Overview and Risk Factors
Anemia is a condition in which too few red blood cells are in circulation. Iron deficiency is the most frequent cause of anemia, and it results from inadequate levels of iron in the body, causing decreased production of red blood cells. Symptoms are nonspecific and include weakness and fatigue, irritability and mood swings, headache, exercise intolerance, decreased appetite (especially in children), pica (which may include chewing ice), pallor (in dark-pigmented persons, pallor may be evident in sclera and palmar surfaces), shortness of breath, and restless leg syndrome.
The most common cause of iron deficiency is blood loss, usually through menorrhagia or gastrointestinal bleeding. The condition may also be caused by inadequate iron intake, increased iron utilization due to rapid growth (as in infancy, adolescence, and pregnancy), malabsorption (eg, celiac disease or previous gastric surgery, including gastric bypass), phlebotomy, hemolysis, or other rare instances such as intense athletic training. Anemia develops after iron stores (found mainly in the liver, spleen, bone marrow, and the blood itself) are depleted.
According to the Centers for Disease Control and Prevention (CDC),1 an estimated 7% of toddlers, 4% to 5% of children, 9% to 16% of menstruating females, and 2% of pubescent and adult males have iron deficiency, with smaller percentages having anemia. Mild iron deficiency with depleted iron body stores may produce symptoms without resulting in an anemia.
Age. Children have a greater risk of iron deficiency anemia due to rapid growth, particularly in the first 2 years of life.
Gender. Women generally consume less iron than men (due to a lower energy requirement) and may have a greater need for iron, depending on their stage of life. On average, a menstruating woman loses 30 to 45 mg of iron per month. Pregnancy and delivery together use about 1 gram of maternal iron. On average, breast-feeding a child uses a total of about 1 gram of maternal iron in the first year of life.
Peptic ulcer disease and gastritis. These disorders lead to blood loss, which can deplete iron stores. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are often contributing factors.
Malignancy. Esophageal, gastric, and other gastrointestinal cancers often cause occult bleeding.
Excessive exercise. Blood losses may occur due to intense exercise: for example, as occurs in "foot strike" hemolysis in distance runners. Iron losses also result from increased sweating. Such losses may predispose adolescent female athletes in particular to frank anemia.2
Dietary and absorptive factors (see Nutritional Considerations).
Laboratory testing is necessary to diagnose iron deficiency anemia. A complete blood count (CBC) reveals a low hematocrit and hemoglobin concentration and usually a decreased mean corpuscular volume. The red blood cell distribution width (RDW) is elevated. Iron deficiency is one of the most common causes of an elevated platelet count.
The current preferred means of diagnosis is a serum ferritin test, which reflects total body iron stores. Note, however, that ferritin is an acute-phase reactant that may be elevated in cases of inflammation, infection, malignancy, and liver disease, producing a false-negative result.
A blood smear may reveal hypochromic, microcytic red blood cells. However, such cells are also found in the context of other disorders, such as anemia of chronic disease and thalassemia.
Additional useful tests include transferrin (often measured indirectly as the total iron-binding capacity, which is elevated in iron deficiency) and serum iron, which is usually decreased. These tests are less reliable during acute illnesses or in patients with severe chronic diseases. Transferrin is also elevated in women who are pregnant or using oral contraception.
Bone marrow biopsy to determine marrow iron stores was a standard means of diagnosis in the past, but now is only rarely necessary to diagnose iron deficiency anemia.
An interesting finding is that the ingestion of beets in a person with iron deficiency may cause red-tinged urine. In persons with normal iron levels, the beet pigment loses its color through a redox reaction with ferric ions.3
Dietary iron is available in 2 forms: heme and nonheme. Heme iron is found in animal muscle and blood, whereas nonheme iron is found both in animal products and in a variety of plant-based foods.
Heme iron in the diet is absorbed at a relatively constant rate of about 23%, independent of other dietary factors. On the other hand, nonheme iron absorption varies, depending on other dietary factors, as described below. As body stores of iron decrease, the percentage of nonheme iron absorbed increases significantly.
Iron deficiency is common in developing countries (30% to 70%).4 In industrialized countries, the prevalence of iron deficiency is much lower-roughly 20%-due partly to iron fortification of grain products.4 However, only one third to one half of iron-deficient individuals actually have iron deficiency anemia.5
Healthful sources of iron include greens and legumes. Although the myth persists that meat is a preferred iron source, a balanced vegetarian diet that includes legumes, fortified grains, and green vegetables easily provides adequate iron. Studies have shown that the incidence of iron deficiency anemia is not greater among individuals consuming a healthy vegetarian diet than among omnivores.6
Dairy products and eggs decrease iron absorption. Caseins from milk and certain forms of calcium inhibit iron absorption.7 In addition, infants who are allergic to cow's milk may be particularly susceptible to intestinal blood losses due to the irritating effect of dairy products.5 Iron status measured as serum ferritin is inversely associated with greater consumption of dairy products in toddlers, particularly when they displace foods that contain iron or that facilitate iron absorption.8 Eggs (especially yolks) also appear to inhibit iron absorption.9,10
Fruits and vegetables aid the absorption of nonheme iron. Fruits and vegetables contain vitamin C and organic acids (eg, citric acid) that keep iron in a reduced form, allowing for better absorption of nonheme iron. Vitamin A and carotenoids also appear to enhance iron absorption, by overcoming the inhibiting effect of iron on absorption caused by the polyphenols and phytates in whole- grain foods. Adding vitamin A to an iron supplement regimen has also been shown to result in greater anemia reduction than iron alone produces.7
Tea, coffee, and cocoa should not be consumed with meals if poor iron status is suspected. Polyphenols in these beverages inhibit the absorption of nonheme iron. Black tea appears to be the most potent in this regard.7
Taking in adequate iron before pregnancy can help prevent anemia in both mothers and infants. Iron deficiency is more common in women of child-bearing age, especially during pregnancy.5 The physiologic need for iron increases almost 10-fold during pregnancy and lactation, and iron deficiency in the first trimester results in significantly poorer indicators of fetal growth, neural development, and behavior in offspring, compared with what happens when mothers have adequate iron status.11 In mothers with iron deficiency, exclusive breast-feeding often results in iron deficiency in infants.12 Without adequate iron stores prior to conception, iron supplementation may be necessary during pregnancy (see below).
Breast milk contains significant iron. Human milk and cow's milk contain similar equal concentrations of iron (0.5 mg/100 ml, although breast-feeding is preferable for many reasons (see Healthy Diets at All Stages of Life chapter). Unfortified infant formula contains about 20% of the iron found in breast milk, whereas fortified formula has over twice the iron concentration. Despite this higher level, iron in breast milk is more absorbable than that in soy- or dairy-based formulas.
Iron supplementation should be individualized. The CDC recommends that iron supplementation be individualized based on hemoglobin screening of at-risk individuals.13 Iron supplementation should be avoided in cases lacking documented need, because excess iron stores are associated with greater risks for colon cancer, coronary heart disease, and insulin resistance.14,15
Alcohol intake enhances iron absorption, but should not be used as a means of regulating iron status. Consumption of any amount of alcohol is associated with a 40% reduction in the risk of iron deficiency anemia. However, the prevalence of markers of iron overload, which may be more harmful than mild reductions in iron status, was found to be significantly elevated among individuals who consumed > 2 alcoholic drinks per day.16 Increasing alcohol consumption is obviously not a recommended treatment for improving a person's iron status.
Avoid tea, coffee, and cocoa with meals.
What to Tell the Family
Iron deficiency anemia is usually preventable and highly treatable. A diet of fortified grains, legumes, nuts and seeds, and fruits and vegetables can provide for healthy iron balance. During times of increased iron requirements or when an iron deficiency has been diagnosed, iron supplementation may be needed. Simple blood tests can accurately assess a person's iron status.
1. Centers for Disease Control and Prevention. MMWR. 2002;51:897-899.
3. Tunnessen WW, Smith C, Oski FA. Beeturia: A sign of iron deficiency. Am J Dis Child. 1969;117:424-426.
6. Craig WJ. Iron status of vegetarians. Am J Clin Nutr. 1994;59:1233S-1237S.
7. Camara-Martos F, Amaro-Lopez MA. Influence of dietary factors on calcium bioavailability: a brief review. Biol Trace Elem Res. 2002;89:43-52.
8. Thane CW, Walmsley CM, Bates CJ, Prentice A, Cole TJ. Risk factors for poor iron status in British toddlers: further analysis of data from the National Diet and Nutrition Survey of children aged 1.5-4.5 years. Public Health Nutr. 2000;3:433-440.
11. Beard JL. Effectiveness and strategies of iron supplementation during pregnancy. Am J Clin Nutr. 2000;71:1288S-1294S.
13. Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep. 1998;47 (RR-3):1-29.
14. Hunt JR. Bioavailability of iron, zinc, and other trace minerals from vegetarian diets. Am J Clin Nutr. 2003;78:633S-639S.
15. Fernandez-Real JM, Lopez-Bermejo A, Ricart W. Cross-talk between iron metabolism and diabetes. Diabetes. 2002;51:2348-2354.
16. Ioannou GN, Dominitz JA, Weiss NS, Heagerty PJ, Kowdley KV. The effect of alcohol consumption on the prevalence of iron overload, iron deficiency, and iron deficiency anemia. Gastroenterology. 2004;126:1293-1301.