Intestinal Iron Absorption: Regulation by Dietary & Systemic Factors

2010 ◽  
Vol 80 (45) ◽  
pp. 231-242 ◽  
Author(s):  
Paul A. Sharp
Keyword(s):  
Iron Homeostasis ◽  
Iron Absorption ◽  
Iron Status ◽  
Heme Iron ◽  
Dietary Factors ◽  
The Body ◽  
Excess Iron ◽  
Non Heme Iron ◽  
Systemic Factors ◽  
And Function

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.

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.

scholarly journals Role of Dietary Flavonoids in Iron Homeostasis

2019 ◽  
Vol 12 (3) ◽  
pp. 119 ◽  
Author(s):  
Marija Lesjak ◽  
Surjit K. S. Srai
Keyword(s):  
Iron Metabolism ◽  
Iron Homeostasis ◽  
Iron Absorption ◽  
Therapeutic Potential ◽  
State Of The Art ◽  
Iron Status ◽  
Dietary Factors ◽  
The Body ◽  
Dietary Flavonoids

Balancing systemic iron levels within narrow limits is critical for human health, as both iron deficiency and overload lead to serious disorders. There are no known physiologically controlled pathways to eliminate iron from the body and therefore iron homeostasis is maintained by modifying dietary iron absorption. Several dietary factors, such as flavonoids, are known to greatly affect iron absorption. Recent evidence suggests that flavonoids can affect iron status by regulating expression and activity of proteins involved the systemic regulation of iron metabolism and iron absorption. We provide an overview of the links between different dietary flavonoids and iron homeostasis together with the mechanism of flavonoids effect on iron metabolism. In addition, we also discuss the clinical relevance of state-of-the-art knowledge regarding therapeutic potential that flavonoids may have for conditions that are low in iron such as anaemia or iron overload diseases.

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.

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 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 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 Intestinal Mucosal Mechanisms Controlling Iron Absorption

Blood ◽  
1963 ◽  
Vol 22 (4) ◽  
pp. 406-415 ◽  
Author(s):  
MARCEL E. CONRAD ◽  
WILLIAM H. CROSBY ◽  
Betty Merrill
Keyword(s):  
Iron Deficiency ◽  
Epithelial Cells ◽  
Iron Absorption ◽  
The Body ◽  
Iron Store ◽  
Dietary Iron ◽  
Receptor System ◽  
Excess Iron ◽  
Metabolic Requirement ◽  
Iron Receptor

Abstract Radioautographic studies provide evidence to support a concept of the mechanism whereby the small intestine controls absorption of iron. Three different states of the body’s iron stores have been considered in this regard: iron excess, iron deficiency and normal iron repletion. As the columnar epithelial cells of the duodenal villi are formed they incorporate a portion of intrinsic iron from the body’s iron store, the amount depending upon the body’s requirement for new iron. It is predicated that with iron excess the iron-receptor mechanism in these cells is saturated with intrinsic iron; this then prevents the cell from accepting dietary iron. In the normal state of iron repletion the receptor mechanism remains partly unsaturated, allowing small amounts of dietary iron to enter the cell. Part of this proceeds into the body to satisfy any metabolic requirement for iron. Part is retained in the mucosal epithelial cells to complete the saturation of the iron-receptor mechanism. This bound iron is subsequently lost when the epithelial cells are sloughed at the end of their life cycle. In iron deficiency it is postulated that the receptor system is inactive or diminished so that entry of dietary iron into the body is relatively uninhibited.

Food iron absorption in idiopathic hemochromatosis

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 2187-2193 ◽  
Author(s):  
SR Lynch ◽  
BS Skikne ◽  
JD Cook
Keyword(s):  
Serum Ferritin ◽  
Iron Absorption ◽  
Iron Status ◽  
Normal Subjects ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Ferritin Concentration ◽  
Normal Volunteers ◽  
Idiopathic Hemochromatosis ◽  
The Relationship

Abstract The relationship between iron status and food iron absorption was evaluated in 75 normal volunteers, 15 patients with idiopathic hemochromatosis, and 22 heterozygotes by using double extrinsic radioiron tags to label independently the nonheme and heme iron components of a hamburger meal. In normal subjects, absorption from each of these pools was inversely correlated with storage iron, as measured by the serum ferritin concentration. In patients with hemochromatosis, absorption of both forms of iron was far greater than would be predicted from the relationship between absorption and serum ferritin observed in normal volunteers. Nevertheless, there was still a modest but statistically significant reduction in absorption of nonheme iron with increasing serum ferritin. This relationship could not be demonstrated in the case of heme iron absorption. In heterozygotes, nonheme iron absorption from a hamburger meal containing no supplementary iron did not differ significantly from that observed in normal volunteers. However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated. These studies confirm the presence of excessive nonheme iron absorption even from unfortified meals in patients with idiopathic hemochromatosis and suggest in addition that they are particularly susceptible to iron loading from diets containing a high proportion of heme iron. Impaired regulation of nonheme iron absorption was also observed in heterozygous individuals, but a statistically significant abnormality was demonstrable only when the test meal contained a large highly bioavailable iron supplement.

scholarly journals Dietary Factors Moderate the Relation between Groundwater Iron and Anemia in Women and Children in Rural Bangladesh

2019 ◽  
Vol 3 (10) ◽  
Author(s):  
Amanda S Wendt ◽  
Jillian L Waid ◽  
Sabine Gabrysch
Keyword(s):  
Iron Deficiency ◽  
Vitamin C ◽  
Fruits And Vegetables ◽  
Iron Absorption ◽  
Cluster Randomized Trial ◽  
Heme Iron ◽  
Dietary Factors ◽  
Baseline Survey ◽  
Women And Children ◽  
Cluster Randomized

ABSTRACT Background Anemia affects ∼1.6 billion people worldwide, often owing to iron deficiency. In Bangladesh, high levels of anemia have been observed alongside little iron deficiency. Elevated concentrations of groundwater iron could constitute a significant source of dietary iron. Objective We aimed to quantify the effect of groundwater iron on anemia in nonpregnant women and young children in Bangladesh, taking into account dietary factors that may affect iron absorption. Methods We analyzed data on 1871 nonpregnant women and 987 children (6–37 mo) from the 2015 baseline survey of the Food and Agricultural Approaches to Reducing Malnutrition cluster-randomized trial in Sylhet, Bangladesh. We used logistic regression with robust standard errors to assess effects of self-reported groundwater iron, dietary intake, and sociodemographic characteristics on anemia, considering interactions between groundwater iron and dietary factors. Results Groundwater iron presence was associated with less anemia in women (OR: 0.74; 95% CI: 0.60, 0.90) and children (OR: 0.58; 95% CI: 0.44, 0.76). This effect was modified by dietary factors. In women, the effect of groundwater iron on anemia was stronger if no vitamin C–rich or heme-iron foods were consumed, and there was a clear dose–response relation. In children, intake of vitamin C–rich foods strengthened the effect of groundwater iron on anemia, and there was no evidence for interaction by intake of iron-rich foods. Conclusions Heme-iron and vitamin C consumption reduced the effect of groundwater iron on anemia among women but not children in Bangladesh, which may be due to higher levels of iron deficiency and lower levels of iron intake among children. Vitamin C consumption appears to enhance iron absorption from groundwater in children and they may thus benefit from consuming more vitamin C–rich fruits and vegetables. Even among women and children consuming heme-iron or vitamin C–rich foods and groundwater iron, anemia prevalence remained elevated, pointing to additional causes of anemia beyond iron deficiency. This trial was registered at clinicaltrials.gov as NCT02505711.

High specific activity heme-Fe and its application for studying heme-Fe metabolism in Caco-2 cell monolayers

2002 ◽  
Vol 283 (5) ◽  
pp. G1125-G1131 ◽  
Author(s):  
Jennifer R. Follett ◽  
Yasushi A. Suzuki ◽  
Bo Lönnerdal
Keyword(s):  
Iron Absorption ◽  
Specific Activity ◽  
Iron Status ◽  
Basolateral Membrane ◽  
High Specific Activity ◽  
Heme Iron ◽  
Nonheme Iron ◽  
Serum Free Medium ◽  
Factors Affecting ◽  
Cell Monolayers

Heme-Fe is an important source of dietary iron in humans. Caco-2 cells have been used extensively to study human iron absorption with an emphasis on factors affecting nonheme iron absorption. Therefore, we examined several factors known to affect heme iron absorption. Cells grown in bicameral chambers were incubated with high specific activity [59Fe]heme alone or with 1% globin, BSA, or fatty acid-free BSA (BSA-FA) to examine the effect of protein source on absorption. Heme iron absorption was enhanced by globin and inhibited by BSA and BSA-FA. Absorption of heme iron in cells pretreated for 7 days with serum-free medium containing 1, 25, 50, or 100 μM Fe was higher in the 1-μM-Fe pretreatment group than in all other groups ( P < 0.05), showing an effect of iron status. Increased heme concentrations resulted in decreased percent absorbed but increased total heme iron absorption and increased transport rate across the basolateral membrane. Finally, cells treated with 10 μM CdCl2, which induces heme oxygenase, demonstrated higher absorption of [59Fe]heme than control cells ( P < 0.05). Our results from Caco-2 cells are in agreement with human studies and make this a promising model for examining intestinal heme iron absorption.

Sign in / Sign up

Export Citation Format

Share Document