CFS is a metabolic condition!

[Dr.Patient]

Hello everybody,

As a physician and a patient of CFS for the last 3 years, I have an opportunity to view this from both sides. I made some interesting observations with my illness, and my training has helped me to look at it deeply.

My theory is that CFS is a metabolic condition- not infectious, immunologic, neurologic, muscular, gastrointestinal etc. There is a fundamental abnormality in energy production and distribution- and this is the defect present in ALL patients. Other symptoms, present in some and not others, are secondary to this. Here is an explanation of this theory, in a copy of the email I sent to Dr. Ron Davis, who heads the CFS research center at Stanford.

Hello Dr. Davis,

Thank you for starting the CFS research center at Stanford. As a 44-yr old family physician who has been suffering with this for 3 years, the last two of them homebound, I am aware of both sides of the coin.

I was excited to see that your center will be working on microarray analysis to look for gene expressions in the mitochondrial genomes as well. I had been wondering if such research was being done at all, and I'm thrilled to see that you will be. Two common themes here, lack of energy and maternal transmission, both point towards mitochondria, and I'm positive you will find the culprits here!

My theory is that CFS is a disease of metabolism- since during periods of good energy, all my other symptoms like brain fog, headache, muscle pains, tremors, constipation, chemical sensitivities, photo and phono phobia, depression, anxiety, all disappear. I feel completely normal! But when my energy levels are low, they all come back like drinking buddies (of fatigue).

There are clearly anomalies of energy production ( low energy is the common denominator in ALL patients, regardless of their other symptoms); and also energy distribution (like the occasional boosts in energy; and the delayed build up of energy after an activity).

My suggestion is if you could please look into mitochondrial gene expressions by microarrays during such episodes of low and 'normal' energy states, you will hit the motherload!

This is clearly a syndrome, and all other systems affected are secondary to this metabolic abnormality, and in my opinion, looking at other systems infectious, immunologic, neurologic, gastrointestinal, etc, will not be of substantial benefit.

Please know that I will be available to help in any way I can in the research of my disabling condition!

Thank you!

 

[maddietod]

Could you explain how you are homebound, but also have periods "of good energy" and all of your symptoms disappear? I can't wrap my head around this description of CFS.

 

[Adster]

Could you explain how you are homebound, but also have periods "of good energy" and all of your symptoms disappear? I can't wrap my head around this description of CFS.

I thought lots of folks with a CFS/ME diagnosis had occasional periods of better functioning.

 

[maddietod]

I thought lots of folks with a CFS/ME diagnosis had occasional periods of better functioning.

Yes, but relapsing-remitting doesn't usually mean housebound - normal function - housebound etc. I've never heard of "all symptoms" disappearing. I'd like to know how to do that.

 

[SOC]

I thought lots of folks with a CFS/ME diagnosis had occasional periods of better functioning.

Better functioning usually doesn't mean all symptoms disappear. Since even mild ME/CFS, by definition, requires a 50% reduction in activity level, it is hard to imagine significant periods where all symptoms disappear unless the ME/CFS is very, very mild.

 

[alex3619]

My own modelling of CFS, from about 1997 to 2002, was based on CFS being metabolic. Indeed, the doctor who started me down this path was Dr. Andriya Martinovic, who thought it was due to hormonal (primarily immune) regulation issues. My model is obsolete, but it was based on science at the time. I was looking at mitochondrial defects, including oxygen dumping mechanisms, with a primary force being hypercriticemia.

There is no question there are deep and disabling metabolic issues. These things have causal pathways that run in circles though, making definitive causes hard to pin down. So it pays to remember the Isaac Asimov quote: "A circle has no end."

 

[Dr.Patient]

The 'normal' periods are may be a few to several hours (not every day, though) when I don't feel I have an illness. I feel like I have the energy to ride in a car. But invariably the bad periods set in, and I feel weak, and the other symptoms. This pattern is quite common in several patients.

 

[SOC]

@Dr.Patient,
Have you looked into dysautonomia as a cause of your symptoms? Have you done the 2-day CPET (or even the std CPET) yet to see if you have the abnormalities generally found in ME patients?

If ME is not infectious or immunological, how do you explain the immune abnormalities and multiple intracellular pathogens commonly found in well-characterized patients? Or are you referring to chronic fatigue, the symptom of many different disorders, rather than ME the WHO-designated neurological disease?

Have you read Myalgic encephalomyelitis: International Consensus Criteria aka the ICC definition? The abstract starts:

The label ‘chronic fatigue syndrome’ (CFS) has persisted for many years because of the lack of knowledge of the aetiological agents and the disease process. In view of more recent research and clinical experience that strongly point to widespread inflammation and multisystemic neuropathology, it is more appropriate and correct to use the term ‘myalgic encephalomyelitis’ (ME) because it indicates an underlying pathophysiology. It is also consistent with the neurological classification of ME in the World Health Organization’s International Classification of Diseases (ICD G93.3).

It goes on to say:

Myalgic encephalomyelitis is an acquired neurological disease with complex global dysfunctions. Pathological dysregulation of the nervous, immune and endocrine systems, with impaired cellular energy metabolism and ion transport are prominent features. Although signs and symptoms are dynamically interactive and causally connected, the criteria are grouped by regions of pathophysiology to provide general focus.
 A patient will meet the criteria for postexertional neuroimmune exhaustion (A), at least one symptom from three neurological impairment categories (B), at least one symptom from three immune/gastro-intestinal/genitourinary impairment categories (C), and at least one symptom from energy metabolism/transport impairments (D).

While there is general consensus that ME/CFS includes impairment of cellular energy metabolism, the idea the it is only a metabolic disorder is now largely outdated. The idea that ME/CFS is

not infectious, immunologic, neurologic, muscular, gastrointestinal etc.

has been largely overcome by research and expert clinical experience.

 

[alex3619]

My main point about causal circles is this. Everyone focuses on their little favourite bit. Yet ME could be metabolic, immune, neurological, hormonal or pathogenic ... or some of these, or even all of these. There is a failure in command and control systems, and when one such system is stuffed, they all tend to be.

Personally I still favour the enterovirus hypothesis. I also think though it might be many pathogens, several different disorders under the same umbrella terms (even ME) or that its an autoinflammatory disorder. Something is driving the metabolic issues. A novel pathogen might also to be to blame, but lets not forget that we keep discovering new hormones and new immunological processes. Science is not a done deal, its a work in progress.

One final point, weakly defined CFS (Fukuda, Oxford) is almost certainly many different disorders.

 

[Dr.Patient]

Thank you for that. Yes, I am familiar with the criteria. I have undergone the CPET, and in my case, that precipitated another relapse lasting a year now. Hence the need for a noninvasive diagnostic test. Research should be looking at the common denominator in all these patients first and foremost, and not at 'accessory' symptoms, which are not present in all patients, whether for creating a working definition, or a diagnostic test. In my opinion, even the treatment of all the symptoms of this condition will come about by treating the basic problem.

I am not stating that cfs is only a metabolic condition. The fundamental abnormality is metabolic, the cellular energy dysfunction. When it permeates other systems, these other symptoms appear. There are patients with different systems affected. There were periods in my life when I just had disabling fatigue, with none of the other symptoms.

Yes, I am standing in opposition to the very medical community I belong to. They,'ve got it wrong!

 

[Gingergrrl]

Thank you for that. Yes, I am familiar with the criteria. I have undergone the CPET, and in my case, that precipitated another relapse lasting a year now. Hence the need for a noninvasive diagnostic test. Research should be looking at the common denominator in all these patients first and foremost, and not at 'accessory' symptoms, which are not present in all patients, whether for creating a working definition, or a diagnostic test. In my opinion, even the treatment of all the symptoms of this condition will come about by treating the basic problem.

I am not stating that cfs is only a metabolic condition. The fundamental abnormality is metabolic, the cellular energy dysfunction. When it permeates other systems, these other symptoms appear. There are patients with different systems affected. There were periods in my life when I just had disabling fatigue, with none of the other symptoms.

Yes, I am standing in opposition to the very medical community I belong to. They,'ve got it wrong!

@Dr.Patient, I also understand what it is like to be on both sides of the coin as (I am not a doctor) but I am a licensed social worker and am no longer able to work in my career due to CFS. I considered CPET testing and made the initial phone calls but then my doctors did not think I was well enough and that it could trigger a relapse so I postponed. I am sorry to hear that your CPET testing triggered a year long relapse and I wish there was a non-invasive diagnostic test like you said.

I both agree and disagree with what you said as I do believe CFS is a metabolic disorder but I also feel it is an infectious disorder, an autonomic disorder and many components rolled into one. Although I had multiple triggers prior to getting CFS, in my case what pushed it over the edge was getting mono from EBV in 2012. This led to multiple autonomic issues including the systems that regulate my heartbeat, temperature, blood pressure, etc, none of which I had prior to mono. The tachycardia can be disabling for me and did not exist prior to mono so there has to be an infectious component IMO.

But I love your letter and so appreciate the advocacy and wish I could do more myself.

 

[brenda]

I agree with the Dr. and have also noted that my other symptoms are energy related. If the metabolism can be fixed then the immune system will function better and the infections will go and the various other expressions of the illness.

 

[heapsreal]

One way to work out if something is an issue or not is to treat it and see if there is a good response.
how does one effectively treat the metabolic dysfunction? Is it hormonal? Mitochondrial? Neurotransmitters?
Trying to think what else drives the metabolic rate and effects cellular metabolism?

I have tried the above with minor success. I had a lot more improvement treating infections and immune dysfunctions. Once I had the immune/infections mostly sorted, I seem to respond better to the things that affect the metabolic rate and cellular metabolism.

so for me infections were closer to being the driver of my cfsme than anything else I have tried. I'm sure there are others that are different too.

 

[lansbergen]

Did anyone consider ongoing cell danger response caused by an infection that is not cleared? The one I suspect accumulates. Cells usely can handle low dose with low frequency but high dose and high frequency are disastrous.

 

[ukxmrv]

Would metabolic "only" explain fatigue though?

My symptoms are viral and infectious (glands, swollen infected throat, flu like, sinus infections etc)

Does that fit into a metabolic model?

 

[Seven7]

@Dr.Patient I was the same in the first 3 years, periods of total energy and felt normal. I was a slow progressive case, I didn't feel any viral stuff until year 3 or so. Today I am what you would call remitting relapsing type. I have good days and I have bad days. SOme days I am house bound, and some I work full time and go about my life. As time goes by my good days are less.

I have treated the viral stuff and I feel better, but the lack of ability of produce energy on demand is my constant companion. I cannot seam to fix my broken aerobic system (I had the excercise test). My AT us 115BPM.

 

[Dr.Patient]

CFS is a multi-hit condition. The initial susceptibility ( bad genes) should be there. Not everybody who has EBV or gets the flu ends up with CFS. Next there should be a trigger- a virus, surgery, etc. Not all patients need this second trigger. There are many patients who have a slow onset CFS unrelated to any event.

The manifestations of this syndrome are several- as you all know. Because some patients have some systems affected, and some do not, should not confuse us as to the real culprit here- lack of ATP in all of us. There is no need for the medical community to confuse people as to - "We don't know what this is, it affects different patients differently"- instead, they should be focusing on what is common to all of them. Just like any other syndrome- lupus, MS, the manifestations are different in different patients. So what?

Different effects of a syndrome ( like Down's for eg) do not point to different causes of it. We should make sense out of chaos, not chaos out of sense.

 

[heapsreal]

CFS is a multi-hit condition. The initial susceptibility ( bad genes) should be there. Not everybody who has EBV or gets the flu ends up with CFS. Next there should be a trigger- a virus, surgery, etc. Not all patients need this second trigger. There are many patients who have a slow onset CFS unrelated to any event.

The manifestations of this syndrome are several- as you all know. Because some patients have some systems affected, and some do not, should not confuse us as to the real culprit here- lack of ATP in all of us. There is no need for the medical community to confuse people as to - "We don't know what this is, it affects different patients differently"- instead, they should be focusing on what is common to all of them. Just like any other syndrome- lupus, MS, the manifestations are different in different patients. So what?

Different effects of a syndrome ( like Down's for eg) do not point to different causes of it. We should make sense out of chaos, not chaos out of sense.

Interested in your opinions on how to treat the lack of atp? Something im persuing now?
it seems alot of supps we take for mito function we maybe underdosing such as q10.
Maybe also not a single supp but a sum of its parts type of scenario to help treat this issue??

 

[Gingergrrl]

I have been focusing on mitochondrial supplements as well and taking liposomal glutathione, Vit C, CoQ10, D Ribose, Acai berries, and may soon start IV Glutatione. I am also pursuing a treatment called EECP to increase blood flow to my heart and cardiac output.

My ND feels that we need to more aggressively treat the viral component (EBV and possibly HHV6) with things like Monolaurin, Maitake Mushrooms, and Lomatium. I started down this path for several months and had improvement but my stomach could not tolerate the anti viral supplements so we stopped and my condition deteriorated rapidly especially the cardiac symptoms.

We are now trying to fix my stomach with multiple probiotics, enzymes, GI Repair powder and very strict diet. If we can fix the leaky gut, I can try the anti viral supplements again. Now I am also taking Florinef which has been helpful.

 

[Dr.Patient]

All treatments for CFS so far have been supportive- treat underlying conditions, viruses, etc. Those are all good only under two conditions- 1.) They do not worsen the CFS - either the treatment itself; or the moving of the body out for multiple visits to doctors and 2.) They actually help the CFS.

In my opinion, a treatment is worth pursuing if the above conditions are satisfied.