Today we are joined by Morley Robbins for a third time for an episode all about the interplay between iron, insulin, and hormones in aging and longevity, the dangers of glyphosate, the importance of managing stress, and the PAM enzyme's role in signaling and communication. Tune in to this fascinating conversation to learn all of this and more! Don’t forget to read our other articles with Morley to learn more about The Root Cause Protocol and copper deficiency.
What has come to more intense light is how dysregulated iron is in our body. In a recent article, it was described as the Trojan horse. There is a delivery mechanism I learned about iron a few weeks ago in a 1983 study – when insulin presents to a fat cell, there is a two to three-fold increase in iron uptake in that fat cell. What is fascinating about it is that the use of sugar is a silent Trojan horse for delivering iron. Iron causes aging, and copper causes longevity. If you can internalize and act on this, you will do pretty well. But if you get caught up in everything else then you will lose sight of the big picture. It is amazing how little the scientists and practitioners know about iron.
Robert Lustig wrote a book called “Fat Chance” where he stated that we need twice as much insulin to clear the same amount of glucose as we did 30 years ago. The reason why that is so important is because that means that copper is involved in glucose regulation – insulin is a backup plan. Insulin is a very powerful hormone but I do not think the body runs on hormones. It runs on minerals and hormones respond to mineral dysregulation – which responds to oxygen status.
I think what has happened is farming has changed, and commercial herbicides and fertilizers are very prevalent. The most prevalent one is glyphosate which chelates copper a billion times faster than it will chelate magnesium. It will chelate copper, 1000x faster than it chelates zinc or iron. We cannot relate to these numbers but what it means is that we have a copper crisis. This happens because no one is acknowledging the mineral concentration of the soil.
A great book to learn about restoring our soil, getting regenerative farming back into the mainstream, and figuring out what minerals are in our soil is “Dirt to Soil” by Gabe Brown. People are so quick to use nutrient tubes but they have not been updated since the 1950s. This is garbage data. People think they are eating copper-rich and mineral-rich food but they aren’t. The challenge is that the concept of minerals is very boring. There is no appeal so people do not know these basic underlying components of our environment that have tremendous influence over our metabolism, our ability to make energy, and our ability to signal and communicate.
We have two complementary terms: glucose intolerance and insulin resistance. They are interconnected but not the same thing. Glucose is a very abrasive oxidant and insulin is an antioxidant. No one article says, “Here's the answer to your wonderful question about copper and glucose.” but there are 1,000 different hints in the literature. One of the more powerful ones is a 1986 article by Leslie Klevay. He is an MD PhD, a cardiologist by training, and a copper expert. In 2022, the wrote another article called “Chronic Copper Deficiency” We have known since 1920 that if you do not have enough copper then iron is going to build in your system.
In 1986, Dr. Klevay was studying two men who had high glucose and he was trying to understand what was causing it. He made a powerful observation that children with Menkes disease, a genetic defect where you do not have a copper pump, so they have next to no copper in their tissue. This means that these children are glucose intolerant.
There is the triopathy of diabetes which is three conditions: retinopathy, neuropathy, and nephropathy. Those three conditions are taking place in tissue that is insulin-independent. Insulin does not work in the retina, the nerves, and the kidneys. So there is a backup mechanism for regulating sugar being traded off with sodium to get the sugar into the tissue – but it requires the presence of an enzyme called ascorbate oxidase. This is a copper-dependent enzyme, so if copper is not present to regulate that flow and we're getting into vitamin C metabolism, it is a very different beast.
We also know that ceruloplasmin is the master antioxidant of the body and its priority focus is to keep oxygen and iron properly regulated so they do not cause oxidative stress. It does this through the action of an enzyme called Ferroxidase. What happens in the state of hyperglycemia (high blood glucose) is it blows up the ceruloplasmin molecule and then the copper comes out and gets oxidized. It goes from copper one to copper two and is immediately bound up by albumin. Albumin does not have the same metabolic properties as ceruloplasmin. There are many different references to copper status and sugar status.
In a corollary fashion, people are probably familiar with the fact that estrogen rises when we get older. Iron also rises when we get older and what is not being accounted for is copper and ceruloplasmin. If ceruloplasmin is the master antioxidant and it is going down as we age, then the body has to go to its backup plan. So if iron is rising and there is not enough copper to run ceruloplasmin, the body is going to rely on estrogen. I think the same dynamic is taking place on the sugar side. If ceruloplasmin is not present, the body has to default to insulin as the backup plan. I do not have 100 articles to back this up, I am relying on my intuition and connecting the dots. I have read 10,000 articles over the last 15 years trying to piece this together and that is what makes sense to me.
What we need to do is lower stress. There are 4 different categories of stress:
- Physical stress. If you just fell down a flight of stairs, you are feeling physical stress.
- Environmental stress. The toxins in our water, air, and food.
- Metabolic stress. If we do not have the right nutrient profile in our body we are not able to run the right metabolic pathways. As soon as the pathways do not work right, there is going to be oxidative stress, which is probably the greatest stress of all.
- Psychological or emotional stress. This is what people think of when they hear the word stress.
As soon as you go into a state of emotional stress, you are creating metabolic stress at a physiological level, and you are operating out of fear. Fear triggers very powerful hormones like cortisol and adrenaline, but it also triggers noradrenaline (if you have enough copper to make this). The cortisol and adrenaline response creates functional hypoxia. This means that inside the cell there is not enough bioavailable copper to activate the oxygen to create water to release energy.
We all have to lower our stress. Whether this is dealing with bills to pay, facing difficult relationships, or dealing with our neighbors or colleagues. The world keeps getting crazier so we need to be able to get our stress under wraps. We also have to lower the amount of iron in our tissue. A good rule of thumb for iron is to multiply your age by 365 and that is how much we have coercing through our bodies. Stay on top of your iron status because this will help you manage your oxidative stress.
Having a good diet and taking supplements that are in the root cause protocol like copper, iron, and magnesium is key. There is a very serious shortage of bioavailable copper on this planet. If you are relying on historical sources of copper you might want to supplement with Recuperate IQ instead. Within the root cause protocol, we focus on those three minerals. In a state of acute stress, we lose magnesium very quickly, in a state of chronic stress, we lose access to copper, and we must have copper and magnesium to make energy. Iron is what is getting in the way of copper and magnesium. We can get on top of this, control our environments, and begin to bring greater balance and homeostasis back into our being.
One of the adjustments we will make this year is Sugar Shift. We are also adding things like light therapy. We do not want to make it overwhelming so we are trying to be respectful of how we add to the base. The origin of The Root Cause Protocol was an article written by Ray Peat. Towards the end of the article he said “To my knowledge, no one has ever come up with a recipe to increase ceruloplasmin” so I thought that is what I am going to do. The Root Cause Protocol began with two stops and two starts – but the focus was on building more bioavailable copper. Now it has about a dozen stops and a dozen starts, but the purpose behind it is still to increase the bioavailability of copper.
We cannot make energy without copper. We need to knit collagen and elastin together to give our tissues their strength and flexibility and only one enzyme does this – lysyl oxidase. Another enzyme called melanin makes color and this is activated by another enzyme called tyrosinase. Tyrosine has two copper atoms inside so you cannot color any human or animal unless you have copper acting on that enzyme function.
I have also been focusing on the spleen. The spleen is supposed to be the color of eggplant and the deeper and darker the purple the more viability and energy it is. I had a surgeon share with me that he has never seen a purple spleen. This means that the organs can get vitiligo. If our organs are not the right color this means they do not have enough energy to function properly.
Copper plays these many-faceted roles in the body that nobody knows about. If we focus on the least likely component that is going to have the biggest impact – it is biometric copper. And its relationship with Iron goes back to the beginning of time. So many doctors do not realize the powerful interplay between these. Copper and iron are called redox active minerals which means they have a relationship with oxygen. This does not just happen, it is regulated and managed. Copper is the general and iron is the foot soldier. Copper rungs the show and no one knows this. It is also very important for gut health because we cannot have the microbiome without minerals.
I was reading an article from 2017 that was profiling the epidemic of chronic kidney disease in India with their rice farms. They use glyphosate which is chelates copper which will lead to oxidative stress and kidney disease. In the article, they said “It would be useful to tell you about a recent study done in France. They were opposed to glyphosate from the very beginning yet 99% of French people have glyphosate in their urine.” This means it is in the air and the water. People have to wake up to the fact that organic farming is a joke. They are allowed to use glyphosate because it has carbon in it and anything that has carbon in it is okay.
Originally, sources of copper-rich food would have been grass-fed organ meats, seafood, nuts, seeds, leafy green vegetables, beets, corn, alfalfa, and lentils. Any food that has been turned into GMO was a good source of copper but now it is probably not the case.
We are up against an evil empire and we have to be light-hearted about it because if not we can easily get depressed. We have to bob and weave and the idea that the food is safe, we have to be more discerning now. We are going to come out of it but it's going to take some time for people to realize how deep the problem is and how important these minerals are because I think they have been messed with in ways that people do not realize.
“I think, admittedly, I've kind of lapsed a little bit in my discipline. So I'll certainly be gone back to a lot of these first principles forms of thinking.” -Kriben Govender
The PAM enzyme was first discovered in the 1980s and for the past 45 years, Betty Eipper and Richard Mains have been studying this enzyme. When I first became aware of this, I was reading the book “Mastering Leptin”, and it refers to the hypothalamus, which I'm fascinated by. In this book, the author made reference to this PAM enzyme. This was in 2010 and back then I thought that it only activated 13 peptides. Now I realize it signals 4,700 peptides.
If we think about a phone, they are amazing when they work but if they do not have a signal, they are not good. If you have insulin resistance you are either blaming the lack of insulin production or the lack of insulin sensitivity by the tissue. But there is more to the story. There are seven signaling peptides involved in sugar metabolism:
- Insulin
- Insulin growth factor
- Incretin
- C-peptide
- Humanin
- Spexin
- Chromogranin-A
All of these peptides have to be communicating with each other or the show does not work. There is fierce communication between insulin and Chromogranin-A & insulin and C-peptide. I have recently learned about somatostatin which is the peptide that turns off the response. The body is not designed to be in hyperbolic activated response. The body is supposed to be able to make noradrenaline. Noradreniline means “No R Group” the R group is a methyl group. When the methyl group is on adrenaline, it is not bad – but noradrenaline is activating somatostatin to turn off the stress response. This is good because we are not supposed to be in sympathetic overdrive all the time.
Nobody knows that the PAM enzyme is two copper atoms that need to be at a critical point when oxygen's there to cleave off a carboxyl group and put on a glycine group. And when the glycine group goes on these peptides are turned on. In the way the proteins are made there is an N-terminus and a C-terminus – nitrogen and carbon. And what we have learned is that the carboxyl group gets cleaned off and that is where the peptides get activated 4,700 times.
If you were going to design lab tests to test peptides and hormones, would you study the nitrogen side or the carbon side? All tests focus on the nitrogen side because it is neutral and yet we end up flying blind in hormone testing. We have no idea what peptides are there, we do not know if it is active, and it is rare for a doctor who will measure insulin and C-peptide. Yet, when you get insulin and C-peptide together, you have a better understanding of how much is being made and being used.
I think it is important for people to realize that there is a very beautiful blueprint that runs our body and metabolism. This blueprint runs on the chassis of energy and signaling peptides. How do you make energy? You have to have copper in the mitochondria. How do you have signaling peptides that can talk to each other? You have to have copper in that PAM enzyme. It is really important to realize that there is a simplicity and an enormity to the copper metabolism. People do not think about it because it is so small. 100 milligrams of copper is regulating 5,000+ milligrams of iron.
A very influential copper researcher, Maria Linder, who passed away in 2022, had an article published that year that talked about the fact that she thinks that humans do not have 100 milligrams of copper, she believed that we had around 70. If we put that into context, our ideal body temperature is 98.6. A 4% rise in body temperature from 98.6 to 102, is called a fever. And you know how bad you feel when you have a fever. That's a 4% differential. The magnitude of a 30% loss of copper blows my mind. This is not taught in any sort of school. We need to be willing and open to learning this information and recover our vitality to bring this enzyme back to life.
In 2008 and 2012 Betty Eipper and Richard Mains had some very gifted graduate students and they did interesting studies with rodents. The gist of the two experiments were:
- Let's take a group of rats and deny copper in their diet.
- Let's take another group of rats and alter the PAM enzyme.
And let's create identical expression of the PAM enzyme based on diet and based on genetic defect. In both experiments they did the same thing –they fed them copper supplements.The result was that the enzyme came back on. In the dissertation, the author talked about Haploinsufficiency as a sign of copper deficiency.I believe that all gene defects are signs of copper deficiency. Can they be easily corrected with copper? Probably not but I do believe that they can be corrected in time.
