Mitochondrial Health Part 5 – Cu-re Your Fatigue

Apart from excess copper in a few conditions such as Wilson’s disease, Intrahepatic Cholangiocarcinoma, or a genetic disease called Menke’s syndrome, copper is a forgotten mineral and seldom discussed as a deficiency in functional medicine. Before reading this book by Morley Robbins who cleverly used the chemical symbol Cu for copper, I was unfamiliar with the importance of this vital mineral, its role in the mitochondria, and its ability to control the oxidative effects of iron in our body.
 

Morley Robbins is a retired hospital administrator who wanted to be a physician as a young man. When he retired, an encounter with a Chiropractor who helped his frozen shoulder fostered a curiosity about why people get sick and spurred Robbins to dig into research articles for three or more hours every day for ten years. The result was finding research over the past one hundred years that developed into what he calls The Root Cause Protocol. Simply put, his focus in the book was to explain how the important balance of three minerals: magnesium, copper, iron, and ceruloplasmin (a protein) relate to most chronic degenerative diseases. For this newsletter, I will focus on fatigue and the effects of these four pieces have on the mitochondria.

The Iron-y of it all

Anemia or low iron is a widespread problem. Almost 6% of the U.S. population met the criteria for anemia and the W.H.O. thinks about two billion people worldwide (mostly women and children) are deficient in iron. This should be surprising because iron is the most abundant mineral on the planet, with thirty six percent of the earth being iron. To understand this more deeply first consider that 70% of the iron in our body is in the hemoglobin of the red blood cell and 10% of the iron is stored in the tissues as ferritin. Hemoglobin is made up of four heme (iron) groups and ferrochelatase is a copper enzyme that acts like a crane operator dropping iron into the hemoglobin to knit these heme groups together. The two forms of iron (hemoglobin and ferritin) function like a teeter-totter where if the hemoglobin is low it would draw from the tissue ferritin or if the iron in the blood were high, more iron would be put into storage as ferritin. If someone has low hemoglobin and normal to high ferritin this would mean that the person has a conversion problem of getting the iron out of storage from ferritin. Ferroxidase enzyme (discovered in 1948) is what moves iron from ferritin to the blood and ferroxidase enzyme is a copper dependent enzyme. Ninety five percent of the body’s copper is complexed within the ferroxidase enzyme! Ferroxidase is the active form of ceruloplasmin. In cases of perceived anemia and mitochondrial dysfunction what might really be going on is that there are two copper dependent enzymes in insufficient amounts. Ferrochelatase to load the iron heme into the red blood cell or  ferroxidase move iron in and out of ferritin.

While iron is essential for our health, it can create a broader issue of inflammation. Iron can be an extremely oxidizing element. When iron is mixed with oxygen outside the body it forms rust. When iron and oxygen mix inside the body it is “oxidative stress.” Where iron has four unpaired electrons, ferritin has 10,000 unpaired electrons. Therefore, high ferritin levels are a problem because those unpaired electrons are more reactive to oxidative stress and inflammation. Ferritin can also accumulate in the mitochondria. This is called mitoferritin. Another form of iron, hemosiderin has 100,000 unpaired electrons. Hemosiderin can be stored in the skin where a brown patch might be observed but it is more often stored in macrophages (a type of white blood cell) and enterocytes (cells in the intestinal tract). With those unpaired electrons, hemosiderin can cause ten times the amount of oxidative stress and inflammation as ferritin. Robbins describes this process of unchecked iron as “similar to a four-year old with a hammer.” Therefore, elevated iron in the form of hemosiderin in macrophages can adversely affect the immune system, and elevated iron in the enterocytes could cause intestinal problems.

Addressing this oxidative stress and inflammation is where ceruloplasmin and ferroxidase come in. Ceruloplasmin has six to eight copper atoms surrounding two oxygen atoms which can reduce iron’s reactivity to a more benign state. Without enough copper, inflammation runs rampant from the stored iron. Understanding all of this makes one realize that what is commonly thought of as an iron deficiency is really an iron dysregulation problem due to a copper deficiency.

Jerome L. Sullivan III, M.D. PhD originated the “Iron-Heart Hypothesis” This theory pointed to the iron-copper dysregulation in the endothelial layer of the arteries and/or heart muscle cells (cardiomyocytes). His seminal paper in 1981 published in The Lancet, attributed myocardial failure in men to iron overload and for women in menopause who gradually accumulate iron when they stop menstruating and are no longer losing iron each month. 

Magnesium

For the past forty years an average of 2,000 scientific studies per year about the health benefits of magnesium have been published in medical journals around the world. One study in 2012 showed that magnesium binds to 3,751 human proteins. Because our heart and brain mitochondria demand so much magnesium to create Mg-ATP, and because ATP is essential for energy, the first signs of magnesium deficiency usually show up as fatigue.

Therefore, it is important to understand what contributes to magnesium loss. Mostly it is from stress, fluoride, and medications. Assuming there is adequate magnesium input from your diet, these factors increase what Robbin calls: the magnesium burn rate (MBR).

Conclusions

Bioavailable copper is an important and overlooked nutrient for maintaining the iron equilibrium in the body. The highest food sources for copper include organ meats, cod liver oil, and most of all beef liver. It is also present in dark leafy vegetables, shitake mushrooms, nuts and seeds, and dark chocolate. Beef liver is a high source of iron, but it has twice the amount of copper. Interestingly, organ meats are a source of nutrition that has been lost by modern humans. Wild predators consume the organs first and leave the muscle meat for the scavengers. Do animals intuitively know something that we do not?

Considering that most packaged foods are fortified with iron, and that there is more access to red muscle meat in most people’s diets, achieving adequate copper levels to balance this potential iron overload makes sense. Most blood tests usually check hemoglobin, serum iron, and TIBC (total iron binding capacity), but they do not routinely check for copper, ferritin or ceruloplasmin. If you have fatigue issues or chronic inflammation of any kind or are looking to see if this association could be related to potential heart disease, then these markers could be added to your yearly checkup. Ideally ferritin should not be higher than 100 ng/ml in a woman, or 120 ng/ml in a man. Ceruloplasmin should be in the 35 mg/dl range.

I have hardly scratched the surface of how Robbins’ research into the interplay of these minerals affect so many health issues. He had some more controversial opinions about certain supplements that I am still “digesting,” but in the copper-iron connection to oxidative stress and its effect on the mitochondria, he did a brilliant job. You can investigate more of his work at www.rootcauseprotocol.com.