of iron metabolism, in the diagnosis of IDA, as well as the differential diagnosis of AI/ID and AI in patients with RA.Methods:The study was undertaken 96 patients with RA, 67 of them were diagnosed anemia according to WHO criteria (104,3±21,4 g/l). Anemic patients and anemia-free patients with RA (n=29) were comparable (p>0.05) in age (44.4±14.8 and 49.8±9.3 years), disease duration (73.5±65.4 and 59.8±48.3 months) and DAS28 (6.3±1.6 and 5.9±1.9). All cases were subjected to following tests: complete blood count with peripheral smear, serum C-reactive protein, serum interleukin-6, iron studies, serum soluble transferrin receptor (sTfR), and serum hepcidin. Patients with RA and anemia were divided two groups: 25 patients with IDA and 42 - with AI. The AI cases were subdivided into pure AI and AI with coexistent ID (n=15).Results:The mean serum hepcidin concentration was significantly increased in pure AI patients (123.85±25.8 ng/mL) as compared to those in IDA patients (63.9±22.8 ng/mL, P < 0.05) and anemia-free patients with RA (88.1±39.09 ng/mL). Also, compared to pure AI patients [normal sTfR levels (<3 µg/mL)], the serum hepcidin concentration was reduced significantly in AI patients with ID [high sTfR levels (≥3 µg/mL)] with a mean of 79.0±23.97 ng/mL.Conclusion:Hepcidin measurement can provide a useful tool for differentiating AI from IDA and also help to identify an iron deficiency in AI patients. This might aid in the appropriate selection of therapy for these patients.Disclosure of Interests:None declared

Download Full-text

IRON ABSORPTION AND RESPONSE TO ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA ASSOCIATED TO ASYMPTOMATIC GIARDIASIS.

Pediatric Research ◽

10.1203/00006450-199306000-00039 ◽

1993 ◽

Vol 33 (6) ◽

pp. 661-661

Author(s):

Helena U Suzuki ◽

Mauro B Morais ◽

Jose N Corral ◽

Ulisses Fagundes-Neto ◽

Nelson L Machado

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Oral Iron Therapy

Download Full-text

Reply: Intravenous Ferumoxytol in Pediatric Patients With Iron-Deficiency Anemia

Annals of Pharmacotherapy ◽

10.1177/1060028017726796 ◽

2017 ◽

Vol 51 (12) ◽

pp. 1146-1146

Author(s):

Nabil E. Hassan

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Pediatric Patients ◽

Iron Absorption ◽

Deficiency Anemia

Iron Deficiency in children is common problem. Its mechanism could be nutritional or due to lack of iron absorption. Several conditions are associated with IDA. Presence of inflammation further complicate attempts to make a definitive diagnoses or accurately quantify reponse to therapy.

Download Full-text

Comparative Study of the Effects of Lactoferrin versus Oral Iron Therapy in Obese Children and Adolescents with Iron Deficiency Anemia

Journal of Advances in Medicine and Medical Research ◽

10.9734/jammr/2021/v33i2131138 ◽

2021 ◽

pp. 104-114

Author(s):

Manal Mahmoud Atia ◽

Rasha Mohamed Gama ◽

Mohamed Attia Saad ◽

Mohammed Amr Hamam

Keyword(s):

Iron Deficiency ◽

Children And Adolescents ◽

Iron Deficiency Anemia ◽

Interleukin 6 ◽

Oral Iron ◽

Iron Therapy ◽

Deficiency Anemia ◽

Obese Children ◽

Oral Iron Therapy ◽

Serum Hepcidin

Greater prevalence of iron deficiency (ID) has been observed in overweight and obese children and adolescents. Hepcidin acts as a key regulator of iron metabolism. Hepcidin synthesis increases in response inflammatory cytokines especially Interleukin-6 (IL-6). Considering that obesity represents a low grade chronic inflammatory state, a high concentration of hepcidin has been found in obese children. Elevated hepcidin level in obese children is associated with diminished response to oral iron therapy. Lactoferrin is an iron-binding multifunctional glycoprotein and has strong capacity to modulate the inflammatory response by its capacity to reduce pro-inflammatory cytokine expression in vivo, including IL-6 and hepcidin. Aim of the Work: To compare the efficacy of lactoferrin versus oral iron therapy in treatment of obese children and adolescents with iron deficiency anemia and the effect of therapy on serum hepcidin and interleukin 6 levels. Methodology: This prospective randomized clinical trial was conducted on 40 obese children and adolescents aged between 6 –18 years suffering from iron deficiency anemia (IDA). They were equally randomized into one of 2 groups. Group A received regular oral lactoferrin in a dose of 100 mg/day. Group B received regular oral iron supplementation (Ferric hydroxide polymaltose) in a dose of 6 mg elemental iron/kg /day.Baseline investigations included complete blood count (CBC), iron profile (Serum ferritin, serum iron, total iron binding capacity (TIBC), transferrin saturation), serum Interleukin 6, and serum hepcidin. Reevaluation of CBC was done monthly while iron status parameters, serum IL-6 and serum hepcidin were reevaluated after 3 months of receiving regular therapy. Results: Significant elevations in hemoglobin, MCV, MCH, Serum ferritin, serum iron and transferrin saturation with lactoferrin therapy compared to oral iron therapy. Significantly Lower TIBC after 3 months of lactoferrin therapy while the decrease in TIBC was insignificant in the iron therapy group.Lower serum hepcidin and IL6 after 3 months of lactoferrin therapy with no significant change in serum hepcidin and IL6 after iron therapy. Conclusion: This study clearly demonstrated the superiority of lactoferrin over iron use as oral in the treatment of iron deficiency anemia in obese children not only for the better response of hematological and iron status parameters and less gastrointestinal side effects but also for its effect on decreasing inflammatory biomarkers as hepcidin and IL6.

Download Full-text

Iron Amino Acid Chelates

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.74.6.435 ◽

2004 ◽

Vol 74 (6) ◽

pp. 435-443 ◽

Cited By ~ 29

Author(s):

Hertrampf ◽

Olivares

Keyword(s):

Amino Acid ◽

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Ferrous Sulfate ◽

Iron Absorption ◽

Iron Status ◽

Deficiency Anemia ◽

Efficacy Trials ◽

Food Matrices ◽

The Cost

Iron amino acid chelates, such as iron glycinate chelates, have been developed to be used as food fortificants and therapeutic agents in the prevention and treatment of iron deficiency anemia. Ferrous bis-glycine chelate (FeBC), ferric tris-glycine chelate, ferric glycinate, and ferrous bis-glycinate hydrochloride are available commercially. FeBC is the most studied and used form. Iron absorption from FeBC is affected by enhancers and inhibitors of iron absorption, but to a lesser extent than ferrous sulfate. Its absorption is regulated by iron stores. FeBC is better absorbed from milk, wheat, whole maize flour, and precooked corn flour than is ferrous sulfate. Supplementation trials have demonstrated that FeBC is efficacious in treating iron deficiency anemia. Consumption of FeBC-fortified liquid milk, dairy products, wheat rolls, and multi-nutrient beverages is associated with an improvement of iron status. The main limitations to the widespread use of FeBC in national fortification programs are the cost and the potential for promoting organoleptic changes in some food matrices. Additional research is required to establish the bioavailability of FeBC in different food matrices. Other amino acid chelates should also be evaluated. Finally there is an urgent need for more rigorous efficacy trials designed to define the relative merits of amino acid chelates when compared with bioavailable iron salts such as ferrous sulfate and ferrous fumarate and to determine appropriate fortification levels

Download Full-text

Intestinal expression of genes involved in iron absorption in humans

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00371.2001 ◽

2002 ◽

Vol 282 (4) ◽

pp. G598-G607 ◽

Cited By ~ 58

Author(s):

Andreas Rolfs ◽

Herbert L. Bonkovsky ◽

James G. Kohlroser ◽

Kristina McNeal ◽

Ashish Sharma ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Genetic Disorders ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

High Serum ◽

Deficiency Anemia ◽

Dependent Manner ◽

Expression Levels

Hereditary hemochromatosis (HHC) is one of the most frequent genetic disorders in humans. In healthy individuals, absorption of iron in the intestine is tightly regulated by cells with the highest iron demand, in particular erythroid precursors. Cloning of intestinal iron transporter proteins provided new insight into mechanisms and regulation of intestinal iron absorption. The aim of this study was to assess whether, in humans, the two transporters are regulated in an iron-dependent manner and whether this regulation is disturbed in HHC. Using quantitative PCR, we measured mRNA expression of divalent cation transporter 1 (DCT1), iron-regulated gene 1 (IREG1), and hephaestin in duodenal biopsy samples of individuals with normal iron levels, iron-deficiency anemia, or iron overload. In controls, we found inverse relationships between the DCT1 splice form containing an iron-responsive element (IRE) and blood hemoglobin, serum transferrin saturation, or ferritin. Subjects with iron-deficiency anemia showed a significant increase in expression of the spliced form, DCT1(IRE) mRNA. Similarly, in subjects homozygous for the C282Y HFE mutation, DCT1(IRE) expression levels remained high despite high serum iron saturation. Furthermore, a significantly increased IREG1 expression was observed. Hephaestin did not exhibit a similar iron-dependent regulation. Our data show that expression levels of human DCT1 mRNA, and to a lesser extent IREG1 mRNA, are regulated in an iron-dependent manner, whereas mRNA of hephaestin is not affected. The lack of appropriate downregulation of apical and basolateral iron transporters in duodenum likely leads to excessive iron absorption in persons with HHC.

Download Full-text

Mutation of the gastric hydrogen-potassium ATPase alpha subunit causes iron-deficiency anemia in mice

Blood ◽

10.1182/blood-2011-04-350082 ◽

2011 ◽

Vol 118 (24) ◽

pp. 6418-6425 ◽

Cited By ~ 17

Author(s):

Lara Krieg ◽

Oren Milstein ◽

Philippe Krebs ◽

Yu Xia ◽

Bruce Beutler ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Osmotic Fragility ◽

Microcytic Anemia ◽

Deficiency Anemia ◽

Α Subunit ◽

Hypochromic Microcytic Anemia ◽

Gastric Proton Pump ◽

Potassium Atpase

Abstract Iron is an essential component of heme and hemoglobin, and therefore restriction of iron availability directly limits erythropoiesis. In the present study, we report a defect in iron absorption that results in iron-deficiency anemia, as revealed by an N-ethyl-N-nitrosourea–induced mouse phenotype called sublytic. Homozygous sublytic mice develop hypochromic microcytic anemia with reduced osmotic fragility of RBCs. The sublytic phenotype stems from impaired gastrointestinal iron absorption caused by a point mutation of the gastric hydrogen-potassium ATPase α subunit encoded by Atp4a, which results in achlorhydria. The anemia of sublytic homozygotes can be corrected by feeding with a high-iron diet or by parenteral injection of iron dextran; rescue can also be achieved by providing acidified drinking water to sublytic homozygotes. These findings establish the necessity of the gastric proton pump for iron absorption and effective erythropoiesis.

Download Full-text

Iron deficiency anemia induces postural control disorders in young women

Journal of Trace Elements in Medicine and Biology ◽

10.1016/j.jtemb.2021.126868 ◽

2021 ◽

pp. 126868

Author(s):

Mohammed A. Harrabi ◽

Thouraya Fendri ◽

Rahma Ayed ◽

Haithem Rebai ◽

Fatma Chaari ◽

...

Keyword(s):

Iron Deficiency ◽

Postural Control ◽

Iron Deficiency Anemia ◽

Young Women ◽

Deficiency Anemia

Download Full-text

Effects of Oral Vitamin C on Hepcidin Levels and Erythropoietin Requirements in Functional Iron Deficiency Anemia among Hemodialysis Patients

QJM ◽

10.1093/qjmed/hcab100.015 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mahmoud Mohamed Zaki Ali ◽

Maha Abd ElMoniem Behairy ◽

Reem Mohsen El Sharabasy ◽

Ahmed Hamed Ahmed Gharib

Keyword(s):

Iron Deficiency ◽

Vitamin C ◽

Iron Deficiency Anemia ◽

Hemodialysis Patients ◽

Deficiency Anemia ◽

Study Group ◽

Oral Vitamin ◽

Functional Iron Deficiency ◽

Serum Hepcidin ◽

Hs Crp

Abstract Background Hepcidin has long been postulated as a key regulatory peptide in iron homeostasis. Its reduced clearance and elevated levels in hemodialysis (HD) patients lead to functional iron deficiency (FID) and ESA resistance. Vitamin C may be used as adjuvant therapy in FID anemia, but there are limited studies investigating the direct relation between vitamin C and hepcidin levels in HD patients. We aimed to test the reducing effect of Oral vitamin C therapy on hepcidin levels among hemodialysis patients with functional iron deficiency anemia. Patients and Methods This study is an open label randomized controlled clinical trial. It was conducted in the hemodialysis units of Ain Shams University hospitals. 48 adult prevalent HD patients were included and were divided into two groups. Group 1 (study group) included 31 patients who received the conventional treatment of erythropoietin stimulating agents (ESAs) together with oral supplementation of vitamin C 500 mg every other day for 3 months in addition to IV iron therapy. Group 2 (control group) included 17 patients who received only the conventional therapy of ESAs according to their hemoglobin (Hb) levels in addition to IV iron therapy. Laboratory parameters including serum hepcidin levels, highly sensitive CRP (hs-CRP) titer, CBC, kidney function tests and iron indices were measured at the baseline of the study and after 3 months. Results Oral vitamin C therapy resulted in a statistically significant reduction in both hepcidin and hs-CRP levels in the study group after 3 months. The study group showed a significant reduction in serum iron and ferritin levels (P < 0.05). A Decrease in EPO requirements and elevation of hemoglobin level were observed in the study group but were not statistically significant as a short term effect of oral vitamin C, in comparison to the control group. A highly significant correlation was observed between serum hepcidin and hs-CRP (R=0.46, P<0.01). Conclusion Oral vitamin C may be a promising therapy in decreasing serum hepcidin and hs-CRP levels in prevalent hemodialysis patients with functional iron deficiency anemia.

Download Full-text