3 · Iron and Cancer

The incidence of cancer increases with age, and as we've seen, so do iron levels. Could there be a connection?

Men also have higher rates of both cancer and death from cancer than women, and they also have higher iron levels. For some forms of cancer, the risk for men is up to four-fold higher than for women.xxxv Overall, men have around a 37% higher risk of dying from cancer than women. Higher body iron stores in men could explain much of this difference, since men start to accumulate iron after the age of 18, whereas most women do not accumulate excess iron until after age 50.xxxvi

The most striking evidence that iron is involved with cancer comes from a study in which a group of patients were randomized either to phlebotomy (bloodletting) in order to lower their iron leve³⁶ls, or to no treatment.xxxvii The patients were part of a study designed to test whether phlebotomy could treat peripheral arterial disease, and they had no cancer at the start of the study. They were followed for an average of 4.5 years.³⁷

Results showed that those patients assigned to iron-reduction had a 35% decreased rate of cancer, and an approximately 60% reduced rate of death from cancer, compared to those who had no iron-reduction treatment.³⁸

Furthermore, phlebotomy doesn't make iron levels the same in all people. The level of iron depends on the starting point – those with higher iron levels at the beginning require more phlebotomy to lower iron than do those who have a lower iron level to start with. The iron level also depends on compliance, that is, those who consistently show up for their appointments and get their blood drawn and thus have more withdrawn overall end up with lower iron than people who show up less or not at all.

Therefore it's important to note that in this study, those who developed cancer in either the iron-reduction or no-treatment groups had similar and higher levels of iron, but those who did not develop cancer, in either group, had much lower levels of iron. Ferritin (iron) in those who developed cancer averaged 127 ng/ml, while in those that remained cancer free, ferritin was 76.

As we'll see later in this book, it's relatively easy to attain an iron level similar to the group that did not develop cancer. It's also relatively easy to have a level similar to the group that did develop it, if you have a standard Western lifestyle and don't actively do anything about your iron.

A population study found that people with high iron levels, using a cutoff value, had 3 times the risk of colon cancer and 1.5 times the risk of lung cancer.xxxviii

Researchers in Taiwan found that men who were at the high end of the normal range for iron levels, as compared to the low end, had about a 3-fold increase in³⁹ cancer rates.xxxix

A population study of over 6000 American men and women, who were free of cancer at the beginning of the study, found that those in the highest quartile (fourth) of serum i⁴⁰ron had almost double the risk of dying from cancer.xl Noteworthy, at all levels of iron, the men had a cancer death rate of 4.7 per 1000 person-years, while for women it was much lower at 2.8. Iron strikes again.

Iron chelators fight cancer⁴¹

If iron causes cancer, then we would expect to find that iron chelators, synthetic or natural chemicals that bind and remove iron, would lower cancer rates or perhaps even treat cancer.

That is in fact what we find. In lab mice that are implanted with prostate cancer cells, the iron chelator IP6, found in rice bran, reduced the growth of tumors by 75% when added to their drinking water.xli

In another study done in mice, iron chelators had remarkably potent anti-tumor activity, shrinking tumors in mice by half in only five days. The effect of these chelators was comparable to the anti-cancer c⁴²hemotherapy drug doxorubicin.xlii The iron chelators activate a cellular pathway that leads to self-destruction in cancer cells. Their activity left normal cells, including blood cells, untouched.⁴³

There are many other, similar studies, both on lab animals and in cell culture.

Men who had a prostate condition, prostate neoplasia, that gives them a high risk of cancer, were divided into two groups. Thirty men took green tea extract capsules, 200 mg each, three times a day, for a year. Another thirty men took a placebo capsule. After a year, 30% of the men in the placebo group were diagnosed with cancer. In the green tea extract group, only one man, or about 3%, developed cancer. The risk reduction was 90% - a startling result.

These compounds, the catechins in green tea extract and IP6, have a number of other effects on cells besides the removal of iron, so we can't be sure that the iron chelating effect was the cause, or the sole cause, of their cancer-fighting ability. Still, other compounds whose only function is the chelating of iron have been shown effective against cancer cells, and they have been suggested for use in cancer treatment.xliii

Aspirin lowers both iron and cancer rates

Recently it's been found that long-term use of low-dose aspirin results in a significant decrease in cancer rates, as much as 75% lower in the case of esophageal cancer.xliv Other cancers saw 30 to 50% lower rates, and overall, aspirin users had about 20% lower rates of cancer. Since aspirin lowers inflammation, some have speculated that this could be the mechanism of aspirin's anti-cancer effects.⁴⁴

Others have made the connection with iron. Aspirin, even in low doses, causes small amounts of bleeding from the intestines, usually not enough to be detectable. But this bleeding results in lower iron levels among aspirin users.

Long-term use of low-dose aspirin results in a cumulative reduction in iron, similar to what can be achieved by phlebotomy. This mechanism is compatible with the observa⁴⁵tion that the effect of low-dose aspirin on cancer doesn't kick in until about five years of aspirin use.

I'll discuss aspirin further in the section on lowering iron levels.

Smoking, iron, and lung cancer

Interestingly, current American cigarette smokers have a risk of lung cancer far higher, as much as ten times higher, than current Japanese smoke⁴⁶rs.xlv This shows that other, perhaps multiple factors, affect the risk of lung cancer besides smoking.

Aspirin is one factor that can reduce the risk of lung cancer. Men who had a history of aspirin use had about a 26% lower risk of lung cancer. But aspirin showed no effect in women.xlvi This fact may strengthen the case for iron's involvement in lung cancer, since women have lower iron levels than men, lowering those levels further with aspirin had no effect; but lowering the higher iron levels of men lowered their risk of lung cancer.

Cancer as a ferrotoxic disease

Some scientists have been explicit in the relation between iron and cancer, saying that cancer has aspects of a “ferrotoxic disease”.xlvii In pl⁴⁷ain language, that means that iron can cause cancer. Indeed, iron is carcinogenic in lab animals, and many conditions of iron-overload in humans are associated with higher risks of cancer.

Shinya Toyokuni, one such scientist, has said that “fine control of body iron stores would be a wise strategy for cancer prevention”.⁴⁸

In other words, knowing your iron level and controlling it can help prevent cancer. Many people can easily tell you their cholesterol number, since doctors like to measure it often, and the media tells us how important it is. But almost no one knows their iron level, which in the estimation of this writer and that of many others, is far more important for health than cholesterol.

That needs to change.

The link between iron and cancer is underrated⁴⁹

There are a number of other studies that I could cite on the relation between iro⁵⁰n levels and cancer, but let's stop with these. The reason for citing studies at the risk of boring the reader is because in mainstream health and fitness writing, how often do you hear that excess iron may cause cancer?

Never. That's how often.

Have you ever heard your doctor mention the cancer risks of too much iron? For 99.9% of readers, the answer is surely “no”.

The common belief about cancer is that, except for the case of smoking and lung cancer, it somehow just appears and there's nothing much anyone can do about it. Cancer is often treated as a literal tragedy, a fate which strikes at random, a destiny which can't be avoided.

That is just not the case. While iron is not the only thing that causes cancer or increases its risk, it's an important cause, especi⁵¹ally among otherwise healthy people who appear to have few other risk factors.

Even with smoking and cancer, the high concentration of iron in tobacco smoke means that it could be one of its most important cancer-causing components.xlviii

How iron causes cancer

Iron causes the formation of harmful free radicals, particularly the hydroxyl radical, and this can interact with cell structures and damage them. Among the structures damaged is DNA, and mutations in DNA can lead to cancer.xlix DNA damage can be prevented with iron chelators – chemicals that bind and remove iron.

Cancer cells are characterized by uncontrolled growth and make high demands on a number of nutrients, notably glucose and iron, so once cancer has been initiated, iron can fuel its growth. In mice, tumors grow twice as fast when fed a normal iron as opposed to a low iron diet.

Another way that iron can promote cancer is by suppressing immune function. Normally, the cells of the immune system monitor the body for cancer cells, and destroy them when encountered. Failure of immunity is therefore crucial in cancer development, and too much iron can cause a decrease in immune cell function. Cancer cells then either escape detection or cannot be destroyed.

So to avoid cancer, keeping iron levels low will help, and we'll discuss how to do that and what level of iron you should target in a later chapter.

If you don't smoke, don't drink alcohol to excess, exercise, avoid processed foods, stay lean, and get enough vitamin D, you may think you've done everything in your power to stay healthy and avoid cancer. Unfortunately, that's not the case, because if you have a high iron level, that's an important risk factor you haven't touched.

Takeaway points

Men have both higher iron stores than women and higher risk of cancer

Phlebotomy (bloodletting) dramatically lowers the risk of cancer⁵²

Men or women with high ferritin (iron) levels have greater risk of cancer

Iron chelators fight cancer⁵³

Aspirin lowers the risk of cancer, and also lowers iron stores

Cancer cells require large amounts of iron

Iron fuels tumor growth