The Energy Conundrum
Excerpted from: https://paradigmchange.me/wp/cheney...Ieg9aZM2j6goro3ChWzK1LE_52m3nudQFVmmgn_cUnneYby Dr. Paul Cheney
That brings me to a model that I’ve developed based on some of those earlier slides I showed you.
Don’t concentrate on the red part. Just concentrate on the white part.
You have the mitochondria, and of course the red cells carry oxygen in the bloodstream. And then the oxygen is translated into the mitochondria to help you make ATP, which is the primary energy source in this impressive oxidative phosphorylation system that we call mitochondria.
There’s an interesting feedback loop right in here, where from the oxygen you generate energy, and then you couple that energy into systems, which is a magnesium-dependent process.
And by the way, it’s one of the big deals in chronic fatigue syndrome. Magnesium is wonderful for these patients. It’s probably the simplest, safest, best thing I’ve ever used to treat energy problems in this disease.
But tablets don’t work. Tablets are ineffective. Either you have to put it on your skin in a cream, or you have to squirt it on your tongue, or you have to inject it. And you don’t need very much for this.
You’ll notice that the magnesium couples ATP to ADP. That is sort of like taking your foot off the clutch. You’re making the same amount of energy, but when you take your foot of the clutch, the car actually moves.
The same is true here. You’re not making more energy with magnesium. You’re actually coupling it.
It’s coupled into ADP and then from there into AMP. This actually is a feedback loop for oxygen transfer. This means that if you’re not coupling ATP to ADP, there will be no oxygen transfer into the system. It’s a feedback locked-loop system.
If you look at a textbook of physiology, you’ll notice that oxygen transfer into the cell is primarily determined by ADP levels. If they’re low, there will be no oxygen transfer. That’s an important idea.
Of course, when you make ADP, you also make superoxide. And that’s a conundrum. An energy conundrum.
You cannot make energy without making oxidative stress in the form of superoxide.
The body knows this, of course, and it’s developed a fantastic redox cooling system composed of several different enzymes – SOD, GPx and catalase.
These are the kinetic speeds of these enzymes. These are the fastest enzymes systems in the human body. They’re incredibly speedy. And they have to be that way, because if they fail to take superoxide down to water, which is their job, then you cannot make energy. Because if you do, you’re just going to fry the mitochondrial membrane.
Because if this superoxide is not taken first to hydrogen peroxide and then to water by two different pathways, then the superoxide will turn into free radicals.
It will react with nitric oxide to form peroxynitrate. This is the OH/ONOO hypothesis of Marty Pall, which some of you may have heard or read about.
Or it reacts with hydrogen peroxide to form hydroxyradicals.
This impressive production of these free radicals will actually destroy the membranes – the mitochondrial membranes – and bring energy production to a halt.
The reason you do this is to save yourself. Because if you continue to generate energy and you cannot cool the system, then you have to bring down energy to save your life. And we think this is exactly what is going on.
In other words, the energy downregulation is not the problem.
The energy downregulation is the solution to prevent a deeper problem.
And the problem is that something’s wrong with this redox cooling system.
Studies on some of these elements – SOD and GPx and catalase and the NADPH which reduces glutathione made in the liver – there’s something wrong with this system. And you can see it and prove it and measure it in every single patient.
It’s there if you just look for it.
If you have a defect in redox cooling, then there will be increased oxidative stress, and if you’re lucky, that will feedback loop inhibit mitochondria from producing energy. And then you will equilibrate at a lower energy state to save your life.
That doesn’t mean that the low-energy state is pleasant. It doesn’t mean that there aren’t complications from that. But your life is preserved.
And that brings me to one of the interesting phenomena in this disease. I’ve watched these patients for 25 years, and they simply as a group don’t die that much. They go on and on and on.
They fade away, sure. But they’re not dropping dead like flies. As a matter of fact, I’m an internal medicine doctor, and if you ask internists my age “How many of your patients are left after thirty years?” the answer is only about half are left. Why? Because you only see an internist if you have a significant illness.
But not anywhere near that number have died in my hands. So there’s something preserving these patients. And what’s preserved is that they are equilibrating to a low energy state to prevent some sort of disease progression.
Excerpted from https://paradigmchange.me/wp/cheney...Ieg9aZM2j6goro3ChWzK1LE_52m3nudQFVmmgn_cUnneYEvidence of Mitochondrial Dysfunction
So what is the evidence for some of this?
This was performed in the cell biology department at UNC Chapel Hill, believe it or not, in 1992, because the chairman of that department’s daughter had this syndrome. He called me up and said, “Is there anything I can do to help you?”
I was in Charlotte at the time. I said, “Yes, do you do any kind of energy measurements?” And he said, “Oh, that’s what we do here.”
And I said, “How do you do it?”
They used fluorescent tags of the mitochondrial membrane, and the intensity of the fluorescence is related to the degree of energy production. The higher the energy being produced, the brighter the intensity, and the lower the energy being produced, the lower the intensity of the fluorescence.
What you see here are the cells plated on a glass plate. And then they stain these lymphocytes on a plate and then they look at them with a confocal microscope that’s focused right on this plate. Then they stain it with these fluorescent dyes, and then they take off the dye in direct proportion to how much energy is being produced.
When he did this, he called me back and said, “It’s really quite shocking. Your patients don’t have any energy in their lymphocytes.”
Unfortunately, they applied for a grant to do this work, and of course, because the grant was labeled “Studying mitochondria in chronic fatigue syndrome,” it was promptly denied by the NIH.
But twenty years later, Garth Nicholson did pretty much the identical experiment using, again, fluorescent dyes and mitochondria to compare controls to chronic fatigue syndrome. They are significantly downregulated in terms of energy production.
Another investigator in the UK, John McLaren Howard, using layered polarization fluorescence imaging, was able to look at the plasma membranes of peripheral mononuclear cells, and found – guess what? – oxidative damage to the plasma membranes, as identified by these arrows – showing various kinds of oxidative changes (the white areas), certain kinds of what appeared to be microbial damage, elongated fatty acids, and unusual lipid binding.
There’s oxidative stress going on, which is damaging the membranes. If that damage occurs in the inner mitochondrial membrane, it will downregulate energy production.
Yep, the clinicians and researchers in the early days basically figures out all the stuff that keeps being announced as new discoveries.This section of the seminar is particularly annoying to read but is typical of the lack of proper funding for this illness:
This testing has been available for decades and yet we still have doctors claiming it's all in our heads and we just need to exercise.
The deeper cause in ME is an ongoing immune signal.
Consider that it's not so much 'an immune response' as a defect in switching the 'Response off'
immunolpgical issues not mutually exclusive with oxidative stress. The oxidative stress could be from mycotocins or high viral load. CFIDS is not different from “classic CfS” which cheney saw in his practice. He did not see people with mild cfs or idiopathic chronic fatigue I believe. How would you know that you don’t have oxidative stress. ? I believe the oxidative stress is why we can’t cure ourselves with thyroid , stimulants , or oxygenHe is right about there being a deeper cause of downregulation but I dont think it is oxidation in my case, since I have CFIDS and I think it is immunological.
Some of his patients with CFS may have oxidation problems, I wouldnt know but I think that is a different situation and subtype to CFIDS.
i think the innate immune system is very intelligent. This isn’t an autoimmune disease. There’s something affecting the immune system constantly. We don’t know what yet.I agree. Although immune activation causes oxidative stress. So the oxidative stress found in ME/CFS, I think is secondary to the immune response.
i think the innate immune system is very intelligent. This isn’t an autoimmune disease.
There’s something affecting the immune system constantly. We don’t know what yet.