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Iron
When can iron deficiency occur?
The World Health Organization considers iron deficiency the number one nutritional disorder in the world [33]. As many as 80% of the world's population may be iron deficient, while 30% may have iron deficiency anemia [34].
Iron deficiency develops gradually and usually begins with a negative iron balance, when iron intake does not meet the daily need for dietary iron. This negative balance initially depletes the storage form of iron while the blood hemoglobin level, a marker of iron status, remains normal. Iron deficiency anemia is an advanced stage of iron depletion. It occurs when storage sites of iron are deficient and blood levels of iron cannot meet daily needs. Blood hemoglobin levels are below normal with iron deficiency anemia [1].
Iron deficiency anemia can be associated with low dietary intake of iron, inadequate absorption of iron, or excessive blood loss [1,16,35]. Women of childbearing age, pregnant women, preterm and low birth weight infants, older infants and toddlers, and teenage girls are at greatest risk of developing iron deficiency anemia because they have the greatest need for iron [33]. Women with heavy menstrual losses can lose a significant amount of iron and are at considerable risk for iron deficiency [1,3]. Adult men and post-menopausal women lose very little iron, and have a low risk of iron deficiency.
Individuals with kidney failure, especially those being treated with dialysis, are at high risk for developing iron deficiency anemia. This is because their kidneys cannot create enough erythropoietin, a hormone needed to make red blood cells. Both iron and erythropoietin can be lost during kidney dialysis. Individuals who receive routine dialysis treatments usually need extra iron and synthetic erythropoietin to prevent iron deficiency [36-38].
Vitamin A helps mobilize iron from its storage sites, so a deficiency of vitamin A limits the body's ability to use stored iron. This results in an "apparent" iron deficiency because hemoglobin levels are low even though the body can maintain normal amounts of stored iron [39-40]. While uncommon in the U.S., this problem is seen in developing countries where vitamin A deficiency often occurs.
Chronic malabsorption can contribute to iron depletion and deficiency by limiting dietary iron absorption or by contributing to intestinal blood loss. Most iron is absorbed in the small intestines. Gastrointestinal disorders that result in inflammation of the small intestine may result in diarrhea, poor absorption of dietary iron, and iron depletion [41].
Signs of iron deficiency anemia include [1,5-6,42]:
feeling tired and weak
decreased work and school performance
slow cognitive and social development during childhood
difficulty maintaining body temperature
decreased immune function, which increases susceptibility to infection
glossitis (an inflamed tongue)
Eating nonnutritive substances such as dirt and clay, often referred to as pica or geophagia, is sometimes seen in persons with iron deficiency. There is disagreement about the cause of this association. Some researchers believe that these eating abnormalities may result in an iron deficiency. Other researchers believe that iron deficiency may somehow increase the likelihood of these eating problems [43-44].
People with chronic infectious, inflammatory, or malignant disorders such as arthritis and cancer may become anemic. However, the anemia that occurs with inflammatory disorders differs from iron deficiency anemia and may not respond to iron supplements [45-47]. Research suggests that inflammation may over-activate a protein involved in iron metabolism. This protein may inhibit iron absorption and reduce the amount of iron circulating in blood, resulting in anemia [48].
Who may need extra iron to prevent a deficiency?
Three groups of people are most likely to benefit from iron supplements: people with a greater need for iron, individuals who tend to lose more iron, and people who do not absorb iron normally. These individuals include [1,36-38,41,49-57]:
pregnant women
preterm and low birth weight infants
older infants and toddlers
teenage girls
women of childbearing age, especially those with heavy menstrual losses
people with renal failure, especially those undergoing routine dialysis
people with gastrointestinal disorders who do not absorb iron normally
Celiac Disease and Crohn's Syndrome are associated with gastrointestinal malabsorption and may impair iron absorption. Iron supplementation may be needed if these conditions result in iron deficiency anemia [41].
Women taking oral contraceptives may experience less bleeding during their periods and have a lower risk of developing an iron deficiency. Women who use an intrauterine device (IUD) to prevent pregnancy may experience more bleeding and have a greater risk of developing an iron deficiency. If laboratory tests indicate iron deficiency anemia, iron supplements may be recommended.
Total dietary iron intake in vegetarian diets may meet recommended levels; however that iron is less available for absorption than in diets that include meat [58]. Vegetarians who exclude all animal products from their diet may need almost twice as much dietary iron each day as non-vegetarians because of the lower intestinal absorption of nonheme iron in plant foods [1]. Vegetarians should consider consuming nonheme iron sources together with a good source of vitamin C, such as citrus fruits, to improve the absorption of nonheme iron [1].
There are many causes of anemia, including iron deficiency. There are also several potential causes of iron deficiency. After a thorough evaluation, physicians can diagnose the cause of anemia and prescribe the appropriate treatment.
Does pregnancy increase the need for iron?
Nutrient requirements increase during pregnancy to support fetal growth and maternal health. Iron requirements of pregnant women are approximately double that of non-pregnant women because of increased blood volume during pregnancy, increased needs of the fetus, and blood losses that occur during delivery [16]. If iron intake does not meet increased requirements, iron deficiency anemia can occur. Iron deficiency anemia of pregnancy is responsible for significant morbidity, such as premature deliveries and giving birth to infants with low birth weight [1,51,59-62].
Low levels of hemoglobin and hematocrit may indicate iron deficiency. Hemoglobin is the protein in red blood cells that carries oxygen to tissues. Hematocrit is the proportion of whole blood that is made up of red blood cells. Nutritionists estimate that over half of pregnant women in the world may have hemoglobin levels consistent with iron deficiency. In the U.S., the Centers for Disease Control (CDC) estimated that 12% of all women age 12 to 49 years were iron deficient in 1999-2000. When broken down by groups, 10% of non-Hispanic white women, 22% of Mexican-American women, and 19% of non-Hispanic black women were iron deficient. Prevalence of iron deficiency anemia among lower income pregnant women has remained the same, at about 30%, since the 1980s [63].
The RDA for iron for pregnant women increases to 27 mg per day. Unfortunately, data from the 1988-94 NHANES survey suggested that the median iron intake among pregnant women was approximately 15 mg per day [1]. When median iron intake is less than the RDA, more than half of the group consumes less iron than is recommended each day.
Several major health organizations recommend iron supplementation during pregnancy to help pregnant women meet their iron requirements. The CDC recommends routine low-dose iron supplementation (30 mg/day) for all pregnant women, beginning at the first prenatal visit [33]. When a low hemoglobin or hematocrit is confirmed by repeat testing, the CDC recommends larger doses of supplemental iron. The Institute of Medicine of the National Academy of Sciences also supports iron supplementation during pregnancy [1]. Obstetricians often monitor the need for iron supplementation during pregnancy and provide individualized recommendations to pregnant women.
Some facts about iron supplements
Iron supplementation is indicated when diet alone cannot restore deficient iron levels to normal within an acceptable timeframe. Supplements are especially important when an individual is experiencing clinical symptoms of iron deficiency anemia. The goals of providing oral iron supplements are to supply sufficient iron to restore normal storage levels of iron and to replenish hemoglobin deficits. When hemoglobin levels are below normal, physicians often measure serum ferritin, the storage form of iron. A serum ferritin level less than or equal to 15 micrograms per liter confirms iron deficiency anemia in women, and suggests a possible need for iron supplementation [33].
Supplemental iron is available in two forms: ferrous and ferric. Ferrous iron salts (ferrous fumarate, ferrous sulfate, and ferrous gluconate) are the best absorbed forms of iron supplements [64]. Elemental iron is the amount of iron in a supplement that is available for absorption.
The amount of iron absorbed decreases with increasing doses. For this reason, it is recommended that most people take their prescribed daily iron supplement in two or three equally spaced doses. For adults who are not pregnant, the CDC recommends taking 50 mg to 60 mg of oral elemental iron (the approximate amount of elemental iron in one 300 mg tablet of ferrous sulfate) twice daily for three months for the therapeutic treatment of iron deficiency anemia [33]. However, physicians evaluate each person individually, and prescribe according to individual needs.
Therapeutic doses of iron supplements, which are prescribed for iron deficiency anemia, may cause gastrointestinal side effects such as nausea, vomiting, constipation, diarrhea, dark colored stools, and/or abdominal distress [33]. Starting with half the recommended dose and gradually increasing to the full dose will help minimize these side effects. Taking the supplement in divided doses and with food also may help limit these symptoms. Iron from enteric coated or delayed-release preparations may have fewer side effects, but is not as well absorbed and not usually recommended [64].
Physicians monitor the effectiveness of iron supplements by measuring laboratory indices, including reticulocyte count (levels of newly formed red blood cells), hemoglobin levels, and ferritin levels. In the presence of anemia, reticulocyte counts will begin to rise after a few days of supplementation. Hemoglobin usually increases within 2 to 3 weeks of starting iron supplementation.
In rare situations parenteral iron (provided by injection or I.V.) is required. Doctors will carefully manage the administration of parenteral iron [66].
Who should be cautious about taking iron supplements?
Iron deficiency is uncommon among adult men and postmenopausal women. These individuals should only take iron supplements when prescribed by a physician because of their greater risk of iron overload. Iron overload is a condition in which excess iron is found in the blood and stored in organs such as the liver and heart. Iron overload is associated with several genetic diseases including hemochromatosis, which affects approximately 1 in 250 individuals of northern European descent [67]. Individuals with hemochromatosis absorb iron very efficiently, which can result in a build up of excess iron and can cause organ damage such as cirrhosis of the liver and heart failure [1,3,67-69]. Hemochromatosis is often not diagnosed until excess iron stores have damaged an organ. Iron supplementation may accelerate the effects of hemochromatosis, an important reason why adult men and postmenopausal women who are not iron deficient should avoid iron supplements. Individuals with blood disorders that require frequent blood transfusions are also at risk of iron overload and are usually advised to avoid iron supplements.
