Fundamentals of Human Nutrition/Iron

11.1 Iron

Iron is one of the most essential minerals in the body. It helps to keep oxygen circulating throughout the body and also aids in bodily transport of certain essential chemicals. Iron is in every cell in your body and is an important component in hemoglobin – a protein molecule in erythrocytes that carries oxygen throughout the body. If your body has an iron deficiency, it lacks the resources to make healthy oxygen-carrying erythrocytes. Without healthy oxygen-carrying erythrocytes, the body cannot get enough oxygen to the rest of the body, which can cause the body to become tired and fatigued. Iron is also an important part of maintaining skin, hair and nail function.

If you have ever tried to give blood and could not because of your hemoglobin levels were too low, they often tell you to go eat iron-rich foods. Iron can enter the body through iron-rich foods like red meat, spinach and other dark, leafy green vegetables. Some people have such low iron that they take an iron supplement. These over-the-counter supplements are very common.

When iron levels are particularly low and cannot produce enough hemoglobin, a doctor may diagnose you with iron deficiency anemia. Some symptoms of iron deficiency anemia include extreme fatigue, weakness and shortness of breath, increased risk of infections and headaches. There are a few different causes of this disorder; blood loss can be a major reason for iron deficiency anemia. When you lose a good amount of blood you will also lose a good amount of iron. Your body needs an extra source of iron, like a supplement, in order to rapidly make more erythrocytes and hemoglobin. Another very common reason for iron deficiency anemia is simply a lack of iron in a daily diet. This is probably the most common reason for iron deficiency anemia, and also the most easily treatable. Ways to get more iron in a daily diet include eating more iron-rich foods like red meat, poultry, dark leafy green vegetables and eggs. Women who are pregnant have an increase risk of iron deficiency anemia because their body is using twice the amount of iron for themselves as well as for the fetus. Pregnant women can take an over-the-counter iron supplement to combat this issue. Women on their period have an increase risk of iron deficiency anemia because of blood loss. Vegetarians also have an increased iron deficiency anemia because they do not have a very iron-rich diet without red meat and poultry. (Updated by Murphy, E)

11.1.1 Sources

Iron can be found in a wide range of food sources. There are two types of dietary iron sources, heme iron and nonheme iron. Heme iron is derived from hemoglobin, which makes up 40% of iron found in animal sources. Heme iron is well absorbed. Examples of adequate animal source foods are red meats, fish, poultry, shellfish, and eggs. Liver, oysters, chickpeas, pumpkin seeds, soybeans and fortified cereals are especially bulky sources of dietary iron. Nonheme iron is derived from plant sources, making up 60% of iron found in plants and some animal tissues, such as in legumes, lentils, beans, spinach and dried fruits. Our bodies less efficiently absorb nonheme iron but it makes up the majority of our dietary iron. George Mateljan says that plant source foods contain more than 10% of our daily iron requirement per serving. This can be explained by the fact that plant source foods have fewer calories per serving and therefore have a higher density of nutrients per calorie. To assist our bodies in absorption of iron it is beneficial to eat an iron source along with a source of vitamin C. Adding 50 milligrams or more of vitamin to an iron-rich meal will make it possible to triple the absorption of dietary iron. According to nutritionist, vitamin C has a stronger affect on nonheme iron than it does on heme iron. Many vegetables such as broccoli are high in both iron and vitamin C, thus allowing a hefty amount of iron to be absorbed. Certain foods and beverages can decrease iron absorption, for example tea and coffee.

Iron Absorption Iron absorption is used to preserve Iron in the body so that the amount of iron excreted is matching the daily intake of iron. This regulation of iron is important because it could lead to anemia and various other iron deficiencies. Iron absorption takes place in the small intestine; particularly the duodenum and jejunum of the small intestine.1 However, only about 10% of iron in the duodenum becomes absorbed.1 There are a copious amount of factors that influence iron absorption. One factor that influences iron absorption are inhibitors. During absorption, gastric acid is released that lowers the pH inside the stomach to increase the solubility of iron to be absorbed into the enterocytes.1 However, inhibitors cause this gastric acid lowering to be impaired and prevent iron from being absorbed the way that it should. These inhibitors include dairy products, coffee, tea, oregano, soy, and cereals.2 Another factor affecting the absorption of iron are other metals competing for absorption. Iron is absorbed by use of a receptor called DMT-1, and these metal ions compete to attach to this receptor. These metal ions include lead, cobalt, strontium, manganese, and Zinc.1 Facilitators also affect iron absorption and these include iron deficiencies, amino acids, citrate, and ascorbate. Finally iron absorption is affected based on whether the iron is heme (easily absorbed in blood and comes from meat), or non-heme (Fe2+ and Fe3+).3 There are two types of iron that play a role in the absorption process: Heme iron, which is easily absorbed into the blood, and non-heme iron, which is absorbed by a more difficult process.3 The physical state of iron also plays a role in the absorption process. There is ferrous (FE2+) and there is ferric (Fe3+) iron. Ferrous iron is oxidized into the insoluble form of ferric iron by Vitamin C and gastric acid lowers the pH so that the iron is able to be taken up more easily into the cell.1 This absorption process of non-heme iron begins by active transport of iron into a cell (use of ATP) by a transporter cell called DMT-1 or the divalent mental transporter-1. This transporter actively moves the iron into the cell and is situated on the surface of the duodenum in enterocytes.4 This receptor is not iron specific and also transports various other metal ions into cells. Once the iron is absorbed by the transporter and is inside the enterocyte, it can either bind to ferroportin which is a transporter, or it can bind to ferritin which is an intracellular binding protein of iron.4 Iron that binds to ferritin tends to remain there because ferritin is a major storage site for iron as well. Whereas, Iron that binds to ferroportion is transported into the blood and binds to transferrin (iron binding protein of the blood), where iron is then transported to red blood cell precursors.4 Two signals also play a significant role in the absorption of iron into the enterocyte. The first is a hormone called erythropoietin, which is formed in the kidneys, stimulates red blood cell production, and promotes another signal to increase iron absorption. The second signal, hepcidin, is produced when iron stores are full. Hepcidin is produced by hepatocytes and regulates the amount of iron flowing into the blood in order to prevent an over or under amount of iron in the blood.4 The normal range of iron in the blood is about 20-45%. If iron in the blood is above the normal range it could potentially cause Hemochromatosis which will cause damage to cells and promote free radical formation that affect tissues in our body.4

References 1. Harvard University. Information center for sickle cell and Thalassemia Disorders. Iron absorption. 2012; 1. http://sickle.bwh.harvard.edu/iron_absorption.html 2. Hewitt, Doug. Foods That interfere with iron Absorption. Livestrong. 2015;2. http://www.livestrong.com/article/34792-foods-interfere-iron-absorption/ 3. Baggott, James. Heme and Iron. NetBiochem. 1995; 1. http://library.med.utah.edu/NetBiochem/hi9.htm 4. Washington University. Iron Absorption. Washington Education. http://courses.washington.edu/conj/bess/iron/iron.htm

11.1.2 Functions

Iron is an essential nutrient because it is required to make hemoglobin and myoglobin, which are oxygen-carrying proteins in the body’s blood cells. Hemoglobin is located in red blood cells, while myoglobin is located in muscles. About 70% of the bodies iron is found in hemoglobin and myoglobin. Hemoglobin assist in the transfer of oxygen from the lungs to tissues located throughout the body. Iron is what creates the red color to our blood. Myoglobin receives, supplies, carries, and releases oxygen to our body muscles and the heart. Another function of iron is to make other body proteins, such as proteins essential for respiration and energy metabolism. Iron is also a component of enzymes that are involved in the synthesis of DNA, collagen, and certain neurotransmitters. Finally, iron contributes to proper immune function. This function of iron is most important during childhood and pregnancy.

11.1.3 Requirements

Iron, unlike many other minerals is not actively excreted from the body through the intestines and urine. The body looses iron with the loss of cells from the interior and exterior portions of the body, as well as through blood loss. The expected amount of iron lost from the body can be calculated by dividing 14 µg by body weight in kilograms divided by the number of days. It is estimated that there is approximately a 15% variation among each individual’s iron loss (Chapter 13. Iron). Iron requirements vary greatly depending on the sex and stage of life of the person in question. Starting in infancy iron is very important for growth. When a baby is born it has approximately 250–300 mg of iron in its body. This higher concentration of iron is due to the limited amount of oxygen that was available to the infant prior to its birth. As a baby ages to approximately 6 months old, iron is redistributed to iron stores and the child needs to consume very little iron to stay healthy. Between 4 and 6 months of age the baby’s iron requirements will rise significantly to between 0.7 and 0.9 mg per day, and will remain this high throughout the first year of life. In infants born prematurely or underweight extra iron may be necessary to improve or continue health due to the fact that the high increase in iron during the gestational period primarily occurs in the last trimester. A child’s iron stores will double within the first year and then double again between the ages of 1 and 6. After the age of 6 iron requirements will begin to normalize only to spike again during puberty and rapid growth. Another group with higher iron requirements is pre-menopausal women. Large, consistent, amounts of iron are lost during menstruation, however the amount of iron needed to replenish the iron stores is highly variable among each woman. After the occurrence of menopause a woman’s iron requirements are the same as the requirement for men (Chapter 13. Iron). The following is the recommended amount of dietary intake by stage of life and gender. It is important to note that the Recommended Dietary Allowance for vegetarians and others who adhere to no meat diets is 1.8 times higher than the normal recommendation. This is because the heme iron found in meats is both more bioavailable and increases the bioavailability of the nonheme iron found in plant-based foods (Iron, 2015).

References: Chapter 13. Iron. (n.d.). Retrieved December 2, 2015, from http://www.fao.org/docrep/004/y2809e/y2809e0j.htm Iron. (2014, September 4). Retrieved December 2, 2015, from https://www.nrv.gov.au/nutrients/iron Iron. (2015, November 24). Retrieved December 2, 2015, from https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/#h2

11.1.4 Deficiency

Anemia is a common ailment characterized by a lack of healthy red blood cells. It also occurs when red blood cells in your body lack hemoglobin, a protein that enables the cells to carry sufficient oxygen to the tissues of the body (“What is Anemia,” 2012). Although the leading cause of anemia is blood loss, there are multiple types of anemia with various causes. This blood condition can be short term or long term and ranges from mild to severe (“Anemia,” 2014). Common causes of anemia are loss of blood, as mentioned before, low red blood cell production, and high amounts of red blood cells being destroyed. Loss of blood can be caused by heavy menstrual cycles, bleeding in digestive or urinary tracts, surgery, traumas, and even cancer. Furthermore, low red blood cell production can be the result of various factors. These factors include a diet with inadequate iron, low levels of the erythropoietin hormone, and certain chronic diseases, such as kidney disease. Finally, high rates of red blood cell destruction develop due to an enlarged or unhealthy spleen. Certain genetic characteristics may also cause your body to destroy an excessive amount of red blood cells like in the case of sickle cell anemia (“What is Anemia,” 2012). Certain individuals are at more risk of developing anemia than others. Some of these risk factors can be altered or changed, whereas others cannot. An example of a risk factor that can be altered is an iron-deficient diet. By increasing one’s intake of iron, the risk of developing anemia can be reduced. Risk factors that cannot be changed include blood loss from a surgery or trauma, pregnancy, and inherited anemia (“What is Anemia,” 2012). Various symptoms accompany anemia, the most common symptom being fatigue. Other symptoms of anemia include headaches, dizziness, cognitive complications, and shortness of breath. These symptoms may result due to the increased amount of work your heart is exerting in order to pump oxygen enriched blood throughout your body. Sometimes less severe forms of anemia may have mild or no symptoms (“Anemia,” 2014). The primary goal when treating anemia is to increase the red blood cell count in the body so that the blood can carry a much larger amount of oxygen (“What is Anemia,” 2012). Iron fortification or the defense of iron levels in the body is the primary way of both treating and preventing anemia. Individuals, especially pregnant and menstruating women must make the effort to increase their iron intake whether through use of supplements or changes in diet (Miller, 2013, p. 8). Furthermore, medicines, surgeries, and procedures like blood transfusions and bone marrow transplants are alternate ways to treat anemia, particularly severe forms of anemia (“What is Anemia,” 2012).

References Anemia. (2014, August 19). Retrieved from http://www.mayoclinic.org/diseases-conditions/anemia/basics/definition/con-20026209 What is Anemia? (2012, May 18). Retrieved from https://www.nhlbi.nih.gov/health/health-topics/topics/anemia Miller, J. (2013, April 23). Iron Deficiency Anemia: A Common and Curable Disease. Retrieved from http://perspectivesinmedicine.cshlp.org/content/early/2013/04/22/cshperspect.a011866.full.pdf+html

11.1.5 Toxicity

Iron Toxicity, otherwise known as iron overload, occurs when the body cannot prevent excess iron from being absorbed. Normally, when the required dosage of iron is satisfied, and all iron stores in the body are full, the absorption of iron comes to a halt and excess iron is excreted. In certain metabolic, genetic disorders, the body can not adequately control the absorption of iron, and continues to absorb iron even though all iron stores are filled and the body's required iron dosage is satisfied. This disorder is known as hemochromatosis, and is normally caused by the deficiency of the hormone hepcidin (Brissot, 2010). Hepcidin is responsible for maintaining iron homeostasis and regulating iron metabolism (Rossi, 2005). Furthermore, hepcidin is synthesized by the liver, and consist of 25 amino acid peptides (Rossi, 2005). Moreover, when hepcidin is not being produced sufficiently by the liver, excess iron begins to accumulate in or around the body's organs such as the heart, liver, and joints. This excess iron can cause a multitude of problematic health effects, including increasing the damage by free radicals, which have been linked to certain kinds of cancer (Ramm, 2010). Concerning iron toxicity, some symptoms include lethargy, fatigue, and apathy. The symptoms of iron toxicity are also extremely similar to those of anemia, which is why individuals should exhibit caution when dealing with iron supplements. An individual may believe they have iron defiance anemia when in fact they could be suffering from iron toxicity. This confusion might cause the individual to consume iron supplements, which can be extremely dangerous if the body already has toxic levels of iron. Regarding iron supplements, another form of iron toxicity can be achieved by overdosing on iron, which is normally caused by taking excessive iron supplements. Children are especially vulnerable to this form of iron toxicity, since they have smaller livers and in fact iron overdose is one of the leading causes of death in children ("Medscape", 2010). Having these high levels of iron in the blood, also help fuel infections because bacteria and viruses are known to flourish in the iron rich blood (Zheng, 2012) . More symptoms involved with iron overdose include damage to the gastrointestinal tract, nausea, vomiting, diarrhea, hematemesis and abdominal pain ("Medscape", 2010). Iron toxicity is also developed with excess blood transfusions, because the iron is directly transferred into the blood stream and does not manage to go through the small intestine where it can removed if necessary (Fleming, 2012). Iron toxicity can be potentially deadly, and treatment involves donating blood, which helps remove blood from the body, thereby reducing the amount of iron, and introducing a chelate into the bloodstream, which bonds with iron, and helps the body in its excretion (Fleming, 2012).

References
Iron Toxicity. (2012). Retrieved December 4, 2015, from http://emedicine.medscape.com/article/815213-overview#a5
Rossi, E. (2005). Hepcidin - the Iron Regulatory Hormone. Retrieved December 4, 2015, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1240030
Brissot, P. (2010). Molecular diagnosis of genetic iron-overload disorders. Expert Review of Molecular Diagnostics, 10, 755-763.
Ramm, G. (2010). , Iron homeostasis, hepatocellular injury, and fibrogenesis in hemochromatosis: The role of inflammation in a noninflammatory liver disease. Seminars in Liver Disease, 30, 271-287.
Zheng, X. (2011). Hepatic iron stores are increased as assessed by magnetic resonance imaging in a Chinese population with altered glucose homeostasis. American Journal of Clinical Nutrition, 1012–1019.
Fleming, R. (2012). Iron overload in human disease. New England Journal of Medicine, 366, 348-359.