Iron is a vital mineral for human health. While iron deficiency is widely recognized and frequently discussed, the dangers of iron overload often go unnoticed. Hemochromatosis, a condition that leads to excessive iron absorption, is surprisingly common and yet remains under the radar for many. In fact, hereditary hemochromatosis is one of the most prevalent genetic disorders in the United States. This article delves into the nuances of hemochromatosis, exploring its causes, symptoms, diagnosis, and treatment to raise awareness about this overlooked but significant health concern.
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Iron is an essential mineral that plays a key role in various bodily functions. It is primarily known for its involvement in forming hemoglobin, the protein in red blood cells that carries oxygen from the lungs to tissues in the body. Without sufficient iron levels, oxygen transportation, DNA synthesis, energy metabolism, immune function, and neurocognitive processes become impaired.
High iron levels, medically known as iron overload or hemochromatosis, occur when the body has excess iron. Serum ferritin represents the level of iron stored in the body and is used as the first-line biomarker to assess iron status. Ferritin levels greater than 300 ng/mL in males and greater than 150-200 ng/mL in menstruating females can indicate iron overload (26).
However, ferritin is an acute-phase reactant, meaning that it elevates as part of the body's compensatory response to inflammation, infection, and chronic disease. In clinical practice, healthcare providers will evaluate additional biomarkers to differentiate between elevated ferritin due to inflammation and that are due to iron overload:
Serum Iron: the amount of iron circulating in the blood. High levels indicate iron overload.
% Transferrin Saturation: indicates the proportion of transferrin (iron's transport protein) saturated with iron. High levels suggest iron overload.
Total Iron Binding Capacity: measures the capacity of transferrin to bind iron. Low levels indicate iron overload.
The table below summarizes normal reference ranges for markers of iron status. Note that values might vary slightly between different labs.
Understanding Hemochromatosis and Causes of High Iron Levels
Hemochromatosis is a medical condition characterized by iron overload and deposition in various body tissues. Hemochromatosis is more common in men than in women because women lose iron during their menstrual periods and childbirth (25).
Hemochromatosis is classified as either primary or secondary.
Primary Hemochromatosis
Primary, or hereditary, hemochromatosis is a genetic disorder that causes the body to absorb too much iron from the diet. This condition is most commonly associated with mutations in the HFE gene, particularly the C282Y variant. The most common form of the disorder is caused by inheriting two copies of the C282Y mutation, one from each patient. Although hereditary hemochromatosis is a genetic condition, not everyone with the gene mutations will develop symptoms or organ damage. (25)
Secondary Hemochromatosis
Secondary hemochromatosis is caused by factors other than genetics. Underlying causes include:
Iron-loading anemias (anemias characterized by excessive iron accumulation in the body)
Iron levels need to be maintained within an optimal range. When iron levels in the body are elevated, the excess iron creates highly reactive molecules called reactive oxygen species (ROS), which cause cellular oxidative stress and cellular damage. (26)
Symptoms of hemochromatosis usually begin to appear after age 40 and may include:
The organs most affected by iron overload are those that store iron, such as the liver, heart, and pancreas (41).
In the liver, iron-induced oxidative stress can lead to progressive liver disease and cirrhosis.
Oxidative damage to the heart can result in cardiomyopathy, a disease of the heart muscle that reduces the heart's ability to pump blood effectively.
Damage to the pancreas' insulin-producing cells leads to diabetes.
How to Test for Hemochromatosis
Diagnosing hemochromatosis involves a step-wise approach, utilizing clinical evaluation and laboratory testing.
Step 1: Clinical Evaluation
Many patients with hemochromatosis are asymptomatic, contributing to the underdiagnosis of the condition. Sometimes, the only indicator of the disease is a positive family history or abnormal liver or iron studies on a routine health screening. (2)
Hemochromatosis should be on the differential diagnosis for any patients presenting with the following symptoms or health concerns (2):
Transferrin saturation: this is the most sensitive test for hemochromatosis. A transferrin saturation > 45% requires additional testing. (25)
Ferritin: levels > 300 ng/mL and > 200 ng/mL for females may indicate hemochromatosis. It's important to remember that ferritin levels may be normal in early disease and may be elevated due to other causes. (25)
Step 3: Genetic Tests
Genetic testing can diagnose whether a person has the most common HFE variants (C282Y and H63D) (25).
Genetic panels that include the HFE gene available through Rupa Health include:
Patients with two copies of the C282Y variant should be referred to a gastroenterologist and hematologist for additional evaluation.
Step 4: Imaging
Once iron overload has been diagnosed through blood testing, liver biopsy and imaging studies can be ordered to determine the extent of iron deposition in the organs.
Liver biopsy is the gold standard diagnostic test for hemochromatosis; however, given its cost and invasive nature, along with the development of accurate blood testing methods, it has become less commonly utilized during the initial diagnostic workup. Instead, it may be ordered to screen for advanced liver disease, such as fibrosis or cirrhosis. (2)
Imaging studies, such as X-rays, ultrasounds, MRIs, and CT scans, may be ordered to assess the health of the liver and other organs. The imaging technique depends on the specific organ system being evaluated.
Treatment and Management
All patients with iron overload, regardless of symptoms, should receive treatment. The standard of care involves reducing total body iron levels through phlebotomy (venous blood draw) to achieve normal ferritin levels between 50-150 ng/mL. Phlebotomy (500 cc units of blood) is performed once or twice weekly until ferritin and transferrin saturation levels normalize. Once these levels are stabilized, maintenance phlebotomy is recommended every two to six months. (11)
Chelation therapy is offered as a second-line treatment to patients in whom phlebotomy is contraindicated, including those with heart failure or severe anemia. FDA-approved iron-chelating medications include:
Deferoxamine
Deferiprone
Deferasirox
Natural supplements can also be integrated into a holistic hemochromatosis treatment plan, given their natural iron chelating and antioxidant properties. Examples include:
The following lifestyle and dietary modifications can help reduce iron absorption:
The American Association for the Study of Liver Diseases (AASLD) recommends against dietary modifications because the effects of a low-iron diet are small compared to phlebotomy. If desired, patients could limit their intake of iron-rich foods, which include beef, chicken, turkey, beans, lentils, tofu, and dark leafy vegetables.
Patients with hereditary hemochromatosis should avoid eating raw shellfish, as this increases the risk of Vibrio vulnificus infection.
Eat foods that are rich in nutrients that inhibit iron absorption, such as phytates (e.g., legumes, whole grains, nuts, seeds), polyphenols (e.g., coffee, tea), and calcium (e.g., dairy, kale, broccoli).
Avoid taking iron supplements.
Avoid taking vitamin C supplements. Vitamin C enhances the absorption of iron from the intestines.
While iron is an essential mineral the body requires for many physiological processes, iron overload can lead to excessive oxidative stress, systemic inflammation, and organ damage if not treated appropriately.
Evaluating patients who present with a family history or signs of hemochromatosis for serological evidence of iron overload is critical in early diagnosis, effective treatment, and prevention of detrimental long-term health consequences associated with this disease.
Iron is a vital mineral for human health. While iron deficiency is widely recognized and frequently discussed, the potential risks of having too much iron often go unnoticed. Hemochromatosis, a condition that can lead to excessive iron absorption, is surprisingly common and yet remains under the radar for many. In fact, hereditary hemochromatosis is one of the most prevalent genetic disorders in the United States. This article explores hemochromatosis, discussing its causes, symptoms, diagnosis, and management to raise awareness about this significant health concern.
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Iron is an essential mineral that plays a key role in various bodily functions. It is primarily known for its involvement in forming hemoglobin, the protein in red blood cells that carries oxygen from the lungs to tissues in the body. Without sufficient iron levels, oxygen transportation, DNA synthesis, energy metabolism, immune function, and neurocognitive processes may not function optimally.
High iron levels, medically known as iron overload or hemochromatosis, occur when the body has excess iron. Serum ferritin represents the level of iron stored in the body and is used as the first-line biomarker to assess iron status. Ferritin levels greater than 300 ng/mL in males and greater than 150-200 ng/mL in menstruating females can suggest iron overload (26).
However, ferritin is an acute-phase reactant, meaning that it elevates as part of the body's response to inflammation, infection, and chronic disease. In clinical practice, healthcare providers will evaluate additional biomarkers to differentiate between elevated ferritin due to inflammation and that due to iron overload:
Serum Iron: the amount of iron circulating in the blood. High levels may suggest iron overload.
% Transferrin Saturation: indicates the proportion of transferrin (iron's transport protein) saturated with iron. High levels may suggest iron overload.
Total Iron Binding Capacity: measures the capacity of transferrin to bind iron. Low levels may suggest iron overload.
The table below summarizes normal reference ranges for markers of iron status. Note that values might vary slightly between different labs.
Understanding Hemochromatosis and Causes of High Iron Levels
Hemochromatosis is a medical condition characterized by iron overload and deposition in various body tissues. Hemochromatosis is more common in men than in women because women lose iron during their menstrual periods and childbirth (25).
Hemochromatosis is classified as either primary or secondary.
Primary Hemochromatosis
Primary, or hereditary, hemochromatosis is a genetic disorder that causes the body to absorb too much iron from the diet. This condition is most commonly associated with mutations in the HFE gene, particularly the C282Y variant. The most common form of the disorder is caused by inheriting two copies of the C282Y mutation, one from each parent. Although hereditary hemochromatosis is a genetic condition, not everyone with the gene mutations will develop symptoms or organ damage. (25)
Secondary Hemochromatosis
Secondary hemochromatosis is caused by factors other than genetics. Underlying causes include:
Iron-loading anemias (anemias characterized by excessive iron accumulation in the body)
Iron levels need to be maintained within an optimal range. When iron levels in the body are elevated, the excess iron can create highly reactive molecules called reactive oxygen species (ROS), which may contribute to cellular oxidative stress and cellular damage. (26)
Symptoms of hemochromatosis usually begin to appear after age 40 and may include:
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The organs most affected by iron overload are those that store iron, such as the liver, heart, and pancreas (41).
In the liver, iron-induced oxidative stress may contribute to progressive liver disease and cirrhosis.
Oxidative damage to the heart may contribute to cardiomyopathy, a disease of the heart muscle that reduces the heart's ability to pump blood effectively.
Damage to the pancreas' insulin-producing cells may contribute to diabetes.
How to Test for Hemochromatosis
Diagnosing hemochromatosis involves a step-wise approach, utilizing clinical evaluation and laboratory testing.
Step 1: Clinical Evaluation
Many patients with hemochromatosis are asymptomatic, contributing to the underdiagnosis of the condition. Sometimes, the only indicator of the disease is a positive family history or abnormal liver or iron studies on a routine health screening. (2)
Hemochromatosis should be considered for any patients presenting with the following symptoms or health concerns (2):
Transferrin saturation: this is the most sensitive test for hemochromatosis. A transferrin saturation > 45% requires additional testing. (25)
Ferritin: levels > 300 ng/mL and > 200 ng/mL for females may suggest hemochromatosis. It's important to remember that ferritin levels may be normal in early disease and may be elevated due to other causes. (25)
Step 3: Genetic Tests
Genetic testing can help determine whether a person has the most common HFE variants (C282Y and H63D) (25).
Genetic panels that include the HFE gene available through Rupa Health include:
Patients with two copies of the C282Y variant should be referred to a gastroenterologist and hematologist for additional evaluation.
Step 4: Imaging
Once iron overload has been suggested through blood testing, liver biopsy and imaging studies can be ordered to determine the extent of iron deposition in the organs.
Liver biopsy is the gold standard diagnostic test for hemochromatosis; however, given its cost and invasive nature, along with the development of accurate blood testing methods, it has become less commonly utilized during the initial diagnostic workup. Instead, it may be ordered to screen for advanced liver disease, such as fibrosis or cirrhosis. (2)
Imaging studies, such as X-rays, ultrasounds, MRIs, and CT scans, may be ordered to assess the health of the liver and other organs. The imaging technique depends on the specific organ system being evaluated.
Management and Support
All patients with iron overload, regardless of symptoms, should seek guidance from a healthcare provider. The standard of care involves reducing total body iron levels through phlebotomy (venous blood draw) to achieve normal ferritin levels between 50-150 ng/mL. Phlebotomy (500 cc units of blood) is performed once or twice weekly until ferritin and transferrin saturation levels stabilize. Once these levels are stabilized, maintenance phlebotomy may be recommended every two to six months. (11)
Chelation therapy is offered as a second-line option to patients in whom phlebotomy is not suitable, including those with heart failure or severe anemia. FDA-approved iron-chelating medications include:
Deferoxamine
Deferiprone
Deferasirox
Natural supplements can also be considered as part of a holistic hemochromatosis management plan, given their natural iron chelating and antioxidant properties. Examples include:
The following lifestyle and dietary modifications may help manage iron absorption:
The American Association for the Study of Liver Diseases (AASLD) suggests that dietary modifications may have a smaller effect compared to phlebotomy. If desired, patients could consider limiting their intake of iron-rich foods, which include beef, chicken, turkey, beans, lentils, tofu, and dark leafy vegetables.
Patients with hereditary hemochromatosis may want to avoid eating raw shellfish, as this increases the risk of Vibrio vulnificus infection.
Consider eating foods that are rich in nutrients that may inhibit iron absorption, such as phytates (e.g., legumes, whole grains, nuts, seeds), polyphenols (e.g., coffee, tea), and calcium (e.g., dairy, kale, broccoli).
Avoid taking iron supplements.
Avoid taking vitamin C supplements. Vitamin C may enhance the absorption of iron from the intestines.
While iron is an essential mineral the body requires for many physiological processes, iron overload may contribute to excessive oxidative stress, systemic inflammation, and organ damage if not managed appropriately.
Evaluating patients who present with a family history or signs of hemochromatosis for serological evidence of iron overload is important in early diagnosis, effective management, and prevention of potential long-term health consequences associated with this condition.
The information in this article is designed for educational purposes only and is not intended to be a substitute for informed medical advice or care. This information should not be used to diagnose or treat any health problems or illnesses without consulting a doctor. Consult with a health care practitioner before relying on any information in this article or on this website.
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Lab Tests in This Article
Iron by Empire City Laboratories Inc.
Serum
The Iron test measures the level of iron in the blood. Iron is essential for the formation of hemoglobin, which carries oxygen in red blood cells. This test is used to assess iron levels, diagnose iron deficiency anemia, and monitor conditions related to iron overload.
Iron by Access Labcorp Draw
Serum
This is a single-marker test measuring iron. It can be used to assess various conditions related to red blood cell production and destruction, iron metabolism, or iron transport.
Iron by Boston Heart Diagnostics
Serum
This is a single-marker test measuring iron. It can be used to assess various conditions related to red blood cell production and destruction, iron metabolism, or iron transport. Please be advised that Boston Heart Diagnostics policy states that practitioners cannot order labs on themselves or their immediate family members.
Iron, Total by Access Med Labs
Serum
This is a single-marker test measuring iron. It can be used to assess various conditions related to red blood cell production and destruction, iron metabolism, or iron transport.
Hepatic Function Panel by Empire City Laboratories Inc.
Serum
The Hepatic Function Panel provides a comprehensive assessment of liver function through a series of biochemical tests. This panel includes markers such as ALT (Alanine Aminotransferase), AST (Aspartate Aminotransferase), ALP (Alkaline Phosphatase), Total Bilirubin, Direct Bilirubin, and Albumin. It is essential for healthcare practitioners in evaluating liver health, diagnosing liver diseases, and monitoring treatment responses.
Hepatic Function Panel by Access Med Labs
Serum
The Hepatic Function Panel analyzes a variety of important liver health markers to investigate overall hepatic function.
Hepatic Function Panel by Boston Heart Diagnostics
Serum
The Hepatic Function Panel analyzes a variety of important liver health markers to investigate overall hepatic function. Please be advised that Boston Heart Diagnostics policy states that practitioners cannot order labs on themselves or their immediate family members.
Hepatic Function Panel by Access Labcorp Draw
Serum
The Hepatic Function Panel analyzes a variety of important liver health markers to investigate overall hepatic function.
Ferritin by Empire City Laboratories Inc.
Serum
The Ferritin test measures the level of ferritin, a protein that stores iron in the body and releases it when needed. Ferritin levels reflect the amount of iron stored in the body and are crucial for diagnosing and monitoring iron deficiency or overload conditions.
Ferritin by Access Med Labs
Serum
This is a single-marker test measuring ferritin. This test is used to monitor iron metabolism, microcytic anemia, and iron storage diseases.
Ferritin by Access Labcorp Draw
Serum
This is a single-marker test measuring ferritin. This test is used to monitor iron metabolism, microcytic anemia, and iron storage diseases.
Ferritin by Boston Heart Diagnostics
Serum
This is a single-marker test measuring ferritin. This test is used to monitor iron metabolism, microcytic anemia, and iron storage diseases. Please be advised that Boston Heart Diagnostics policy states that practitioners cannot order labs on themselves or their immediate family members.
Ferritin (FER) by ZRT Laboratory
Serum
This is a single-marker test measuring ferritin. This test is used to monitor iron metabolism, microcytic anemia, and iron storage diseases.
DNA Health by DNAlife
Blood Spot
DNA Health® tests for genetic variations that are known to have a significant effect on health and susceptibility to chronic diseases. DNA Health® reports on key biological pathways that govern overall health and helps practitioners and patients understand how genetic weaknesses in these pathways may increase predisposition to chronic diseases of lifestyle.
3X4 Genetics Test + Blueprint Report by 3X4 Genetics
Swab
The 3X4 Genetics Test + Blueprint Report provides 36 key insights and practical, personalized recommendations for patients to start taking control of their health.
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Mobarra, N., Shanaki, M., Ehteram, H., et al. (2016). A Review on Iron Chelators in Treatment of Iron Overload Syndromes. International Journal of Hematology-Oncology and Stem Cell Research, 10(4), 239–247. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5139945/
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