Introduction

 

Iron, one of the most abundant metals on Earth, is essential to most life forms and to normal human physiology. Iron is an integral part of proteins and enzymes that maintain good health. In humans, iron is an essential component of proteins involved in oxygen transport. It is also essential for the regulation of cell growth and differentiation. A deficiency of iron limits oxygen delivery to cells, resulting in fatigue, poor work performance, and decreased immunity. On the other hand, excess amounts of iron can result in toxicity and even death.

Almost two-thirds of iron in the body is found in haemoglobin, the protein in red blood cells that carries oxygen to tissues. Smaller amounts of iron are found in myoglobin, a protein that helps to supply oxygen to muscle, and in enzymes that assist biochemical reactions. Iron is also found in proteins that store iron for future needs and that transport iron in blood.

Iron has the longest and best-described history among all the micronutrients. It is a key element in the metabolism of almost all living creatures.

Food Sources

The amount of iron in food (or supplements) that is absorbed and used by the body is influenced by the iron nutritional status of the individual and whether or not the iron is in the form of haeme. Because it is absorbed by a different mechanism than nonhaeme iron, haeme iron is more readily absorbed and its absorption is less affected by other dietary factors. Individuals who are anaemic or iron deficient absorb a larger percentage of the iron they consume (especially nonhaeme iron) than individuals who are not anaemic and have sufficient iron stores.

Haeme iron is absorbed better than nonhaeme iron, but most dietary iron is nonhaeme iron.

Haeme iron – Haeme iron comes mainly from haemoglobin and myoglobin in meat, poultry, and fish. Although haeme iron accounts for only 10-15% of the iron found in the diet, it may provide up to one third of total absorbed dietary iron. The absorption of haeme iron is less influenced by other dietary factors than that of nonhaeme iron.

Nonhaeme iron – Iron in plant foods such as lentils and beans is arranged in a chemical structure called nonhaeme iron. Minerals from plant sources, however, may vary from place to place because soil mineral content varies geographically.

This is the form of iron added to iron-enriched and iron-fortified foods.

 

Some important food sources of iron (upper row haeme iron, lower row non-haeme iron)

 

Liver	Chicken	Meat	Oysters	Sausages
Lentils	Sesame seeds	Soybeans	Oat/wheat bran	Dried apricots

 

Recommended Dietary Allowance (RDA)

 

The European Union RDA for the general population is set at 15 mg/day.

However, some people need more iron than others:

Infants and children between the ages of 6 months and 4 years
A full-term infant's iron stores are usually sufficient to last for 6 months. High iron requirements are due to the rapid growth rates sustained during this period.

Adolescents
Early adolescence is another period of rapid growth. In females, the blood loss that occurs with menstruation adds to the increased iron requirement of adolescence.

Pregnant women
Increased iron utilization by the developing foetus and placenta, as well as blood volume expansion significantly, increases the iron requirement during pregnancy.

Individuals with chronic blood loss
Chronic bleeding or acute blood loss may result in iron deficiency. One millilitre (ml) of blood with a haemoglobin concentration of 150 grams/litre contains 0.5 mg of iron. Thus, chronic loss of very small amounts of blood may result in iron deficiency. A common cause of chronic blood loss and iron deficiency in developing countries is intestinal parasitic infection. Individuals who donate blood frequently, especially menstruating women, may need to increase their iron intake to prevent deficiency because each 500 ml of blood donated contains between 200 and 250 mg of iron.

Individuals with Helicobacter pylori infection
H. pylori infection is associated with iron deficiency anaemia, especially in children, even in the absence of gastrointestinal bleeding.

Vegetarians
Iron from plant sources is less efficiently absorbed than that from animal sources. It has been estimated that the bioavailability of iron from a vegetarian diet is only 10%, while it is 18% from a mixed diet.

Individuals who engage in regular, intense exercise
Daily iron losses have been found to be greater in athletes involved in intense endurance training. This may be due to increased microscopic bleeding from the gastrointestinal tract or increased fragility and haemolysis of red blood cells. It has been estimated that the average requirement for iron may be 30% higher for those who engage in regular intense exercise.

 

Inhibitors/stimulators:

The following food components have been found to stimulate the absorption of iron:

Vitamin A – Vitamin A deficiency may increase iron deficiency anaemia. The combination of vitamin A and iron seems to improve anaemia more effectively than either iron or vitamin A alone.

Copper – Adequate copper nutritional status appears to be necessary for normal iron metabolism and red blood cell formation. Anaemia is a clinical sign of copper deficiency.

Meat proteins – Meat proteins improves the absorption of nonhaeme iron.

Vitamin C – Vitamin C improves the absorption of nonhaeme iron.

 

The following food components have been found to inhibit the absorption of iron :

 

Calcium – When consumed together in a single meal, calcium has been found to decrease the absorption of iron. However, little effect has been observed on serum ferritin levels (iron stores).

Tannins (found in tea), polyphenols , and phytates (found in legumes and whole grains) can decrease absorption of nonhaeme iron. Some proteins found in soybeans also inhibit nonhaeme iron absorption.

 

Functions in the Body

Oxygen transport and storage

Haeme is an iron-containing compound and found in a number of biologically important molecules. Hemoglobin and myoglobin are haeme-containing proteins that are involved in the transport and storage of oxygen. Hemoglobin is the primary protein found in red blood cells and represents about two thirds of the body's iron.

The vital role of hemoglobin in transporting oxygen from the lungs to the rest of the body is derived from its unique ability to acquire oxygen rapidly during the short time it spends in contact with the lungs and to release oxygen as needed during its circulation through the tissues. Myoglobin functions in the transport and short-term storage of oxygen in muscle cells, helping to match the supply of oxygen to the demand of working muscles.

 

Electron transport and energy metabolism

Cytochromes are haeme-containing compounds that are critical to cellular energy production and therefore life, through their roles in mitochondrial electron transport. They serve as electron carriers during the synthesis of ATP, the primary energy-storage compound in cells. Cytochrome P450 is a family of enzymes that functions in the metabolism of a number of important biological molecules, as well as the detoxification and metabolism of drugs and pollutants. Nonhaeme iron-containing enzymes, such as NADH dehydrogenase and succinate dehydrogenase, are also critical to energy metabolism.

 

Antioxidant and beneficial pro-oxidant functions

Catalase and peroxidases are haeme-containing enzymes that protect cells against the accumulation of hydrogen peroxide, a potentially damaging reactive oxygen species (ROS), by catalyzing a reaction that converts hydrogen peroxide to water and oxygen. As part of the immune response, some white blood cells engulf bacteria and expose them to ROS in order to kill them. The synthesis of one such ROS, hypochlorous acid, by neutrophils is catalyzed by the haeme-containing enzyme myeloperoxidase.

 

DNA synthesis

Ribonucleotide reductase is an iron-dependent enzyme that is required for DNA synthesis. Thus, iron is required for a number of vital functions including growth, reproduction, healing, and immune function.

 

Deficiency

Iron deficiency is the most common nutrient deficiency in the world. There are three general levels of iron deficiency: storage iron depletion, early functional iron deficiency, and iron deficiency anaemia.

Storage iron depletion
Iron stores are depleted, but the functional iron supply is not limited.

Early functional iron deficiency
The supply of functional iron is low enough to impair red blood cell formation, but not low enough to cause measurable anaemia.

Iron deficiency anaemia
There is inadequate iron to support normal red blood cell formation, resulting in anaemia. The anaemia of iron deficiency is characterized as microcytic and hypochromic, meaning red blood cells are measurably smaller than normal and their hemoglobin content is decreased. At this stage of iron deficiency, symptoms may be a result of inadequate oxygen delivery due to anaemia and/or suboptimal function of iron-dependent enzymes.

It is important to remember that iron deficiency is not the only cause of anaemia, and that the diagnosis or treatment of iron deficiency solely on the basis of anaemia may lead to misdiagnosis or inappropriate treatment of the underlying.

 

Toxicity

Accidental overdose of iron-containing products is the single largest cause of poisoning fatalities in children under 6 years of age. Although the oral lethal dose of elemental iron is approximately 200-250 mg/kg of body weight, considerably less has been fatal. Symptoms of acute toxicity may occur with iron doses of 20-60 mg/kg of body weight. Iron overdose is an emergency situation because the severity of iron toxicity is related to the amount of elemental iron absorbed.

Acute iron poisoning produces symptoms in four stages:

1) Within 1-6 hours of ingestion, symptoms may include nausea, vomiting, abdominal pain, tarry stools, lethargy, weak and rapid pulse, low blood pressure, fever, difficulty breathing, and coma.

2) If not immediately fatal, symptoms may subside for about 24 hours.

3) Symptoms may return 12 to 48 hours after iron ingestion and may include serious signs of failure in the following organ systems: cardiovascular, kidney, liver, hematologic (blood), and central nervous systems.

4) Long-term damage to the central nervous system, liver (cirrhosis), and stomach may develop 2 to 6 weeks after ingestion.

 

Regulation

 

Iron response elements are short sequences of nucleotides found in the messenger RNA (mRNA) that codes for key proteins in the regulation of iron storage and metabolism. Iron regulatory proteins (IRP) can bind to iron response elements and affect mRNA translation, thereby regulating the synthesis of specific proteins. It has been proposed that when the iron supply is high, more iron binds to IRPs and prevents them from binding to iron response elements on mRNA.

When the iron supply is low, less iron binds to IRPs, allowing increased binding of iron response elements. Thus, when less iron is available, translation of mRNA that codes for the iron storage protein, ferritin, is reduced because iron is not available for storage. Translation of mRNA that codes for the key regulatory enzyme of haeme synthesis in immature red blood cells is also reduced to conserve iron.

In contrast, IRP binding to iron response elements in mRNA that codes for transferrin receptors inhibits mRNA degradation, resulting in increased synthesis of transferrin receptors and increased iron transport to cells.

 

Iron absorption

Iron absorption refers to the amount of dietary iron that the body obtains and uses from food. Healthy adults absorb about 10% to 15% of dietary iron, but individual absorption is influenced by several factors.

Storage levels of iron have the greatest influence on iron absorption. Iron absorption increases when body stores are low. When iron stores are high, absorption decreases to help protect against toxic effects of iron overload. The type of dietary iron consumed also influences iron absorption. Absorption of haeme iron from meat proteins is efficient. Absorption of haeme iron ranges from 15% to 35%, and is not significantly affected by diet. In contrast, 2% to 20% of nonhaeme iron in plant foods such as rice, maize, black beans, soybeans and wheat is absorbed. Nonhaeme iron absorption is significantly influenced by various food components.

Meat proteins and vitamin C will improve the absorption of nonhaeme iron. It is most important to include foods that enhance nonhaeme iron absorption when daily iron intake is less than recommended, when iron losses are high (which may occur with heavy menstrual losses), when iron requirements are high (as in pregnancy), and when only vegetarian nonhaeme sources of iron are consumed.