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Iron Deficiency and Toxicity

by Larry E. Johnson, MD, PhD

Much of the iron in the body is contained in hemoglobin. Hemoglobin is the component of red blood cells that enables them to carry oxygen and deliver it to the body’s tissues. Iron is also an important component of muscle cells and is necessary for the formation of many enzymes in the body.

The body recycles iron: When red blood cells die, the iron in them is returned to the bone marrow to be used again in new red blood cells. A small amount of iron is lost each day, mainly in cells shed from the lining of the intestine. This amount is usually replaced by the 1 to 2 milligrams of iron absorbed from food each day. Women lose more iron in menstrual bleeding, and sometimes the amount lost is not entirely replaced by iron absorbed from food.

Food contains two types of iron:

  • Heme iron: Animal products contain heme iron. It is absorbed much better than nonheme iron.

  • Nonheme iron: Most foods and iron supplements contain nonheme iron. It accounts for more than 85% of iron in the average diet. However, less than 20% of nonheme iron that is consumed is absorbed into the body. Nonheme iron is absorbed better when it is consumed with animal protein and with vitamin C.

Iron Deficiency

  • Iron deficiency usually results from loss of blood in adults (including bleeding from menstrual periods) but, in children and pregnant women, may result from an inadequate diet.

  • Anemia develops, making people appear pale and feel weak and tired.

  • Doctors base the diagnosis on symptoms and blood test results.

  • Doctors look for a source of bleeding, and if one is identified, they treat it.

  • Iron supplements, usually taken by mouth, are often needed.

Iron deficiency is one of the most common mineral deficiencies in the world. It causes anemia in men, women, and children.

Causes

In adults, iron deficiency is most commonly caused by

  • Loss of blood

In premenopausal women, monthly menstrual bleeding may cause the deficiency. In men and postmenopausal women, iron deficiency usually indicates bleeding, most often in the digestive tract—for example, from a bleeding ulcer or a polyp in the colon. Chronic bleeding due to colon cancer is a serious cause in middle-aged and older people.

Disorders that interfere with absorption from the intestine (see Overview of Malabsorption), such as celiac disease, can also cause iron deficiency.

Iron deficiency may result from an inadequate diet, primarily in infants and small children, who need more iron because they are growing. Adolescent girls who do not eat meat are at risk of developing iron deficiency because they are growing and starting to menstruate.

Pregnant women are at risk of this deficiency because the growing fetus requires large amounts of iron.

Symptoms

When iron reserves in the body are exhausted, anemia develops (see Iron Deficiency Anemia). Anemia causes paleness, weakness, and fatigue. People usually do not notice how pale they are because it happens so gradually. Concentration and learning ability may be impaired. When severe, anemia may cause shortness of breath, dizziness, and a rapid heart rate. Occasionally, severe anemia causes chest pain and heart failure. Menstrual periods may stop.

In addition to anemia, iron deficiency may cause pica (a craving for nonfoods such as ice, dirt, or pure starch), spoon nails (thin, concave fingernails), and restless legs syndrome (an irresistible urge to move the legs when sitting or lying down—see Periodic Limb Movement Disorder and Restless Legs Syndrome).

Rarely, iron deficiency causes a thin membrane to grow across part of the esophagus, making swallowing difficult.

Diagnosis

  • A doctor's evaluation

  • Blood tests

  • Occasionally bone marrow examination

Iron deficiency is diagnosed based on symptoms and blood test results. Results include a low level of hemoglobin (which contains iron), a low hematocrit (the percentage of blood volume that is red blood cells), and a low number of red blood cells. These results indicate anemia. However, doctors need more information to distinguish iron deficiency anemia from other causes of anemia, which are treated much differently. In iron deficiency anemia, red blood cells are abnormally small.

Blood tests also include measurement of the following:

  • Transferrin: Transferrin is the protein that carries iron in blood when iron is not inside red blood cells. If the percentage of iron in transferrin is less than 10%, iron deficiency is likely.

  • Ferritin: Ferritin is a protein that stores iron. Iron deficiency is confirmed if the ferritin level is low.

However, the ferritin level may be normal or high when iron deficiency is present if people have inflammation, an infection, cancer, or liver damage.

Occasionally, a bone marrow examination is needed to make the diagnosis. A sample of bone marrow cells is removed, usually from the hipbone, through a needle and examined under a microscope to determine the iron content.

Treatment

  • Control of bleeding

  • Iron supplements

  • Rarely iron given by injection

Because the most common cause of iron deficiency in adults is excessive bleeding, doctors first look for a source of bleeding. If the source is excessive menstrual bleeding, drugs, such as oral contraceptives (birth control pills), may be needed to control it. Surgery may be needed to repair a bleeding ulcer or remove a polyp in the colon. A blood transfusion may be necessary if the anemia is severe.

Normal dietary intake of iron may not be sufficient to replace lost iron (because less than 20% of iron in a typical diet is absorbed into the body). Thus, most people with iron deficiency need to take iron supplements by mouth usually once or twice a day. Iron in supplements is absorbed best when taken on an empty stomach, 30 minutes before meals or 2 hours after meals, particularly if the meals include foods that reduce the absorption of iron, such as vegetable fibers, foods that contain phytates (including whole-grain bread, bran, beans, soybeans, and nuts), coffee, and tea. However, taking iron supplements on an empty stomach can cause indigestion and constipation. So some people must take the supplements with meals. Antacids and calcium supplements can also reduce iron absorption. Consuming vitamin C in juices or taking it as a supplement enhances iron absorption, as does eating small amounts of meat, which contains the more easily absorbed form of iron (heme iron). Iron supplements almost always turn stools black—a harmless side effect.

Rarely, iron is given by injection. Injections are necessary for people who cannot tolerate tablets or for the few people who cannot absorb enough iron from the digestive tract.

Correcting iron deficiency anemia usually takes several weeks up to about 2 months, even after the bleeding has stopped. After the anemia is corrected, an iron supplement should be taken for 6 months to replenish the body’s reserves. Blood tests are usually done periodically to determine whether people are receiving enough iron and to check for continued bleeding.

Women who are not menstruating and men should not take iron supplements or multiple vitamins with iron unless they are specifically instructed to do so by a doctor. Taking such supplements can make diagnosing bleeding from the intestine difficult. Such bleeding may be due to serious disorders, including colon cancer.

Because a developing fetus requires iron, iron supplements are recommended for most pregnant women. Most babies, particularly those who are premature or who have a low birth weight, need an iron supplement. It is given as an iron-fortified formula or, to breastfed babies, as a separate liquid supplement.

Iron Toxicity

Excess iron can accumulate in the body.

Causes include the following:

  • Repeated blood transfusions

  • Iron therapy given in excessive amounts or for too long

  • Chronic alcoholism

  • An overdose of iron

  • A hereditary disorder called hemochromatosis (see Hemochromatosis)

Excess iron consumed all at once causes vomiting, diarrhea, and damage to the intestine and other organs. Excess iron consumed over a period of time may damage coronary arteries.

Often, deferoxamine is given intravenously. This drug binds with iron and carries it out of the body in urine. Hemachromatosis is treated with bloodletting (phlebotomy).

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