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
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.
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.
Iron plays a role in oxygen transfer in cytochromes, protein
molecules involved in the production of energy in cells.
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
Absorption and metabolism
Healthy people absorb around 5 to 10 percent 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 percent of heme
iron is absorbed compared to only 2 to 5 percent of nonheme iron.
Vitamin C consumed in the same meal as nonheme iron improves absorption
by up to 50 percent. 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
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
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
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 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 percent within a single
person. Serum iron is sensitive to the day's dietary intake and is not a
reliable predictor of iron status.
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 percent). In the iron
overload disease, hemochromatosis, serum iron is normal, TIBC may be
decreased and transferrin saturation may be 100 percent.
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 percent of toddlers aged 1 to 2 years,
and 9 percent to 11 percent of adolescent girls and women of
childbearing age were iron deficient; of these, iron deficiency anemia
was found in 3 percent and 2 percent to 5 percent, 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 percent of older children or those
older than 50 years, and in around 1 percent of teenage boys and young
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
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 birthweight babies, stillbirth
and infant death. Infants born of anemic mothers may also be at risk of
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 percent 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.
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
percent of infants and low iron stores in about 24 percent.6
Some iron-deficient people develop cravings for ice,
clay, soil or other materials, a condition known as pica.
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.
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
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.
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.
All Bran ½ cup 4.5 mg
Beef, cooked, lean and fat ¾ cup, diced 2.6 mg
Cashews, salted ½ cup 2.0 mg
Lambs liver, fried 100g 8.2 mg
Paté 1 tbsp 0.7 mg
Salmon, canned 1 can 3.8 mg
Almonds ½ cup 2.6 mg
Branflakes 1 cup 10.8 mg
Chickpeas, boiled 1 cup 4.7 mg
Liverwurst 1 slice 1.2 mg
Pearl barley, boiled 1 cup 2.1 mg
Sausages, grilled 2 thick, 10cm long 1.3 mg
Apricots, dried 1 cup, halves 6.1 mg
Bread, wholegrain 1 slice 1.1 mg
Hamburger patty 1 serve 2.4 mg
Oats ½ cup 3.7 mg
Pita bread, whole wheat 1 small 0.8 mg
Spinach, cooked 1 cup 6.4 mg
Baked beans 1 cup 0.7 mg
Bulgur, boiled 1 cup 1.7 mg
Lamb 100g 2.0 mg
Oysters, fried 6 oysters 4.4 mg
Raisins ½ cup 1.7 mg
Tuna, canned 1 can 2.5 mg
Recommended dietary allowances
Men (over 19)
Men (under 19)
12 to 16 mg
5 to 7 mg
+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. (See table)
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.
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. The hydrolyzed protein chelate form
of iron (most effective with the amino acid cysteine) may cause the
least side effects but may not be as well- absorbed as other forms.
Supplements are usually best absorbed on an empty stomach and people may
vary in their tolerance to different iron salts.
Women of childbearing age, the elderly, adolescents,
athletes and alcoholics may benefit from supplements. Women who have
heavy menstrual blood loss and who use intra-uterine contraceptive
devices may need extra iron. The contraceptive pill reduces menstrual
blood flow and may lead to decreased iron requirements.
Vegetarians may also benefit from iron supplements as
they avoid easily absorbed iron sources such as meat and seafood. In
addition, there are compounds in plant fiber which lead to reduced iron
absorption. However, increased vitamin C may compensate.
Toxic effects of excess intake
Large doses of iron can cause deterioration of the gut lining,
vomiting and diarrhea, liver damage, abdominal and joint pain, weight
loss, fatigue, excess thirst and hunger. Immediate medical attention is
necessary. It is important to keep iron supplements out of reach of
children as doses as low as 3 g can cause death in children and every
year there are a few cases of fatal poisoning.
Constipation is the most common side effect
associated with iron supplements, although diarrhea can also occur. Side
effects can be reduced if the iron supplements are taken in small
divided doses with meals. Doses of 25 to 75 mg per day have been taken
without side effects, although those with iron overload or kidney
disorders might develop symptoms at lower doses.
In most people iron absorption becomes less efficient
as blood levels reach optimum and dietary excesses pass out in feces.
Accumulation is possible; however, as excesses are not easily excreted
once absorbed. Heme iron absorption may be less affected by the iron
status of the individual than nonheme iron absorption, making it easier
to overdose on diets high in animal foods.
Hemochromatosis is the term used to refer to iron overload
disorders. It may be hereditary, due to excessive intake or due to
chronic alcoholism. Hereditary hemochromatosis is an inherited condition
of defective iron metabolism in which the body lacks the ability to
limit iron absorption from the diet and stores greater than normal
amounts. This iron is stored in the liver, heart, pancreas, skin and
other organs and can generate free radicals which cause serious damage.
In the US, the disorder is known to affect 1.5 million people. Many
experts believe hemochromatosis is under-diagnosed and may occur in as
many as one in 200 people. The effects are usually seen in men over 50
years of age as the disease can often go undetected until mid-life when
iron levels reach five to 50 times normal amounts. The initial symptoms
are fatigue, achy joints and weakness. Other symptoms include heart
disorders, joint pain, cirrhosis of the liver, diabetes and excessive
Researchers involved in the Framingham Heart Study
have found high iron intakes to be common in elderly people with around
91 percent of study participants having intakes above the recommended
dietary levels. Only one percent of the people had iron deficiency
Iron accumulation can contribute to a variety of
disorders such as cancer, heart disease, arthritis, osteoporosis,
diabetes and psychiatric illnesses. The liver is particularly
susceptible to the toxic effects of iron as it is the major site of iron
storage in the body. Treatment for hemochromatosis involves repeated
bleeding (phlebotomy) to remove excess iron. Therapy for hemochromatosis
may also involve a diet rich in bread and cereals, and fruit and
vegetables. The amount of meat and alcohol should be limited. Tea or
coffee may be drunk with meals as this will reduce iron absorption.
Foods and supplements rich in vitamin C, such as fruit and fruit juice,
should be avoided with meals.
Early therapy is very important to prevent
complications and increase the chance of normal life expectancy. A test
is advisable for those with a family history of hemochromatosis.
The evidence from many scientific studies suggests that high iron
levels (above 200 mcg per liter blood ferritin), may lead to an increase
in the risk of cardiovascular disease. The increased risk may be due to
oxidative damage to the heart and blood vessels and increased oxidation
of LDL cholesterol.
A study published in 1998 in the American Journal
of Epidemiology suggests that men and women, particularly those over
60, are at increased risk of heart disease if they have high levels of
iron in their diets. The study, which was conducted in Greece, involved
329 patients with heart disease and 570 people of similar age who were
admitted to hospital with minor conditions believed to be unrelated to
diet. Results showed that for every 50 mg increase in iron intake per
month, men over 60 were 1.47 times more likely to have heart disease
than their peers. In women over 60, the risk was even higher, with a
3.61-fold risk for every 50 mg increase.7
In a paper published in 1997, Austrian researchers
involved in the Bruneck study investigated the links between serum
ferritin concentrations and the five-year progression of carotid
atherosclerosis in 826 men and women aged 40 to 79 years old. Serum
ferritin was one of the strongest risk predictors of overall progression
of atherosclerosis, probably due to increased oxidation of LDL
cholesterol. Changes in iron stores during the follow-up period modified
atherosclerosis risk, in that a lowering was beneficial and further iron
accumulation exerted unfavorable effects. High serum ferritin and LDL
cholesterol also increased the risk of death from cardiovascular
Another study published in 1998 in the American Heart
Association journal Circulation suggests that men with high
levels of stored iron in the body have an increased risk of heart
attack. The Study, which was done in Finland, involved 99 men who had
had at least one heart attack and 99 healthy men matched for background
and age. The results showed that those men with the highest iron levels
had almost three times the risk of heart attack when compared with those
with the lowest levels.9
Donating blood may help prevent a heart attack
according to a 1998 study reported in the American Journal of
Epidemiology. The results of a Finnish study showed that middle aged
men who gave blood had an 88 percent lower risk of heart attack than
those who had not donated. In a group of 2862 men, less than 1 percent
of the blood donors had heart attacks compared with 12.5 percent of the
Some studies have shown that iron can inhibit tumor development
while others have shown that it might enhance it. Iron may increase the
risk of cancer through its effect on free radical formation. In some
population studies, high iron levels have been associated with an
increased risk of throat and gastrointestinal cancers while others have
not shown links.11 Results from a study assessing the links between body
iron stores and cancer in 3287 men and 5269 women participating in the
first National Health and Nutrition Examination Survey (NHANES I) found
an increased risk with high iron levels.12 Some experts believe that the
findings of increased risk are due to causes such as defects in iron
metabolism, rather than diet alone.
High iron levels may also worsen the joint inflammation associated
with rheumatoid arthritis. High iron levels may also lead to an
increased risk of infection as iron is necessary for bacterial growth.
Vitamin A supplementation may help to control the adverse effects in
areas where infections are prevalent.13
Therapeutic uses of supplements
Prevention and treatment of deficiency
Iron supplements are used to treat cases of iron deficiency anemia,
generalized itching and impaired mental performance in the young. The
usual dose for treatment of deficiency is 100 mg per day in adults and 2
mg per kg of body weight per day in children. Doses are low to start
with and increased gradually to reduce side effects. It may take one to
two months to correct anemia and iron supplements may be needed for a
further several months afterwards to replenish iron stores.
Iron supplements are often recommended for pregnant women due to the
high demands of the developing baby and may also be useful after
pregnancy. During the last three months of pregnancy, 3 to 4 mg of iron
are transferred to the baby each day. The number of red blood cells in
the mother's blood increases by 20 to 30 percent. It is often very
difficult to meet these increased needs from diet alone, and many
doctors recommend iron supplements. They are particularly important for
women with low iron stores. Iron is also very important for women who
are breastfeeding, especially if they are recovering from blood loss
during delivery or depletion of body stores during pregnancy.
Breastfeeding causes needs to increase by around 0.5 to 1 mg per day.
Iron supplements may improve verbal learning and memory in those
susceptible to iron deficiency even in those who are not anemic. In a
study published in The Lancet in 1996, researchers at Johns
Hopkins University evaluated 78 adolescent girls with non-anemic iron
deficiency and measured their cognitive ability, memory and
concentration. The girls were then divided into two groups, some were
given a placebo and some were given iron supplements. After eight weeks,
measurements showed an increase in iron levels in the supplement group
while the levels in the placebo group remained low. Tests showed that
the girls who took the iron supplements performed better on the verbal
learning and memory tests than the girls who took placebo. Both groups
scored the same on tests measuring their ability to pay attention and
concentrate. There was a direct relationship between how much the blood
iron levels went up and the ability to learn.14
Interactions with other nutrients
Iron in the ferric form oxidizes vitamin E and reduces its
effectiveness. Ferrous forms of iron do not usually interact with
vitamin E. Vitamin E may reduce the possible harmful oxidative effects
Iron competes with magnesium, copper, calcium and zinc for absorption in
the intestine, and excess intake of one of these minerals could produce
a deficiency of the others. Nicotinic acid seems to enhance iron
Interactions with drugs
Antacids, anti-arthritis drugs, allopurinol for gout, aspirin, and
cholestyramine may decrease iron absorption and should be taken several
hours apart from supplements. Iron may decrease absorption of thyroxin,
tetracyclines, penicillamine, ciprofloxacin or norfloxacin.
Elevated serum levels of iron may reduce the
effectiveness of interferon therapy for the hepatitis C virus.
Children should not be given large doses of iron supplements. Iron
is an important nutrient for bacteria and supplements should be avoided
during acute infections, particularly in the young.
Iron supplements should be avoided in cases of peptic
ulcers and inflammatory bowel disease as iron can have a corrosive
effect and exacerbate these conditions. Blood transfusion recipients and
sufferers of thalassemia, hemochromatosis and hepatitis should also
avoid iron supplements. Iron preparations by injection may cause a
flare-up of rheumatoid arthritis.
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2 García Casal MN et al. Vitamin A
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3 Looker AC; Dallman PR; Carroll MD;
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4 van Iperen CE; Kraaijenhagen RJ;
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9 Tuomainen TP; Punnonen K; Nyyssönen
K; Salonen JT Association between body iron stores and the risk of acute
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10 Salonen et al. Am J Epidemiol.
11 Tseng M; Sandler RS; Greenberg ER;
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12 Stevens R et al. Moderate elevation
of body iron level and increased risk of cancer occurrence and death.
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13 Ribaya Mercado JD Importance of
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14 Bruner A et al. Randomised study of
cognitive effects of iron supplementation in non-anaemic iron-deficient
adolescent girls. Lancet. 1996;348:973, 992-996
15 Agte VV; Paknikar KM; Chiplonkar
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