Author Archives: IHADMIN

Iron: Too Much Can Harm You

Several studies have shown that high blood levels of iron are associated with an increased risk of suffering heart attacks and cancers,particularly those of the esophagus and bladder. A study from Harvard showed that it may be the meat source of iron, rather than just the iron itself, that causes the heart attacks and cancers.

People who eat a lot of meat, fish and chicken have higher blood levels of iron than vegetarians. The iron in meat, fish and chicken is called heme iron, which is absorbed at a very high level, around 10-20 percent. On the other hand, the iron that you get from plants is absorbed very poorly; only one to three percent of the iron from leafy green vegetables and other plant sources of iron is absorbed.

Even though there is an association between high iron levels and cancer and heart attacks, we do not know if the iron causes these diseases. You can find out if your iron level is too high by asking you doctor to draw blood for a test called transferrin iron binding saturation. People with a transferrin iron binding saturation of more than 60 percent are at increased risk for developing heart attacks and cancers. If your level is greater than 60 percent, you can reduce your intake of iron by restricting meat, fish, chicken and iron-supplemented foods, and you can get rid of extra iron by donating blood six or more times a year.

Hemochromatosis is an inherited condition in which a person stores too much iron. It is easily treated by donating blood periodically, and when that is done the person will lead a perfectly normal life. Problems only occur when the condition is not diagnosed.

Dr. Gabe Mirkin has been a radio talk show host for 25 years and practicing physician for more than 40 years; he is board certified in four specialties, including sports medicine. Read or listen to hundreds of his fitness and health reports at

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Article Source:,_M.D.

Hereditary Hemochromatosis – It can be Treated

Hereditary Hemochromatosis (HH) is the most common genetic disorder of persons of northern European extraction. The most common gene involved in causing Hereditary Hemochromatosis (HH) is the HFE gene. Most patients with hemochromatosis have two copies of the HFE mutation C282Y.

In persons of northern European extraction approximately 1 in 10 persons carries one copy of C282Y. Even one copy of C282Y can be associated with too much iron in the liver, high cholesterol, diabetes and the skin disorder porphyria cutanea tarda.

Approximately 1 in 200 to 300 persons of northern European extraction carry two copies of C282Y. In some northern European populations eg Ireland, Iceland and Brittany the percentage of persons carrying one copy of C282Y is higher. Predictably countries settled by northern Europeans eg Australia, South Africa and Canada have high rates of hemochromatosis.

HH is characterised by excessive absorption of dietary iron and a consequent progressive increase in total body iron stores. Iron accumulates in the parenchymal cells of the liver, the heart, pancreas, anterior pituitary and skin. This accumulation of iron in body tissues causes disease.

In severe HH the disorder manifests as potentially life threatening conditions such as septicaemia, cirrhosis of the liver, liver cancer, diabetes, heart failure and heart arrhythmias. Arthritis is common and a severe arthritis involving numerous joints may occur. Ovarian and testicular failure secondary to iron deposition in the anterior pituitary and possibly the hypothalamus may occur. Rarely hypothyroidism may occur.

If HH is not treated liver disease may be fatal. The morbidity and mortality of HH can be reduced by early diagnosis and treatment by phlebotomy or blood letting.

There is frequently a delay between the onset of symptoms and diagnosis. This is because early symptoms such as fatigue and arthralgia are non-specific.

Hereditary Hemochromatosis fits the criteria set by the World Health Organisation for population screening for a disease:

  1. The homozygous genotype is common and is potentially fatal if not treated
  2. The disease has a lengthy latent period with asymptomatic iron accumulation followed by a period of iron overload with reversible organ injury
  3. Treatment during the latent period and the period with reversible organ injury restores the life expectancy to normal. (Treatment is safe, effective and cost effective)
  4. HH can be detected by measurement of the transferrin saturation (TS).

It is very important to make an early diagnosis of HH because patients who have not developed cirrhosis and are treated by phlebotomy have a normal life expectancy.

When the diagnosis of hemochromatosis is made it is important to adjust the diet so that too much iron is not being absorbed because of an improper diet.

  • The biggest considerations are not to take medications which contain iron, consume too much alcohol or Vitamin C.
  • The ingestion of black tea has been shown to decrease the absorption of iron.
  • African tea which is becoming popular may contain iron so too much should not be consumed.
  • Don’t take milk thistle which has often been touted as good for the liver as it can cause severe problems in those with hemochromatosis.
  • Don’t eat raw shellfish. They may be contaminated with Vibrio vulnificans which thrives in an iron rich environment. There have been fatalities in the northern hemisphere. Cooking inactivates this organism.

Hemochromatosis – How it is Treated

The mainstay of hemochromatosis treatment is bloodletting also known as phlebotomy or venesection. This treatment is life long after diagnosis.

Severe cases of hemochromatosis may need up to and sometimes more than the 10g of iron removed by phlebotomy. In very severe cases phlebotomy may need to initially occur once or twice a week. Each unit of blood is usually 500mls and contains 250mg of iron. So it takes the removal of 2 liters of blood to rid the body of 1g of excess iron.

The ongoing need for phlebotomy is highly variable. Small patients may only tolerate phlebotomies of 250 mls at a time. Maintenance phlebotomies may be in the order of 3 or 4 a year in many cases. Some patients are well maintained by becoming blood donors. The aim is to keep the ferritin level at between 25 to 75 ug/L. Ferritin level is used to monitor the iron level. The need for phlebotomies may change in patients with hemochromatosis.

If a patient stops drinking alcohol they may need fewer phlebotomies to maintain a low ferritin level. Similarly an increase in alcohol consumption may increase the need for phlebotomies. Regular exercise may decrease the need for phlebotomies.

If there is no contraindication to blood donation many blood agencies around the world now accept blood from patients with hemochromatosis. This blood may be actually better blood for persons in need of transfusions as it will contain more young blood cells if the patient is being regularly bled. Sometimes they will not accept blood if the patient has an infectious disease such as hepatitis C and other arrangements have to be made.

Sometimes erythropoietin may need to be used to stimulate the production of new blood cells if there is severe iron overload and the patient is being bled very frequently eg 2 or 3 times a week. Such treatment is uncommon and needs close medical management.

Iron chelators are sometimes used to treat patients with hemochromatosis. Such treatment has to be carefully monitored.

With ongoing venesections it often becomes difficult to access damaged veins. So it is important to preserve the veins from the beginning. Cold packs applied immediately after phlebotomy are helpful.

When preparing for a phlebotomy it is important to be well hydrated before. The patient should drink fluids such as juice or tea or coffee afterwards and most people should arrange for someone else to drive them home.

If hemochromatosis is advanced other problems also need to be treated. These can include arthritis, diabetes, heart problems, impotence and cirrhosis. These problems are treated separately but the hemochromatosis is also included in the overall management. For example phlebotomies usually improve diabetes secondary to hemochromatosis. However the diabetes rarely completely clears. Similarly impotence caused by deposition of iron in the hypothalamus/anterior pituitary and causing testicular failure and impotence is usually not reversed by phlebotomy treatment. With successful deironing or removal of excess iron liver fibrosis may improve. Cirrhosis of the liver usually does not improve.

Hemochromatosis- What are the Symptoms

Probably the greatest difficulty in diagnosing early hemochromatosis is that it is non-specific and the symptoms are vague.

Many sufferers are often diagnosed with the “flu” or “chronic fatigue syndrome”. Some have suffered years where they have been suspected of malingering. Paradoxically anemia may firstly be suspected because of decreased energy. If the correct tests are not done sufferers may even be given iron tablets which further worsen their symptoms. Iron overload is insidious and usually takes many years to develop. Women may begin to load iron at menopause as the phlebotomy effect of menstruation has ceased. If this possibility is not suspected the symptoms may be written off as being due to “hormonal changes”.

The earliest symptoms of hemochromatosis are fatigue and arthralgia or aching joints. Once iron has begun to accumulate in body tissues the liver may be affected. In the past it has not been uncommon for sufferers to be suspected or being secret drinkers when abnormal liver function tests are found. As iron continues to accumulate the condition of the liver may worsen and other organs may be affected. Other organs which may be involved include the skin, pancreas, ovaries, testes, heart, digestive system, thyroid and joints. Annoying skin rashes, palpitations, impotence and diabetes may be a consequence of too much iron. Many patients suffer from recurrent infections and may decide to take “immune boosters” which are metabolised by the liver. This can make their condition worse.

Here is an image of a liver affected by hemochromatosis:

Patients with severe hemochromatosis may present with septicemia or blood poisoning, heart failure, failure of the reproductive organs and severe arthritis where joint replacement is necessary. In the worst cases liver transplant may be necessary. Those cases that require liver transplant have a 50% mortality within the year after transplant. This mortality is often due to heart problems or septicemia. Men over 55 years of age with severe hemochromatosis have 200 times the chance of developing liver cancer.

It is important to have a high index of suspicion for the possibility of hemochromatosis as the disorder is a great mimicker of other disorders. With the rapidly advancing knowledge on the disorder it is becoming more common for doctors to order transferrin (transferrin-iron) saturations (TS) on their patients and unsuspected cases of hemochromatosis are being found more frequently. Elevation of TS values is a big clue as to the diagnosis. However if only ferritin levels are ordered an early case of hemochromatosis or even a person with hemochromatosis who has been a blood donor may be missed. Testing for iron studies is not expensive. Taken together the TS value and ferritin level will detect most cases of hemochromatosis.

It is important to diagnose hemochromatosis early as it can be treated easily. Fortunately with increased awareness this is now happening. While the patient with end stage hemochromatosis may save the lives of others as he (usually but sometimes she) has alerted the doctor and relatives that others may have hemochromatosis, this represents an unnecessary tragedy that fortunately is becoming rarer.

Juvenile Hemochromatosis – What is it?

Juvenile hemochromatosis or Hemochromatosis type 2  is different from the more common hemochromatosis type 1 or HFE related hemochromatosis primarily in that it is a more severe disease. Hemochromatosis type 2 affects both sexes equally

While hemochromatosis type 1 has a male predilection, Juvenile hemochromatosis also has faster iron deposition in parenchymal cells of the body and causes clinical symptoms much earlier in life. It does not take the many decades to manifest as does the usual HFE related hemochromatosis. Sufferers are usually severely affected by the second and third decades of life. Juvenile hemochromatosis is associated with a more frequent occurrence of hypogonadism and cardiomyopathies. Premature menopause or heart failure may be presenting symptoms. Although liver dysfunction is part of the syndrome it is not as prevalent as in HFE related hemochromatosis. If the patient with juvenile hemochromatosis is not treated he or she may succumb to heart failure before the age of 30 years. It is not uncommon for a patient with juvenile hemochromatosis to have had hundreds of phlebotomies. Ferritin levels measured in the thousands are frequent occurrences. Juvenile hemochromatosis is very difficult to control because of the repeated need for venesections. If a patient has cardiac complications frequent venesections may place further strain on a damaged heart.

Hemochromatosis type 2 is an autosomal recessive disorder, so two copies of abnormal genes are required for the disorder to occur.

Juvenile hemochromatosis is divided into two forms.

  1. Type 2A is due to a mutation of the protein hemojuvelin which is coded for by the HJV gene. Type 2A is the more usual form of juvenile hemochromatosis. The HJV gene is located on chromosome 1q21. The most common mutation is G320V but over 20 novel mutations have been identified.
  2. Type 2B is due to a mutation of the hepcidin protein which is coded for by the HAMP gene. The HAMP gene is located on chromosome 19q13. Type 2 hemochromatosis may result from homozygous or compound heterozygous mutations in the HJV or HAMP genes.

Recent work identified an Italian brother and sister pair where a form of hemochromatosis resembling juvenile hemochromatosis resulted from the synergistic effect of Q317X homozygous mutations in the TfR2 gene (the cause of hemochromatosis type 3) and HFE C282Y/H63D compound heterozygosity. Hemochromatosis types 1 and 3 are not as severe as type 2 however the combination of hemochromatosis types 1 and 3 has been shown to produce a clinical presentation similar to hemochromatosis type 2

Juvenile hemochromatosis occurs worldwide. In Canada a cluster of patients occurs in Quebec in Saguenay-Lac-Saint-Jean. There are reports from numerous other countries including Greece, USA, Italy, England, Albania, Australia, France, Germany, Slovakia, Croatia, Romania and China. The original identification of the HJV gene came from collaborative work involving Greek, French and Canadian patients.

A mutation in the HAMP gene can pair with a HFE mutation and give a digenic form of hemochromatosis. This combination of single hemochromatosis type 1 and hemochromatosis type 2 mutations is not as severe as juvenile hemochromatosis.

Details on the HFE Gene

What is the official name of the HFE gene?

The official name of this gene is “hemochromatosis.”

HFE is the gene’s official symbol. The HFE gene is also known by other names, listed below.

What is the normal function of the HFE gene?

The HFE gene provides instructions for producing a protein that is located mainly on the surface of intestinal cells, liver cells, and some cells in the immune system. During digestion, this protein helps certain cells regulate the absorption of iron into the small intestine by interacting with other proteins located on the cell surface. The body uses this mechanism to help monitor its supply of iron. When the proteins involved in iron sensing and absorption are functioning properly, the body absorbs only about 10 percent of the iron ingested in the diet.

Research suggests that the HFE protein also helps control levels of another important iron regulatory protein, hepcidin. Adequate levels of hepcidin are necessary to ensure that the body does not absorb and store too much iron in its tissues and organs.

How are changes in the HFE gene related to health conditions?

hemochromatosis – caused by mutations in the HFE gene
Researchers have identified more than 20 mutations in the HFE gene that cause type 1 hemochromatosis. These mutations alter the size of the HFE protein or disrupt its 3-dimensional shape. As a result, the HFE protein cannot function properly. Two particular mutations are responsible for most cases of type 1 hemochromatosis. Each of these mutations changes one of the building blocks (amino acids) used to make the HFE protein. The most common mutation replaces the amino acid cysteine with the amino acid tyrosine at position 282 in the protein’s chain of amino acids (written as C282Y or Cys282Tyr). The other mutation replaces the amino acid histidine with the amino acid aspartic acid at position 63 (written as H63D or His63Asp). As a result of these substitutions, the altered protein is not sent to the cell surface and does not interact with a cell surface receptor called the transferrin receptor. The transferrin receptor plays a critical role in regulating the amount of iron that enters the cell. When the HFE protein does not bind to the transferrin receptor, too much iron enters the body through the cells of the small intestine. This increased absorption of iron leads to the iron overload characteristic of this disorder.
porphyria – increased risk from variations of the HFE gene

Mutations in the HFE gene that cause hemochromatosis are also believed to increase the risk of developing a form of porphyria called porphyria cutanea tarda. These mutations have been found more frequently in people with this condition than in unaffected people. Researchers are not certain how mutations in the HFE gene are related to the signs and symptoms of porphyria cutanea tarda. These mutations likely trigger this condition by increasing iron levels in the liver, as in hemochromatosis.

X-linked sideroblastic anemia – course of condition modified by mutations in the HFE gene
One particular mutation in the HFE gene may increase the severity of symptoms in X-linked sideroblastic anemia when it is present in patients who also have mutations in the ALAS2 gene. The mutation results in a substitution of the amino acid tyrosine for the amino acid cysteine at position 282 (written as C282Y or Cys282Tyr) in the HFE protein. Although it is not known exactly how the mutation affects symptoms, it may cause iron to build up more rapidly in the body’s tissues.

Where is the HFE gene located?

Cytogenetic Location: 6p21.3

Molecular Location on chromosome 6: base pairs 26,195,426 to 26,205,037

The HFE gene is located on the short (p) arm of chromosome 6 at position 21.3.

More precisely, the HFE gene is located from base pair 26,195,426 to base pair 26,205,037 on chromosome 6.

See How do geneticists indicate the location of a gene? ( in the Handbook.

Where can I find additional information about HFE?

You and your healthcare professional may find the following resources about HFE helpful.

  • Gene Reviews – Clinical summary (
  • Gene Tests – DNA tests ordered by healthcare professionals (

You may also be interested in these resources, which are designed for genetics professionals and researchers.

  • PubMed – Recent literature ( DB=PubMed&term= (HFE+gene[TIAB])+AND+english[la]+AND+human[mh] &orig_db= PubMed& filters=ON&pmfilter_EDatLimit=720+Days)
  • OMIM – Genetic disorder catalog (
  • Research Resources – Tools for researchers
    • CDC: Genomics and Disease Prevention (GDPInfo) ( GeneSymbol=HFE)
    • Entrez Gene (
    • GeneCards (
    • HUGO Gene Nomenclature Committee ( 4886)

What other names do people use for the HFE gene or gene products?

  • hemochromatosis, genetic; GH
  • Hemochromatosis, Hereditary; HH
  • HHC
  • HLA-H antigen

See How are genetic conditions and genes named? ( in the Handbook.

What glossary definitions help with understanding HFE?

acids ; amino acid ; anemia ; antigens ; cell ; digestion ; gene ; GH ; HLA ; immune system ; intestine ; iron ; metabolism ; mutation ; protein ; receptor ; sign ; substitution ; symptom ; tissue ; transferrin ; tyrosine

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (


  • Andrews NC. Molecular control of iron metabolism. Best Pract Res Clin Haematol. 2005 Jun;18(2):159-69. Review. ( db=pubmed&dopt= Abstract&list_uids=15737882)
  • Bennett MJ, Lebron JA, Bjorkman PJ. Crystal structure of the hereditary haemochromatosis protein HFE complexed with transferrin receptor. Nature. 2000 Jan 6;403(6765):46-53. ( db=pubmed&dopt= Abstract&list_uids=10638746)
  • Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Hematology (Am Soc Hematol Educ Program). 2003;:40-61. Review. ( db=pubmed&dopt= Abstract&list_uids=14633776)
  • Camaschella C, Roetto A, De Gobbi M. Genetic haemochromatosis: genes and mutations associated with iron loading. Best Pract Res Clin Haematol. 2002 Jun;15(2):261-76. ( db=pubmed&dopt= Abstract&list_uids=12401307)
  • CDC HuGE review: HFE Gene and Hereditary Hemochromatosis (
  • Deicher R, Horl WH. New insights into the regulation of iron homeostasis. Eur J Clin Invest. 2006 May;36(5):301-9. ( db=pubmed&dopt= Abstract&list_uids=16634833)
  • Egger NG, Goeger DE, Payne DA, Miskovsky EP, Weinman SA, Anderson KE. Porphyria cutanea tarda: multiplicity of risk factors including HFE mutations, hepatitis C, and inherited uroporphyrinogen decarboxylase deficiency. Dig Dis Sci. 2002 Feb;47(2):419-26. ( db=pubmed&dopt= Abstract&list_uids=11855561)
  • Fleming RE, Britton RS, Waheed A, Sly WS, Bacon BR. Pathogenesis of hereditary hemochromatosis. Clin Liver Dis. 2004 Nov;8(4):755-73, vii. Review. ( db=pubmed&dopt= Abstract&list_uids=15464654)
  • Fleming RE, Britton RS. Iron Imports. VI. HFE and regulation of intestinal iron absorption. Am J Physiol Gastrointest Liver Physiol. 2006 Apr;290(4):G590-4. Review. ( db=pubmed&dopt= Abstract&list_uids=16537971)
  • Fleming RE, Sly WS. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu Rev Physiol. 2002;64:663-80. Review. ( db=pubmed&dopt= Abstract&list_uids=11826284)
  • Fleming RE. Advances in understanding the molecular basis for the regulation of dietary iron absorption. Curr Opin Gastroenterol. 2005 Mar;21(2):201-6. Review. ( db=pubmed&dopt= Abstract&list_uids=15711214)
  • Kelleher T, Ryan E, Barrett S, Sweeney M, Byrnes V, O’Keane C, Crowe J. Increased DMT1 but not IREG1 or HFE mRNA following iron depletion therapy in hereditary haemochromatosis. Gut. 2004 Aug;53(8):1174-9. ( db=pubmed&dopt= Abstract&list_uids=15247188)
  • Kostler E, Wollina U. Therapy of porphyria cutanea tarda. Expert Opin Pharmacother. 2005 Mar;6(3):377-83. Review. ( db=pubmed&dopt= Abstract&list_uids=15794729)
  • Kowdley KV. Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology. 2004 Nov;127(5 Suppl 1):S79-86. Review. ( db=pubmed&dopt= Abstract&list_uids=15508107)
  • McGregor J, McKie AT, Simpson RJ. Of mice and men: genetic determinants of iron status. Proc Nutr Soc. 2004 Feb;63(1):11-20. ( db=pubmed&dopt= Abstract&list_uids=15070436)
  • NIDDK fact sheet on hemochromatosis (
  • Njajou OT, Alizadeh BZ, van Duijn CM. Is genetic screening for hemochromatosis worthwhile? Eur J Epidemiol. 2004;19(2):101-8. Review. ( db=pubmed&dopt= Abstract&list_uids=15074564)
  • Pietrangelo A. Hereditary hemochromatosis–a new look at an old disease. N Engl J Med. 2004 Jun 3;350(23):2383-97. Review. No abstract available. ( db=pubmed&dopt= Abstract&list_uids=15175440)
  • Roy CN, Andrews NC. Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers. Hum Mol Genet. 2001 Oct 1;10(20):2181-6. Review. ( db=pubmed&dopt= Abstract&list_uids=11673399)
  • Zaahl MG, Merryweather-Clarke AT, Kotze MJ, van der Merwe S, Warnich L, Robson KJ. Analysis of genes implicated in iron regulation in individuals presenting with primary iron overload. Hum Genet. 2004 Oct;115(5):409-17. Epub 2004 Aug 24. ( db=pubmed& dopt=Abstract&list_uids=15338274)

Hemochromatosis – Recommended Diet

When the diagnosis of hemochromatosis is made it is important to adjust the diet so that too much iron is not being absorbed because of an improper diet. However such adjustment need not be at the expense of enjoying life and good food.

The biggest considerations are not to take medications which contain iron, consume too much alcohol or Vitamin C. Excessive alcohol consumption which has shown to greatly increase iron absorption in those with hemochromatosis is set at a level of 60g a day. Thus it is important to stay well below this level. The limit should be 30g a day in men and 20g a day in women. When a patient has two copies of C282Y and drinks excessive alcohol there is a multiplying affect – not an additive affect – on the absorption of iron. It is deadly to drink too much alcohol if you have hemochromatosis. The effect of excessive alcohol consumption on hemochromatosis cannot be overstressed.

Vitamin C enhances the absorption of iron. It is wise only to consume a moderate amount and not take Vitamin C tablets. Vitamin C has been known to precipitate heart palpitations in those with hemochromatosis.

The ingestion of black tea has been shown to decrease the absorption of iron. African tea which is becoming popular may contain iron so too much should not be consumed.

Patients with hemochromatosis should not take supplements unless there are documented deficiencies. There is evidence that those with hemochromatosis may also have an increased ability to absorb other heavy metals. While iron may be removed by bleeding it is very difficult to remove other excess heavy metals.

Don’t take milk thistle which has often been touted as good for the liver. It can cause severe problems in those with hemochromatosis. It is best to avoid herbal medicines with hemochromatosis as the joint effects have not been adequately studied.

Don’t eat raw shellfish. They may be contaminated with Vibrio vulnificans which thrives in an iron rich environment. There have been fatalities in the northern hemisphere. Cooking inactivates this organism.

Vitamin E – as an antioxidant may be of some help because too much iron may act as an oxidant. However it is probably important not to exceed 400 to 800 IU a day of Vitamin E.

Reduce nitric oxide boosting supplements – These supplements include L-arginine, citrulline malate, and agmatine sulfate. There seems to be a link between iron metabolism an nitric oxide levels.

It is non-heme iron or the iron found in sources such as vegetables that is excessively absorbed in hemochromatosis. Thus a patient with hemochromatosis may consume a steak and not be overly concerned. Meat and blood are sources of heme iron.

It is important not to believe that those with hemochromatosis should overly restrict their diet. With the exception of the above pointers restriction of iron intake doesn’t help that much in hemochromatosis. A very strict diet with removal of all other sources of iron will help keep the ferritin level down, however no more than could be achieved by one phlebotomy every 6 months. So it is important to enjoy your food – hemochromatosis is not a barrier to that.