THE SURPRISING EFFECTS OF IRON ON MITOCHONDRIAL HEALTH
You likely think of iron as an important mineral that most people need to consume more of. But while it’s true that having enough iron is an important factor of health, more is not better. In fact, high iron levels are serious threat to your health.
I know it can be difficult to reverse your thinking around a vital nutrient such as iron, especially if you have heard—either directly from your doctor or from the media—that you need to be sure you are getting plenty of it through your diet or supplements. But the research is clear: high iron levels can permanently damage your organs, tissues, and joints. Excess iron can also increase your risk of cancer, heart disease, and premature death; and that’s just for starters.
There is a simple metabolic explanation for why this is so. It has to do with your mitochondria.
One of the normal products of mitochondrial respiration is hydrogen peroxide. Yes, the same one you can buy at the drugstore to clean infections. The hydrogen peroxide that is produced within your mitochondria as a normal part of ATP generation is healthy and necessary to regulate a variety of metabolic pathways. The problem occurs when your iron levels are too high. Through a process called the Fenton reaction, excess iron acts as a catalyst and transforms the relatively harmless hydrogen peroxide to hydroxyl free radical (OH-). Without question, this is one of the most dangerous reactions that occur within your body because the hydroxyl free radical decimates mitochondrial DNA, proteins, and membranes. It also contributes to increased inflammation throughout your body, which is a precursor to all manner of chronic diseases.
This is why I suggest a blood test to determine your iron levels before embarking on MMT. You simply must have normal iron levels if you ever hope to optimize your mitochondrial function. You could be eating the perfect diet, but if your iron levels are high your mitochondrial health will suffer.
The good news is that iron overload is easy to treat—and easy to detect. All it requires is a simple blood test. In fact, I believe this is one of the most important tests that everyone should have done on a regular basis as part of a preventive, proactive health screening. But you need to know which test to get and not let physicians who are mostly uninformed about this danger lead you to get tests that will not accurately measure your risk of iron overload.
I’ll discuss this in greater detail later in this chapter, but the test you want to get is a serum ferritin test. Ferritin is a protein within your cells that stores iron and releases it when your body needs it. It is a powerful predictor of the amount of stored iron in other locations and is the single most accurate and reliable indicator of iron overload.1
YOUR SEX AND YOUR AGE PLAY A LARGE ROLE IN YOUR IRON LEVELS
During their reproductive years, women shed 500 ml of iron each year through menstruation.2 Indeed, the fact that women excrete iron each month for approximately 30 years is likely an important factor in why women have a longer life expectancy than men. Men don’t have a method of regularly shedding significant amounts of iron, so their levels are consistently higher than premenopausal women.
Other than menstruation, the body has no natural mechanism for shedding any significant amount of iron. After menopause, women lose the benefit of shedding excess iron each month. Only about 1 milligram on average leaves the body through sweat, skin cell shedding, and very minor, normal bleeding in the GI tract, while the average amount of iron absorbed from nutritional intake is one to two milligrams.3 This is why the older you are, the more important it is for you monitor and proactively reduce your iron levels.
In addition to damaging your mitochondria and contributing to genetic mutations, excess iron negatively impacts health in the following ways:
A large epidemiological study of adult men from Korea recently showed that moderately elevated levels of serum ferritin8 predicted future weight gain, obesity, and even severe obesity. So if you picked up this book because you are struggling to lose the extra pounds you’ve gained, you have yet another reason to suspect that your failure to lose weight is not simply due to your diet or exercise regimen.
Since the 1980s, researchers have hypothesized that gender differences in iron levels could explain the higher prevalence of heart disease in men. Pathologist Dr. Jerome Sullivan first posited the theory in a paper published in The Lancet titled “Iron and the Sex Difference in Heart Disease Risk.” The Nurses’ Health Study found that women’s risk of heart disease rose significantly after they either went through menopause naturally or had a hysterectomy—in other words, when they stopped excreting iron through menstruation each month—suggesting that there is a link between iron levels and cardiovascular disease.14
A 2014 study found that elevated ferritin levels in cerebrospinal fluid predicted the conversion of mild cognitive impairment to full-blown Alzheimer’s disease.18 Higher levels of iron in the brain have also been shown to correlate with the severity of cognitive impairment.19 Oxidative stress and the resulting inflammation are likely the mechanisms involved in how excess iron impairs brain function.
Body iron stores are also positively associated with polyps and precancerous lesions in the colon. Iron may be why consumption of red meat is a risk factor for colon cancer, as excess iron could promote inflammation in the colon that leads to mucosal damage. Dietary fiber is thought to help prevent this, since fiber binds to iron and helps the metal pass out of the body through the digestive tract.21 Similar data exist to support the belief that iron excess contributes to liver cancer.22 Providing further evidence of the link between excess iron and cancer, those who regularly donate blood have a lower risk of cancer. A randomized trial found that blood draws reduced incidence of all cancers by 37 percent.23
HOW DO YOU KNOW IF YOU HAVE EXCESS IRON?
Because the dangers of excess iron are so great, and because symptoms associated with this excess don’t typically appear until iron levels are already dangerously high, it is important to have your blood tested regularly to help gauge your risk. And given that your health care providers may not understand what your lab results mean, you may need to look beyond your current team to find someone who is more knowledgeable in this area (I provide more information on how to get this test in Chapter 6).
Unfortunately, iron levels sufficient to harm your health do not cause any immediate symptoms (just like high blood pressure or vitamin D deficiency). If they remain severely elevated for prolonged periods, however, they can cause the following symptoms:25, 26
THE IMPORTANCE OF ACCURATE TESTING
As is shown in the table below, physicians use several tests to check iron status. The problem is that most physicians have not carefully studied this area and therefore do not appreciate the importance of the most important screening test to measure ferritin levels in your body. Many will perform the other tests and falsely reassure you that your iron levels are normal and you have nothing to worry about.
Test | Reference Range27 |
---|---|
Serum ferritin | Men: 20–200 ng/mL (nanogram per milliliter) Women: 15–150 ng/mL |
Serum iron | 60–170 mcg/dL (micrograms per deciliter) |
Total iron binding capacity | 240– 450 mcg/dL |
Transferrin saturation | 20–50 percent |
The most important test, serum ferritin, measures the amount of ferritin in your blood. The next two lab tests are used to calculate the transferrin saturation: serum iron, which measures the amount of circulating iron, and total iron binding capacity, which measures the ability of the transferrin molecule to carry iron.28
Please understand that the recommendation is for a serum ferritin test and not a serum iron or total iron binding capacity test, both of which can be normal even though the ferritin is elevated. So don’t let your doctor talk you out of getting this test for one they feel is better. It isn’t.
As you can see, there is a fairly wide window of acceptable levels, but the ranges currently viewed as “healthy” do not reflect optimal levels. This is similar to how we once viewed vitamin D levels: for much of the 20th century, only levels under 20 ng/mL of vitamin D were thought to be deficient, but more recent science has shown that you need at least 40 ng/mL to be in a healthy range.
The disparity between acceptable and optimal reference ranges for ferritin is even worse. To put a finer point on it, multiple epidemiological studies have linked increased longevity with serum ferritin levels below a threshold of 80–90 ng/mL, which is a typical plateau for postmenopausal women.29 The healthy range of serum ferritin lies between 20 and 80 ng/mL. Below 20, you are iron deficient, and above 80, you have an iron surplus. Women in their reproductive years have an average ferritin level of 35 ng/mL, while men in the same age range have an average level of 150 ng/mL.30 Ferritin levels can go really high. I’ve seen levels over 1,000, but anything over 80 is likely going to be a problem. The ideal range is 40–60 ng/mL.
TESTING MY DAD’S IRON LEVELS SAVED HIS LIFE
I first became aware of the dangers of excess iron about 20 years ago. At that time, I checked my dad’s ferritin level and was shocked to discover that it was close to 1,000. While some of that was likely due to his age (65), most of the excess was a result of beta thalassemia, a hereditary blood disorder that causes a high turnover of red blood cells and leads to an accumulation of iron.
With regular blood draws, his iron levels normalized, but the high iron levels had already damaged his pancreatic islet cells. Now he has what is called “bronze” diabetes that requires him to use insulin. Without early detection of this disease, I am absolutely sure he would have died 10 or 15 years ago. As I write this now he is approaching 90 years old.
I inherited beta thalassemia from him. Fortunately, I learned while I was still young and unaffected by it that I needed to carefully control my iron levels and in doing so have managed to sidestep the problems associated with this genetic disease. I aim to keep my serum ferritin under 60 ng/mL by removing about 4 ounces of blood every six weeks.
HOW TO KEEP YOUR IRON LEVELS IN CHECK
There is no magic supplement to take to remove iron from your body. The safest, most effective, and typically least expensive way to remove excess iron is simply to remove blood from your body since your red blood cells are loaded with hemoglobin that contain large stores of iron.
If you determine that you have excess iron levels, you’ll want to schedule blood donations to lower serum ferritin. Blood donation is a simple and life-giving way to treat iron overload while helping others at the same time. One blood donation reduces ferritin by somewhere between 30 and 50 ng/mL.31 Here are my recommendations for your blood donation schedule:
If for any reason you are unwilling or unable to obtain the ferritin test, you may want to consider a general recommendation based on average levels for your age and gender. If you are a postmenopausal female or adult male, you should ideally donate blood two or three times a year to minimize your iron stores. If you are still menstruating, it would be best to have your ferritin level tested and follow the table above.
If you are unable to donate your blood due to age, low weight, or other contraindications, you can get a prescription for therapeutic phlebotomy, which is a fancy word for taking your blood in order to treat a condition. Most any center that accepts blood donations is now required by federal law to accept your prescription for a therapeutic phlebotomy. (The blood is disposed of, not used.)
Alternatively, the best and most convenient option is what I do: find someone you know who can draw blood and come to your home to remove 2 to 4 ounces of blood every month. This creates far less metabolic stress on your biology and closely resembles the iron loss that happens in a woman’s natural menstrual cycle.
Additionally, you should make sure that you aren’t consuming unhealthful levels of iron, nor absorbing too much of the iron you end up consuming. You can do this in two ways:
A final strategy you may wish to pursue, particularly if blood draws are unavailable or seem too extreme to you, is to take low-dose aspirin. Aspirin has long been associated with a decreased risk of heart disease. It was thought this effect was due to its influence on thinning your blood, but it is more likely due to the fact that iron causes low-level, often undetectable, bleeding in the intestines, and over time it lowers iron levels. Taking an aspirin every day results in essentially the same iron level reduction as giving blood, although it can take years of regular use to achieve the same therapeutic benefits as phlebotomies. This reduction in iron levels may be the reason numerous studies have found that long-term use of low-dose aspirin has major anticancer benefits, including 75 percent lower rates of esophageal cancer, 20 percent lower overall cancer rate, and 50 percent lower risk of metastasis.35