Ferritin (a measure of iron storage) is higher in breast cancer patients. Let’s dive into why.
As we age, tissues tend to accumulate iron. Unlike other nutrients, the body has no active mechanism to excrete excess iron. It is lost only through processes like blood loss (e.g., menstruation, injury, or blood donation), shedding of intestinal cells, or minor losses in bile and sweat. However, these mechanisms are not sufficient to actively remove excess iron.
Because of this, the body must tightly regulate absorption in the gut to maintain balance. If iron concentrations are high, the body regulates blood levels by stores it in tissues, primarily the liver, heart, brain, and pancreas. This buildup is referred to as iron overload.
Interestingly, iron is one of the primary nutrients cancer cells uptake, after fatty acids, glucose, and glutamine. Research shows that cancer cells overexpress transferrin receptors, which help import more iron into the cell, and simultaneously reduce ferroportin, the protein that exports iron out of cells.
Many articles suggest that because cancer cells proliferate at a fast rate, they require increased iron which is a key component of DNA synthesis. However, this reliance on iron comes with a cost. Cancer cells also endure high levels of DNA damage caused by oxidative stress—often exacerbated by their iron overload. To cope with this, cancer cells must upregulate DNA repair mechanisms, further amplifying their dependence on iron for survival and growth.
I also theorize that cancer cells hoard iron because it is essential for the structure of the Electron Transport Chain (ETC), the final step in energy production within mitochondria. Iron is a key component of cytochromes and iron-sulfur cluster proteins, which facilitate the flow of electrons in the ETC. The flow of electrons is what enables the production of ATP.
In cancer cells, however, the ETC is overloaded with electrons, which causes a bottleneck in energy production. The heightened demand for iron may be a “misguided” effort to restore electron flow to make ATP. Unfortunately high levels of iron can damage the ETC, creating a cycle of dysfunction in energy production.
Women will normally absorb three times as much iron as men do (Peat, 2006).
- Heightened absorption is due to the actions of estrogen, which inhibits the hormone hepcidin.
- Hepcidin is responsible for regulating iron balance in the body by controlling the activity of ferroportin, the protein that exports iron from cells in the gut and releases it from storage in tissues.
- Inhibited hepcidin increases dietary iron absorption and the release of stored iron into circulation.
This enhanced iron absorption is particularly important for women during their reproductive years because of regular blood loss from menstruation. However, this mechanism is a double-edged sword. After menopause, when menstruation ceases, the absence of regular iron loss combined with continued absorption can lead to iron accumulation in tissues. This may be one factor to why breast cancer rates increase with age.
Iron is also a cofactor for the synthesis and activity of aromatase, an enzyme that promotes estrogen conversion. Aromatase contains a heme group, making iron essential for estrogen production.
Chronically elevated levels of estrogen or estrogen dominance can lead to iron dysregulation. Because more than percent of cancers are driven by estrogen, it makes sense that iron levels are also high in breast cancer patients.
A note on anemia:
It’s estimated that around 30 percent of women have anemia globally. Although it is really common for doctors to give iron supplements, anemia isn’t always caused by iron deficiency. Low thyroid hormones often drive anemia because they stimulate red blood cell production in the bone marrow. When thyroid hormone levels drop, the production of red blood cells decreases, resulting in fewer circulating in the body.
Iron’s ubiquity has deeply influenced our food supply. Modern diets are increasingly iron-fortified, with staples like cereals, bread, flours, and even plant-based milk being enriched with non-heme iron. While these fortifications were initially intended to combat iron-deficiency anemia, they can contribute to iron overload.
Incidentally, anemia can also result from high oxidative stress, which is sometimes caused by iron overload (imagine metal rusting). High chronic ROS can speed up blood cell breakdown.
Addressing the root cause is more effective and safe than simply taking iron based on blood tests. We always have to consider the whole picture, because it is possible to be diagnosed with anemia, while having high levels of iron tissue storage.
It’s also important to recognize iron’s role in our food supply. Modern diets are increasingly iron-fortified, with staples like cereals, bread, flours, and even plant-based milk being enriched with non-heme iron. While these fortifications were initially intended to combat iron-deficiency anemia, they can contribute to iron overload.
To manage iron overload and prevent excess iron buildup:
- Avoid eating high iron foods with vitamin C, which enhances iron absorption
- Make sure you are eating enough calcium, which blocks iron absorption
- Consider blood donation
- Avoid seed oils and PUFAs (PMID: 14577660)
- Balance hormones and manage estrogen levels
Iron chelators:
- Caffeine and coffee
- Vitamin E
- Aspirin
It’s important we understand what is going on in the body from a holistic perspective—hormonal balance, oxidative stress, and nutrient intake. Iron overload doesn’t exist in isolation.