Paul Cheney Seminar on Oxygen Toxicity (2013)


This page provides a transcript of a presentation given by Dr. Paul Cheney on chronic fatigue syndrome in North Carolina in 2013.





Thanks for inviting me to speak about the subject I’ve spent most of my life on studying.

My initial introduction to this was upon my arrival in Lake Tahoe in 1984 after a stint in the Air Force, which was after medical school. Within three or four months of arrival, I began to see my first case of chronic fatigue syndrome.

It seemed to start in the girls’ basketball team. It looked like mononucleosis was simply running through these girls.

Very shortly after that, teachers became sick. Very shortly after that, 20% of the teachers in one high school and 30% of teachers in another high school all became sick over all became ill over about a four-month time frame, peaking in about June or July of 1985.

By August or so, we had 256 cases, in adults primarily, average age 38, coming out of two pockets within two school systems – one in the Lake Tahoe area and one in Truckee – starting out with what looked like a case of mononucleosis in most instances, though some had more of an encephalitic onset and some had more of an influenza outset.

So it wasn’t always the same thing, But they all seemed to get some kind of acute viral syndrome.

And then, after a few months, it began to evolve into something very different than a viral syndrome.

About six months into it, Dan Peterson and I kind of looked at each other and said, “This thing seems to have started in the blood, but it is now getting into the central nervous system.”

We began seeing soft neurological features, including especially vestibular dysfunction. People would fall over on simple tests of balance. People developed hyperreflexia of the extremities. People developed (?) of the ankles.

People suddenly began having trouble getting from one place to another in their cars. They had spatial disruptions and dyscalculia and all kinds of problems of processing information.

People would get lost trying to get home in a one stop sign town. Very odd.

We had never seen anything like this before. There was  no experience for this sort of thing.

Ultimately – I had worked as a graduate assistant at the CDC studying immunology.

So I called them up and said, “You might want to come out and take a look. We have about 250 people who all seem to have gotten the same thing in about a four-to-six month time frame, and they’re not getting any better. In fact, they’re getting worse, and we haven’t seen this before.”

So they said, “Well, we’ll think about it.”

A few weeks later, they called back, and little did I know that they were receiving phone calls from physicians all over the nation seeing exactly the same thing.

Except that when they looked at the map, they noticed that we lived in Lake Tahoe. So they decided to make that their first investigation.

They arrived in September of 1985 and took a look at these patients.

As we saw them, they saw their atypical lymphocytosis. They saw their swollen glands. They saw their low-grade fevers. They saw some of the serology that we had done. They saw that they would fall over on simple tests of vestibular function. They saw that they had hyperreflexia.

And they drew some  blood tubes and they left town. We didn’t hear from them from several months.

What was fortuitous was that there was a reporter from the Sacramento Bee who heard that the CDC was investigating a mystery illness in the Lake Tahoe region. So he went out there and interviewed some of these patients and us. And he wrote an article that went out on the AP in late September 1985.

The next day, that article hit the wires all across the country, and we were getting 50-100 phone calls a day from physicians all over the country having read what was described in the Sacramento Bee article, that they were seeing in their hometown cities as well.

So we realized – it was a very strange sensation, because you hit some kind of nerve that was ringing throughout the entire nation

And that sort of started the journey that would eventually move to this podium tonight.

So my experience is primarily as a clinician, but I rapidly found out that there wasn’t much help out there in terms of specialty care for these people or even much knowledge of this disease.

So we sort of had to build on our knowledge of this illness – which was a combination of observation and listening to people for hours and hours over long periods of time, watching them evolve over time.

And then working with some very good scientists over the years, to get to what we know about this illness, which I will present tonight.


The Chronic Fatigue Syndrome 

There are several criteria out there.

This is the CDC criteria, which is the Fukuda definition of 1994.

It wasn’t the first one. The first one was in 1987.

This is the revised addition. It has several major criteria, and you must meet at least four of the minor criteria, and there are several exclusion criteria.

This has actually served fairly well over the years, although it’s been refined by both the Canadians and the Australians and the British.

The purpose of these kinds of definitions is not to be perfect, but to make sure that everybody is sort of describing the same thing to study it. So it’s an attempt to get everybody on the same page with respect to research.

It doesn’t necessarily mean that this is the end-all of the illness. Certainly there are people who I think have chronic fatigue syndrome who don’t quite meet this definition. And there are some people who sort of meet this definition but I don’t think they have chronic fatigue syndrome. So it’s certainly not perfect.

When you talk to people – and I’ve talked to maybe over 10,000 now – and you listen for this disease, it’s a drum roll. You can hear it in their descriptions of it.

They talk about that their energy is impaired. And it’s not just that they’re fatigued. There’s a dynamic quality to this energy impairment.

People describe it as, “It isn’t so much that that I have no energy, but if I do something, I’ll just crash. I’ll collapse.”

And that collapse of function is dynamic collapse of function. An hour later or a day later or a week later – it lasts for days or weeks or months.

It’s really what characterizes this fatigue state. A dynamic loss of function.

It’s not just chronic fatigue. A lot of people with chronic fatigue, once you stimulate them, they don’t have chronic fatigue any more. And they don’t really crash.

But these people crash and burn. So there is a dynamic quality. And I listen for that.

They also complain significantly of brain dysfunction.

It’s not a cortical dysfunction like Alzheimer’s is. It’s more of a subcortical dysfunction, more aligned to MS and HIV patients.

They can’t process information very well. So they slow down. They can’t sort of figure out what sensory input means in respect to some response somewhere else, that is processed in the subcortex.

Neuropsychometric testing  identifies this as primarily a subcortical dysfunction, not a cortical dysfunction. They know who they are, they know where they are, they know the President, they recognize people. But they can’t process information correctly.

And that really is one of the dominant things. I listen for that even more closely than anything else. If I don’t hear any disturbance of cognitive function, I really don’t think they have this illness.

Pain is very common, but I do have patients who do not have any pain at all. They have severe dynamic energy problems and cannot function for that reason. And their brain is shot. That is all that I really need to hear to think they probably have this.

Pain can be significant and it can be dominant. In some of these patients it is dominant.

Maybe because of some of the treatments we render, pain does not seem to be quite as big of a deal today as it was earlier in the course of this illness. I don’t know if we’re doing a better job of dealing with pain or whether the disease is evolving.

Cognitive problems are seen in 99% of cases.

What happens to the 1%? Well, you have 1% of people say they don’t have cognitive problems, and they don’t think they do, but when you test them, it’s significantly impacted, when they get to some of these isolated aspects of subcortical function. There’s a wipe-out. They’re shot in terms of what they cannot do.

So sometimes they’re unaware of this. It’s focal and multi-focal knockout of certain processing pathways.

Short-term memory is affected, auditory more than visual. There’s sensory and information overload.

They have trouble going down the aisles of the grocery store and making decisions about what to purchase and not purchase, what to put into the cart and what not to put in the cart. They’re completely overwhelmed.

Word-searching, multi-tasking problems, and spatial disorganization.

There are mood disturbances seen in about 60% of cases. What’s interesting to me is that the depression is actually not that severe in these people. They seem to be depressed because of the circumstances of their lives, not so much because they have some severe internal depression. Although we do see that, it is not for some reason the dominant problem that I see.

We see a lot more anxiety disorders in this disease than depression. And some mood lability.

Again there’s a symptom dysfunction, which I call “The Misery Component.”

And then there is this dynamic dysfunction, which I call “The Action Component” or the push/crash phenomenon.

And there’s an evolution of this. These people begin typically with a symptom dysfunction but they end up primarily with a dynamic functional impairment and less misery component.


Disease Stages

You can see that in this chart. I have the misery index on the side, from low to high, and at the bottom you have the functional problem, from low to high.

In the beginning, in Phase 1 of this illness, you see a lot of misery complaints. “I have sore throats and my glands are swollen, and I ache all over, and I feel absolutely terrible.”

And yet, they’re working. They’re actually relatively functional.

We saw this in Lake Tahoe, with people trying to work or trying to go to school, but feeling absolutely horrible.

And that’s the early part of the disease.

Then it sort of evolves, and they have somewhat less misery and somewhat more dysfunction as they start to complain of things like “I feel like I’m poisoned” or “I feel like something is dreadfully wrong, I can’t even put my finger on it” as they search for the adjective to describe how they feel.

When they eat, they get worse. They often say things like, “I feel best when I don’t eat, I feel worse when I do eat.”

So there’s a toxic component that arises that we were curious about. There’s been some research on this. This is sort of midway through the disease.

And then finally, when you see that it’s sort of strange – you see the misery index is contained.

They are not complaining so much about how bad they feel, and instead they are complaining about what they cannot do. “I can’t do anything anymore.”

And they’re quite impacted. They’re homebound or bedbound. And we begin to see evidence of a significant cardiomyopathy and significant metabolic encephalopathies develop in these patients, which we will talk about extensively tonight. Because this seems to be the third phase of this illness.

There’s some belief that there may be DNA epigenetic adaptations that occur over time in this disease or even damage to certain parts of the dark matter DNA, which shifts how the codon regions of the DNA express themselves.

So these people end up with a sort of locked-in epigenetic shift that may be driving some of this dysfunction.

It also makes it incredibly difficult to treat.


Exercise Ergometry

Does chronic fatigue syndrome have a cellular energy defect?

The first indication that there might be a problem with cellular energy is this study that we did in the 1990’s in Charlotte. This is doing exercise ergometry with gas analysis.

You’ll notice the controls over here. This is referenced to the percentile predicted.

You’ll notice because they’re controls, with 25, their oxygen consumption maximum obtained at peak exercise sort of oscillates around 100%, which you would expect to see.

Down here, at the bottom, are the couch potatoes. They’re healthy, otherwise.

And at the top are the elite trained athletes.

You can see to some extent that oxygen consumption can be trained, or you can be deconditioned simply by not training. And that’s the normal range.

You will notice over in the chronic fatigue syndrome patients that their median is around 2/3 of the normal or 1/3 below normal.

And although there is a little bit of overlap with some couch potatoes, some of these people are incredibly low.

I always will remember one case – she’s actually not plotted on here. But her development of the V02 was simply a flat line. She was peddling faster and faster and faster, and was not using any oxygen at all.

Quite incredible. I call her my Martian, because she would do really well on Mars.

Some people would argue this isn’t really an energy problem. They just aren’t doing anything.

But the Social Security Administration believes that if you study deconditioning, you rarely get below the 85th percentile, and that if you fall below the 85th percentile, that it’s an organic process. That you can’t get there simply by being deconditioned.

So there’s something terrible going on with oxygen utilization or therefore something wrong with their energy production system.


Magnetic Resonance Spectroscopy

Another piece of evidence with regard to energy problems is Magnetic Resonance Spectroscopy. This is work done by Dr. Dikoma Shungu at the Weill Cornell Center in New York City. We’ve been sending patients to him for a decade now.

He sees evidence of lactate peaks in some of the (?). These are small areas of the brain. Using homogeneity shifting of the magnetic fields, they can actually focus on very tiny areas of the brain, and map the biochemistry with these peaks and valleys.

See, the lactate peak is not normal. It’s certainly not normal at this level.

Lactate is produced when the mitochondria are not working. You lose oxidative phosphorylation as your primary energy producer, and you switch over to anaerobic metabolism. When you do that, you start generating lactic acid.

So this was some interesting evidence in the central nervous system, at least, that there was an energy problem at the cell level and they were generating lactate peaks.

I think at the beginning, the incidence of this was at about 70% or so. As time has gone on and they have developed the technology, it’s really above 90% now that we see these lactate peaks.

Back in 2005, Dr. Shungu did a comparative study of normals, people with generalized anxiety disorder and chronic fatigue syndrome, simply by integrating the lactate peaks. The CFS patients have significant lactate elevation, indicating severe disruption of the oxidative phosphorylation system in their brains and the loss of energy at the cell level.

Kind of interesting with respect to this generalized anxiety disorder patients that had slight elevation of lactate peaks is a Harvard professor in the 1930’s who injected lactic acid into the veins of his medical students. That’s something they would never be able to do today, but he did it back then. He was reliably able to induce panic attacks and anxiety disorder by injection of lactic acid.

Another way to look at it is that if you are producing lactic acid like this, then you have lost significant oxidative phosphorylation and there is a reduction of oxygen input into the brain. To the brain’s eye, that is like being smothered. The brain does not know why there is no oxygen coming in or why there is no energy, but it perceives it as being smothered. And if you’ve ever watched anyone being smothered, it’s the most anxiety provoking thing you’ll ever view. These people are actually acting like they’re being smothered in the central nervous system.


This is the most recent publication by Dr. Shungu. It was published fairly recently, in 2012.

They have expanded their interrogation of biochemistry in the brain in chronic fatigue syndrome, and this is what they found.

“Thus, in exploratory correlation analyses, we found that levels of ventricular lactate and cortical glutathione were inversely correlated, and significantly associated with several key indices of physical health and disability.”

That is, with these lactate peaks, the higher they got, the more disabled they were. And with the cortical glutathione, the lower it was, the more disabled they were.

They looked at other things, such as cerebral blood flow. They looked at high-energy phosphate bonds. None of it correlated very well. It was the lactate peaks and glutathione levels that correlated.

So he concludes, “Collectively, the results of this third independent study support a pathophysiological model of CFS in which increased oxidative stress may play a key role in CFS etiopathophysiology.”

This is a key idea that we will explore more.



Another phenomenon that we have observed for twenty years is that these people lose their fingerprints.

Not all of them do. But you will see degradation to varying degrees in the great majority. And in 10 or maybe 15 percent, they really cannot be fingerprinted at all. In about half of them, they’ll have trouble fingerprinting them.

This is a normal fingerprint, on the right. And on the left is a chronic fatigue syndrome patient.

We really got interested in this when a patient came to me and said that her fingers were hurting, and that it seemed like she’d taken her fingers and dipped them in hot oil and then stuck them in a sandbox.

I said, “Give me your fingers.” Then I looked at them, and I couldn’t see any fingerprints.

Then I started looking at other patients and realized that these people were losing their fingerprints.

These people are not old. They are in their 20’s and 30’s and 40’s.

We took 16 of these fingers and we biopsied them with punch biopsies and sent them to UNC Chapel Hill pathology division and then go the results back. They were very telling.

One defect was a perilymphacitic vasculitis, which is a signature of immune activation in which the cytokines are produced against lymphocytes migrate into the tissues and cut off the small nutrient vessels. That could affect the skin surfaces, because of this.

It is seen in lupus. It is seen in other vasculitities (?). It is seen in chronic fatigue syndrome.


The other thing he saw was even more interesting. He saw punched-out lesions in the fibroblasts, which will impair collagen formation, and that will impair the ability to make a fingerprint, because the ridges will tend to collapse and smooth out.

I asked the pathologist to tell me what diseases cause punched-out lesions in the fibroblasts. He said the only thing that seems to do that is scurvy. And I said, “Scurvy?” Then I thought for a minute, and I thought – scurvy is Vitamin C deficiency, but what if you simply had severe oxidative stress? Would this display the same phenomenon?

So these people are not Vitamin C deficient. They are under severe oxidative stress, and it’s taking their fingerprints.


The Energy Conundrum

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.


Evidence 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.

Looking at other areas, he found problems with disordered fatty acid structures. This finding of oxidative damage to the membranes has led some people to treat this with various lipid therapies.

Dr. Patricia Kane in New Jersey is probably the best person in the world working in this area. She does get benefits from lipid therapy.

The problem is that we don’t think the problem is lipids per se. They’re just being hit by oxidative stress. The problem is failure to cool off superoxide production with the cooling system.

The point there being that if you don’t fix that, then  by simply repairing the membrane, you will increase energy production and increase oxidative stress in the system. So I don’t think it’s going to go very far until they address the real problem, which is containment of oxidative stress.



Is there a CFS associated cardiomyopathy? Yes there is, if you want to talk about cardiomyopathy in its most general form, as some sort of metabolic disturbance of the heart.

That requires a conceptual breakthrough in what it means by diastolic function and systolic function.

In the case of systolic function, there’s an EKG signal, causing depolarization, calcium influxes, myofibril contraction, and the heart squeezes.

With diastolic function, ATP is required to pump out the calcium into the sarcoplasmic reticulum, causing myofibril relaxation, and the heart fills with blood.

You’ll notice that this is not intuitive. This means that energy production is used to relax the heart, not to squeeze the heart. When the heart is squeezing, we’re not consuming energy. You’re actually releasing energy that was already put into the heart when it was relaxing.

Here’s an analogy. A dam worker arrives at the base of Hoover Dam. On the console, he presses a button and opens a gate. Water comes out of the base of Hoover Dam and lights Las Vegas.

He just took his little finger and pushed a button and lit Las Vegas? You would think, if you were from outer space, that there was some energy that was in his finger.

No, the energy was already pumped into Lake Mead over decades before, and all he did was release the energy.

Likewise, with diastolic function, you are actually pumping energy into the system during relaxation by pumping all the calcium out. As you do that, the heart fills with blood.

And then the EKG signal just releases the energy that’s been pumped in, and the heart squeezes.

So the squeeze is not where the energy entered the system. The energy entered in the filling action.

That’s very important, because if we look at the heart from an energy perspective, you do not look at the squeeze. You look at the fill. And that’s an important idea.


The first person to investigate whether there actually was evidence of an energy defect in chronic fatigue syndrome was Hollingsworth. He was an investigator in the UK using – guess what – MRSI of the heart, as opposed to MRSI of the brain.

He showed that cardiac bioenergetic abnormalities were a feature of CFS with lower phosphocreatine to ATP ratios compared to healthy controls (1.76 for CFS as a group vs. 1.9 for controls) and that a subgroup of CFS cases comprising 33% of all CFS cases were in the cardiomyopathic range with an average of 1.57 +/- 0.22 for the phosphocreatine to ATP ratio.

When you look at cardiology textbooks, when you are at 1.57, you’re not going to survive that. That is lethal. These people are all dead in five years at that level.

So my patients have an energy level equal to people with heart disease that would kill them. Except that mine don’t die.

The reason for that is that our patients’ systolic function is maintained, whereas in other heart diseases where they have this problem, the systolic function is not maintained. And that is the difference.

This correlates in my practice, where 1/3 of my patients have a cardiac index in the cardiogenic shock range below 1.8. Furthermore, MRSI supports the pure energy deficit hypothesis for diastolic dysfunction in chronic fatigue syndrome.

My first introduction to problems with the heart was from a Peckerman paper published in 2003 in the American Journal of Medical Sciences using impedence cardiography. He looked at controls and noticed that when they were lying down, they had an average output of 7 liters per minute, and when they stood up, they dropped to about 5 liters per minute. That’s normal.

You’ll notice that even in normal people, when you stand up, you lose 30% of your cardiac output. That’s normal.

In the case of chronic fatigue syndrome, when they’re supine, they’re at about 5.5 liters per minute, and when they stand up, they go down to 3.7.

What’s interesting about this is that you are effectively in cardiogenic shock when you drop below about 4. So when they stand up, they are not being perfused very well. And that’s one of the reasons that these patients have significant problems standing.

They don’t like to stand. If they do stand, they have to move around. If they stand around, they have to sit down or lie down or fall down. That’s because if you have this kind of drop when you stand, you drop below a certain threshold. And it’s not tolerated.

So one of the features of diastolic dysfunction is orthostatic intolerance. They don’t like standing.

Interestingly, it’s almost the opposite of systolic failure, where they don’t like lying flat and do better sitting up.

Our patients are the exact opposite. They don’t like standing up. They like lying down. Because they don’t have systolic dysfunction. They have diastolic dysfunction, because they have an energy defect at the cell level.


I repeated this experiment, because when I first saw it, I didn’t believe it, because I didn’t think there was anything wrong with the hearts in chronic fatigue syndrome. I was an expert, right? So I knew there wasn’t any problem with these patients’ hearts. When I saw this, I was pretty shocked, and so I re-did this experiment in my clinic to prove them wrong.

But in fact, my patients were sicker than that recorded in the literature. Because what’s a peculiarity about my practice is that when people are studied by academics, they’re not very sick, because academics don’t treat anybody. When they come to people like me, I treat them, so I see all the sick people. So what we see is a lot different than what the academics tend to see.

So with respect to this data, I was pretty shocked about this.

Peckerman never asked the question that should have been asked: Why do they have low cardiac output?

By the way, he also showed that the lower the output was, the more disabled they were, and the higher the output was, the less disabled they were. There was a significant correlation to this. I thought that was important to know.

So I thought, well, why do they have low cardiac output?

So I ordered three of the patients who scored the lowest on this and I had them echoed in three different centers around the nation where they lived. The echoes all hit my desk at the same time, and they all said the same thing. They said, “Normal wall thickness. Normal chamber size. Normal valve function. Normal everything. Except, Type 1 Diastolic Dysfunction.”

They all said the same thing, that last sentence. Type 1 Diastolic Dysfunction. But everything else was normal.

And so I was shocked, because I didn’t know what that meant. And I was embarrassed, because I went to Emory and am supposed to know everything about the heart.

So I called up a friend of mine that I went to school with and I said, “Why don’t I know what that means?”

He said, “That’s a new term. It didn’t exist when you and I went to school.”

I said, “This is a new term to me. This is something about the heart that no one knew existed?”

He said, “Yes, until about ten years ago, it did not exist.”

Well, it actually does exist, and it is a significant feature of chronic fatigue syndrome. Almost all of them have this.

So I said, “Would you tell me what it means?”

He said, “That is what the heart looks like when there is no energy in it at the cell level.”

I was shocked, and I asked if he would allow me to repeat what he just said back to him.

I said, “You mean that an energy defect at the cell level would manifest as diastolic dysfunction?”

He said, “Yes, absolutely.”

I said, “Would it drop the cardiac output?”

He said, “You betcha, especially when they stand up and you get gravity filling problems on top of energy filling problems.”

So I knew I was onto something, so I asked him, “So how do I measure this?”

He said, “You need to get a really good echo machine, one  with tissue doppler capacities and sufficient power.”

I said, “Which would you recommend?”

He said, “Vivid 7 made by GE.”

So I called up GE and had them demo this big machine in my office. They brought it in in three different boxes, and they echoed six of my patients in a row. This was in early 2005.

After they finished, the echo stenographer turned to me and said, “We have never seen this before. They all have diastolic dysfunction and they’re relatively young.”

I said, “That’s interesting, but why do you seem so surprised?”

He said, “Oh, we’ve never seen this before in such young people. Could you tell me what they have?”

And I said, “They have chronic fatigue syndrome.”

And he said, “What’s that?”

So clearly, no one had even looked at this.

So I decided to get this machine, and I’ve been doing echocardiography ever since. And it’s been quite a journey because there’s not been a lot of help in the cardiology community.

They see diastolic dysfunction as an old person’s disease. Or it’s related to underlying conditions like diabetes or hypertension. And none of my patients have any of that. They’re not old, they’re not diabetic and they’re not hypertensive.

So it doesn’t really click with cardiologists that there might be such a thing as a pure energy deficit. Otherwise the heart is completely normal.

That’s a good thing, because with a normal heart, you can compensate for diastolic dysfunction. And it turns out that the major compensation mechanism is to squeeze your ventricles as hard as you can. And so you see high ejection fractions in these people. We call it cavitation. The ventricle squeezes really, really hard.

And that creates several complications that we’ll get into. But it’s not just that they have diastolic dysfunction. It’s that they have maintained systolic function and they use the systolic function to compensate.

As a result, if you squeeze hard enough, you can fire the C fibres, causing neuromediated hypotension. And you’ll pass out and hit the floor. That was reported at Johns Hopkins back in the 1990’s, that a certain percentage of these patients have NMH, POTS or difficulty standing, which they blamed on autonomic dysfunction.

It has absolutely nothing to do with autonomic dysfunction. They have diastolic dysfunction. And it’s not good for them to stand up. Partly because they have good systolic function.



This is an example of cardiac output measured by echo. Here you put the transducer in the (?), and you’ll see the time and velocity in the aortic channel.

This is basically that the aortic valve opens and the blood starts rushing out at peak velocity, and then it comes back to zero as the aortic valve shuts.

If you integrate this with your little mouse, that generates the stroke volume, which you see over here – LV Stroke Volume, 124 cc’s.

Then if you take the mouse and put it at the head of the next opening, it gives you your heart rate.

Heart Rate x Stroke Volume = Cardiac Output

Cardiac output here is 8.3 liters per minute.

If you divide by the size of the person, that will give you the cardiac index in square meters.

And then we began to look at the cardiac index in my patient population, using this methodology.


This is what we got. Here’s chronic fatigue syndrome.

The normal range for cardiac index is between 3 and 3.5. It tends to be a little higher in younger people, closer to 3 in older people.

These are all diseases associated with either an elevated cardiac index or depressed cardiac index.

My patients average about 2.36.

30% of them are less than 1.8.

That means 30% of them are in the cardiogenic shock range.

This was also matched by Hollingsworth.

On average, our patients lie somewhere between mild shock and traumatic shock.

This is, to me, absolutely incredible. They have a lower cardiac output than people with myocardial infarction.

And this output correlates with disability. The lower this output is, the more disabled they are. The higher the output is, the less disabled they are.

Notice some of the things that produce high outputs. Hyperthyroidism. Anxiety disorders. Pulmonary disease. Hypertension tends to be high.

Myocardial infarction is low. Mild shock is low. Chronic fatigue syndrome is lower. Traumatic shock is lower. Cardiogenic shock, which is the end of the road, is lowest, and that is where 1/3 of my patients are.


Stroke Volume

This is some of the data on stroke volume.

This is a case/control study with 15 age- and sex-matched controls and patients, with a high degree of difference. The average stroke volume in the control population that was age- and sex-matched was about 80, whereas our patients are sitting at about 60.



These are some of the diastolic parameters that we look at.

Over the years, I’ve really looked at this a lot, and of course, you see different patients meet different criteria for diastolic dysfunction.

What’s important is that they also compensate for diastolic dysfunction by big left ventricular squeezes.

One of the aspects of that big squeeze is that when it relaxes, it actually sucks blood in. And that actually helps you fill the heart – not by a relaxation mechanism in particular, but by a rebound off that big squeeze.

So this compensation mechanism turns out to be a really good thing to look at – not so much whether they have diastolic dysfunction or they don’t, because it can be (?) by these compensatory mechanisms.

But anyway, this is the early fill and the late fill. Notice that in a normal person, the E-wave is bigger than the A-wave.

Think of this as E is for Energy, and A is for Atrium.

E actually stands for Early Filling, and that’s due to the early relaxation of the myocardium, which is energy dependent.

With the initial kick, it tops off the left ventricle as it squeezes, giving you a little more kick to fill it.

In Type 1 dysfunction, the E is lost and the A increases, because one of the early compensatory mechanisms for the lack of filling is for the atrium to squeeze harder.

If it squeezes a lot harder for a long time, it starts to dilate. And dilation of the left atrium is one of the early features of diastolic dysfunction.

At the end of the road, you get this Type 2 diastolic dysfunction, A very high fill, but look here, the Atrium is dying and doesn’t give  you much of a kick any more. This has a 75% five-year death rate. I have never seen this in chronic fatigue syndrome. Cardiologists see this all the time, but I don’t. I see either the first one or the second one.


Looking at tissue doppler, which is a little more sensitive to diastolic dysfunction, we’re looking at tissue rather than blood flow.

We see the e-prime, which corresponds to the E-wave, and the a-prime, which corresponds to the A-wave.

The tissue is moving in the opposite direction of blood flow.

In chronic fatigue syndrome, you can see that the e-prime is lost and the a-prime expands. That’s consistent with diastolic dysfunction.

Sometimes it is known as pseudo-normal type in the literature.


My favorite is pulmonary vein interrogation, where you shoot all the way through the heart, all the way to the entry point where the pulmonary vein’s coming back into the left atrium.

If you put it there, you see in normal people an S-wave, which is the right ventricle squeezing, filling the left atrium, for that right ventricular squeeze.

Then you get the D-wave, which is the early filling, where the left ventricle has started to relax in its energy phase, and the blood is moving out of the lung across that pulmonary vein, creating the so-called D-wave, for diastolic

Here’s the A-wave squeeze. In the sensation of squeezing, some of that blood goes back up into the pulmonary vein before it goes in the opposite direction. And that’s normal.

In chronic fatigue syndrome, you see this. You see a huge S-wave. That’s because they have normal systolic function. And they have hyper systolic function and they’re using it to fill the left side with. They’re using it as compensation.

People with heart disease don’t have this so much, because they don’t have enough squeeze to do that. So you see this  big S-wave, this small D-wave, and this sort of widened A-wave.

This is the most sensitive indicator of diastolic dysfunction in chronic fatigue syndrome, because it captures two things the others don’t capture. It captures the E/A reversal, but it also captures even more importantly the systolic squeeze or systolic compensation, which we’ll get into in the major complications of this illness.


This is what it looks like in real time.

This is a normal person, this is the E-wave and early filling, and then the late atrial kick filling.

This is chronic fatigue syndrome. This is the early E-filling with the big atrial squeeze to compensate. This is diastolic dysfunction. I see this in about 40% of my cases. It tends to be more obvious in the older crowd, less often see in the younger crowd because they compensate better.


This is tissue doppler.

This is normal over here. This is early fill, late fill, squeeze out through the aorta. The early fill is big, the late fill is small.

It’s reversed in chronic fatigue syndrome, with a lower early fill and a bigger atrial kick. This is seen in about 60% of our cases.


This is the pulmonary vein interrogation.

This is normal. You get a little bit of S-wave and then a big D-wave filling. The A-wave is down here, that’s normal.

In CFS, you see the opposite. Big S-wave, little D-wave and then widened A-wave.

I see this in 97% of chronic fatigue syndrome, because it captures the systolic compensation which otherwise you miss if you just concentrate on the classical indicators.


Cardiac Data

This is some of my data on 70 patients. You can see this D/S reversal of 96% and one or more of these at 97%.


This is an atrial cavitation in CFS. When you stand them up, they not only can’t fill to begin with, but they get gravity filling problems too.

Interestingly, the heart actually collapses in size so much that if you X-ray them in the upright position – the Japanese did this – you’ll notice that the cardiac (?) was extremely narrow.

So they published a paper called “Small Heart Syndrome.”

The reason that it’s small is not actually because it’s small. It’s that when they stand up, all the blood drains out of it.

It just collapses, because the blood drains out of it.

You can see the left atrium right here. When they stand up at 70 degree tilt, look at this left atrium. It just pancakes.

Normal people do not do this. No normal person does this.

The implications of this are pretty phenomenal. Because if you collapse the left atrium, there’s a little valve that is open when you are in utero called the foramen ovale. During the first year of life, that valve shuts and seals. We call that a (?). About 70-odd percentage of people seal that in the first year of life. About 20% of us don’t, and we call that a patent foramen ovale.

I’ll show this in a few minutes, but almost all of my patients have a hole in their heart right here. Their patent foramen ovale is blown completely open. And the reason that it is blown open is because if you collapse the left atrium, there’s no pressure in it. If there’s no pressure in it, it’s like a beer can. If you pour the air out of it, the beer can just collapses so the right side can go right through the seal of the foramen ovale and blow it wide open.

The importance of this is that the most common complication of patent foramen ovale is migraine headache.

Another complication is mini-strokes, which produce unidentified bright objects on MRI scans of these patients, which we see all the time.

Another problem with PFO is that you’d better not decide to climb to high altitudes because at high altitudes you can shunt across and get into serious trouble or maybe even cause a sudden death at high altitude-climbing for people with PFO’s.

Some of my patients have a hard time in airplanes because of this.


This is the LD squeeze. This is normal.

You can see during diastole when the ventricle is sort of relaxed and notice that this (?) septum is pretty small – it’s only about 8.5mm. And then when we squeeze, the (?) septum, which is part of the ventricular wall, squeezes up from 8 to 10 mm.

That’s what normal looks like.


This is what chronic fatigue syndrome patients look like.

In the diastolic position, they’re not much different than normal people.

But when they squeeze, they go not from 8 to maybe 10/12, but from 8 to  15. I’ve seen them go all the way to 24mm.

They squeeze the living hell out of the left ventricle.

And the left ventricle gets real, real thick.

That may be the case of some of the chest pain they have – it’s part of the general (?) from this big squeeze.

This causes significant complications that i will get into later.


This is a use of a type of technology where we can see the movement of 400 little places in the left ventricle and look to see if there is dysynchronization.

We see that all the time in these patients.

This is abnormal synchronization where different parts of the ventricle are different colors.

In the normal people, they are all moving in synch – the early fill, the late fill and the systolic ejection. Everything in the ventricle is moving at the same time and synchronized.

This is what chronic fatigue syndrome patients look like.

They’re completely dysynchronized. This is really going to just kill your cardiac output.

One of the interesting treatments for this is magnesium.


This just shows positive strain patterns, such as oversqueezing of the left ventricle in an attempt to compensate for poor filling.





I’ll talk a little bit about fibromyalgia and how I think that integrates with chronic fatigue syndrome.

The most important thing to know about fibromyalgia, I think, is to give you a story about the fibromyalgia clinic in Charlotte where I practiced medicine for a decade.

There was a rheumatologist in Charlotte, and he ran a fibromyalgia clinic. We tended to trade patients for different reasons.

His clinic was right next door to a facility that he had rented, and he had twenty-odd stationary bicycles set up in rows outside his clinic.

His primary treatment for fibromyalgia was exercise. So all his fibromyalgia patients would come in, and they would climb on the exercise bike and pedal away for an hour. He’d have thirty people pedaling away for an hour. And over time, they got slowly better.

That’s not chronic fatigue syndrome. It will never be chronic fatigue syndrome.

In fact, my chronic fatigue syndrome patients who he put on the bicycle got crushed by this, so they would come over to see me.

So I used him as a screening tool. People that he hurt I got to have as chronic fatigue syndrome. People that he helped had fibromyalgia.

But that doesn’t speak to the broad issues of what exactly is fibromyalgia and how does it integrate with chronic fatigue syndrome?

Certainly, many chronic fatigue syndrome patients have fibromyalgia symptoms. And I think there is a lot that could be integrated between fibromyalgia and chronic fatigue syndrome. There is a lot that we could help with in terms of fibromyalgia.

But I don’t study that condition. These people tend to not gravitate toward my clinic. They tend to gravitate toward people who exercise them.

You’ll notice that in the definition of chronic fatigue syndrome, exercise makes them worse. That’s part of the case definition.

Another difference observed over the years is that if you read the original fibromyalgia literature, there is almost no significant complaint of cognitive impairment. Or if there was, it was minor concentration problems, such as number 20 on a list.

Significant cognitive impairment is not a feature of fibromyalgia. So if you see someone with significant cognitive impairment, that’s not fibromyalgia syndrome.

Another difference is the neurologic examination. As far as I know, the neurologic exam of fibromyalgia patients is completely normal.

Not so in chronic fatigue syndrome patients. In fact, it’s a very rare person who has a normal neurologic exam.

Now, it’s conceivable – I wouldn’t be surprised to find that diastolic dysfunction is an issue in fibromyalgia.

There are studies of fibromyalgia where they cut down into the muscle and oxygen probes demonstrate low oxygen saturations in the tissue. So if there’s an oxygen transfer deficit or a microcirculatory problem in fibromyalgia, then that might cause pain.

And certainly exercise might improve mircocirculation for a variety of reasons.

So I think they’re overlapping syndromes. They’re not exactly the same.

Sleep disorders is one of the key features of fibromyalgia and one of the key features of chronic fatigue syndrome. And both of them will respond to addressing sleep disturbance.

But my core patient population would get creamed by exercising.

So they do not meet the case definition for primary fibromyalgia even though they overlap.


Mt. Everest Studies

This is the Everest III study. This is a very key paper. It’s a French paper.

They took eight healthy young men and put them in a hypobaric chamber and then mimicked a climb of Mt. Everest at different altitudes – 5000 meters, 7000 meters and 8000 meters.

They all were in their 20’s and 30’s.

And they echoed them at each of these different altitudes and recorded the results.

What they recorded were these findings.

This list of findings for these healthy young men at 8000 meters is exactly the findings in chronic fatigue syndrome, to a T.

So when I read this, I got very excited because I started to look at people with chronic fatigue syndrome as being on a mountaintop who need oxygen. And their problem is that they cannot get oxygen into the system.

In the case of the study, when they gave oxygen to these healthy young men at altitude, all of those echocardiograph features completely disappeared within a minute or so.

In other words, they were simply manifestations of a low energy state, because there wasn’t enough oxygen getting into the system at such altitudes and they were not properly compensated because they moved up to those altitudes fairly quickly.

So this was my instantaneous model of my patients.


Administering Oxygen

You’ll notice in the photo the oxygen mask.

I said, “All I need to do is give these patients oxygen, and I’ll cure them.”

I was so excited. I couldn’t wait to get an oxygen tank in the office. I couldn’t wait for the next patient to come in.

I slapped them on the table and I gave 4 liters of oxygen. First I showed the diastolic parameters, exactly what you see here.

So I put oxygen on them and was waiting for them to clear. For all these diastolic parameters to completely go away.

But in fact, they all got worse.

This was a very seminal moment in my education about this disease.

Suddenly it was not that they can’t get oxygen into the system, like this.

Their problem is that they are trying to keep oxygen out of the cells.

And you’d better not try to get any oxygen into the cells or you will kill them.

That’s a very big deal.

It was a transformation of thinking.

They’re trying to keep oxygen out for some reason. What might the reason be?

The reason is that if you can’t control oxygen metabolites such as superoxide, and you can’t reduce it down to water, then you have to restrict oxygen. You have to do that.

And if you do that, you get an energy problem at the cell level, as diastolic dysfunction. Not as your problem, but as a solution to the problem.

And that changes forever how you approach these diseased patients.

Exercising is not a way to do this. That just drives more oxygen into the system.

And you can’t give them stimulants to make them simply work faster or work harder.

You have to deal with the underlying defect, which appears to be problems controlling oxygen metabolism.

We call that a redox impairment.



This is the IVRT. It measures isovolumetric relaxation time.

It looks like this on the echo. You have aortic outflow. Then the aortic valve closes. There’s a pause. The mitral valve opens. Blood goes in the opposite direction, because blood’s flowing out of the heart into the aorta, but it’s flowing back into the left ventricle. So it’s going in the opposite directions. So this is the mitral inflow.

This distance from this high velocity aortic valve closure (which is easy to spot on the echo) and this beginning of mitral inflow is called the isovolumetric relaxation time.

It’s measured in milliseconds.

Normally this is typically under 75 milliseconds.

What that is is the time it takes for the heart to pump all the calcium out of the myocardial cell to cause relaxation of the heart. And it fills with blood when it relaxes.

So this is a measure, in effect, of energy production. Because the more energy you have, the faster you pump the calcium out, and the shorter this distance is. The less energy you have in the cell, the slower you pump the calcium out, and the wider this distance is.

In other words, this is a direct measure in echocardiography of the free energy of the mycocardial cell.

I can put a number to it and I can measure this in roughly 30 seconds.

So in the case of the (Everstreet?) study, when they took these healthy young men up to 24,000 feet, the IVRT got longer, because they were dropping their energy at higher altitudes, because there wasn’t enough oxygen getting into the system.

And when they gave them oxygen, the IVRT simply went right back to normal as it was at sea level in very short order.

In my patients, when I gave them oxygen, it didn’t get shorter. It was long to begin with, and it got longer when I gave them oxygen.

It’s like they were toxic to oxygen at the energy level.


This is an example of a couple of patients. Again, here’s the IVRT measurement – the aortic closure and the mitral opening. It’s 100 milliseconds. Normally it should be 75 milliseconds. This is Patient #2.

And here’s the aortic closure click, which is thought to be the mitral opening.

This measurement of the mitral opening is difficult to make. It’s subjective in character. It takes really good stenographers to make this measurement reproducible.

We don’t really use this measurement to follow people necessarily over time. We use it to follow them on the table in real time. So we take measurements on the IVRT before we do something to them, and then see what happens after we do something to them in 30 seconds to 60 seconds.

So all that the stenographer has to do is whatever his subjective tendencies are to measure this mitral opening, he just applies those same subjective determinations. So you subtract out any subjective error as long as he tries to make it the same way.


This is an example of a patient who is at baseline at 92 milliseconds between aortic closure and mitral opening.

And this is after four liters of oxygen. You’ll notice that it went from 92 milliseconds to 111 milliseconds.

After a few more minutes, it goes from 111 milliseconds back to 92 milliseconds.

So what we are seeing is a transient loss of energy with the oxygen, and then a return to baseline.

It never is stuck there. It always moves out – they’re losing energy and then they come back.

That’s a very important observation, because it suggests that this is being buffered. Something is actually buffering this.

And that’s what really leads to what this probably represents. This (?) represents the inability to properly buffer the person’s redox state – suggesting the redox mechanism is impaired so that they don’t buffer very well.

But that buffer impairment simply takes time to recover. It’s not a permanent thing on the table.

These are not permanent changes. It’s rather transient. And that’s an important idea.

This is another patient with a baseline of 85 milliseconds.

And after 4 liters of oxygen, it jumps up to 98 milliseconds.


So we’ve come to a conclusion after looking at this for a long time.

There’s evidence of oxygen toxicity by IVRT criteria, which is the opposite of what you see in normal people.

In 100% of cases, with an N value of greater than 500.

Since IVRT response to oxygen (or anything else) always returns to baseline, this suggests that IVRT is buffered.

Since 1/IVRT is proportional to the free energy, and since free energy is equal to this equation, you can examine which of these elements – G and H and T and S.

The only one that is likely to be buffered is the entropy or chaos of the system, which is driven by oxidative stress.

You have to buffer the oxidative stress. If you don’t, you’re going to die. These people will always buffer it.

It’s just that they take time to do it.



Here are some of the complications of this systolic compensation mechanism.

We see PFO’s in 89% of 60 consecutive patients using (?) standard studies, which is the gold standard for this.

You might expect this number to be something around 27 or 28%. So these patients have the highest rate of PFO reported in any other illness. The mechanism, I’ll go over in a second.

They also have CCSVI – chronic cerebrospinal venous insufficiency. This is flow reversal back and forth of the deep cerebral veins, in 100% of cases. That’s going to destroy capillary function in the central nervous system.

We have tested about 20 to date. We do not not see this.

And then we have chronic hepatic venous insufficiency. That should be an H, not an S – CHVI.

That is also seen in 100%. We’re up to 20 patients now.

This brain flow reversal in the capillary bed and the hepatic flow reversal in the liver is a complication of right ventricular squeeze compensating for diastolic dysfunction.

It is probably the most serious complication I’ve ever found in chronic fatigue syndrome.

It will destroy effective capillary function in the brain and in the liver.

The results are catastrophic, because if you don’t have proper capillary flow in the brain, you neither deliver sufficient oxygen and nutrients to the brain, nor do you remove toxins from the brain.

With the liver, you just knock out important liver function ranging from detoxification – which will put you at risk for food sensitivities and drug sensitivities. And you will create xenobiotic toxicity from all kinds of things.

And worst of all, it’s your center of gravity for redox control. The primary redox control center, particularly for NAPDH production, is in the liver. And that’s going to be impaired.



This is an example of a PFO. This is a patient in which we injected saline bubbles – these are small air bubbles – into the vein.

They quickly (?) the entire right side of the heart. Because there’s a hole right here, those bubbles pass through to the left atrium, and then when the mitral valve opens, all the bubbles appear on the left side.

These bubbles, of course, go right out the aorta and right into the central nervous system. They can be responsible for migraine and also mini-strokes.

Again, we find this in almost 90% of chronic fatigue syndrome.


The cause of this is that left atrial cavitation.

In the left atrium, when they stand up, it collapses. There’s a pressure differential created across that foramen ovale, and it blows it open, creating this hole again.

It was present when you were born in the utero. It closes off in about 75% of cases.

In the rebound filling on the recoil of this massive ejection fraction in the left ventricle, as it squeezes really hard and then pops back off its rebound, it sucks blood right out of the left atrium, causing a pressure drop that blows right through the PFO.

That leads to migraines, poor altitude tolerance, mini-strokes and UBO’s.





This is where CHVI most likely comes from.

Because of the big squeeze, you get a very high tricuspid regurgitant flow. It’s passing from the right ventricle through the tricuspid valve going in the opposite direction of venous return.

This pressure pulse – in this case, it’s almost 30 millimeters of mercury, which is pretty high – that pressure pulse going in the opposite direction meets a return blood flow that’s actually low because of the (?) output. And the pressure is actually low.

Therefore the return pressure meeting a high pressure pulse going in the opposite direction – you have potential to reverse the flow of blood.


And that’s what you see over here. This is one of the early pictures we saw. That red splash is a flow reversal in the hepatic vein.

What you see in the hepatic vein is blue-red, blue-red, blue-red. That is the doppler shifting.

It’s supposed to be blue when the blood’s moving toward the heart, and it’s red when the blood is moving from the heart to the liver.

That’s called hepatic reflux.

That is not normal. It is never normal.

And it is unbelievably seen in 100% of my cases.

The cause of it is that big RV cavitation, to compensate for diastolic dysfunction.

And there is enough of a drop in output sufficient that the venous return is actually low.

So you have a low return coming back and a big powerful squeeze pushing blood the other way.

That will knock out effective liver capillary function.

And a lot of problems will ensue.



This is our first attempt to treat this. We’re using vasoactive intestinal peptide.

This was developed by Ritchie Shoemaker, who just recently published a paper on the use of nasal VIP, which I will go over in a second.

This is the TRmaxPG pre-treatment.

And in five minutes post, what we saw was a degradation of this TRmaxPG, which is a pressure pulse causing reversal flow.

It dropped by 8%, 22% and 38%, respectively, in three consecutive patients.

If you can drop out this pressure pulse, you can actually stop refluxing in the liver.

Because what VIP does, it’s a potent vasodilator in the vascular bed. So a squirt up your nose will cause the pulmonary vasculature to dilate, which means that when the right ventricle squeezes, blood goes out the pulmonary artery rather than back through the tricuspid valve.

You’re just reducing the pressure so that it moves in the right direction, and much less of it moves in the wrong direction, causing these big drop-offs in the TRmaxPG.


This is what they did to CHVI, or chronic hepatic venous insufficiency.

This is pre-VIP therapy. See this big red blotch right there? That’s a flow reversal.

If  you watch that in real time, it would be blue-red, blue-red, blue-red. I just stopped it when it was reversing.

Five minutes after nasal VIP treatment, we completely abolished it.

No more blue-red, blue-red. It’s just blue, blue, blue.

Very odd, very impressive and very encouraging, because to date, no one has had any idea of how one might actually reverse either CCSVI or CHVI, which can have tremendous clinical impacts in these patients.


So what is vasoactive intestinal peptide?

(Reads list.)

It’s responsible for circadian rhythm, which means that low VIP – which has been found in CFS patients – will cause day/night reversal in your sleep pattern. That is very common in this patient population. It will actually knock out appropriate sleep – which, by the way, would have a serious effect on fibromyalgia as well.

Maybe low VIP is one of the reasons that we see reduced biliary ejection fractions in the gall bladders of almost every patient.

VIP is being looked at for chronic heart failure.

But most importantly, VIP is a potent pulmonary vasodilator. It’s FDA approved for that.

If you dilate the pulmonary vascular bed, you will promote forward flow and stop flow reversal.

We think that is the primary mechanism and it certainly explains why it does it so quickly.


This is Dr. Shoemaker’s paper, which is going to be an important one. He just published this, this week actually.

Using nasal VIP in 20 patients with what he calls chronic inflammatory response syndrome related to water-damaged buildings, because he’s a mold expert.

By the way, there is no clinical difference between CIRS-WDB and chronic fatigue syndrome. We trade patients. I get his patients that he can’t seem to fix with the mold, and he gets some of my patients, because I can’t seem to fix them, because maybe they have mold. So we keep trading patients. And we can’t tell the difference between them.

This 18-month therapy with nasal VIP corrected numerous inflammatory biomarkers and numerous hormone derangements.

This is important right here – reduced pulmonary artery systolic pressure.

It increased T regulatory cells – which means it tends to reduce some of the pro-inflammatory aspects at the core of this disease.

No doubt, if you can reverse flow reversal in the brain and liver, you will get better.


CCSVI & CHVI Physiology

This is what we think the physiology of both CCSVI and CHVI is.

Again, due to diastolic dysfunction, the primary compensation mechanism is a big RV squeeze.

Of course, there’s an LV squeeze too.

You see ejection fractions commonly of 80% in these people.

If you squeeze really, really hard, then this little tricuspid valve, which is tethered by weak (?) muscles, will give way.

And when it gives way, a jet of blood from this squeezing right ventricle will shoot into the right atrium, will shoot right up the vena cava, and if the return is low, will create flow reversal.

In the case of the inferior vena cava, you get blood flowing down into the liver, and cause flow reversal.

I have observed a respiratory component. When they inhale, you get greater return and we see the flow reversal stop, because there’s not blood coming back that can’t be reversed. And then on the exhalation, there’s much lower return, and that’s when we see the red flash. Which physiologically makes sense.

All of this is caused by diastolic dysfunction, and the diastolic dysfunction is caused by an energy defect.

And the energy defect is caused by redox impairment.

And we do not know what causes redox impairment.

It’s like an onion. You keep peeling away the layers.

We can get down to the basis of it, as far as we can go. But we don’t know what causes this loss of redox control.



Are viruses linked to chronic fatigue syndrome?  Yes, they are.

The first observation of a viral link was made in Lake Tahoe, during the Ampligen investigations. It was found in this antiviral pathway which degrades viral RNA.

It was extremely activated in all patients with chronic fatigue syndrome in the Lake Tahoe region, during at least the early phases of their illness.

The findings of this strongly suggest some sort of viral insult, at least in the beginning.


This is some of the data. I’m not going to explain this except to say that this is proof of the tremendous activation of this pathway in these patients.


When we sent blood to NIH, what we found was that the patient population was affected by what was then thought to be a novel virus called HHV6. We thought it might be the cause of this disease.

But they we found that this virus is found in all humans in the first year of life.

In the second year of life, we call it roseola.

But then it was discovered there are two strains – an A strain and a B strain.

The B strain is a typical cause of infantile roseola.

The A strain has been primarily linked to HIV. It is easily cultured out of HIV patients and was easily cultured out of my patients in the Lake Tahoe region.

This could have been the cause of the high Rnase-L activity in the Lake Tahoe region.


This is what HHV6A can do.

Using a cell line, if you put patients’ blood in with it, it will form these big giant cells, which explode with hundreds of virions of HHV6. This was found in about 85% of cases of chronic fatigue syndrome patients in the Lake Tahoe region.


The primary infection is usually with the B strain. But the A strain is associated with AIDS, MS and chronic fatigue syndrome.

It can persist your entire life in various tissues.

It can also integrate genomically into human DNA and become part of your DNA, which is not a good thing to happen and may be a problem in some of our patients.


Other viruses linked to this disease have been the Epstein Barr virus, which causes primary infectious mono.

It persists in a number of tissues and can also have genomic integration.

Both EBV and HHV6 are capable of activating human endogenous retroviruses.


Retroviral associations have been long and interesting.

First described by Elaine De Freitas in her study in 1992. Her studies, however, were not replicated by others and subsequently were relegated to possibly some error in her technique.

Then there was Judy Mikovits finding another piece of evidence of retroviral infection. It also could not be reproduced by others. Although her study is probably a little stronger than De Freitas’s.

There’s a suggestion of retroviral infection but it’s somewhat unknown as to what retrovirus it might be, because no pathogen was ever isolated.

Most recently, published just a month or two ago, is a study by Kenny de Meirleir.


This is an example from this paper. These are biopsies of the duodenum. And these cells that are lighting up in red are dendritic cells by subsequent probing of membrane markers for dendritic cells, which are antigen processing cells in the duodenum.

What you’re seeing in this red is different types of reactivity to antibodies raised in mice or other animals against human endogenous retroviruses, different ones. And they’re lighting up. There was no lighting up among the controls, which are along the bottom.

What’s important about this is that maybe there’s activation of human endogenous retroviruses in these patients. And that could explain the flirtationthat we’re seeing with evidence of  retroviral infection.

It may not be an external retrovirus, but rather an internal retrovirus integrated into the human DNA.

8% of your DNA has retroviral inserts dating back from millions and millions of years.

What’s important about this is they used envelope proteins proteins.

Retroviral envelope proteins tame nagalase activity. Nagalase activity will make your immune system incompetent.

The treatment for nagalase elevation is GcMAF.

When we saw elements of nagalase activity – by the way, that was one of the things that so confused us. We were looking around with a hostile retrovirus infection. We know that retrovirus envelope produces nagalase activity. All these patients have nagalase activity. But we can’t find the retrovirus.

But HERVs – human endogenous retroviruses – when expressed make envelope protein.

It could be that the nagalase activity is coming from the human endogenous retrovirus activity.

So we decided to try GcMAF therapy, based on this observation of nagalase.


GcMAF Therapy

Natalase is an enzyme activity in the blood that destroys the precursor for GcMAF.

GcMAF is very important for immunocompetence.

So you can imagine which diseases have nagalase activity.

The disease with the highest nagalase activity is a retroviral disease called AIDS.

AIDS patients have the highest nagalase activity because they have because they have highly expressed HIV envelope protein, which carries the nagalase activity.

The next highest nagalase activity is in cancer patients. Most cancer patients, if not all cancer patients, have nagalase activity.

Nagalase activity may, in fact, produce immunoincompetence, which is why cancer patients don’t survive.

What survival requires is not only getting the core cancer but also bringing back immune competence.

If nagalase is elevated, they will never have immune competence, and it will probably be incurable if you don’t get the primary cancer.

So our patients’ nagalase activity averages that of a cancer patient, approximately 3.5.

We also found that if you plotted the clinical severity, where 100 is normal and 30 is intensive care unit, you’ll notice that there’s kind of a regression line. The higher the nagalase gets, the sicker the patients are.

By the way, similar to HIV. You see this same kind of regression curve in HIV.

We’re really very excited about this, because by using GcMAF – which is known to to knock out nagalase – we might be able to restore immune competence to our patients.



GcMAF is part of the Vitamin D access.

At dinner I had a discussion with a physician who’s interested in Vitamin D metabolism.

It turns out that Gc protein and GcMAF and Vitamin D are all integrated in a very complicated and very regulated access called Vitamin D access.

Activated T-cells and B-cells tend to deglycosylate the Vitamin D binding protein producing GcMAF, which is necessary for immunocompetence.




We found that there were indicators of who would response based on calcitriol response.

Calcitriol is a very powerful hormone. Vitamin D is converted into calcitriol by different cell types.

We found that if the calcitriol was either high or low, and moved to the mid range, those were responders.

But if the calcitriol stayed low or stayed high, they were non-responders.

Vitamin D made no difference. Only the active form of Vitamin D seemed to predict response.

It wasn’t the pre-treatment with the calcitrol. It was the predicted response.


GcMAF Assessment

This is the clinical assessment we used.



We also so a degradation of nagalase activity, which was nice to see.

Not impressively so, in the case of chemical GcMAF, but it did drop.


This is the calcitrol.

The best responders are in white. You’ll notice that they tended to rise from low values to medium values.

Non-responders tended to remain the same, to not respond.

Non-responders tended to be somewhat high sometimes, but to move toward the middle.

I don’t understand the reason for this, but this seemed to be a characteristic of response and non-response – how the Vitamin D axis responded to GcMAF.


This is just a summary of those findings I mentioned earlier.


Probiotic GcMAF

Then we decided to turn to another type of GcMAF, using probiotic GcMAF.

This is not made in a laboratory from human gammaglobulin, but made with yogurt and kefir.

This was developed by Marco Ruggiero and his wife at the University of Florence.

They came all the way over because they had developed this probiotic form of GcMAF.

This is the Gc protein, which is a Vitamin D protein, which has three sugar molecules.

And you can progressively lop off one sugar molecule, and then lop off the second sugar molecule, leaving a final one.

You’ve converted Gc protein to GcMAF.

The enzymes that do this are interestingly present in in probiotics, which was discovered by Ruggiero.

So he figured out which type of probiotic would produce this kind of deglycosolation.

He found a yogurt that he designed that would lop off one sugar, and a kefir that he designed that would lop off the other sugar.

So we will have the patients make a yogurt with one group of ferment that he developed, and then make a kefir with another group of ferment that he developed, and then mix them together, and you get GcMAF in the probiotic.

His sense is that what happens in nature is that babies suckle on colostrum when they’re born. Colostrum is incredibly rich in Gc protein. In fact, the richest source of Gc protein in nature is in colostrum. So the baby suckles on colostrum, and it goes down into its GI tract, where the microorganisms called the microbiome. And those microorganisms can selectively deglycosolate the Gc protein. And the baby forms GcMAF in its little gut, and the GcMAF gains for it immunocompetence during its first days or weeks of life, preventing illness and sickness and death in infants from dysentery.


That’s how Dr. Ruggiero worked backwards. He said, “Nature has already designed this, so I’ll just redesign what nature has used to make GcMAF and I’ll give it to chronic fatigue syndrome patients.”

So basically over on the left side is the yogurt that we made from fresh milk. It contains a ferment capable of lopping off one sugar molecule from Gc protein.

And this is the kefir made with a different ferment capable of lopping off the second sugar. And the two combined wind up producing GcMAF in essentially a probiotic mixture of yogurt.

We pretty much set up the same experiment with this that we did with the chemical.

What we observed was that this study was much more potent and much more powerful in improving clinical status in our patients than the chemical GcMAF.

In some ways it’s more potent, and it’s also more natural.

The target turns out to be largely the cells in the gut that refer to the dendritic cells that have the infection with HERV’s. Maybe that’s why it works so well, because you put this right where the biggest problem is, in the gut.


We pretty much found the same thing as with the chemical. Although we did not find a VDR polymorphism that predicted success. It didn’t matter what their VDR polymorphism was. They would respond.



Calcitrol also was somewhat predictive similar to the chemical GcMAF.

When the calcitrol was low and went to normal, or was high and went to normal, they tended to respond. And if it stayed low or if it stayed high, they tended to not respond.

So it’s almost as if, if their Vitamin D axis would regulate, they were responders.

If it didn’t regulate, they were non-responders.


We also looked at another parameter. We looked at urinary thiosulfates, which measures the degree of GI tract toxicity.


This is calcitrol. It’s not quite so striking as for the chemical, but the trend is there.

The best responders tend to go from low to high.

The non-responders tend to stay low.

The moderate responders tend to go from high to medium.


There was a dramatic impact on nagalase. Much stronger drop-out of nagalase.

From an average of 3.34 almost back to normal with the probiotic GcMAF.


This is the urinary thiosulfates, which indicate levels of toxicity in the gut.

It makes sense if you use a powerful probiotic, you might improve the microbiome and reduce gut toxicity.

We saw this very significantly in these patients.


Again we used the same kind of clinical interrogation.

Higher numbers mean you are getting better, and lower numbers mean you are getting worse.


In the probiotic GcMAF study, we saw fairly similar results, but perhaps a little better in terms of the significant response.

Almost 50% has significant response.

About 28% had a modest response.

About 23% failed to respond or even got worse, especially if their calcitrol or Vitamin D access didn’t respond.


The final slide is really a presentation of what I’ve learned about GcMAF therapy.

If you take people with high nagalase activity, who are pretty sick, and you treat them with GcMAF, you will drop nagalase.

It will drop from high to slightly elevated to low.

And this decline corresponds – as they drop from high when they’re sick to medium, they get significantly better.

If you keep treating them, and drive this nagalase to slightly elevated, they will turn around and get significantly worse.

That is the take-home message of GcMAF therapy.

It suggests to me that the nagalase activity may be regulating something, and when it’s too high, you don’t have an immune system, and when it’s too low, your immune system is way too active.

And when it’s sort of in the middle, your immune system is working the best.

What we do now is that we don’t even treat anybody with GcMAF unless their nagalase level is above 3. That’s in the cancer range.

And it will drop it into the 1.5 range.  It does never not drop it into the 1.5 range.

And then we take them off.  Because if you keep them on it, then it will keep dropping. And when they drop into this lower range, it’s like their entire immune system blows up. Which suggests that this nagalase can be acting as a regulator.

Again, since nagalase activity may be an envelope protein from a human endogenous retrovirus sequences, it is known that human endogenous retroviruses participate in immune regulation.

As a matter of fact, they’re responsible for pregnancy, in the sense that the females use them as downregulators during pregnancy to prevent attacking the fetus.

It’s possible that what we’re actually watching is the regulation of the human endogenous retrovirus sequences in envelope protein expression.

Treating high is good, but you need to stop right here, or it will get worse. That is the take-home message for GcMAF.

And that’s it.






Q: For the treatment with the probiotics, do you treat for a while and then take people off of it? 

It’s fine to use probiotics in general, to improve gut function and improve microbiome toxicity. We’ve been using probiotics for twenty years.

This is a special probiotic designed by a professor in Italy to create GcMAF out of colostrum Gc protein.

What that does – it’s a whole magnitude of order different than probiotics, because you’re actually regulating the immune system, particularly in the gut, where 80% of the immune system lies.

What we’re using the probiotic GcMAF to do is to downregulate high nagalase activity.

That’s what we’re using it for. Because if someone has a high nagalase activity, they’re incapable of controlling viruses and bugs and bacteria and parasites. The immune system is incompetent.

It’s also incapable of killing cancer cells.

So we use probiotic GcMAF to bring the nagalase down into slightly elevated levels, because if we bring it down to the normal range, or even low, it blew up.

So when we get them down to the slightly elevated level, we pull them off.

We may continue to use probiotics, but not this probiotic.

This is a special probiotic. This is not something you get at the grocery store.


Q: Which lab do you use to test the nagalase? 

It’s tested at a laboratory that used to be called Vitamin Diagnostics Laboratory in South Amboy, NJ. It has a different name now, but it’s connected with the European Laboratory of Nutrition.

The director at this laboratory is a professor at NYU. A wonderful, wonderful man. A brilliant scientist. The top scientist at Johnson & Johnson for twenty years. He finally got burned out in corporate America and became a professor at NYU in biochemistry.

He has developed a lot of the tests at this laboratory that we have most enjoyed employing. Because unlike a lot of laboratory pathologists and biochemists, he’s really a scientist at heart, and he’s a very good one.

So we do a lot of testing in that laboratory. We do a lot of SOD testing, GPX testing, methylation block testing, NAPDH testing, SOD/GPX/catalase, nagalase activity. They’re very good.

(Editor’s Note: The current name of the laboratory is Health Diagnostics and Research Institute.)


Q: Can you tell us when GcMAF will be available? 

GcMAF is available from Europe now. You can actually go on the Internet and buy GcMAF in the UK. You can buy it from the Netherlands. You can buy it from Israel. You can buy it from a lot of places, but you can’t buy it from the United States.

That’s problematic because physicians are not allowed to administer GcMAF. So you sort of have to get it yourself.

But there are some loopholes that allow physicians to follow patients who choose to use it.

We have sort of gotten away from chemical GcMAF, because probiotic GcMAF, I think, is better.

It’s more natural. You’re not using a blood product. You don’t depend on some laboratory in Europe.

You just mix up yogurt and kefir in your own kitchen.

It’s cheaper and works better.

You can purchase the ferment for this special yogurt. You can purchase the ferment for this special kefir.

It’s from an online source developed by Dr. Ruggiero from Italy.

I have nothing to do with this. He just set it up independently with health doctors interested in using probiotic GcMAF of all stripes. There are physicians at cancer clinics that are integrating it into their cancer therapy. There are clinics that have integrated it into HIV therapy. There are clinics such as mine that are integrating it into chronic fatigue syndrome.

The danger of this, as I mentioned, is that you have to be very careful with this.

If nagalase is high, you can defend using it for a time. As nagalase starts to come down to the slightly elevated range, you need to get off of it.

If you keep dropping nagalase all the way into the low level, you will typically see reversal of chronic response. People start getting sicker.


Q: An average person cannot afford your fees. Why is that? 

The problem with chronic fatigue syndrome patients is that they take hours and hours and hours of meeting and dealing with them.

You might ask how many patients I see a day.

I see one patient per day, and I see them almost all day long.

So what happens when you see a physician who spends almost the entire day with you, I have to load the costs of the clinic onto your shoulders.

I can’t see 30 or 40 people. If I could, the expense would be low to you, but you would get exactly nothing.

That’s the reason.

If you think about it – I went to my dermatologist recently. I calculated that he was charging me $3000 per hours.

I don’t charge anything like that. I’m pretty modest on an hourly basis. But I spend three or four or five hours with you. And I only charge for my time. I don’t charge for anything else except what’s between my ears.

And when you leave, I don’t charge you any more. I order very few tests. People don’t walk into my clinic and spent $15,000 on tests. I don’t do that.

When we did a cost analysis of what we do, I think we’re relatively inexpensive when amortized over an entire year. Because you see us for four or five hours per year, and that’s about it.

Most people are seen once a year. Sometimes we’ll have a short phone call. Sometimes a short email for contact, but they’re generally seen annually.

If you amortize my hourly costs for three or four hours times one year, we’re really cheap.


Q: How can I tell if I have chronic fatigue syndrome vs. fibromyalgia? If I go to see my grandchildren, which is a fun activity, it may take me a week to get over that. 

Then you have chronic fatigue syndrome.

I don’t spend too much time trying to determine what  you have, other than listening to see if you sound like a chronic fatigue syndrome patient, with or without complicating fibromyalgia.

The best treatment for fibromyalgia in chronic fatigue syndrome is to address the sleep disturbance. It is the absolutely best way to address fibromyalgia in this illness.

Now, that is  not easy. Sleep disturbance is a big deal in chronic fatigue syndrome.

It could be the refluxing of these cerebral vessels has a great deal to do with the sleep disturbance.

But we learned right away that if we can’t get our patients to sleep well, nothing else will help. Especially the fibromyalgia gets worse.

Magnesium is also wonderful for fibromyalgia.

So there are a couple of things that we do that are inherent to the treatment of chronic fatigue syndrome that, quite frankly, makes fibromyalgia not a big deal.

It stops being a complicating factor after a while.


Q: Why don’t other clinicians believe that this is real? 

Usually they don’t know much about it. It’s a shame that they will pontificate an opinion when they haven’t studied the subject.

I see a lot of physicians at the scientific meetings that I go to all over the world. Literally hundreds of physicians are in the audience, and they all believe in this disease. Because they’re studying it.

The only time I see physicians who don’t believe it exists or who pontificate about it or give an opinion about it – you don’t have to drill down too far to find out that they know absolutely nothing about it.

So I wouldn’t worry about that too much. It doesn’t bother me, and it shouldn’t bother you.

If they don’t know anything about it, then I don’t know they should give an opinion about something that they don’t know and study.

That is not true of the physicians that I know of.


Q: Who should come to your clinic? People with chronic fatigue syndrome or fibromyalgia?

I’ve seen both. We see people from all over the world.

Fibromyalgia is really easy to treat, in my opinion. As time has gone on, it’s become a smaller and smaller fraction of my practice.

I don’t know if it’s because I’m selecting out CFS patients and deselecting fibromyalgia, or whether – which I think is more likely – fibromyalgia patients tend to get better, a lot of them. They don’t get super-sick. I tend to see the super-sick people.

Also, therapeutic approaches tend to work pretty well in fibromyalgia. So after a while, I’m not really dealing with that particular problem.

I don’t worry too much about the name. I do kind of listen for the drumbeat. “My brain isn’t working like it used to and I have these processing difficulties. And when I push myself, I crash and burn.” That’s all I need to hear.

Whether they have fibromyalgia or not, that makes no difference to me. Because at that point, we’re dealing with chronic fatigue syndrome patients, with or without fibromyalgia.

Personally, if I see someone who says, “I don’t sleep very well, I’m fatigued a lot and I hurt, but my brain is perfect, and when I have to go to work, I can, and I don’t crash and burn,” that’s not chronic fatigue syndrome. That’s just fibromyalgia. And that’s a much easier thing to treat.


Q: Where does Lyme disease fit into this whole picture? 

Very nice question. I’m not exactly sure on Lyme, but I’ll give you an idea. It’s not necessarily the idea, but it’s an idea.

I met some Lyme doctors who belong to an email listserv – about 80 clinicians from four continents. Quite a few of them are Lyme experts, and some of them are the best Lyme disease doctors in the world.

One of them, who I respect the most, a physician in Long Island, who actually was one of the people who described chronic Lyme disease initially – I was talking to him, and he told me that he saw acute Lyme disease in the Long Island area for a decade, between 1970 and 1980.

People would get a tick bite, they would get a bull’s eye rash, they would get arthritis. He’d put them on doxycyline, and they would get over it.

Sometimes they would get a tick bite, and they would get a bull’s eye rash, they would get arthritis, and they weren’t even treated, and they would get over it.

He said that was the way it was for a decade, for ten years.

This is important.

He said, “I never saw a single case of chronic Lyme disease between 1970 and 1980. Not one.”

Then, in 1980, which is when the CFS epidemic seems to have erupted in the major cities of San Francisco and New York City, he began to see people get a tick bite and a bull’s eye rash and acute Lyme, but he treated them and they did not get better. And they went on to develop what he called chronic Lyme disease.

Studies at NYU and SUNY comparing classic Lyme cases to classic CFS cannot find any clinical difference between them.

Furthermore, the P41 band important in the diagnosis of Western blot of Lyme disease, is also the early antigen of HHV6.

It’s also the envelope protein of the HERV that I just showed you.

So if you remove the P41 band from counting, very few people will ever meet the diagnosis of chronic Lyme disease.

So I have a feeling that while Borrelia may be involved in some people, I have a feeling that chronic Lyme and chronic fatigue syndrome are exactly the same thing.

That’s my opinion.

Of course, I have a skewed view of this, because you understand that I’m the one who sees chronic Lyme patients who went to numerous Lyme doctors and have been treated for years and years with potent multispectrum antibiotics and failed therapy.

And they end up at my door. And when I look at them with all this technology, they have chronic fatigue syndrome.

While I’d hesitate to say that Lyme doesn’t exist – I think it does, it causes acute disease.

But I’m not sure that it causes chronic illness. Because it never did.


Q: Can people have the push/crash syndrome without having chronic fatigue syndrome?

There are a lot of diseases that have chronic fatigue. In fact, most chronic illnesses have an element of chronic fatigue.

But often in those diseases, people push through it.

My patients will do minimal effort, like just walking across the room. Or they’ll fix dinner and will have stood too long. And then they’re wiped out for days, just doing this minimal effort.

I don’t know of another disease that looks quite like that and that also demonstrates severe cognitive derangement and abnormal neurological findings and has some of these other features that I’ve been talking about.

You can probably find someone who has push/crash phenomena for some reason and may not have chronic fatigue syndrome.

But that is so characteristic of this disease that if you add in the other elements – the cognitive complaints and the neurological findings – that’s chronic fatigue syndrome.

And I’m pretty confident of that.


Q: How do you decide whether exercise is a good idea in this disease? 

One advice that I have is do not rationalize exercise.

The rationalization of exercise goes something like this.

I’m going to get up and I’m going to walk a mile on Monday, and then two miles on Wednesday, and then three miles….that’s called rationalization of an exercise program.

That doesn’t work in this illness.

What seems to work is, I’m going to walk around the house today, and then answer the question the next day and the next day whether I did okay.

And if I did, then maybe I’ll advance a little bit. And then ask the question, Am I all right?

Sometimes it’s not quite evident whether you overdid it or didn’t at the time.

But you kind of begin to internalize a sense of self.

“I think this is helping me at some deep level.”

You almost intuit

When you start going from your brain thinking about exercise to feeling what it’s doing, then you start to exercise correctly.

There are several good exercises for this disease.

The best exercise that I know of that’s simple and inexpensive is simply to walk. Walking on flat ground.

Try to do it every day if you can, but  not too far. As much as you can, but don’t overdo it.

The human being is designed to walk very efficiently. And when we walk, our legs are squeezing blood, so we actually pump blood back up, so you actually fill the heart.

So people do pretty well when they walk. They don’t have to walk fast – just walk. That’s very good for this disease.

Pilates is excellent for this disease. Because you are in a supine position – remember, your cardiac output goes up 30% when you’re lying down. And just do gentle types of exercise.

The important thing about Pilates is to not get into the vertical position. There are vertical exercises in Pilates that are not good.

Resistance is pretty good, but do not use the heavy weights, just use the light ones for range of motion. Use light resistance for short periods of time. That seems to be good.

Another one is vertical immersion in water. People will just stand in water to their neck.

Believe if or not, the pressure in your body goes down as a square of the depth. So the further down you go, the pressure differential pushes blood back up into the intravascular space and improves lymphatic drainage.

That’s excellent for chronic fatigue syndrome. They don’t have to do very much. They just have to float or stand vertically for an average of 20 to 40 minutes, three times a week. That’s one of the best things that I’ve done.

I think the mobilization of lymphatic fluid is an immune modulator for these patients.

It’s functionally difficult sometimes for these patients to get to the pool. It’s physically difficult, or the water temperature isn’t right. So walking and Pilates.

What’s not good is running or bicycling or significant aerobic activity. That’s not good for these people. They don’t fare well.

Resistance training is a little better tolerated, if there is not too much of it.

So don’t be rational in exercise. Be intuitive in exercise.

Don’t overdo it. But do something.


Q: What if I’m cold all the time? How is that with the thyroid? 

Very good question. The thyroid’s interesting.

You remember how I talked about how the body adapts to a low-energy state?

It has to, because if it tries to stay at a high-energy state, it generates too much oxidative stress, which is deadly. So it adapts to a low-energy state.

How do you think the body creates a low metabolic rate?

The answer is that it downregulates thyroid function.

So the lowered thyroid function – get this – is not the problem. It’s the solution.

The way that you can tell is – if you look at the TSH level, which comes from the brain, it’s generally very low. It’s down around 0.

Then you’ll see low thyroid hormone in the body, but you’ll see a low TSH.

That’s the body downregulating to a low metabolic rate. That’s not thyroid disease.

So what we find is – we’re very careful about treating thyroid. I try to resist treating thyroid.

I try to look to see if they are really hypothyroid, as indicated by a high TSH, we you almost never see, or whether they’re downregulated to a low metabolic rate.

Admittedly, that’s going to produce stuff like being cold, because that’s what it’s like to be at a low metabolic rate.

But you may think about how we treat heart attacks and strokes these days.

What do we do? We pack them in ice.

If we do that, we produce less damage.

It may be that what you are doing is downregulating to a low energy state to save your life.

That is manifested by a low metabolic rate and feeling cold, but it is, believe me, not your problem.

Exceptions do occur. If your TSH is 30, then yes, you need to be treated with thyroid.

But if it’s 0, I would never touch you with thyroid, even if you were hypothyroid.


Q: So should I be on medication or not? 

I’m not your doctor, I have no idea.

There’s a larger story with this disease.

Physicians are taught to draw blood and react to it.

So what we think is that if someone’s blood is out of range, that’s bad, and we need to bring it in range.

Never do we think that sometimes blood is out of range for a reason for that person. The body is adapting to some deeper issue.

I’ve seen this in chronic fatigue syndrome over and over and over. I try not to react to blood tests. Because often those blood tests are simply compensatory mechanisms at work, and if you try to address that, you can make them worse, not better.

So that’s worked a lot better than to hack abnormal blood tests.

Admittedly, I do this in the context of chronic fatigue syndrome. Not in the context of some other diseases where you might legitimately react to blood tests.

Because I believe these people, typically, they go for decades relatively stable. They don’t die en masse. They don’t degenerate en masse. When they die, you autopsy them and the autopsy is normal.

So they seem to be compensating, compensating, compensating.

So why should I intervene with a lab test which may be part of their compensation scheme?

And that’s especially true with thyroid.


Q: How should I use magnesium?

Magnesium is probably the simplest, cheapest and the best thing for these patients.

It’s available in different forms.

It’s available from Kirkman’s Laboratory as a paste. It’s excellent. You just dip your fingers in the paste and rub it on your arm. You’re getting magnesium in your body in very short order. It’s relatively inexpensive.

I have people take the bottle with the paste and put it behind their pillow or on their bedrest. If they wake up in the middle of the night, they’ll just reach back, open it up, dip their finger in, and rub the paste on their forehead or the back of their neck, and then they’ll fall right back asleep.

If they hurt somewhere, they just rub it into where they hurt.

It’s very inexpensive and works very well.

But it doesn’t last very long. It may only last for a few hours.

There are also sprays that you can spray under your tongue. That’s excellent, especially for panic attacks and anxiety disorders and muscle cramps.

And finally, probably the most effective of all is an injection. I teach my patients to self-inject 0.1 cc of magnesium sulfate in the leg. They can do it once or twice or thrice a day. That’s a very tiny injection and that lasts for about 4 to 6 hours.

There’s no way you can overdose on this, unless you have renal disease. Because you are leaking magnesium out constantly from the cell and pissing it out in the urine. And you can’t correct it because it’s not a nutritional problem. It’s an energy-related phenomenon.

All you can do is try to keep up with the losses on a very regular and consistent basis.


Q: When would you recommend that a patient get a second opinion if they aren’t getting any better? 

It’s ultimately the patient’s decision about whether the doctor’s doing all that he can to help.

If he’s not helping, he may be missing something.

It may be a treatment-resistant case. They do occur. And no matter who you went to, they wouldn’t do much better.

I fail also. I have patients who don’t respond.

What I try to do is that I don’t give up on them. We just keep trying different approaches.

My sense is that as long as I’m trying as hard as I can, and I don’t give up on them, then they’re happy even though they may not be responding.

When you get a sense that the physician just doesn’t really care any more or can’t think of anything or would rather that you not come, that’s the time to move on.


There is not enough money being spent on this disease. Is there other research that is going on? 

There is other research going on in the  U.S.

One large grant was just given to Dr. Shungu at Cornell Weill based on his MSRI scan work. He’s collaborating with a number of clinics in the New York City area.

That could be a very important group that’s emerging. I can’t remember how many millions of dollars they were given, just recently.

That’s going to be an area to watch in New York City.

There are probably other areas as well.

But you’re right, the research dollars spent on chronic fatigue syndrome does not match the severity of this problem and the numbers that are afflicted and the economic cost.

It’s just simply – it doesn’t get the respect of what the disease is. And there’s a long and complicated history behind that.


Is the nagalase test or other tests you recommend reimbursed by anybody or are they a research project? 

There are some tests that are compensated, especially the tests done at the major labs like Lab Corp and Quest, which there are some tests done there.

But what I found is that these specialty laboratories that specialize in niche lab work, usually insurance doesn’t cover that.

The good news is that the cost for a nagalase test is $65. So a lot of these tests are not terribly expensive.


My daughter was diagnosed with chronic fatigue at age 14. How would I have her tested for ventricular lactate?

I would have that done at Cornell Weill medical center on the east side of Manhattan by Dr. Shingu.

He is a wonderful scientist. He’s from Nigeria.

He is wonderful and really believes in this disease and has been doing MRSI scans on the brains of CFIDS patients since 2005. So a period of eight years.

And he got the largest grant from NIH to do this work of anyone I know of.

I only send patients to him. I don’t send patients to anyone else.

And by the way, they have a study going on, and if you’re willing to be in the study, they’ll do the MRSI for free.


Do you have anything to add about teenagers?

There are two vulnerable periods in chronic fatigue syndrome.

One’s around puberty. Young girls are particularly vulnerable. Sometimes boys as well. So around puberty is when  you’ll see this disease hit.

In the case of females, the hormonal shifts that occur in puberty are dragging the immune system up and down, up and down. So it tends to be pro-inflammatory.

So it tends to feed this disease and this vulnerability spike in terms of when people get this disease.

Another spike tends to occur for some reason in their 30’s. Often when people are just hitting their stride and are really working hard and their careers are blossoming, and they are at their peak physical condition, and then – wham.

I don’t see a lot of this disease develop in elderly populations. I don’t see a lot of it in children under the age of 10. There are physicians that do, but I don’t. So I can’t speak much to that.

But I do see spikes in the pubescent/teenager and then the adult. That’s where the spikes occur.

It falls off in the older crowd and it falls off in the children.

There probably is a good explanation for that. I mentioned one of them. But that’s just what we see.

Children, by the way, although they can be very very ill, their prognosis is much better than the adults. So often if the children are correctly treated, they do rather well, most of them.