A Deep Dive Into Iron Metabolism: Part 4 Iron Overload

Welcome to part 4 of the ODX "Deep Dive Into Iron Metabolism" Series. In the 4th post in our series, we cover iron overload.

The ODX Iron Metabolism Series

Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

1. Iron Metabolism Part 1 - Introduction to Iron Metabolism
2. Iron Metabolism Part 2 - The physiology of iron
3. Iron Metabolism Part 3 - Disorders associated with altered iron status: Iron Deficiency Anemia
4. Iron Metabolism Part 4 - Disorders associated with altered iron status: Iron Overload
5. Iron Metabolism Part 5 - Biomarkers of iron status
6. Iron Metabolism Part 6 - Addressing disorders associated with altered Iron status
7. Iron Metabolism Part 7 - ODX Optimal Takeaways and References

Disorders Associated with Altered Iron Status: Iron Overload

Iron overload is characterized by excess storage of iron throughout the body, including vital organs such as the liver and heart (McDowell 2022). Excess iron can also damage the pancreas and other endocrine glands, disrupt the gastrointestinal mucosa, and impair immune surveillance activity (Kotze 2009).

Overload may be caused by iron intake above the Tolerable Upper Intake Level of 45 mg/day, accidental overdose that exceeds transferrin’s carrying capacity (Gropper 2021), or excessive blood transfusions (Gatterman 2021). Iron overload is also associated with thalassemia, iron-loading anemia, and sideroblastic anemia, in which increased erythropoiesis causes increased iron absorption (Gropper 2021).

Hemochromatosis

Iron overload is often associated with mutations in the HFE gene and is accompanied by increased inflammation and oxidative stress. Hemochromatosis is the most severe form of hereditary iron overload, characterized by notably elevated ferritin and transferrin saturation. Early disease recognition is essential to avoid irreversible hepatic, cardiac, and endocrine tissue damage. Early hemochromatosis can present with the same chronic fatigue associated with iron deficiency, and blood chemistry analysis is vital to differentiating the two. Early stages can also be associated with nonspecific symptoms such as joint pain, abdominal pain, and decreased libido (Kotze 2009).

The early stages of iron overload may not be associated with overt dysfunction, but supplementation with iron or vitamin C can promote its progression in susceptible individuals. Advanced stages of iron overload may be associated with impaired liver function, cirrhosis, ascites, glucose intolerance, cardiac dysfunction, and abnormal skin pigmentation (Raymond 2021). Phlebotomy or chelation therapy is often required to reduce iron load (Gropper 2021).

Hemosiderosis is a form of iron overload characterized by excess iron storage in the body. It is associated with an overdose of iron-containing supplements or frequent transfusions. Restriction of dietary iron is indicated (Raymond 2021).

Symptoms and signs of inherited iron overload.

Source: Abbaspour, Nazanin et al. “Review on iron and its importance for human health.” Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences vol. 19,2 (2014): 164-74. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported.

NEXT UP: Iron Metabolism Part 5 - Biomarkers of iron status