Nutrition 411: Understanding Iron Deficiency and Anemia
Patients with wounds frequently have low levels of hemoglobin and hematocrit, and clinicians often automatically think “iron deficiency.” Although in many cases that diagnosis may be correct, identifying a specific type of anemia takes a bit more investigation, including a nutrition-focused physical examination and additional biochemical data. This article reviews the basics about iron deficiency and anemia.
Functions of Iron
Although regarded as a trace element (the human body requires only small amounts), iron is considered an essential element because there are serious consequences when it is deficient. Iron has numerous functions in the body; it serves as a cofactor for dozens of enzymes involved in diverse bodily processes such as ATP production, DNA synthesis, and amino acid metabolism. Most importantly, it functions as a component of heme-containing proteins, such as hemoglobin and myoglobin. Iron is required for the synthesis of the heme, which occurs within the erythropoietic cells in the bone marrow. Iron is delivered to these cells by the iron-binding transport protein transferrin. Because there are approximately 25 trillion red blood cells in the body, and each red blood cell contains millions of hemoglobin molecules, each with four heme groups apiece, the synthesis of heme accounts for the largest use of iron in the body. Hemoglobin binds oxygen within red blood cells for transport from the lungs to body tissues. The atom of iron at the center of the heme molecules in hemoglobin binds to oxygen loosely for easy transfer to bodily tissues. Myoglobin has a structure similar to hemoglobin — it consists of an iron-containing heme group — but it is found in the cytosol of muscle cells instead of in red blood cells. Its function is to facilitate the diffusion of oxygen from the hemoglobin in red blood cells into muscle cells, where it then is used for aerobic metabolism.1
Anemia: Types, Causes, and Stages
Anemia is defined as a deficiency in the size or number of red blood cells or in the amount of hemoglobin they contain, the consequence of which is an inadequate supply of oxygen to body tissues.2 Not all forms of anemia result from an iron deficiency. Hemorrhagic anemia occurs as a result of either acute blood loss from injury or from chronic blood loss, such as seen in gastrointestinal bleeding. This leads to a substantial reduction in the number of red blood cells and impaired oxygen delivery. Hemolytic anemia refers to the destruction of red blood cells, which can occur as a result of genetic abnormalities in red blood cell membranes or from repeated damage to blood capillaries, sometimes seen in long-distance runners.
Deficiencies in nutrients other than iron can also cause anemia by affecting the size or composition of red blood cells. Deficiencies in vitamin B12 or folic acid, both of which function in DNA synthesis and cell division, can cause megaloblastic macrocytic anemia, in which normally anucleated red blood cells differentiate incorrectly within the bone marrow and develop into abnormally large, nucleated red blood cells.1 These deformed red blood cells then function poorly and diminish the blood’s oxygen-carrying capacity. Iron-deficiency anemia results in microcytic and hypochromic red blood cells, because iron gives red blood cells their red color.3 Iron-deficiency anemia is the most common nutritional anemia and affects many different groups; groups most at risk are children under the age of 2, menstruating women, pregnant women, and frail elderly persons, particularly those with chronic wounds.3 Iron-deficiency anemia has many causes, including inadequate iron intake in the diet (vegetarians, vegans), poor absorption of iron in the gastrointestinal tract (celiac disease, drug interference), and increased need for iron in the body (infancy, pregnancy). Clinical signs and symptoms of anemia are listed in Table 1. It is important to note that in mild cases of anemia, no symptoms may be present.
Assessing Iron Status
Iron-deficiency anemia develops in progressive biochemical stages (see Table 2), with a drop in serum iron levels occurring late in the progression. Additionally, serum iron levels change significantly throughout the day, even in healthy individuals; therefore, assessing only serum iron levels is not an accurate way to determine iron status. Hematocrit (packed red blood cell volume) and hemoglobin are usually used together to evaluate iron status, but this method is not sufficient for diagnosing iron-deficiency anemia because low values are seen in all types of anemia, not just iron-deficiency anemia.
Ferritin is the storage protein that sequesters iron in the liver, spleen, and bone marrow. As iron supply increases, so does the amount of ferritin. A small amount escapes into the bloodstream, and this amount can be measured and used to estimate the amount of stored iron. Ultimately, plasma ferritin is the most sensitive indicator of iron deficiency, because plasma ferritin levels drop early in negative iron balance.2
Another biochemical marker of iron status is transferrin, a protein that transports iron to the bone marrow for hemoglobin production. When iron stores are low, transferrin synthesis increases in an attempt to capture more iron. Total iron-binding capacity also increases for this same reason. Conversely, transferrin saturation percentage decreases with limited available iron. High transferrin and total iron-binding capacity levels and low transferrin saturation percentages are seen in iron-deficiency anemia.
Another factor to consider in diagnosing iron-deficiency anemia is the size of red blood cells, because they are microcytic in iron-deficiency anemia. Mean corpuscular volume (MCV) is the biochemical marker used to determine the average size of red blood cells; it is lowered in iron-deficiency anemia. Also lowered in iron-deficiency anemia are mean corpuscular hemoglobin (MCH, the average weight of hemoglobin per red blood cell) and mean corpuscular hemoglobin concentration (MHCH, the average concentration of hemoglobin in the red blood cells).2 Because clinical symptoms of iron-deficiency anemia do not usually present until later stages of development, it is important to use biochemical markers such as serum ferritin to identify and correct deficiencies before they cause serious symptoms.
Treatment for Iron-Deficiency Anemia
Recommendations for iron are provided in the Dietary Reference Intakes (DRIs) developed by the Institute of Medicine of the National Academy of Sciences.4 Table 3 outlines the recommendations for various age groups.
The first step in the treatment of iron-deficiency anemia is to identify and correct its cause. A common cause of iron-deficiency anemia is the lack of iron-rich foods in the diet. Iron in food is found in one of two forms: heme iron and nonheme iron. Heme iron in food is derived directly from the hemoglobin and myoglobin of animals; therefore, it is found only in animal products. Good sources of heme iron include red meat, liver, egg yolks, oysters, clams, and the dark meat of chicken.5 Because it is a soluble compound, heme iron is readily absorbed across the brush border of the small intestine.1 Nonheme iron is commonly found in its oxidized, or ferric (Fe3+) form in food. Stomach acid reduces some of the ferric iron to ferrous iron (Fe2+), but the ferric iron absorbed frequently complexes into ferric hydroxide, an insoluble compound that aggregates and precipitates, making the iron less available in the body.1 Certain dietary factors enhance the absorption of nonheme iron. Sugars, especially fructose and sorbitol, certain acids, such as ascorbic and citric acid, and meat products containing heme iron all aid in the absorption of nonheme iron. Good sources of nonheme iron, such as spinach, kidney beans, dried fruits, and enriched cereals, should be consumed with foods rich in vitamin C or with meat products in order to increase their biological value.5 Unfortunately, several substances inhibit the absorption of nonheme iron. Polyphenols such as those found in tea and coffee; oxalic acid found in spinach, chard, chocolate, and berries; phytic acid found in whole grains and legumes; and divalent cations, such as calcium found in dairy foods, all complex with nonheme iron and make it less absorbable. Persons who follow strict vegan diets often are at risk for iron-deficiency anemia because of the low bioavailability of iron from plant foods. Once a person is diagnosed with iron-deficiency anemia, iron supplementation usually is the prescribed course of action. Ferrous salts (Feosol, Media Consumer Healthcare, Marietta, GA; Fer-In-Sol, Mead Johnson, Glenview, IL; mol-iron) or tablets (Feostat, Forest Pharmaceuticals, St. Louis, MO; Fergon, Bayer Consumer Care Products, Morristown, NJ) improve absorption with fewer side effects than ferrous sulfate pills.5 Several drug interactions inhibit iron absorption or render medication ineffective when taken with an iron supplement (see Table 4). It usually takes 4 to 30 days to see improvements after initiation of iron therapy, and iron stores are usually replaced after 1 to 3 months of treatment.5
Proper diagnosis and timely correction of iron-deficiency anemia is important for all patients with chronic wounds. The diagnosis of iron-deficiency anemia requires both biochemical data and a nutrition-focused physical examination to look for clinical symptoms. Biochemical values should be looked at as a whole to determine the extent of the anemia. Serum ferritin is the first biochemical value to decrease in negative iron balance. Note that when anemia is mild, there may be no overt physical symptoms. In addition, not all cases of anemia are caused by lack of iron in the diet. Clinicians should assess for deficiencies in folic acid or B12, as well as for chronic bleeding or absorption issues. Ascorbic acid and heme iron enhance the absorption of nonheme iron. Food sources of nonheme iron should be consumed with foods rich in vitamin C or with meat products in order to increase their biological value. In practical terms, this might mean serving a glass of orange juice with dinner. Many medications have interactions with iron supplements, so it is important to educate the patient to take iron supplements 2 hours before or after other medications. Iron supplements often can cause gastrointestinal distress, so patients should try several brands and forms (eg, pills, liquid) to find the one that agrees with them. Often, patients with chronic wounds have other nutritional challenges as well such as unintended weight loss, increased blood glucose levels, or a host of other concerns. Keying into nutrition and consulting a registered dietitian (RD) when necessary is essential for healing.
Nancy Collins, PhD, RD, LD/N, FAPWCA, is founder and executive director of Nutrition411.com and Wounds411.com. For the past 20 years, she has served as a consultant to healthcare institutions and as a medico-legal expert to law firms involved in healthcare litigation. Allison Schnitzer is a dietetics student at the University of Nevada, Las Vegas and will soon be entering her internship.
This article was not subject to the Ostomy Wound Management peer-review process.
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3. Nelms M, Sucher KP, Lacey K, Roth SL. Nutrition Therapy and Pathophysiology, 2nd ed. Belmont, CA: Brooks/Cole Cengage Learning;2011.
4. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington, DC: National Academy Press;2001.
5. Escott-Stump S. Nutrition and Diagnosis-Related Care. Baltimore, MD: Lippincott Williams & Wilkins;2012.