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
2005 ◽  
Vol 75 (6) ◽  
pp. 436-445 ◽  
Author(s):  
Sean Lynch

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.


2010 ◽  
Vol 82 (2) ◽  
pp. 429-436 ◽  
Author(s):  
Bo Lönnerdal

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.


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

2012 ◽  
Vol 150 (1-3) ◽  
pp. 68-73 ◽  
Author(s):  
Diego Gaitán ◽  
Manuel Olivares ◽  
Bo Lönnerdal ◽  
Alex Brito ◽  
Fernando Pizarro

2005 ◽  
Vol 75 (6) ◽  
pp. 405-412 ◽  
Author(s):  
Manju B. Reddy

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.


Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1686
Author(s):  
Xiaoyu Wang ◽  
Mingzhen Zhang ◽  
Regina R. Woloshun ◽  
Yang Yu ◽  
Jennifer K. Lee ◽  
...  

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.


2010 ◽  
Vol 80 (45) ◽  
pp. 231-242 ◽  
Author(s):  
Paul A. Sharp

Iron is an essential trace metal in human metabolism. However, imbalances in iron homeostasis are prevalent worldwide and have detrimental effects on human health. Humans do not have the ability to remove excess iron and therefore iron homeostasis is maintained by regulating the amount of iron entering the body from the diet. Iron is present in the human diet in number of different forms, including heme (from meat) and a variety of non-heme iron compounds. While heme is absorbed intact, the bioavailability of non-heme iron varies greatly depending on dietary composition. A number of dietary components are capable of interacting with iron to regulate its solubility and oxidation state. Interestingly, there is an emerging body of evidence suggesting that some nutrients also have direct effects on the expression and function of enterocyte iron transporters. In addition to dietary factors, body iron status is a major determinant of iron absorption. The roles of these important dietary and systemic factors in regulating iron absorption will be discussed in this review.


PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153885 ◽  
Author(s):  
Lichen Yang ◽  
Yuhui Zhang ◽  
Jun Wang ◽  
Zhengwu Huang ◽  
Lingyan Gou ◽  
...  

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