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.

The Use of Caco-2 Cells to Estimate Fe Absorption in Humans - a Critical Appraisal

2010 ◽  
Vol 80 (45) ◽  
pp. 307-313 ◽  
Author(s):  
Ann-Sofie Sandberg
Keyword(s):  
Iron Uptake ◽  
Iron Absorption ◽  
Cell Model ◽  
Iron Bioavailability ◽  
Dietary Factors ◽  
Cell Uptake ◽  
Epithelial Cell Line ◽  
Cellular Iron ◽  
Cellular Iron Uptake

The Caco-2 cell model is widely used to assess the bioaccessibility/availability of iron from foods and diets. Analysis of iron uptake in this human epithelial cell line is usually preceded by a two-step digestion to simulate the conditions in the stomach and small intestine. Moreover, culturing the cells on inserts permits the measurement of iron transport. The cellular iron uptake is determined by direct measurements using radioisotopes, or indirectly by measurement of ferritin, the intracellular storage form of iron. There is a good correlation between Caco-2 cell uptake and human iron bioavailability for a number of dietary factors known to affect iron absorption. However, recent data suggest that in some cases there is no correlation. Possible reasons for such discrepancies, the benefits, and limitations of the Caco-2 cell model are discussed. In conclusion, in vitro experiments with Caco-2 cells are important tools for ranking foods with respect to bioavailability, for mechanistic studies of iron absorption, and for studies of dietary factors influencing absorption. The results need to be confirmed in humans.

scholarly journals GENERIC ALGORITHM SOLUTION IN ESTIMATION OF THE IRON ABSORPTION POTENTIAL FROM COMPLEX SCHOOL MEALS

2021 ◽  
Vol XXVIII (4) ◽  
pp. 167-179
Author(s):  
Rodica Sturza ◽  
◽  
Nina Mija ◽  
Olga Deseatnicov ◽  
Eugenia Covaliov ◽  
...  
Keyword(s):  
Absorption Rate ◽  
Iron Absorption ◽  
Heme Iron ◽  
Iron Bioavailability ◽  
Dietary Factors ◽  
School Meals ◽  
Vitro Assay ◽  
Nutritional Factors ◽  
Dialyzable Iron

New analytical tools to study iron bioavailability are proposed in this article. An algorithm was devised to predict dietary iron abortion from school meals based on the contents of dietary factors that have the ability to promote or inhibit heme or non-heme iron absorption. The highest absorption rate of iron from representative meals was observed in the presence of ascorbic acid (27,73%) or meat ingredients (27,70%), and the lowest absorption rate – in the presence of Ca (12,40%), tannins (5,83%) and polyphenols (5,36%). Relationships between quantities of total iron intake from foods (dialyzable iron, in vitro assay) and the value of nutritional factors in those are described as exponential equations allowing calculations at any stationary state. In elaborated formula the rate of iron absorbance can be predicted considering one, two or three nutritional factors at the same time. The results emphasize the fact that it is important to understand the meal composition for the correct estimation of iron bioavailability.

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.

Acute Copper Supplementation Does Not Inhibit Non-Heme Iron Bioavailability in Humans

2009 ◽  
Vol 136 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Manuel Olivares ◽  
Fernando Pizarro ◽  
Daniel López de Romaña ◽  
Manuel Ruz
Keyword(s):  
Heme Iron ◽  
Iron Bioavailability ◽  
Non Heme Iron ◽  
Copper Supplementation

Low Cytosolic Non-Heme Iron Levels in Erythroid Cells Prevent IRP2-Mediated Ferritin Upregulation during Differentiation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 705-705 ◽  
Author(s):  
Matthias Schranzhofer ◽  
Manfred Schifrer ◽  
Bruno Galy ◽  
Matthias Hentze ◽  
Prem Ponka ◽  
...  
Keyword(s):  
Terminal Differentiation ◽  
Heme Iron ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Erythroid Cells ◽  
High Iron ◽  
Cellular Iron ◽  
Non Heme Iron ◽  
Irp1 And Irp2 ◽  
In Erythroid Cells

Abstract Erythroid cells are the major consumers of iron in the human body. Differentiating erythroid cells shuttle the metal with very high efficiency towards mitochondria for the formation of heme. To satisfy their high iron needs, developing red blood cells (RBC) have to sustain high expression of transferrin receptor 1 (TfR) despite increasing cellular iron concentration. Moreover, synthesis of ferritin must not be activated by incoming iron, since this would represent a counterproductive storage during the phase of high iron demand. Recently we have demonstrated that during terminal differentiation primary erythroid cells satisfy their exceptionally high requirements for iron by switching to a mode where the post-transcriptional, iron-dependent regulatory system, formed by iron responsive proteins (IRP1 and IRP2) and iron responsive elements (IREs), seems to sense a low-iron state. This occurs despite a massive net increase of iron import into the cell (Schranzhofer et al., Blood107:4159, 2006). To examine the hypothesis that erythroid cells have low non-heme iron levels in their cytosol, we experimentally increased the cytosolic iron pool by either inhibiting heme biosynthesis or overloading cells with iron. Both block of heme synthesis by either succinylacetone or isonicotinic acid hydrazide (INH) or administration of ferric ammonium citrate, resulted in a clear increase in ferritin levels. This increase was directly proportional to the increase in the cellular concentration of non-heme-iron. Moreover, the effect of INH, the inhibitor of 5-aminolevulinic acid (ALA) synthase, could be reversed by the addition of ALA. Strikingly, increases in ferritin expression upon perturbation of cellular iron homeostasis strongly correlated with the loss of IRE-binding activity of IRP2 but not IRP1, as determined by mobility shift assays. This suggests that IRP2 is the major regulator of ferritin expression in erythroid cells. To further elaborate on this observation, we cultured primary erythroblasts derived from IRP1−/− and IRP2−/− mice (kindly provided by Drs. M. Hentze and B. Galy). In agreement with the published phenotype of microcytic hypochromic anemia, only erythroblasts lacking IRP2 exhibited a reduction in hemoglobinization. Moreover, only IRP2−/− cells showed a significant increase in ferritin expression, whereas developing RBC lacking IRP1 had levels of ferritin protein equal to wild type cells. We conclude that in erythroid cells efficient shuttling of incoming iron towards mitochondria and its prompt use for heme formation is important to keep the cytosol in an iron-deprived state and consequently ferritin protein levels low. This translational repression seems to be mainly achieved by IRP2. Together with the observation that surface expression of TfR was reduced in IRP2−/− erythroblasts during self renewal but not during terminal differentiation, our results suggest that not only down-regulation of TfR, but also up-regulation of ferritin may be a major factor for the anemic phenotype observed in IRP2−/− mice.

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

The Importance and Bioavailability of Phytoferritin-Bound Iron in Cereals and Legume Foods

2007 ◽  
Vol 77 (3) ◽  
pp. 152-157 ◽  
Author(s):  
Lönnerdal
Keyword(s):  
Iron Absorption ◽  
Proteolytic Enzymes ◽  
Human Subjects ◽  
Human Study ◽  
Heme Iron ◽  
Dietary Factors ◽  
Whole Body ◽  
Significant Difference ◽  
Staple Foods

Ferritin is present in several types of plants in low concentrations, but it is possible to enhance this content by plant breeding, or by inserting the gene for ferritin into staple foods. Since each ferritin molecule can bind thousands of iron atoms, this may be a sustainable means to increase the iron content of plants. Before launching such efforts it is important to determine whether ferritin-bound iron is bioavailable. We assessed this in vitro using Caco-2 cells and in vivo using radiolabeled ferritin and whole body counting in human subjects. In Caco-2 cells, we found that dietary factors affecting iron absorption, such as ascorbic acid, phytate, and calcium, had very limited effect on iron uptake from intact ferritin, suggesting that ferritin-bound iron is absorbed via a mechanism different from that of non-heme iron. Using in vitro digestion, we found that ferritin was relatively resistant against proteolytic enzymes. Binding of ferritin to Caco-2 cells was found to be saturable and the kinetics for binding characteristic for a receptor-mediated process. In human subjects, we found that iron absorption from animal ferritin was similar to that from ferrous sulfate, suggesting that iron is well absorbed from ferritin. We did not find any significant difference between iron absorption from ferritin reconstituted with high-phosphate (plant-type) and low-phosphate (animal-type) ferritin mineral, suggesting that plant ferritin-iron is bioavailable. In a subsequent human study we also found that iron from purified soybean ferritin given in a meal was as well absorbed as ferrous iron. In conclusion, iron is well absorbed from phytoferritin and may represent a means of biofortification of staple foods.

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
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