Ilex paraguariensis (A. St.-Hil.) leaf infusion decreases iron absorption in patients with hereditary hemochromatosis: a randomized controlled crossover study

2021 ◽  
Author(s):  
Cristiane Manfé Pagliosa ◽  
Francilene Gracieli Kunradi Vieira ◽  
Bruno Vieira Dias ◽  
Vivian Karla Brognoli Franco ◽  
Hanna Pillmann Ramos ◽  
...  
Keyword(s):  
Iron Overload ◽  
Crossover Study ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Heme Iron ◽  
Ilex Paraguariensis ◽  
Overload Control ◽  
Randomized Controlled ◽  
Non Heme Iron ◽  
Acute Intake

The acute intake of Ilex paraguariensis leaf infusion significantly inhibited the absorption of non-heme iron in hereditary hemochromatosis patients with the HFE genotype and should be considered as a potential adjuvant for iron overload control.

scholarly journals Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1686
Author(s):  
Xiaoyu Wang ◽  
Mingzhen Zhang ◽  
Regina R. Woloshun ◽  
Yang Yu ◽  
Jennifer K. Lee ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Heme Iron ◽  
Dietary Iron ◽  
Iron Loading ◽  
Body Iron ◽  
Iron Restriction ◽  
Sirna Treatment ◽  
Non Heme Iron

Intestinal iron transport requires an iron importer (Dmt1) and an iron exporter (Fpn1). The hormone hepcidin regulates iron absorption by modulating Fpn1 protein levels on the basolateral surface of duodenal enterocytes. In the genetic, iron-loading disorder hereditary hemochromatosis (HH), hepcidin production is low and Fpn1 protein expression is elevated. High Fpn1-mediated iron export depletes intracellular iron, causing a paradoxical increase in Dmt1-mediated iron import. Increased activity of both transporters causes excessive iron absorption, thus initiating body iron loading. Logically then, silencing of intestinal Dmt1 or Fpn1 could be an effective therapeutic intervention in HH. It was previously established that Dmt1 knock down prevented iron-loading in weanling Hamp (encoding hepcidin) KO mice (modeling type 2B HH). Here, we tested the hypothesis that Dmt1 silencing combined with dietary iron restriction (which may be recommended for HH patients) will mitigate iron loading once already established. Accordingly, adult Hamp KO mice were switched to a low-iron (LFe) diet and (non-toxic) folic acid-coupled, ginger nanoparticle-derived lipid vectors (FA-GDLVs) were used to deliver negative-control (NC) or Dmt1 siRNA by oral, intragastric gavage daily for 21 days. The LFe diet reduced body iron burden, and experimental interventions potentiated iron losses. For example, Dmt1 siRNA treatment suppressed duodenal Dmt1 mRNA expression (by ~50%) and reduced serum and liver non-heme iron levels (by ~60% and >85%, respectively). Interestingly, some iron-related parameters were repressed similarly by FA-GDLVs carrying either siRNA, including 59Fe (as FeCl3) absorption (~20% lower), pancreatic non-heme iron (reduced by ~65%), and serum ferritin (decreased 40–50%). Ginger may thus contain bioactive lipids that also influence iron homeostasis. In conclusion, the combinatorial approach of FA-GDLV and Dmt1 siRNA treatment, with dietary iron restriction, mitigated pre-existing iron overload in a murine model of HH.

The Precision of in vitro Methods and Algorithms for Predicting the Bioavailability of Dietary Iron

2005 ◽  
Vol 75 (6) ◽  
pp. 436-445 ◽  
Author(s):  
Sean Lynch
Keyword(s):  
Iron Absorption ◽  
Heme Iron ◽  
Iron Bioavailability ◽  
Cell Uptake ◽  
In Vitro Tests ◽  
Cellular Iron ◽  
Non Heme Iron ◽  
Human Volunteers ◽  
Dialyzable Iron

Three factors determine how much iron will be absorbed from a meal. They are the physiological mechanisms that regulate uptake by and transfer through the enterocytes in the upper small intestine, the quantity of iron in the meal, and its availability to the cellular iron transporters. Established methods exist for predicting the effect of physiological regulation and for measuring or estimating meal iron content. Three approaches to estimating bioavailability have been advocated. Two are in vitro screening procedures: measurement of dialyzable iron and Caco-2 cell uptake, both carried out after in vitro simulated gastric and pancreatic digestion. The third is the use of algorithms based on the predicted effects of specific meal components on absorption derived from isotopic studies in human volunteers. The in vitro procedures have been very useful for identifying and characterizing factors that affect non-heme iron absorption, but direct comparisons between absorption predicted from the in vitro tests and measurements in human volunteers have only been made in a limited number of published studies. The available data indicate that dialysis and Caco-2 cell uptake are useful for ranking meals and single food items in terms of predicted iron bioavailability, but may not reflect the magnitudes of the effects of factors that influence absorption accurately. Algorithms based on estimates of the amounts of heme iron and of enhancers and inhibitors of non-heme iron absorption in foods make it possible to classify meals or diets as being of high, medium, or low bioavailability. The precision with which meal iron bioavailability can be predicted in a population, for which a specific algorithm has been developed, is improved by measuring the content of the most important enhancers and inhibitors. However, the accuracy of such predictions appears to be much lower when the algorithm is applied to meals eaten by different populations.

scholarly journals Iron age: novel targets for iron overload

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 216-221 ◽  
Author(s):  
Carla Casu ◽  
Stefano Rivella
Keyword(s):  
Iron Overload ◽  
Iron Age ◽  
Iron Metabolism ◽  
Iron Absorption ◽  
Hereditary Hemochromatosis ◽  
Therapeutic Approaches ◽  
Hepcidin Expression ◽  
Beneficial Effects ◽  
Excess Iron ◽  
Major Factors

Abstract Excess iron deposition in vital organs is the main cause of morbidity and mortality in patients affected by β-thalassemia and hereditary hemochromatosis. In both disorders, inappropriately low levels of the liver hormone hepcidin are responsible for the increased iron absorption, leading to toxic iron accumulation in many organs. Several studies have shown that targeting iron absorption could be beneficial in reducing or preventing iron overload in these 2 disorders, with promising preclinical data. New approaches target Tmprss6, the main suppressor of hepcidin expression, or use minihepcidins, small peptide hepcidin agonists. Additional strategies in β-thalassemia are showing beneficial effects in ameliorating ineffective erythropoiesis and anemia. Due to the suppressive nature of the erythropoiesis on hepcidin expression, these approaches are also showing beneficial effects on iron metabolism. The goal of this review is to discuss the major factors controlling iron metabolism and erythropoiesis and to discuss potential novel therapeutic approaches to reduce or prevent iron overload in these 2 disorders and ameliorate anemia in β-thalassemia.

Ineffective Erythropoiesis in β-Thalassemia Is Characterized by Increased Iron Absorption Mediated by down Regulation of Hepcidin and up Regulation of Ferroportin.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1543-1543 ◽  
Author(s):  
Sara Gardenghi ◽  
Maria Marongiu ◽  
Pedro Ramos ◽  
Ella Guy ◽  
Laura Breda ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Content ◽  
Iron Absorption ◽  
Hematological Parameters ◽  
Iron Concentration ◽  
Dry Weight ◽  
Heme Iron ◽  
Ineffective Erythropoiesis ◽  
Transfusion Therapy ◽  
Expression Levels

Abstract Progressive iron overload occurs in β-thalassemia as a result of increased gastrointestinal absorption. Our goal is to investigate the relationship between ineffective erythropoiesis (IE), iron-related genes and organ iron distribution in mice that exhibit levels of anemia consistent with thalassemia intermedia (th3/+) and major (th3/th3), as we described previously. The th3/th3 mice die in 8 weeks due to severe anemia but can be rescued by transfusion therapy. We analyzed up to 90 animals at 2, 5 and 12 months, as appropriate. We monitored various hematological parameters, tissue iron content and quantitative-PCR levels of Hamp, Fpn1, Smad4, Cebpa, Hfe, Tfr1 and other genes involved in iron metabolism in liver, spleen, kidney, heart and duodenum. At 2 months, th3/th3 mice had the highest total body iron content and highest degree of IE. The total iron was 53.6±21.0, 406.1±156.1, 657.7±40.3 μg in the spleen, and 107.5±35.7, 208.5±24.9 and 1298.7±427.5 μg in the liver of +/+, th3/+ and th3/th3, respectively (n≥5 per genotype). However, if the organ size was not taken in account, the iron concentration in the spleen of th3/+ was higher, in average, than that of th3/th3 mice (3.8±1.5 and 2.9±0.5 μg/mg), while in the liver was the opposite (0.6±0.1 and 5.1±2.0 μg/mg of dry weight, P<0.001). Heme and non-heme iron analyses provided similar results. Surprisingly, the distribution of iron within organs also differed. In th3/+ mice, the hepatic iron was almost exclusively located in Kupffer cells, whereas in th3/th3 mice in parenchymal cells. Our data suggest that Hamp is responsible for the increased iron absorption, being reduced to 20% and 70% in 2 month-old th3/+ and th3/th3 mice compared to +/+ animals (P<0.001). Hfe was reduced by 50% (P<0.05) in the liver of the animals that expressed low Hamp levels, indicating that Hfe could be directly responsible for Hamp regulation or share the same regulatory pathway. Low levels of Smad4 and Cebpa were observed only in the liver of mice with the lowest Hamp expression (P<0.05), indicating that these proteins might contribute to further decreased Hamp synthesis. In addition, while Tfr1 in th3/+ mice was 40% lower in the liver, it was up-regulated (400%) in th3/th3 mice (P<0.001), which may explain why iron is increased more in the liver of th3/th3 mice. In 5 and 12 month-old th3/+ mice, the surprising observation was the normal expression level of Hamp. However, in the duodenum, the Fpn1 RNA and protein levels were augmented (300%, P<0.001). In transfused th3/+ and th3/th3 animals, Hamp, Hfe, Cbpa and Smad4 expression levels were normalized or increased, while Tfr1 was down-regulated in both groups, which may explain the increased splenic iron deposition in these animals. Our data suggest that IE, together with the relative expression levels of Hamp and Tfr1, is largely responsible for the organ iron overload observed in young thalassemic mice. However, in older mice, it is the increase of Fpn1 levels in the duodenum that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the genesis of iron overload in β-thalassemia.

Alternative pathways for absorption of iron from foods

2010 ◽  
Vol 82 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Bo Lönnerdal
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
Age Groups ◽  
Heme Iron ◽  
Dietary Factors ◽  
Iron Binding ◽  
Alternative Pathways ◽  
Non Heme Iron ◽  
Lactoferrin Receptor ◽  
Iron Binding Proteins

Iron is known to be absorbed from foods in two major forms, heme iron and non-heme iron. Iron status as well as dietary factors known to affect iron absorption has limited effect on heme iron absorption, whereas inhibitors and enhancers of iron absorption have pronounced effects on non-heme iron absorption. The enterocyte transporter for non-heme iron, DMT1, is strongly up-regulated during iron deficiency and down-regulated during iron overload. A transporter for heme iron, HCP1, was recently characterized and is present on the apical membrane of enterocytes. Two other pathways for iron absorption have been discovered and may serve to facilitate uptake of iron from two unique iron-binding proteins, lactoferrin and ferritin. Lactoferrin is an iron-binding protein in human milk and known to survive proteolytic digestion. It mediates iron uptake in breast-fed infants through endocytosis via a specific lactoferrin receptor (LfR). Recently, lactoferrin has become popular as a food additive and may enhance iron status in several age groups. Ferritin is present in meat, but also in plants. The ferritin content of plants can be enhanced by conventional breeding or genetic engineering, and thereby increase iron intake of populations consuming plant-based diets. Ferritin is a bioavailable source of iron, as shown in recent human studies. Ferritin can be taken up by intestinal cells via endocytosis, suggesting a receptor-mediated mechanism.

Dietary gelatin enhances non-heme iron absorption possibly via regulation of systemic iron homeostasis in rats

2019 ◽  
Vol 59 ◽  
pp. 272-280 ◽  
Author(s):  
Lingyu Wu ◽  
Yaqun Zou ◽  
Yu Miao ◽  
Jiayou Zhang ◽  
Suqin Zhu ◽  
...  
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Heme Iron ◽  
Non Heme Iron

Inhibitory Effect of Calcium on Non-heme Iron Absorption May Be Related to Translocation of DMT-1 at the Apical Membrane of Enterocytes

2010 ◽  
Vol 58 (14) ◽  
pp. 8414-8417 ◽  
Author(s):  
Ben A. V. Thompson ◽  
Paul A. Sharp ◽  
Ruan Elliott ◽  
Susan J. Fairweather-Tait
Keyword(s):  
Iron Absorption ◽  
Apical Membrane ◽  
Inhibitory Effect ◽  
Heme Iron ◽  
Non Heme Iron

Non-heme Iron as Ferrous Sulfate Does Not Interact with Heme Iron Absorption in Humans

2012 ◽  
Vol 150 (1-3) ◽  
pp. 68-73 ◽  
Author(s):  
Diego Gaitán ◽  
Manuel Olivares ◽  
Bo Lönnerdal ◽  
Alex Brito ◽  
Fernando Pizarro
Keyword(s):  
Ferrous Sulfate ◽  
Iron Absorption ◽  
Heme Iron ◽  
Non Heme Iron

Algorithms to Assess non-Heme Iron Bioavailability

2005 ◽  
Vol 75 (6) ◽  
pp. 405-412 ◽  
Author(s):  
Manju B. Reddy
Keyword(s):  
Iron Absorption ◽  
Iron Status ◽  
Interactive Effect ◽  
Population Level ◽  
Heme Iron ◽  
Iron Bioavailability ◽  
Dietary Factors ◽  
Interactive Effects ◽  
Sufficient Information ◽  
Non Heme Iron

While sufficient information exists on the effect of individual factors on iron absorption, their net effect in a mixed meal is less well characterized, being dependent on the combination and quantity of the factors present in the meal. Over a period of more than 25 years, several models have been developed to estimate non-heme iron bioavailability, either to assess iron absorption from a meal or iron sufficiency in populations. Initially, a model was developed to calculate iron absorption in individuals with varying iron status that included only enhancers. This model was useful in classifying the diets but has limited value for accurale assessment. Later models were modified and improved by including inhibitors in the calculations. However, some included either phytate or tea but not in combination. The models that included all the factors in calculations assumed their effect was independent and additive rather than interactive, which is an important issue in addressing iron bioavailability. Although some of the models correlated estimated bioavailability with iron status of the population, the accuracy of the estimations is of concern due to lack of quantitative measurements of bioavailability modifiers, inability to consider interactive effects, and the use of non-iron status measurements. Recent research has led to the development of refined models to assess iron bioavailability of complex meals by comprehensively taking into consideration the interactive effect among enhancers and inhibitors. However, the models are based on single-meal studies and their application to whole diets at a population level is not clear. Accurate measurements of dietary factors and independent validation are needed before using these models. To date, no single model is applicable to all diets and additional studies are needed to develop new models to predict bioavailability of whole diets accurately, in addition to addressing dietary adequacy in all populations.

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