Iron

Iron deficiency anemia is a well-known and all-too-common problem, even with our modern knowledge about the condition and the attention given to preventing it. The preanemia state is not easy to diagnose. Decreasing iron stores and a relative decrease in serum iron levels and protein-bound iron may cause symptoms before low tissue iron levels or anemia are measurable. More of this important mineral is needed during growth; iron deficiency is more common in infancy, childhood, adolescence, and pregnancy. Even the elderly may become deficient due to poorer absorption and diet. Women in their reproductive years have a greater problem with iron deficiency because of losses in menstrual blood and higher requirements. Minority and low-income people tend to have a higher incidence of low iron-related problems, primarily caused by dietary deficiency. Women in their childbearing years require at least 18 mg. of iron daily, but more than 25 percent of them probably obtain less than this amount. Usually, when the body needs more iron, absorption improves through an increase in iron-carrying proteins in the blood, called iron transferrin.

Iron absorption from the intestinal tract is a very subtle process; poor absorption is one of the main reasons, along with low-iron diets, that iron deficiency is so prevalent. Along with calcium, which is also difficult to absorb, iron and zinc are the minerals most commonly deficient in our diet.

Average iron absorption is about 8-10 percent of intake. All vegetable sources contain the “nonheme” form of iron, which is poorly absorbed and utilized. “Heme” iron, a special formulation of iron, is found only in flesh foods, beef and liver being the best sources. Between 10 and 30 percent of heme iron is absorbed. Combining heme foods with nonheme foods improves the absorption of iron from the nonheme foods. This is why complete vegetarians have trouble obtaining sufficient iron from the diet alone. Phytates present in whole grains and oxalates found in certain vegetables may bind up some of the iron and make it unabsorbable. Meat foods improve absorption, possibly by stimulating increased stomach acid production and by the fact that the iron contained is already bound into muscle and blood tissue, the iron proteins myoglobin and hemoglobin.

Iron absorption is a slow process, usually taking between two and four hours. The food-natural ferrous (+2) ion is absorbed much better than iron in the ferric (+3) form. Vitamin C in the gut along with iron converts any ferric iron to ferrous and thus improves absorption. Iron absorbed into the blood is usually bound to the protein transferrin and goes mainly to the bone marrow, where it can be used to make red blood cells. Some also goes to the liver and spleen. About 25 percent of body iron is stored bound to the protein ferritin and as the iron complex hemosiderin. Ferritin has good iron-binding capacity. A fully saturated ferritin molecule, which is actually ferric oxide surrounded by the protein apoferritin, can contain about 4,000 iron atoms. Ferritin stored in the liver, spleen, and bone marrow, for example, provides a good reserve of iron to meet body needs. Measuring serum ferritin levels is a fairly new medical test that provides a good indication of iron storage levels. A normal value is 15-200 mcg. A level below 15 mcg. suggests very depleted iron reserves. Iron toxicity may show ferritin levels in the thousands.

About three-quarters of the iron in our bodies is active. Of that, about 70 percent is in hemoglobin, 5 percent is in myoglobin (muscle oxygenating protein), and the rest is part of iron cofactors and enzymes such as catalases, peroxidases, and the cytochromes. Some is also in transition, attached to transferrin, which transports iron to the bone marrow, liver, and other tissues for its functions in processing hemoglobin, myoglobin, and various enzymes. Fortunately, the body conserves iron very well, though this increases the possibility of toxicity. Toxicity has not been a great concern until recently, when the possibility of liver irritation and the increased risk of heart disease in men and postmenopausal women due to the oxidant effect of iron was suggested. About 1 percent of red blood cells are recycled each day (their average life span is 120 days), and we use the iron from them (about 30-50 mg. daily) to manufacture new cells. The recycled iron provides about 90 percent of the iron required to make new cells and to carry out other functions; therefore, we need only a little more for full functioning, unless, of course, there is blood loss.

Iron lost from the body must be replaced through dietary iron, but this often takes time and requires a regular source from food or supplements. A pint of blood contains about 200 mg. of iron. Even though iron absorption increases with increased need, it can still take several months to replenish the iron lost when we donate blood. About 30-40 mg. of iron will be lost during an average female menstrual cycle; this is why menstruating women need a consistently higher iron intake than men, a minimum of 18 mg. per day. During breast-feeding, the nursing mother will lose about 1-2 mg. per day. In pregnancy, the mother transfers 500-1000 mg. of iron to her growing baby, most of that (500-700 mg.) during the last few months. Since there are usually less than 500 mg. stored in the bone marrow and other tissues, the mother needs a regular, good dietary and supplemental intake of iron, or she will become very depleted and will be less able to obtain the extra oxygen she requires during pregnancy, labor, and delivery of her baby. After delivery, iron depletion could cause her to feel run-down and to have difficulty caring for her infant.

Many factors can increase iron absorption from the intestines and improve our chances of maintaining adequate body levels. Absorption improves when there is increased need for iron, as during growth periods, pregnancy, and lactation or after blood loss. Acids in the stomach, such as hydrochloric acid, and ascorbic acid (vitamin C) in the small intestine help change any ferric iron to the more easily absorbable ferrous form. Citrus fruits and many vegetables contain vitamin C and therefore help our iron absorption. The animal flesh foods have the more easily absorbed “heme,” or blood, iron and also provide amino acids, which stimulate production of hydrochloric acid in the stomach. Cooking with an iron skillet will add iron to the food and make more of it available for absorption. Copper, cobalt, and manganese in the diet also improve iron absorption.

Likewise, many factors can reduce the body’s iron absorption. Low stomach acid or taking antacids or other alkalis will diminish iron absorption. Rapid gastric motility reduces the chance to absorb iron, which is a slow process anyway. Phosphates, found in meats and soft drinks; oxalates, in spinach, chard, and other vegetables; and phytates, in the whole grains, all can form insoluble iron complexes or salts that will not be absorbed. Soy protein is being researched, as it may also reduce iron absorption. The caffeine and tannic acid in coffee and tea lower absorption of iron. Low copper in the gut and in the body reduces iron absorption, and high calcium can compete with iron. Supplementing calcium with iron may create a more alkaline digestive medium, which further reduces iron absorption. Iron absorption usually decreases with age as well.

Increased by:

• Body needs during growth, pregnancy, and lactation
  
• Hydrochloric acid
  
• Vitamin C
  
• Blood loss or iron deficiency
  
• Meats (heme iron)
  
• Protein foods
  
• Citrus fruits and vegetables
  
• Iron cookware
  
• Copper, cobalt, manganese
  

Decreased by:

• Low hydrochloride acid
  
• Antacids
  
• Low copper
  
• Phosphates in meats and soft drinks
  
• Calcium
  
• Phytates in whole grains
  
• Oxylates in leafy green vegetables
  
• Soy protein
  
• Coffee and black tea
  
• Fast gastrointestinal motility
  

Any unabsorbed iron is eliminated in the feces. Otherwise, only minute amounts are lost in the urine, sweat, nail clippings, and hair. Other than through blood loss, most body iron is retained fairly well. Normal iron loss in the average person is about 1 mg. per day.

When we have plenty of iron, we can say we’re “in the pink.” Usually we will have good circulation, with rosy cheeks, pink earlobes, and pink tongue. (Yet we can also be “too pink” or red, with excess iron and blood cells.) If the tongue or the mucosal lining of the mouth is pale, we should look for anemia, so it is good for us to know what we can about iron, especially where we can find it in our foods.

Sources: Some of our soil is iron deficient, so the plants grown or the animals grazed there may contain relatively smaller amounts, though this is not yet a major concern. The milling of grain removes about 75 percent of the iron present in whole grains, as much of the iron is found in the outer bran and germ. The fortified or enriched grain foods, such as cereals and breads, contain some iron (plus vitamins B1, B2, and B3), but this iron is in the poorly absorbed ferric state. Cooking in iron pots or skillets will add absorbable iron to food, but if this is done excessively over time, iron toxicity is a possibility.

Heme iron, as found in meats, is generally thought to be the iron that is best absorbed, several times more absorbable than the nonheme iron found in the vegetable kingdom. This does not mean that we need to eat meats in order to get sufficient iron, though that is often recommended in cases of iron deficiency. The 18 mg. of iron a day needed by a woman in the childbearing years is not always easy to obtain through diet. Though eating 22 slices of whole wheat bread or 13 cups of cooked kale would supply 18 mg., these are obviously not desirable ways to get it. In addition to beef, liver, and other organ meats that have relatively high amounts of absorbable iron, pork, lamb, chicken, and shellfish such as clams and oysters contain reasonable iron levels. Egg yolks are fairly good sources, and salmon is the best of the other seafood.

From the vegetable world, whole grains are the overall best source. Wheat, millet, oats, and brown rice are all iron-containing grains. The legumes-dried peas and beans-are good; lima beans, soybeans, kidney beans, and green peas are examples. Nuts, such as almonds and Brazil nuts, and most seeds contain iron. Green leafy vegetables such as spinach, kale, and dandelion are good sources, as are broccoli and asparagus. Dried fruits such as prunes, raisins, and apricots have a good amount of iron. Prune juice often gives us additional iron. Unsulfured molasses is concentrated in iron; one tablespoon contains about 3 mg. Tomatoes, strawberries, and many other fruits and vegetables contain some iron, so it is possible to obtain adequate amounts of iron from dietary sources without consuming a lot of meat by eating wholesome foods, especially whole grains, green vegetables, and the legumes, nuts, and seeds.

Functions: The primary function of iron in the body is the formation of hemoglobin. Iron is the central core of the hemoglobin molecule, which is the essential oxygen-carrying component of the red blood cell (RBC). In combination with protein, iron is carried in the blood to the bone marrow, where, with the help of copper, it forms hemoglobin. The ferritin and transferrin proteins actually hold and transport the iron. Hemoglobin carries the oxygen molecules throughout the body. Red blood cells pick up oxygen from the lungs and distribute it to the rest of the tissues, all of which need oxygen to survive. Iron’s ability to change back and forth between its ferrous and ferric forms allows it to hold and release oxygen. Each hemoglobin molecule can carry four oxygen molecules. This large protein molecule makes up approximately 30 percent of the RBCs. Amazingly, there are some 20 trillion RBCs in the average human body (men have more than women), and about 115 million red blood cells are made every minute. As mentioned before, approximately 90 percent of the iron needed to make those cells comes from recycled RBCs that are normally destroyed by the spleen at the end of their 120-day life span.

Myoglobin is similar to hemoglobin in that it is an iron-protein compound that holds oxygen and carries it into the muscles, mainly the skeletal muscles and the heart. It provides our ability to work by increasing oxygen to our muscles with increased activity. Myoglobin also acts as an oxygen reservoir in the muscle cells. So muscle performance actually depends on this function of iron, besides the basic oxygenation by hemoglobin through normal blood circulation.

Hemoglobin—and therefore iron—really does give us our strength and the look of good health—our “rosy cheeks.” One of the first symptoms of low iron is weakness, fatigue, or loss of stamina. Anemia results only after longer deficiency of iron or other nutrients; then, less hemoglobin and usually fewer red blood cells are made, and our ability to carry oxygen through the body is diminished. Iron and hemoglobin improve our respiratory activity. Many of the oxygen-dependent diseases (diseases that have symptoms based on circulation and the delivery of oxygen to tissues), such as coronary artery disease and vascular insufficiency, are worsened with iron deficiency. Many other symptoms, both psychological and physical, occur when we do not have enough iron. On the other hand, Jerome Sullivan, a researcher on iron metabolism, has recently shown that excess iron intake and storage may increase our risk of atherosclerosis and heart disease.

Iron is needed by some important enzymes for energy production and protein metabolism. The cytochrome system (a class of protein molecules that play a role in oxidative processes) depends on iron enzymes, which may work within the mitochondria (energy factories) of the cells to produce energy. The iron cytochromes, iron catalase, and iron peroxidase probably help protect our tissues and cells from oxidative damage, although most of the research in this area has been done on animals, and it is not clear yet whether the findings are analogous in humans, or if, in fact, iron can be an irritant to the vascular lining. Research is also being done on iron’s role in the formation and health of tissue collagen and elastin and the involvement of iron in the immune system’s health. When iron in the body is low, there seems to be an increased incidence of infections, possibly because of a decrease in lymphocyte proliferation and other white blood cells’ ability to kill microorganisms. Iron also is helpful in the production of carnitine, a nonessential amino acid important for the oxidation and utilization of fatty acids.

Uses: Of course, the main use of iron is in the prevention and treatment of iron deficiency and iron deficiency anemia, whether caused by blood loss, pregnancy, or a low-iron diet. When total body iron or circulating iron is low, fatigue, learning difficulties, irritability, and other subtle symptoms may occur long before actual anemia is seen. Many emotional symptoms may occur in children as well.

Iron is used routinely during pregnancy and breastfeeding to prevent iron deficiency. Because of increased iron needs during these times, it is difficult to obtain all the required iron from the diet alone. The infant will usually get enough iron but will pull stores from the mother, who could become very depleted. Also, whenever there are menstrual periods with more than normal amounts of bleeding (medically called menorrhagia), iron is often suggested as a regular supplement. Iron has also been helpful in reducing pain in some women who have painful menstrual periods.

Sometimes fatigue, especially muscle fatigue and poor physical stamina, will respond to iron supplements. Subtle oxygen-deficit respiratory problems may be helped by attaining adequate iron levels, probably because the iron provides increased hemoglobin production and improved oxygenation of the tissue. There is some question as to whether iron acts as a mild antioxidant, protecting the cells and tissues from oxidative damage, or whether it actually stimulates oxidation and can cause problems.

Deficiency and toxicity: There is a controversy about iron toxicity-is everyone sensitive to iron overload from supplements, or does it affect only people who are genetically predisposed to iron accumulation and irritation? Iron overload is seen most commonly in older men because they tend to take supplements or iron tonics though losses may be small and through the years tend to accumulate iron stores, primarily in the liver. Usually, it takes moderately high amounts over a long period with minimal losses of this mineral to develop any iron toxicity problems. Further research by Jerome Sullivan suggests that iron overload is a factor in the development of atherosclerosis. A high-meat diet, separate iron supplements, or even the extra 18 mg. of iron that is contained in the average RDA-type multivitamin is more than many people, particularly men, require. Men lose very little iron, since the body recycles most of it; their needs are only about 10 mg. daily. Consuming much more than this may increase the risk of atherosclerosis and heart disease by an as-yet-undetermined mechanism, possibly through increased oxidation and free-radical formation. Women in the menstruating years seem to be protected from this increased risk, though they lose this protection after menopause, when their risk of heart disease rises to a level close to men’s.

Children have been known to develop acute toxicity from eating extra vitamins or finding some of mother’s ferrous sulfate or other iron supplement. Each year there are about ten deaths reported of young children who eat more than ten 300 mg. iron tablets-that is, more than 3 grams of iron-at one time.

It is unlikely that one would develop any iron toxicity from dietary sources alone, even with 50-75 mg. per day intake, unless all food is prepared in iron cookware, as is done in some African tribes, or unless the genetic iron storage disease called hemochromatosis is present. If this disease occurs, tissue damage may result from iron deposits in the liver, pancreas, spleen, skin, or heart. These iron deposits can cause cirrhosis of the liver, fibrosis of other tissues, a bronze color to the skin, and diabetes due to pancreatic disease, as well as joint problems or cardiac insufficiency. Hemochromatosis, a genetic metabolism problem that probably affects the regulation of iron absorption, can be discovered through blood tests and occurs in about 1 person in 20,000. Treatment includes a low-iron diet, avoidance of iron supplements, and giving regular donations of blood so that the iron stores will be used to make new red blood cells.

The term for excess iron storage in the body is hemosiderosis, or siderosis. Here an amorphous brown pigment called hemosiderin (about 35 percent iron as ferric hydroxide) is deposited in the liver and other tissues, which is not usually a problem unless there are excessive amounts. These increased iron stores usually come not from diet but from iron supplements or blood transfusions. Symptoms of iron toxicity include fatigue, anorexia, weight loss, headaches, dizziness, nausea, vomiting, shortness of breath, and a grayish hue to the skin. Iron has been found in increased levels in joints of patients with rheumatoid arthritis and may contribute to inflammation through increased hydroxyl free radicals. Supplementation should be avoided by patients with arthritis unless a proven iron deficiency is present.

Our digestion does not really screen excess iron, and our elimination is low after we absorb it. Therefore, it is fairly easy to get iron overloads in the body, although it is much easier to develop an iron deficiency.

Those most vulnerable to iron deficiency are infants, adolescents, pregnant or lactating women, vegetarians, people on diets, premenopausal women, and people with bleeding problems. People taking certain drugs, such as allopurinol for gout, tetracyclines, or high amounts of aspirin, may have impaired absorption of iron and thus may develop iron deficiency over time.

Both iron deficiency anemia and iron deficiency without anemia occur fairly commonly when a rapid growth period increases iron needs which are often not met with additional dietary intake. Several studies have shown that often more than half of children aged 1-5, teenagers, and women aged 18-44 had iron intakes below the RDA.

Females need more iron than men but often consume less. Iron deficiency is particularly common in pregnancy, especially later pregnancy, when the fetus needs about 7-8 mg. per day. Even though there is better absorption at this time than the average 10-20 percent of intake, the average diet supplies only 15-25 mg. per day, which is not enough to meet the needs of both mother and child.

Iron deficiency anemia is characterized as microcytic (the RBCs are small) and hypochromic (the RBCs are pale because of decreased hemoglobin). This type of anemia can be determined by doing a complete blood count and checking the hemoglobin, hematocrit, and red blood cell count, along with the RBC indices-the MCV (mean corpuscular volume), MCH (mean corpuscular hemoglobin), and MCHC (mean corpuscular hemoglobin concentration). The doctor or lab technician can also easily see small, pale red blood cells under the microscope. Iron deficiency can occur and generate vague symptoms before clinical anemia actually occurs. This state may be assessed by checking the serum iron concentration. If this is low, it may suggest iron deficiency, usually from low intake or increased losses. Even before serum iron is low, iron saturation, serum transferrin (iron-carrying protein), total iron binding capacity (TIBC), or, more recently, the ferritin level may be measured to detect low iron stores. The body will draw on these muscle and tissue stores to maintain normal serum levels.

Anemia is basically defined as a reduction in the number of red blood cells. Other factors besides iron, such as low copper, manganese, zinc, pyridoxine (vitamin B6), folic acid, and vitamin B12 may also affect the RBCs. Vitamin B6 and zinc deficiency may mimic iron deficiency, but giving iron may lead to iron toxicity problems in these cases. Measuring serum iron is the best way to ensure that the problem is actually iron deficiency, and measuring B6 and zinc levels can help diagnose those hidden, though common, deficiency problems as well. So iron deficiency is but one cause of anemia. I have discussed the B12 and folic acid vitamin deficiency anemias in Chapter 5, Vitamins; copper, zinc, and manganese are some minerals whose deficiency can cause other forms of anemia. Thyroid problems or lead toxicity may cause anemia as well. We also need adequate protein, calcium, and vitamins E and C to keep our red blood cells healthy. Thus, many nutritionally related problems can lead to anemia; decreased production or increased destruction of RBCs and bleeding, however, are the most common causes. Overall, it is wise to diagnose and treat the definitive cause of anemia, not just give iron.

Many symptoms may arise from iron deficiency. Fatigue and lack of stamina usually arise first, caused by fewer red blood cells, low hemoglobin, and a reduced ability to hold and carry oxygen. Children who are iron deficient may experience psychological problems, learning disabilities based on hyperactivity or a decreased attention span, and even a lower IQ, besides other symptoms of anemia. Headaches, dizziness, weight loss from decreased appetite, constipation, and lowered immunity (a weakened resistance) may occur. With anemia, paleness of the skin, cheeks, lips, and tongue may occur, as can a sore tongue, canker sores in the mouth, hair loss, itching, and brittle nails. Not uncommon is a general state of apathy, irritability, and/or depression—a lack of enthusiasm for life—which can, however, improve rapidly with iron supplementation. Decreased memory may also occur. In children particularly, iron deficiency may cause a strange symptom called “pica”—eating and sucking on inedible objects, such as toys, clay, or ice. This usually disappears with iron treatment. In pregnancy, morning sickness may occur more frequently with low iron, perhaps because of the relatively low oxygen distribution to cells. It can take several months for improved absorption and increased intake to catch up to needs.

In general, it is wise to discover the cause of iron deficiency. Is it from low intake? If so, the diet should be evaluated. Or is it due to poor absorption? Then check the absorption factors such as low stomach acid. Or is there some bleeding problem, especially a slow blood loss? Intestinal bleeding, as in colitis, ulcers, or even hemorrhoids, is not uncommon. Excess menstrual bleeding, often with the presence of uterine fibroids, is a common cause of iron loss in women. Parasites can cause iron deficiency anemia, as can cancer. Donating blood too frequently can lead to anemia and iron deficiency symptoms. Supplementing iron may help over time, but it is especially important to rule out any internal bleeding.

Requirements: The RDA for adult men and postmenopausal women is 10 mg. per day; for teenagers and women of childbearing age, it is 18 mg. per day. This is based on an average absorption of 10 percent to replace daily losses and to maintain iron storage levels of about 500 mg.

Iron needs increase with growth and development, when more red blood cells and body tissues are being made; during pregnancy, when extra iron is going to the growing fetus; and for at least several months postpartum during lactation, when losses through milk are high. But the average daily intake is only about 6 mg. per 1,000 calories consumed, so a 2,000-calorie diet supplies only 12 mg., which is less than is needed by most teenagers and women, especially during pregnancy and lactation. Luckily, when body needs increase, iron absorption improves, and we usually develop a craving or taste for iron-containing foods as part of our natural survival and health instincts.

Most people, especially women, should be aware of iron intake and absorption. Eating vitamin C-containing foods along with the high-iron foods or taking an ascorbic acid supplement, even 50–100 mg., improves the absorption of iron in supplements. Protein foods improve absorption and usually have a higher iron content, so eating more of these foods, such as meats and legumes, as well as leafy greens, helps get more iron into the body.

Iron supplements are strongly recommended when there are increased requirements, as with teenagers and most women, especially with heavy or long menstrual flow and definitely during pregnancy and lactation, when iron needs may triple. Most men, however, unless there is some bleeding problem, do not require additional iron. When there is sufficient iron intake, more will not necessarily help; in fact, it could lead to problems associated with excess iron storage over a period of time.

The ferrous (2+) forms of iron, not the ferric (3+) state, are the forms to have in supplements. Ferrous sulfate is the most commonly prescribed form of iron, although ferrous fumarate and gluconate are also prescribed by doctors. As an example, 325 mg. (5 grains) of ferrous sulfate contains about 120 mg. of elemental iron. With at least a 10 percent absorption rate, that allows more than 12 mg. of iron per tablet to get into the body; if these are taken several times daily in pregnancy or in anemia, as some doctors recommend, this may be excessive.

To improve iron absorption, take the iron with 250 mg. of vitamin C and between meals, if tolerated. During pregnancy, the increased need will also improve the percentage absorbed. Ferrous sulfate is often used because it is inexpensive and fairly assimilable for most women, though it can also be irritating to the gastrointestinal tract and cause constipation or blackening of the stools, which could cover up an intestinal bleeding problem (blood in the stool can also cause it to be black). Ferrous gluconate and fumarate are considered organic irons (as found in living tissues) and are also inexpensive and have good absorption, and they tend to cause fewer symptoms (constipation, intestinal upset) than the inorganic ferrous sulfate. The dosages are similar; 325 mg. of ferrous gluconate taken two or three times daily during pregnancy or to treat iron deficiency or blood losses. These amounts should not be taken regularly as a preventive or safeguard.

The form that probably is best assimilated and easiest on the intestinal tract is the hydrolyzed protein chelate of iron—that is, “chelated” iron. Usually about 50 mg. of chelated elemental iron taken once or twice daily will satisfy most iron needs during pregnancy or with iron deficiency. This can be used until the iron and red blood cell levels are normalized. The choice of form for iron supplements is based on absorption and gentleness. In order of preference, the suggested forms are chelated iron, such as iron aspartate, ferrous succinate, and ferrous fumarate, followed by ferrous gluconate and ferrous lactate. Ferrous sulfate is commonly used but produces more symptoms than the other forms.

There is some concern about vitamin E’s interaction with iron. It can bind the iron to a nonutilizable form, which then can oxidize and thus inactivate the vitamin E when the two are taken together, though this occurs more so with the ferric forms of iron. Ferrous sulfate has some interaction with E. The organic forms of iron—gluconate, aspartate, and fumarate—as well as the chelated iron have little effect on reducing vitamin E. But, to be safe, it is best not to take vitamin E with iron but to take it by itself at night or in the morning.

Overall, iron is a very important mineral of which we must be constantly aware. Extra iron is not needed by everyone, but when it is required, we must increase iron foods or take supplemental iron to prevent loss of energy and enthusiasm for life and the many other problems caused by iron deficiency.