Iron

The therapeutic use of iron dates back thousands of years. The Egyptians prescribed it as a cure for baldness and the Greeks recommended iron in wine as a way to restore male potency. Iron is the most abundant element on earth and is an essential trace mineral for humans. The human body contains about 3.5 to 4.5 g of iron. Two thirds of this is present in blood and the rest is stored in the liver, spleen, bone marrow and muscles.

What it does in the body

Oxygen transport and storage

Red blood cells contain a protein called hemoglobin and each hemoglobin molecule contains four iron atoms. The iron in hemoglobin binds oxygen when it passes through blood vessels in the lungs and releases it in the tissues. After releasing the oxygen, hemoglobin binds carbon dioxide, the waste product of respiration, and carries it back to the lungs to be released. Red blood cells and the iron they contain, are recycled and replaced every 120 days. Another iron-containing molecule, myoglobin, carries and stores oxygen in the cells and is therefore essential for cellular activities in all body tissues.

Metabolism

Enzymes involved in many metabolic functions require iron. It is necessary for cell division and growth through its role in DNA synthesis. It is also essential for protein metabolism.

Energy production

Iron plays a role in oxygen transfer in cytochromes, protein molecules involved in the production of energy in cells.

Other functions

Thyroid hormones, which regulate metabolic processes, require iron for production. Iron is involved in the production of connective tissue and several brain neurotransmitters, and in the maintenance of a healthy immune system.

Absorption and metabolism

Healthy people absorb around 5 to 10 per cent of the iron in their daily diets. Absorption is highest in childhood, and reduces with age. Iron is present in animal foods in organic 'heme' form and in plant foods in inorganic 'nonheme' form. The heme and nonheme forms of iron are absorbed by different mechanisms.1 About 20 to 30 per cent of heme iron is absorbed compared to only 2 to 5 per cent of nonheme iron. Vitamin C consumed in the same meal as nonheme iron improves absorption by up to 50 per cent. Vitamin A and beta carotene can also improve nonheme iron absorption.2

Iron must be in ferrous form to be absorbed and the hydrochloric acid of the stomach converts ferric iron to ferrous iron. Iron absorption is a slow process, taking between two and four hours. Iron levels in the body are regulated by absorption, rather than by excretion and low body iron levels lead to improved absorption. In cases of iron deficiency absorption efficiency increases to around 10 to 20 per cent.

Various food factors affect iron absorption and the overall amount of iron absorbed from a meal will depend on the interactions between these factors. Sugars and amino acids may boost absorption. Calcium supplements, zinc supplements, oxalates in green vegetables such as spinach, and tannins in tea and coffee can reduce absorption. Phytates in unleavened whole grain bread reduce iron absorption although this may be reversed in the presence of meat and vitamin C. Milk proteins, albumin and soy proteins may also reduce absorption.

As it is highly chemically reactive, iron can cause damage to proteins and fats in cell membranes. It is therefore bound to proteins in the body to limit its toxic effects and is not excreted in the urine. A protein known as transferrin, binds to iron and is responsible for its transfer to the bone marrow. Iron is stored in the form of ferritin, mostly in the bone marrow, liver and spleen. Body iron stores depend on the iron absorbed from the diet. They are usually in the range of 300 to 1000 mg for adult women and 300 to 1500 mg for men. The levels vary considerably between people and some healthy adult women have almost no body stores. In the iron overload disorder, hemochromatosis, body iron stores may reach 30 g.

About 24 mg iron is released daily from normal breakdown of red blood cells in the liver and spleen, but most of this is conserved by the body. Iron is lost from the body through bleeding, sloughing of cells, menstrual flow and transfer to a developing fetus. Iron losses during a typical menstrual period are about 15 mg. Losses during breastfeeding are about 0.5 mg daily.

Tests which measure iron levels

There are various blood tests to measure the levels of iron in the body.

Serum ferritin

Serum ferritin is the most useful measure of iron status as it accurately reflects body stores and is the earliest laboratory measure to reflect iron deficiency. It can be used to detect iron deficiency and excess. Normal serum ferritin levels are 40 to 160 mcg per liter, with iron deficiency anemia indicated by a level of 12 mcg per liter.

Serum iron

Serum iron is the concentration of iron in the serum (clear) part of the blood. Normally it is about 100 mcg per 100 ml of blood, although this varies during the day by as much as 30 per cent within a single person. Serum iron is sensitive to the day's dietary intake and is not a reliable predictor of iron status.

TIBC

Total iron-binding capacity (TIBC) is the total amount of iron that can be bound by transferrin. Normally it ranges from 250 to 450 mcg per 100 ml of blood. Transferrin saturation is calculated from serum iron and TIBC. It is an index of iron transport rather than storage. In conditions of deficiency TIBC is increased, serum iron is low and transferrin saturation is reduced (around 15 per cent). In the iron overload disease, hemochromatosis, serum iron is normal, TIBC may be decreased and transferrin saturation may be 100 per cent.

Deficiency

Iron deficiency may be the most common nutritional deficiency in the USA. Results from the third National Health and Nutrition Examination Survey (1988-1994) suggest that iron deficiency and iron deficiency anemia are still relatively common in toddlers, adolescent girls, and women of childbearing age. Nine per cent of toddlers aged 1 to 2 years, and 9 per cent to 11 per cent of adolescent girls and women of childbearing age were iron deficient; of these, iron deficiency anemia was found in 3 per cent and 2 per cent to 5 per cent, respectively. These prevalences correspond to approximately 700,000 toddlers and 7.8 million women with iron deficiency; of these, approximately 240,000 toddlers and 3.3 million women have iron deficiency anemia. Iron deficiency occurred in around 7 per cent of older children or those older than 50 years, and in around 1 per cent of teenage boys and young men.3

Infants under two years of age are at risk due to their rapid growth rate, low iron reserves and the low iron content of milk and other foods. Teenagers, particularly girls who menstruate, are at risk due to the large amount of iron needed for rapid growth. Deficiencies are also common in women during childbearing years as menstruation, pregnancy and lactation draw heavily on the body's iron stores. Iron deficiency is also common in the elderly as they have reduced stomach acid and therefore reduced absorption ability. Surgery also leads to anemia and this is related to the extent of the surgery.4

Other causes of iron deficiency include heavy menstrual periods, frequent blood donation, and diseases of the stomach or bowel which reduce absorption. Some anti-arthritis drugs, which may cause repeated small bleeds from the stomach, may also lead to deficiency. It is important to carefully investigate the source of iron deficiency as slow blood loss from the gut or the uterus may be the cause.

Symptoms of iron deficiency include anemia, fatigue, rapid heartbeat, breathlessness, inability to concentrate, giddiness, disturbed sleep, severe menstrual pain and bleeding, cracks in the corners of the mouth, eye inflammation, mouth ulcers and hair loss. Low blood plasma levels of iron can cause generalized itching especially in elderly people. Fingernails may become thin, brittle and white.

A pregnant woman with an iron deficiency is more prone to infection after delivery, spontaneous abortion and premature delivery. Iron deficiency also increases the risk of low birth weight babies, stillbirth and infant death. Infants born of anemic mothers may also be at risk of anemia.

A new National Institute of Aging study suggests that low iron levels are linked to an increased likelihood of death in elderly people. Researchers looked at the iron status of nearly 4000 men and women aged 71 and over. Results of the five-year study showed that low iron levels increased the risk of total and coronary heart disease deaths. Those with higher iron levels had decreased risk. Men with the highest iron levels had only 20 per cent of the risk of dying of heart disease of those with the lowest levels. Women with the highest levels were about half as likely to die of heart disease compared to those with the lowest levels. Iron levels tend to be lower in people with chronic disease as the body's needs are higher and normal dietary intake may not be sufficient to meet the body's needs. Other research has linked high iron levels with an increased risk of heart disease. This new study suggests that the picture is not that simple.5

Anemia

Anemia is the final stage of iron deficiency. Before the red blood cells show anemia, deficiency affects iron-dependent enzymes and immune functions. Symptoms include small pale red blood cells, extreme fatigue, difficulty concentrating, breathlessness and dizziness. Symptoms of anemia can develop gradually and may continue without being recognized for some time. Hemoglobin and hematocrit blood tests may not show evidence of anemia in the early stages and serum ferritin and TIBC tests are the best and most sensitive measures of iron levels. Iron levels may also vary from day to day, and the average value from multiple tests provides the best readings.

Iron deficiency anemia is the most common nutritional deficiency in children. It can lead to depressed growth and impaired mental performance. The baby of a well-nourished mother is born with enough iron to last four months and must also obtain iron from breast milk or formula. Although it is low in iron, breast milk is high in lactose and vitamin C which enhance absorption. Infant formula is fortified with iron and vitamin C. Researchers involved in a 1997 Canadian study assessed iron status and feeding practices at 39 weeks of age in 434 infants in Vancouver. They found iron-deficiency anemia in 7 per cent of infants and low iron stores in about 24 per cent.6

Some iron-deficient people develop cravings for ice, clay, soil or other materials, a condition known as pica.

Immune system

Immune response can be impaired in iron-deficient people. Chronic yeast infections and herpes infections are more common in those who have low levels of iron in their diets. Certain types of immune cells rely on iron to generate the oxidative reactions that allow these cells to kill off bacteria and other pathogens. When iron levels are low these cells cannot function properly.

Athletes

Heavy exercise may lead to iron deficiency with distance runners particularly at risk. "Sports anemia" is often used to describe a low hemoglobin condition which impairs exercise tolerance and is relatively common at the beginning of training. Symptoms of iron deficiency in athletes include reduction in exercise time, increased heart rate, decreased oxygen consumption and increased blood lactic acid. The deficiency may result from increased metabolic requirements, increased red blood cell breakdown and increased iron losses in sweat. However, unless a person is iron-deficient, supplements do not appear to improve athletic performance. After adaptation, the anemia seems to subside. It may be due to inadequate dietary intake of iron or the use of protein for tasks other than red blood cell production during the early training stages. Iron intake of athletes needs to be carefully monitored.

Other symptoms

Iron deficiency has also been associated with Plummer-Vinson syndrome where a thin web-like membrane grows across the top of the esophagus, making it difficult to swallow. This disease, once fairly common in Sweden, has been eliminated with the use of iron supplements.

Marginal iron deficiency may also contribute to sleeping difficulties, headaches, rheumatoid arthritis and restless legs syndrome.

Low iron levels may increase the risk of menstrual difficulties including behavioral changes and sweating and dizziness, decreased efficiency, poor performance at work and daytime napping. Iron deficiency can also adversely affect the heart. Iron-deficient people have abnormal electrocardiogram readings.

Sources

Good sources include liver, meat, beans, nuts, dried fruits, poultry, fish, whole grains or enriched cereals, soybean flour and most dark green leafy vegetables. Flour is enriched with iron. Cooking in cast iron pots can increase the level of iron in food by as much as 20 times, although this form of iron may not be well-absorbed. Acidic foods such as chili and spaghetti sauce are especially good at leaching out the iron from cooking pots. The longer the food cooks in the pot the more iron is absorbed. The substitution of aluminum, stainless steel or plastic pots has reduced iron intake.

Those who choose not to eat red meat, which is the best source of dietary iron, should include dark green leafy vegetables, dried beans and whole cereal grains in their diet. A vegetarian diet is often high in vitamin C which helps in iron absorption.

Bran flakes 1 cup 10.8 mg

Lambs liver, fried 100g 8.2 mg

Spinach, cooked 1 cup 6.4 mg

Apricots, dried 1 cup, halves 6.1 mg

Chickpeas, boiled 1 cup 4.7 mg

All Bran ½ cup 4.5 mg

Oysters, fried 6 oysters 4.4 mg

Salmon, canned 1 can 3.8 mg

Oats ½ cup 3.7 mg

Beef, cooked, lean and fat ¾ cup, diced 2.6 mg

Almonds ½ cup 2.6 mg

Tuna, canned 1 can 2.5 mg

Hamburger patty 1 serve 2.4 mg

Pearl barley, boiled 1 cup 2.1 mg

Cashews, salted ½ cup 2.0 mg

Lamb 100g 2.0 mg

Bulgur, boiled 1 cup 1.7 mg

Raisins ½ cup 1.7 mg

Sausages, grilled 2 thick, 10cm long 1.3 mg

Liverwurst 1 slice 1.2 mg

Bread, wholegrain 1 slice 1.1 mg

Pita bread, whole wheat 1 small 0.8 mg

Pâté 1 tbsp 0.7 mg

Baked beans 1 cup 0.7 mg

Recommended dietary allowances

USA

Men 10 mg

Women
Premenopause 15 mg
Postmenopause 10 mg

Pregnancy 30 mg

UK

Men (over 19) 8.7 mg
(under 19) 11.3 mg

Women 14.8 mg

Pregnancy 8.7 mg

Australia

Men 7 mg

Women 12 to 16 mg

Pregnancy 5 to 7 mg

Lactation +10 to 20 mg

Because the iron from red blood cells is recycled and re-used, recommended requirements are small for healthy men and postmenopausal women. Iron requirements increase in pregnancy due to the increase in the mother's blood volume and the demands of the developing baby. 

Iron intakes in North America and Europe average around 5 to 7 mg per 1000 calories. Thus those on low calorie diets may be at risk of deficiency.

Supplements

Iron supplements come in a variety of preparations including syrups, tablets, capsules and injections. These contain varying forms and amounts of iron. Ferrous salts are absorbed better than ferric salts. Ferrous fumarate and ferrous succinate contain the most iron (31.2 and 32.6 mg per 100 mg respectively). Ferrous succinate and ferrous sulfate (the most common) may be the most easily absorbed forms of iron but ferrous sulfate can cause gut irritation. Ferrous gluconate and ferrous fumarate are also well-absorbed and usually less irritating.

Iron supplements are also available in the form of ferritin, an iron protein complex.