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Iron Toxicity, What You Don't Know

The toxicity of iron is governed by absorption. The more you take in the more you are at risk. The iron is absorbed in the ferrous state by cells of the intestinal mucous. Gastric and intestinal secretions can reduce ferric ions (the unusable form of the iron) to the ferrous (absorbable) state. Ferrous iron reacts with hydrogen peroxide (H202) to form OH, in the reaction: Fe(II) + H2O2--> OH. + OH- + Fe(III) Under normal conditions, the free radicals formed are controlled and removed by antioxidants, but if you have an over abundance of iron in your body, the free radicals will not be removed fast enough and there will be a build up.

Factors that influence iron toxicity are:

  • Copper Level
  • Phosphorus Level
  • Vitamin E level

Factors that enhance iron absorption are:

  • Valine and Histidine
  • Ascorbic Acids, with or without Vitamin E
  • Succinate
  • Pyruvic Acid
  • Citric Acid

Ferritin is a unique iron storage protein containing 24 storage proteins. When excess dietary iron is absorbed, the body produces more ferritin. Ferritin is greatly abundant in the heart and liver, therefore there is a large amount in these organs, and iron rushes to these organs for storage. The body can only produce so much of these proteins, however, so excess iron builds up in these organs and causes tissue destruction. Iron Overload is characterized by increased levels of ferritin (the iron storage protein), haemosiderin (another storage protein), and iron catalyzed lipid peroxidation.

There are many reasons why certain people absorb more iron than others:

  1. Not everyone takes in the same amount of iron.
  2. When alcohol and food are consumed together, the alcohol facilitate the absorption of iron.
  3. Many people develop alcoholic cirrhosis (disease of the liver), and, hence , lose their ability to control iron uptake.
  4. Dietary patterns such as drinking orange juice with a meal, increases iron absorption.

Diseases that Can Cause Iron Toxicity

Iron toxicity is not always due to an increase in dietary iron. There are many diseases that can lead to a problem in iron absorption and in turn iron toxicity. With acute iron poisoning, much of the damage to the gastrointestinal tract and liver may be a result of a high localized iron concentration and free radical production, leading to heptatoxicity via lipid peroxidation and the destruction of the hepatic mitochondria. Therefore, the patient needs rapid removal of iron from the gut to prevent tissue damage.

The iron accumulating disease is Hemochromatosis. This is an iron storage disease the results from the inability of the intestine to keep out unneeded iron. Instead, iron accumulates in the liver causing siderosis (the accumulation of storage iron in tissues) and damage to the storage organs. A normal man will usually absorb 1 mg of iron/day, but with this disease, he will absorb 3mg/day. This is a very common problem, 1 out of every 15 people have a form of this disease.

There are two types of this disease:

  1. Heredity or Primary Hemochromatosis
  2. Acquired or Secondary Hemochromatosis

Hereditary Hemochromatosis is a hereditary disease where the intestines lack the normal ability to keep out the available but unneeded dietary iron. Patients suffering from this disease take in the iron, but have problems excreting it. The excess is therefore placed into storage. It has been shown numerous times, that with an increased uptake from the diet of 1-3 mg of iron, more than required, per day, in a period of 40-50 years, 20-40g of iron will be accumulated in the body. This accumulation especially occurs in the liver and heart, and will eventually lead to necroses and cardiopathy. This condition can be spotted at an early stage by determination of serum ferritin concentration and liver biopsy. This condition can be treated and cured if caught before the tissue damage begins.

Acquired Hemochromatosis is an intestinal abnormality occurring with acquired diseases.

Some of the diseases this may happen with are:

Anemia and Ineffective Erythropoiesis
These diseases may result when a patient receives blood transfusions, but receives them for too long and the iron begins to build up.
Liver Disease
if a patient has a liver disease, he will not be able to control the iron uptake from the liver and the iron will begin to accumulate.
High Intake of Iron
Many times people are diagnosed with anemia, but the confidence rating in this diagnosis is only 95%. Therefore, many people are given supplements that they do not need and the iron in their body increases.

Problems Resulting From Iron Toxicity

There are many problems that may result from iron toxicity, these include: anorexia, oligura, diarrhea, hypothermia, diphasic shock, metabolic acidosis, and death. In addition to these, the patient may experience vascular congestion of the gastrointestinal tract, liver, kidneys, heart, brain, spleen, adrenals, and thymus.

As a result of iron storage disease, the liver becomes cirrhotic. Hepatoma, the primar cancer of the liver, has become the most common cause of death among patients with hemochromatosis. Also, when siderosis becomes severe in young people, myocardial disease is a common cause of death.

Impotence may occur in young men, and amenorrhea may occur in young women. Both of these sexual related problems are due to iron loading in the anterior pituitary.

Children are at Risk as Well

The lethal dose of iron for a 2 year old child is 3 g, and 1 g leads to severe poisoning. Accidental iron poisoning occurs in children consuming 10-50 iron tablets in the form of ferrous sulfate, over a period of a few hours. The ingested iron enters the stomach where the pH is low. The ferrous sulfate will remain in a soluble form, leading to irritation of the gastric mucosa. When the ferrous sulfate leaves the stomach, the pH is changed again by the pancreatic bicarbonate in the duodenum. This leads to the formation of insoluble iron complexes, causing further mucosal damage.

There was a study conducted from 1983-1990, reported in Pediatrics. This study reported that 53 children younger than 6 died as a direct result of unintentional ingestion. Iron supplements caused the death of 16 of these children. Iron supplements, causing 30.2% of fatalities, are the single most frequent cause of pediatric pharmaceutical unintentional fatalities.

The reason for this high percentage involves many factors, including:

  • The ready availability of prenatal vitamins and iron supplements in homes with young children.
  • The similar appearance of iron supplements to candy.
  • The unrestricted over the counter marketing of high strength iron.

These problems could be eliminated by increasing parental education, repackaging and reformulating iron supplements, and making the warning labels more clear.

Treatment for Iron Toxicity

The following are treatments for iron toxicity:

  • Removal of the patients blood, one unit at a time. This is the cheapest, safest, and most efficient way to reduce siderosis.
  • Dietary restriction. This not an efficient way to cure the problem, but patients with iron storage disease should avoid heavily iron enriched foods, vitamins supplemented with iron, and therapeutic iron.
  • Chelating agents. Deferoxamine is the best and least dangerous. It is expensive and administered by painful intramuscular injections. These result in the excretion of 5-15mg of iron. This is very dangerous, however, because the dose and route of administration are limited by the hypotensive effect of the drug. Deferoxamine has an LD50 of 250mg/kg body weight. This drug can only be used for a certain amount of time, not only because of it's toxicity, but also because it results in the removal of other mineral such as copper and zinc.
References

Chapman and Hall. Iron Nutritional and Physiological Significance. The British Nutrition Foundation. 1995.

Emery, T. Iron and Your Health: Facts and Fallacies. CRC Press Inc. 1991.

Iron. Mineral Tolerance of Domestic Animals. 242-255.

Lag, J. Geomedical Problems Related to Aluminum, Iron, and Magnesium. The Norwegian Academy of Science and Letters. 1993.

Lauffer, R. Iron and Human Diseases. CRC Press Inc. 1992.

Litovitz, T. and Manoguerra, A. Comparison of Pediatric Poisoning Hazards: An Analysis of 3.8 Million Exposure Incidents. Pediatrics. 89:1992.

Riederer, P. and Youdim, M. Iron in Central Nervous System Disorders. Springer-Verlag, New York. 1993.