scholarly journals Iron and Zinc Homeostasis and Interactions: Does Enteric Zinc Excretion Cross-Talk with Intestinal Iron Absorption?

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1885 ◽  
Author(s):  
Palsa Kondaiah ◽  
Puneeta Singh Yaduvanshi ◽  
Paul A Sharp ◽  
Raghu Pullakhandam
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
The Body ◽  
Zinc Homeostasis ◽  
Iron Accumulation ◽  
Intestinal Cell ◽  
Deficiency Anemia ◽  
Intestinal Iron Absorption ◽  
Tissue Iron ◽  
Iron And Zinc

Iron and zinc are essential micronutrients required for growth and health. Deficiencies of these nutrients are highly prevalent among populations, but can be alleviated by supplementation and food fortification. Cross-sectional studies in humans showed positive association of serum zinc levels with hemoglobin and markers of iron status. Dietary restriction of zinc or intestinal specific conditional knock out of ZIP4 (SLC39A4), an intestinal zinc transporter, in experimental animals demonstrated iron deficiency anemia and tissue iron accumulation. Similarly, increased iron accumulation has been observed in cultured cells exposed to zinc deficient media. These results together suggest a potential role of zinc in modulating intestinal iron absorption and mobilization from tissues. Studies in intestinal cell culture models demonstrate that zinc induces iron uptake and transcellular transport via induction of divalent metal iron transporter-1 (DMT1) and ferroportin (FPN1) expression, respectively. It is interesting to note that intestinal cells are exposed to very high levels of zinc through pancreatic secretions, which is a major route of zinc excretion from the body. Therefore, zinc appears to be modulating the iron metabolism possibly via regulating the DMT1 and FPN1 levels. Herein we critically reviewed the available evidence to hypothesize novel mechanism of Zinc-DMT1/FPN1 axis in regulating intestinal iron absorption and tissue iron accumulation to facilitate future research aimed at understanding the yet elusive mechanisms of iron and zinc interactions.

scholarly journals New findings on iron absorption conditioning factors

2004 ◽  
Vol 4 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Rute Cândida Pereira ◽  
Alcides da Silva Diniz ◽  
Luiz Oscar Cardoso Ferreira
Keyword(s):  
Iron Absorption ◽  
The Body ◽  
Vulnerable Groups ◽  
Deficiency Anemia ◽  
Public Health Issue ◽  
Conditioning Factors ◽  
Risk Increase ◽  
New Findings ◽  
Intake Regulation ◽  
The Impact

The authors focus iron intake regulation in the body and the probable mechanisms related to iron absorption. They analyze the impact of iron absorption deficiency resulting in iron deficiency anemia, a public health issue of great impact in the world influencing child and maternal health risk increase. This paper aims at highlighting the problems affecting the uptake or inhibiting processes of iron absorption in an attempt to correlate information on conditioning factors and current findings. This study is a document based descriptive study comprising literature review. In food, iron has different forms, such as the heme and non-heme forms following different absorption pathways with different efficiency rates, depending on conditioning factors, such as diet profile, physiological aspects, iron chemical state, absorption regulation, transportation, storing, excretion and the presence of disease, They also discuss the current difficulties in dealing with iron nutritional deficiency in vulnerable groups, children and pregnant women, and focus data on iron consumption, adhesion to breast feeding and the frequency of prenatal care visits.

Iron Amino Acid Chelates

2004 ◽  
Vol 74 (6) ◽  
pp. 435-443 ◽  
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

Zinc, cadmium, and iron interactions during intestinal absorption in iron-deficient mice

1978 ◽  
Vol 56 (3) ◽  
pp. 384-389 ◽  
Author(s):  
D. L. Hamilton ◽  
J. E. C. Bellamy ◽  
J. D. Valberg ◽  
L. S. Valberg
Keyword(s):  
Zinc Chloride ◽  
Binding Sites ◽  
Iron Absorption ◽  
High Capacity ◽  
Test Dose ◽  
The Body ◽  
Zinc Uptake ◽  
Iron Deficient ◽  
Zinc Cadmium ◽  
Iron And Zinc

Zinc absorption from a test dose of (65Zn) zinc chloride was increased in mice with a high capacity to absorb iron induced by a low-iron diet. When radiolabelled zinc chloride in concentrations varying from 0.025 to 0.30 mM was perfused through open-ended duodenal loops of mice fed this diet, the proportion of zinc taken up from the lumen and transferred to the body was greater from lower than from higher doses. The addition of iron to the perfusate inhibited zinc uptake and transfer, and zinc had a similar effect on iron absorption. Cadmium, a potent inhibitor of iron uptake in mice fed a low-iron diet, impaired zinc uptake under these dietary conditions. These results suggest that in dietary-induced iron deficiency there are analogous mucosal binding sites for the uptake of iron and zinc. There also appear to be mutually exclusive binding sites for the absorption of these metals: radiolabeled iron absorption from an intragastric test dose was enhanced in mice with a high capacity to absorb iron produced by bleeding, whereas the absorption of zinc was not increased.

scholarly journals Mechanistic and regulatory aspects of intestinal iron absorption

2014 ◽  
Vol 307 (4) ◽  
pp. G397-G409 ◽  
Author(s):  
Sukru Gulec ◽  
Gregory J. Anderson ◽  
James F. Collins
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Regulatory Protein ◽  
Whole Body ◽  
Deficiency Anemia ◽  
Inherited Disorders ◽  
Intestinal Iron Absorption ◽  
Body Iron ◽  
Proximal Small Bowel

Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands.

scholarly journals CHARACTERISTICS OF ANEMIA AND IRON STATUS AND THEIR ASSOCIATIONS WITH BLOOD MANGANESE AND LEAD AMONG CHILDREN AGED FROM 3 TO 19 YEARS OLD FROM FOUR NORTHERN FIRST NATION COMMUNITIES IN QUEBEC

2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e40-e40
Author(s):  
Emad Tahir
Keyword(s):  
Risk Factors ◽  
Iron Deficiency ◽  
Serum Ferritin ◽  
Iron Status ◽  
Multiple Logistic Regression Analysis ◽  
The Body ◽  
First Nation ◽  
Deficiency Anemia ◽  
Elevated Blood ◽  
Prevalence Of Anemia

Abstract BACKGROUND Prevalence of anemia and iron deficiency (ID) are higher among indigenous children in Canada, although few data are available in Quebec. Iron is metal that interact with the absorption of manganese (Mn) and Lead (Pb) cobalt (Co). ID is known to upregulate these metals, thereby increasing their absorption, concentration inside the body and their toxicity. OBJECTIVES The objectives of the present study are to: (i) Characterize ID and anemia prevalence and their protective/risk factors; and (ii) Study associations between blood Mn, Pb and iron status biomarkers. DESIGN/METHODS Data from The 2015 First Nation Youth Health and Environment Pilot Study was conducted among children (3 to 19 y, n = 198) from four First Nations communities in Quebec will be used in these study where, blood samples and anthropometric measures were collected, hemoglobin was measured on site using an Hemocue analyser. Protective/risk factors including education, food security, housing conditions and lifestyle and dietary habits were documented using interview-administered questionnaire to children’ parents. Serum ferritin and blood Pb, Mn, Co, Zn and Ca were measured by Modular P analyser and ICPMS. Descriptive and multiple regression statistical analyses adjusting for relevant co-variables were used. RESULTS Results showed ID and anemia prevalence of 20.7% and 17.6% respectively, among which 8.8% presented iron deficiency anemia. Moreover, up to 11.9% had elevated blood Mn (median = 15.9 µg/L, range 7.1 to 31.9 µg/L) of which 27.5% presented ID. However, blood Pb was low (median = 5.4 µg/L, range 1.8 to 50.8 µg/L). Multiple logistic regression analysis showed that crystal juice intake was associated with lower ID and anemia (OR (95%): 0.50 (0.30 - 0.82) and 0.47 (0.26 - 0.87) respectively) in girls. Likewise, the presence of hunter in the household was associated with lower anemia in girls (0.09 (0.02 - 0.53)). No factors were associated with ID in boys, and for anemia, lower serum ferritin and older age was associated with higher prevalence of anemia (1.08 (1.01 - 1.14) and 1.23 (1.02 - 1.48) respectively). In adjusted models, blood Mn was negatively associated with serum ferritin concentrations (ß = -0.05; p < 0.02) in girls and positively associated with blood Co (ß = 8.50; p < 0.01) in boys. CONCLUSION Findings on high prevalence of ID, anemia and elevated blood Mn among children form these First Nation communities support that, community and family activities increasing traditional foods consumption improve nutritional status and suggest that foods and beverages naturally rich in vitamin C - but lower in added sugar than crystal juice - would improve iron intake in girls, which would contribute to improve their iron status, decrease anemia and restore normal Mn blood levels.

Iron supply determines apical/basolateral membrane distribution of intestinal iron transporters DMT1 and ferroportin 1

2010 ◽  
Vol 298 (3) ◽  
pp. C477-C485 ◽  
Author(s):  
Marco T. Núñez ◽  
Victoria Tapia ◽  
Alejandro Rojas ◽  
Pabla Aguirre ◽  
Francisco Gómez ◽  
...  
Keyword(s):  
Translational Regulation ◽  
Fluorescent Protein ◽  
Iron Absorption ◽  
Iron Status ◽  
Basolateral Membrane ◽  
Membrane Domains ◽  
Divalent Metal Transporter 1 ◽  
Intestinal Iron Absorption ◽  
Divalent Metal Transporter ◽  
Iron Supply

Intestinal iron absorption comprises the coordinated activity of the influx transporter divalent metal transporter 1 (DMT1) and the efflux transporter ferroportin (FPN). In this work, we studied the movement of DMT1 and FPN between cellular compartments as a function of iron supply. In rat duodenum, iron gavage resulted in the relocation of DMT1 to basal domains and the internalization of basolateral FPN. Considerable FPN was also found in apical domains. In Caco-2 cells, the apical-to-basal movement of cyan fluorescent protein-tagged DMT1 was complete 90 min after the addition of iron. Steady-state membrane localization studies in Caco-2 cells revealed that iron status determined the apical/basolateral membrane distribution of DMT1 and FPN. In agreement with the membrane distribution of the transporters,55Fe flux experiments revealed inward and outward iron fluxes at both membrane domains. Antisense oligonucleotides targeted to DMT1 or FPN inhibited basolateral iron uptake and apical iron efflux, respectively, indicating the participation of DMT1 and FPN in these fluxes. The fluxes were regulated by the iron supply; increased iron reduced apical uptake and basal efflux and increased basal uptake and apical efflux. These findings suggest a novel mechanism of regulation of intestinal iron absorption based on inward and outward fluxes at both membrane domains, and repositioning of DMT1 and FPN between membrane and intracellular compartments as a function of iron supply. This mechanism should be complementary to those based in the transcriptional or translational regulation of iron transport proteins.

scholarly journals Iron Overload in the Face of Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. SCI-38-SCI-38
Author(s):  
Yatrik Shah
Keyword(s):  
Transcription Factors ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Absorption ◽  
Conflicts Of Interest ◽  
Iron Accumulation ◽  
Cell Disease ◽  
Divalent Metal Transporter 1 ◽  
Tissue Iron

Abstract Several distinct congenital disorders can lead to tissue-iron overload with anemia including β-thalassemia and sickle cell disease. We show that intestinal absorption of iron is highly increased and significantly contributes to tissue iron accumulation in these disorders. The present work describes a novel pathway by which oxygen sensing transcription factors are highly upregulated in iron overload anemias and are subsequently essential for the increase intestinal iron absorption. Oxygen signaling is mediated through well-conserved hypoxia driven transcription factors, hypoxia-inducible factor (HIF)1a and HIF2a. In the intestine, HIF2a directly activates divalent metal transporter 1 (DMT1), duodenal ferric reductase (DcytB), and Fpn1, which are iron transporters critical for adaptive changes in iron absorption. We demonstrate that HIF2a and its downstream target gene, DMT1 are essential for iron accumulation in mouse models of β-thalassemia and sickle cell disease. Furthermore, studies of thalassemic mouse model with established iron overload demonstrated that loss of intestinal HIF2a and DMT1 signaling led to decreased tissue iron accumulation in the livers. Interestingly, disrupting intestinal HIF2a not only improves tissue iron accumulation, but a marked improvement of anemia was also observed. These novel findings suggests that inhibition of HIF2a signaling pathway could be a novel and robust treatment strategy for several conditions that cause iron overload with anemia. Disclosures No relevant conflicts of interest to declare.

Algorithms for Iron and Zinc Bioavailability: Are they Accurate?

2010 ◽  
Vol 80 (45) ◽  
pp. 257-262 ◽  
Author(s):  
Janet R. Hunt
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
Large Data ◽  
Iron Bioavailability ◽  
Dietary Factors ◽  
Current Evidence ◽  
Zinc Absorption ◽  
Data Set ◽  
Zinc Bioavailability ◽  
Iron And Zinc

Several bioavailability algorithms have been proposed for iron and zinc, confirming the need for these tools while emphasizing the challenge of deriving algorithms with accepted accuracy. This manuscript briefly reviews current evidence on the accuracy of proposed algorithms. Iron absorption is strongly influenced by both body iron status and dietary availability, and most evidence suggests that these do not interact. There is considerable evidence of a logarithmic relationship between percent iron absorption and serum ferritin that allows a simple and accurate computation of how human iron status affects absorption (in the absence of inflammation). Computing the effect of dietary variation on nonheme iron absorption has been challenging because of multiple influential dietary factors and incomplete knowledge of their chemical characteristics, food composition, interactions, and dose-response relationships. At present there is no fully validated algorithm for dietary iron bioavailability. Predicting zinc absorption is less complex. Fractional zinc absorption is substantially influenced by the amount of zinc consumed, and this factor, together with ingested phytic acid, account for a considerable degree of the variance. A multivariate saturation model based on these two variables has been derived using data from multiple studies and independently validated with a single large data set.

Limited value of routine iron studies prior to initiation of erythropoietin therapy in patients with ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 19677-19677
Author(s):  
G. Riebandt ◽  
S. A. South ◽  
K. Odunsi ◽  
S. Lele ◽  
K. Rodabaugh
Keyword(s):  
Ovarian Cancer ◽  
Growth Factors ◽  
Iron Deficiency ◽  
Cancer Patients ◽  
Iron Status ◽  
Ferritin Level ◽  
The Body ◽  
Deficiency Anemia ◽  
Functional Iron Deficiency ◽  
Iron Deficient

19677 Background: Anemia is a common consequence of cancer which significantly impacts patient quality of life. The mainstay of treatment for cancer- and chemotherapy-related anemia is erythropoietin therapy. However, approximately 30% to 50% of patients will not respond to these growth factors. The literature attributes this lack of response to functional iron deficiency, when iron stores are normal but the body cannot meet the increased rate of erythropoiesis. We evaluated the iron status of patients with ovarian malignancies receiving chemotherapy and erythropoietin therapy to establish a baseline for implementation of an intervention service. Methods: After obtaining Institutional Review Board approval, we identified 55 ovarian cancer patients receiving erythropoietin therapy from January to December 2005. We then performed a retrospective chart review for patients who had iron studies available. Results: Thirty-four patients had complete iron studies performed, while an additional 10 had only a ferritin level obtained. The mean hemoglobin for all patients was 9.9g/dl (6.9–13.1) with a mean MCV (mean corpuscular volume) of 92.7fl. Four (12%) patients were iron deficient based on ferritin <100ng/ml and iron saturation <20%. However, these patients had normal MCVs, indicating iron deficiency was not the etiology of their anemia. A few patients were assessed for B12 and folate deficiency, but none were identified. Interestingly, we had 22 patients with elevated ferritin levels (greater than 322ng/ml), with the highest being 2178ng/ml. Conclusions: Our results identified a few patients who were iron deficient, but none were diagnosed with iron deficiency anemia. Therefore, the role of routine iron screening in patients with a normal MCV prior to initiation of erythropoietin therapy is in question. We believe that functional iron deficiency may contribute to anemia in our population. Therefore, we suggest that all patients receive iron supplementation at erythropoietin therapy initiation. We plan to prospectively assess the optimal route of iron administration in ovarian cancer patients in order to improve the response rate to erythropoietic growth factors. No significant financial relationships to disclose.

Modulation of the HIF2-NCOA4 axis in enterocytes attenuates iron loading in a mouse model of hemochromatosis

Blood ◽  
2022 ◽  
Author(s):  
Nupur K Das ◽  
Chesta Jain ◽  
Amanda D. Sankar ◽  
Andrew J Schwartz ◽  
Naiara Santana-Codina ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Mouse Model ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Hypoxia Inducible Factor ◽  
Whole Body ◽  
Deficiency Anemia ◽  
Null Mouse ◽  
Intestinal Iron Absorption

Intestinal iron absorption is activated during increased systemic iron demand. The best-studied example is iron-deficiency anemia, which increases intestinal iron absorption. Interestingly, the intestinal response to anemia is very similar to that of iron overload disorders, as both the conditions activate a transcriptional program that leads to a hyperabsorption of iron via the transcription factor hypoxia-inducible factor (HIF)2a. However, pathways to selectively target intestinal-mediated iron overload remain unknown. Nuclear receptor co-activator 4 (NCOA4) is a critical cargo receptor for autophagic breakdown of ferritin (FTN) and subsequent release of iron, in a process termed ferritinophagy. Our work demonstrates that NCOA4-mediated intestinal ferritinophagy is integrated to systemic iron demand via HIF2a. To demonstrate the importance of intestinal HIF2a/ferritinophagy axis in systemic iron homeostasis, whole body and intestine-specific NCOA4-null mouse lines were generated and assessed. These analyses revealed that the intestinal and systemic response to iron deficiency was not altered following disruption of intestinal NCOA4. However, in a mouse model of hemochromatosis, ablation of intestinal NCOA4 was protective against iron overload. Therefore, NCOA4 can be selectively targeted for the management of iron overload disorders without disrupting the physiological processes involved in the response to systemic iron deficiency.

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