Inorganic Iron Absorption in Subjects with Iron Deficiency Anemia, Achylia gastrica and Alcoholic Cirrhosis Using a Whole-Body Counter

Absorption of dietary iron requires uptake of iron by the brush border of the intestinal epithelial cells, intracellular transport, and transfer to the systemic circulation. In iron-deficiency anemia, iron absorption is greatly increased, but the individual steps responsible for this increase have not been identified. We have developed a method to evaluate the rate constants for each of these steps, and we report here our results in beagle dogs a) under normal conditions and b) after phlebotomy to produce iron-deficiency anemia. Simultaneous administration of oral 59Fe3+-citrate and intravenous 55Fe-transferrin was used to investigate the kinetics of mucosal iron transport. Plasma levels of both isotopes and the whole-body excretion pattern of 59Fe were monitored sequentially, and the fractional mucosal transport rates were estimated by nonlinear least-squares fit of a physiologically based mathematical model to these data. Under normal conditions the fractional rate of mucosal iron uptake from the intestinal lumen was rate limiting, being less than 1% of the fractional rate of either iron incorporation into the mucosal storage pool or transfer of iron from the mucosa to the plasma. After induction of iron-deficiency anemia, the fractional mucosal iron uptake rate increased sixfold (P less than 0.005), while the rate of incorporation into the mucosal storage pool decreased ninefold (P less than 0.02); in contrast, the fractional rate of iron transfer to the plasma did not change. These results indicate that the enhanced iron absorption in iron-deficiency anemia is attributable to an increase in mucosal iron available for transfer to the plasma, leading in turn to a net increase in iron absorption, despite a normal fractional transfer rate.

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

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: A comprehensive review on iron absorption, bioavailability and emerging food fortification approaches

Trends in Food Science & Technology ◽

10.1016/j.tifs.2020.02.021 ◽

2020 ◽

Vol 99 ◽

pp. 58-75 ◽

Cited By ~ 18

Author(s):

Kumar Shubham ◽

T. Anukiruthika ◽

Sayantani Dutta ◽

A.V. Kashyap ◽

Jeyan A. Moses ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Deficiency Anemia ◽

Food Fortification ◽

Comprehensive Review

Download Full-text

Effect of green tea on iron absorption in elderly patients with iron deficiency anemia.

Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics ◽

10.3143/geriatrics.27.555 ◽

1990 ◽

Vol 27 (5) ◽

pp. 555-558 ◽

Cited By ~ 3

Author(s):

Kazuo Kubota ◽

Toshio Sakurai ◽

Kyoumi Nakazato ◽

Toyoho Morita ◽

Takuo Shirakura

Keyword(s):

Iron Deficiency ◽

Elderly Patients ◽

Green Tea ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Deficiency Anemia

Download Full-text

Brief Note: A Note Concerning the "100 Per Cent Value" in Iron Absorption Studies by Whole Body Counting

Blood ◽

10.1182/blood.v23.6.757.757 ◽

1964 ◽

Vol 23 (6) ◽

pp. 757-761 ◽

Cited By ~ 18

Author(s):

LEWIS M. SCHIFFER ◽

D. C. PRICE ◽

J. CUTTNER ◽

S. H. COHN ◽

EUGENE P. CRONKITE

Keyword(s):

Iron Absorption ◽

Whole Body ◽

Body Counter ◽

Whole Body Counter ◽

Absorption Studies ◽

Body Counting ◽

Whole Body Counting ◽

Body Count

Abstract The 4-hour whole body count is found to be clinically valid as a "100 per cent value" in iron absorption studies performed with a whole body counter. Measurement of iron absorption can be made 2 weeks after ingestion of radioiron, but not prior to this period.

Download Full-text

Respiratory infections drive hepcidin-mediated blockade of iron absorption leading to iron deficiency anemia in African children

Science Advances ◽

10.1126/sciadv.aav9020 ◽

2019 ◽

Vol 5 (3) ◽

pp. eaav9020 ◽

Cited By ~ 11

Author(s):

Andrew M. Prentice ◽

Amat Bah ◽

Momodou W. Jallow ◽

Amadou T. Jallow ◽

Saikou Sanyang ◽

...

Keyword(s):

Iron Deficiency ◽

Iron Deficiency Anemia ◽

Iron Absorption ◽

Respiratory Infections ◽

Fecal Calprotectin ◽

Deficiency Anemia ◽

Low Grade ◽

Reactive Protein ◽

African Children ◽

Low Grade Inflammation

Iron deficiency anemia (IDA) is the most prevalent nutritional condition worldwide. We studied the contribution of hepcidin-mediated iron blockade to IDA in African children. We measured hepcidin and hemoglobin weekly, and hematological, inflammatory, and iron biomarkers at baseline, 7 weeks, and 12 weeks in 407 anemic (hemoglobin < 11 g/dl), otherwise healthy Gambian children (6 to 27 months). Each child maintained remarkably constant hepcidin levels (P < 0.0001 for between-child variance), with half consistently maintaining levels that indicate physiological blockade of iron absorption. Hepcidin was strongly predicted by nurse-ascribed adverse events with dominant signals from respiratory infections and fevers (all P < 0.0001). Diarrhea and fecal calprotectin were not associated with hepcidin. In multivariate analysis, C-reactive protein was the dominant predictor of hepcidin and contributed to iron blockade even at very low levels. We conclude that even low-grade inflammation, especially associated with respiratory infections, contributes to IDA in African children.

Download Full-text