Iron is the fourth most abundant element in the earth’s crust; but it is only a trace element in biologic systems, making up only 0.004% of the body’s mass. Yet it is an essential component or cofactor of numerous metabolic reactions.
Every living cell in both plants and animals contains iron. The adult body contains about 50 mg of iron per 100 ml of blood. Total body iron ranges between two and six grams, depending on the size of the individual and the amount of hemoglobin the person’s cells contain.
Approximately two-thirds of this iron (70%) is contained in the hemoglobin; the other third is stored in the bone marrow, spleen, liver, and muscles. Myoglobin and enzymes use about 15% of the iron, while ferritin uses almost as much (14%). Only about 1% is in transit in serum.
Most of the iron in the body is a component of the proteins hemoglobin in red blood cells and myoglobin in muscle cells. Hemoglobin in the blood carries oxygen from the lungs to tissues throughout the body. Myoglobin holds oxygen for the muscles to use when they contract. If an individual has an iron deficiency, the iron stores are depleted first, followed by a reduction in hemoglobin. As a result, red blood cells (RBCs) are small in size and diminished in number.
As part of many enzymes, iron is vital to the processes by which cells generate energy. Iron is also needed to make new cells, amino acids, hormones, and neurotransmitters. When a red blood cell dies, the liver saves the iron and returns it to the bone marrow, which uses it to build new red blood cells. Thus, only tiny amounts of iron are lost, mainly in urine, sweat, shed skin, and blood (if bleeding occurs).
Iron is present in greatest concentration in meat and dark green vegetables. The RDA for adults is 10 mg for males and 18 mg for menstruating females every day. The average daily American diet contains about 10 mg iron, of which only about 1 mg is absorbed, and that 1 mg is almost exclusively lost in the stool.
For reproductive-aged females, an additional route is the menstrual flux, which accounts for a wildly variable loss. While the average monthly menstrual blood loss is 40 mL (equivalent to 16 mg iron), some women who consider themselves healthy may lose up to 495 mL blood (about 200 mg iron) per menstrual period, or an average of about 7 mg iron per day (200 mg iron ÷ 28 days/cycle). Therefore, it is not surprising that iron deficiency anemia is relatively common in women of this age group.
Since only a small portion is normally absorbed, or if the body’s supply is diminished, or if its needs an increase for any reason, absorption increases. The body makes several provisions for absorbing iron.
A special protein in the intestinal cells captures iron and holds it in reserve for release into the body as needed. Another protein transfers the iron to a special iron-carrier in the blood. The blood protein (transferrin) carries the iron to tissues throughout the body. When more iron is needed, more of these special proteins are produced so that more than the usual amount of iron can be absorbed and carried. If there is a surplus of iron, special storage proteins in the liver, bone marrow, and other organs will store it. Storage proteins for iron are called “ferritin” and “hemosiderin”.
Iron transport has been studied extensively, especially since the 1940s. Two New York scientists (Schade and Caroline) noted an anti-infective agent in human plasma, which they named siderophilin. This name was later changed to transferrin.
The term siderophilin also applies to lactoferrin. Transferrin and lactoferrin form a unique class of proteins, but transferrin remains the best-known transporter for iron and is nearly identical to lactoferrin. However, lactoferrin has an iron-binding capacity 260 times greater than that of transferrin.
Lactoferrin is found in human secretions (tears, perspiration, vaginal and seminal fluid, as well as mother’s milk). Although lactoferrin binds with iron, it is not considered a transporter of iron. Its role is entirely defense-related and can withhold iron from such invading microorganisms as H. pylori, one of the main causes of gastric ulcers. This microbe seeks out iron for its nourishment and bores through the stomach wall where it then tries to obtain iron directly from hemoglobin since serum iron is more likely to be bound with transferrin.
Iron can also be a toxic substance. Normally, transferrin is 25% to 35% saturated with the metal; but, when too much iron is available for transferrin to carry, problems occur. Transferrin molecules that are heavily saturated lose the ability to tightly bind iron. Unbound, or free, iron is highly destructive and dangerous since it triggers free radical activity. Free iron provides nourishment for such pathogens as Yersinia, Listeria, and Vibrio bacteria. These bacteria are harmless for people with normal levels, but when transferrin is highly saturated with iron, these bacteria (found mostly in raw shellfish) can be deadly.
Other microorganisms are also skilled in extracting iron from their human hosts. For example, Staphylococcus can break open red blood cells and extract the iron it needs. Protozoa responsible for malaria can also enter the red blood cell to obtain iron necessary to thrive. Such bacteria as the one that causes tuberculosis grow best inside macrophages that are iron loaded. This is crucial because macrophages are white blood cells that protect against disease; but when such an opportunistic microorganism renders them useless, our defence system begins to break down.
Too much iron accumulating in vital structures (especially the heart, pancreas, and liver) produces potentially fatal conditions. Two such kinds are hemochromatosis (caused by a hereditary defect) and hemosiderosis (caused by the ingestion of too much iron, usually in combination with excessive alcohol consumption).
Alcohol enhances the absorption of iron; and certain wines contain substantial amounts of iron. The result is tissue damage, especially to the liver, not only from the alcohol, but also from the iron overload.
Although iron overload produces toxicity, this happens rarely; but it is not unknown. Normally the body protects itself from absorbing too much iron by setting up a block in the intestinal cells. However, the system can be overwhelmed, resulting in an overload which is more common in men than women.
This is a valid argument against the fortification of foods with iron first introduced to protect women and children. However, evidence from Sweden has shown that when foods were generously fortified with iron, the incidence of overload in men increased. It is interesting to note that people with iron overload can actually set off metal detectors. “What sets off airport metal detectors is the metal itself. Iron, after all, is a metal,” says Eugene Weinberg, PhD, Professor of Microbiology, Indiana University.
Following ingestion, iron is absorbed primarily in the duodenum, although any portion of the small bowel is efficient at iron absorption (in contrast to the situation with B12). However, only the ferrous form of iron can be absorbed. The normal gastric acidity provides an optimal environment for the reduction of any ferric iron to the ferrous version.
In states of iron depletion, a greater proportion of iron is absorbed than in states of normal iron availability. After uptake through villi which line the surface of the intestinal wall, the ferrous iron is transported to the subepithelial capillaries by transferrin, and released into the bloodstream. There it is oxidized to the ferrous form and again taken up by plasma transferrin. It is then conveyed to the erythron (and reduced again to the ferrous version) or to marrow histiocytes for eventual incorporation into hemoglobin.
Since the transit time through the duodenum may be rapid, or the duodenum is by-passed altogether, for whatever reason, an iron supplement is given to correct any deficiency caused by these two conditions.