Professor Ron Davis's response to Naviaux study, including Q and A with Dr Naviaux

[CFS_for_19_years]

I was only 28 when this halt of colds, flu, gastro and hay fever happened. I've literally not had any of them for 6 years. Not even once. I had one last big flu then nothing.

I don't think it has anything to do with getting older. I'm surrounded by people a lot older than me that get colds, flu all the time and even hay fever. I also still have MCS, Eosinophilic Esophagitis and MCADs (I'm tube fed), so I'm not short of sensitivities, just short of hay fever. I also still test positive for IgE allergy to wheat, soy and dust mites.

Your description of catching cold or flu several times a year and taking months to recover was basically how I was my whole life pre-ME/CFS and for the first few years of my decline.

At your age of 28, you are correct, your age would have nothing to do with your decline in catching colds and flu. Plus it sounds like your other allergies are in full swing.

 

[Nielk]

Since I got sick with ME 13 years ago, I had so many sinus infections that I needed surgery six years ago and still battle allergies and sinus issues.

I had radiation for a meningioma in the brain.

I had kidney operation because I was diagnosed with kidney cancer.

I was diagnosed with RA three years ago.

I suffer from high sugar, high cholesterol and fatty liver. (All signs of metabolic syndrome)

All this while fluctuating between housebound and bed bound from ME.

All this while hybernating?

 

[Sidereal]

I was only 28 when this halt of colds, flu, gastro and hay fever happened. I've literally not had any of them for 6 years. Not even once. I had one last big flu then nothing.

I don't think it has anything to do with getting older. I'm surrounded by people a lot older than me that get colds, flu all the time and even hay fever. I also still have MCS, Eosinophilic Esophagitis and MCADs (I'm tube fed), so I'm not short of sensitivities, just short of hay fever. I also still test positive for IgE allergy to wheat, soy and dust mites.

Your description of catching cold or flu several times a year and taking months to recover was basically how I was my whole life pre-ME/CFS and for the first few years of my decline.

Your story sounds almost identical to mine. I am not tube fed but if my swallowing were to get any worse, I will have no choice. At one point I lost 40 lbs due to not being able to eat enough.

 

[JenB]

Yes. The chemical signature that we discovered is evidence that CFS is an objective metabolic disorder that affects mitochondrial energy metabolism, immune function, GI function, the microbiome, the autonomic nervous system, neuroendocrine, and other brain functions. These 7 systems are all connected in a network that is in constant communication. While it is true that you cannot change one of these 7 systems without producing compensatory changes in the others, it is the language of chemistry and metabolism that interconnects them all.

Dr. Naviaux, the vagus nerve is a superhighway connecting all of these systems. I wonder what you make of the hypothesis that some kind of infection or perhaps autoimmunity to the vagus nerve might be at play? It would explain the observation that 1/3 of ME/CFS patients have autoantibodies to the same acetylcholine receptors as patients with Myasthenia Gravis as well as the observation that some (not all but some) patients find significant relief on acteylcholinesterase inhibitors like Mestinon.

http://me-pedia.org/wiki/Acetylcholine
http://me-pedia.org/wiki/Vagus_nerve_infection_hypothesis
http://me-pedia.org/wiki/Vagus_nerve

Also it seems that different herpesviruses can trigger acetylcholine receptor autoantibodies, which could explain the association between this disease and herpesvirus onset, why so many patients get symptomatic relief from antivirals (yes the anti-inflammatory effects could also be at play but personally, when I go off my antivirals, I DO get an obvious HSV-1 flare within days and become concomitantly bedridden, so in my case, we aren't guessing about reactivation), and could explain why B-cell depletion seems to be beneficial for some with this disease (*in particular* if you have those acetylcholine auto-antibodies).

 

[rosie26]

Hi @paolo

Its nothing to do with OMI. The shipping container will be provided when ordering the test, so no need to worry about sourcing LN2.

Laurel has it all worked out


B

This is so great and thanks to all for opening this up for international patients. Would the costs be under $500 roughly do you think? I need to get saving. Thanks so much again.

 

[rosie26]

Since I got sick with ME 13 years ago, I had so many sinus infections that I needed surgery six years ago and still battle allergies and sinus issues.

I had radiation for a meningioma in the brain.

I had kidney operation because I was diagnosed with kidney cancer.

I was diagnosed with RA three years ago.

I suffer from high sugar, high cholesterol and fatty liver. (All signs of metabolic syndrome)

All this while fluctuating between housebound and bed bound from ME.

All this while hybernating?

That's a lot to go through @Nielk with ME. Hope things are brighter for us soon on the ME horizon.

 

[Nielk]

That's a lot to go through @Nielk with ME. Hope things are brighter for us soon on the ME horizon.

Thank you @rosie26 -

My point in mentioning all this was that I really doubt that I would have this hypo metabolic signature.

I am an ME patient though - diagnosed by Dr. Enlander. I fit the ICC criteria. I know of others with similar experiences with ongoing pathogens, high cholesterol, inflammatory markers, frequent infections. It doesn't seem like the hypo metabolic state described in this study - yet they suffer from ME- ICC as well.

I'm skeptical that this metabolic signature will be found in us. Therefore, this signature will not be a bio marker for ME-ICC.

 

[Research 1st]

If that was true, understanding the hypometabolic state which underlies chronic fatigue syndrome, could offer a way to treat severe infections: it might be useful to artificially induce a CFS-like hypometabolism in order to prevent tissue damage during acute infections!

I politely beg to differ.

Tissue damage is uncontrolled in ME (Oxidative stress the key culprit) and PWME harbour multiple intracellular infections, and viruses. This is all in the literature from Mycoplasma, to Parvovirus B19 to EBV.

On top of this PWME/CFS report adult onset Asthma (more tissue damage) and chronic allergic syndromes such as Mast Cell Activation Syndrome (MCAS) = more tissue damage once more. Over time this will wreck your DNA.

So what you do is test your cfDNA. Do PWME CFS report very high cell free DNA? Yes, some as high as patients having chemotherapy, except these patients aren't and are lying in bed. So imagine how high the inflammation would be if PWME/CFS started to exercise. (cFDNA is out of the cell due to oxidative damage, from inflammation), bitts of DNA floating around outside the cell. Normal, but not normal at high levels.

That's the one give away ME is an inflammatory disease, irrespective if you believe it's due to chronic infection, or post infectious autoimmunity.

Once you get an autoimmune illness, don't treat it, your inflammation will tend to cause a cascade effect and you develop other conditions on top of your original one (called co-morbid conditions).

You may ask:
Why is none of this is in the literature?

Answer:
The people most sick, severely affected, aren't researched.
Worst still, people with explained reasons of fatigue who have ME CFS are excluded from the research also!
This is the 'beauty' of Fukuda CFS criteria, it makes sure people with demonstrated fatigue, can't be detected. Such a tragedy for the patients and so wrong, scientifically never mind morally. We have CDC to thank for that, as they created it.

So proving Dr Navieux/Dr Davis's work is going to be hard, as we need to exceed Fukuda Criteria to get a robust answer. This is why they ,sensibly, used Fukuda, CCC and IOM criteria. To increase the size of the 'net'- the exact opposite response that psychiatry would do as psychiatry is repulsed by Science and prefers religion (belief) that ME CFS is a belief in ME CFS.

Oxidative stress, would wreck your brain long term, effectively making it shrink. Is there evidence of brain atrophy in CFS? Yes.

Some ME sufferers even end up with pulmonary fibrosis, cancer and stroke from the effects of this. Why? Chronic Inflammation via infection/autoimmunity causes tissue damage.

What's the easiest way to prove your circulation is under attack other than Inflammatory Cytokine/Chemokine Assays? Test VEGF. Raised VEGF shows your body is growing new blood vessels for a reason. Why? Tissue hypoxia, probably via inflammation, via infection, via autoimmunity.

BUT.... I still believe this is likely induced by the immune system becoming disabled at an atomic level, in other words, if the immune system has no ATP, it won't work correctly (or certain parts of it).

So I'm waiting to get my hands on this new Metabolic Mitochondria test we're queuing up for, and to compare my results with someone without inflammation, without infections - but who is housebound or bedridden.

That will be an incredible time for all of us, as it will show if 'severe' in ME is related to 'severe' in CFS (CFS diagnosis doesn't require inflammation) i n terms of 'sharing' the same Mitochondrial defect.

 

[Research 1st]

Something similar could be happening in ME/CFS if there is an excess of hydrogen sulphide producing pathogenic bacteria in the gut.

Which we've already tested for experimentally at Redlabs and the urine test turns dark color confirming high Hs2
Then what you do is test your D-Lactate, should also be raised.
Even better, check your ammonia (must spin + freeze sample) now if that's raised you're living with hyperammonaemia which long term will damage your brain. (In extreme cases, it's fatal).

The answer? Low grade chronic sepsis from some form of intracellular infection (Lyme the no:1 culprit), which may translocate to other organ sites such as the brain = neurological disease, aka there is your Myalgic Encephalopathy demonstrated.

Question: Do this infections infect Mitochondria causing them to go to sleep - causing the Dr Navieux/Dr Davis finding?

If so, as Alan Partridge would say, back of the net!

 

[Kati]

I think that patients with ME and those 'on the spectrum' if you will, would benefit from real personalized medicine. By real I mean access to what science and technology has to offer, through a variety of testing and understanding of metabolome, microbiome, brain science, cytokines, virology, immunology. It's the synthesis of all of the above which makes us sick. There will be variation from patient to patient. For instance, some experience pain, and others don't. Why? Some crash just talking on the phone, while others don't, why? Some have intense gut issues, while others don't. Why? Then some clearly get sick from a viral onset, while others have a more gradual presentation with no infectious onset. How does that work, at the cellular level? Some have drastic weight changes, either ways, while others, not so much. Why?

There is so much work to do, and so much more to understand. Metabolomics is like a footprint. It's giving clues as of what is happening in the body, what is working and what is dysfunctional. It also represents a moment in time, the day the blood was drawn.

What strikes me is that the authors found common deficiencies despite the cohort varying in term of disease presentation. There are also differences and variations depending on sex. That's very interesting.

We are making progress. We are not necessarily 'there' yet. It may not explain eveything for everyone. But i think it is safe to say we are moving forward and we are adding more pieces to the puzzle.

 

[valentinelynx]

I have to go away and reread the science every time I want to talk about it in detail.

LOL, me, too. Memory like a sieve. Thank the Powers-that-Be for smartphones. Make me look like a smarter doctor than I might really be...

 

[valentinelynx]

This is something that has always intrigued me; it's almost a hallmark of ME/CFS that benefits from drugs or supplements are often temporary.

Yes, wow. I was very nearly 100% cured by a single dose of IV ketamine administered by Dr Goldstein in 1997 - for one whole week. I went for long, happy walks. And then, it gradually faded (over a day or two) and I was back to being unable to take long walks, back to having PEM, etc. (though this was in my relative remission phase). Never been able to regenerate that response despite trying the same dose or even a higher dose, again.

 

[valentinelynx]

Does anyone else feel that minor gut upset can result in a systemic response with worsening of all symptoms? It seems to be able to trigger relapses that can, surprisingly, last a week or even longer.

Yes

 

[hixxy]

I know when I hear even slight grumbles in my gut things are going downhill, usually within minutes.

 

[knackers323]

Does anyone else feel that minor gut upset can result in a systemic response with worsening of all symptoms? It seems to be able to trigger relapses that can, surprisingly, last a week or even longer.

Are you thinking leaky gut or an immune reaction to foods or something?

 

[A.B.]

Are you thinking leaky gut or an immune reaction to foods or something?

Why not both? I'm not sure how LPS could get into the blood at increased rates without some sort of immune reaction. And once there it could trigger a body wide defense strategy that persists even after the problematic food is no longer in the gut.

 

[alex3619]

'm not sure how LPS could get into the blood at increased rates without some sort of immune reaction.

LPS is a super-antigen. Which means it only takes tiny amounts to cause a major immune response.

 

[Hip]

Yes, wow. I was very nearly 100% cured by a single dose of IV ketamine administered by Dr Goldstein in 1997 - for one whole week. I went for long, happy walks. And then, it gradually faded (over a day or two) and I was back to being unable to take long walks, back to having PEM, etc. (though this was in my relative remission phase). Never been able to regenerate that response despite trying the same dose or even a higher dose, again.

I had a similar near full remission experience with another of Goldstein's drugs: Wellbutrin (bupropion). The remission lasted for two weeks, and I was joyous that I had finally found an effective treatment; but then, after exactly two weeks, even though I had not changed the dosage or any other factors, this drug just suddenly stopped working for me, literally overnight. Absolutely bizarre. More info about my Wellbutrin experience in this post.

After reading these sort of accounts of temporary remission induced by medications, it almost seems to me as if this disease knows where in the body extra energy is being expended, so that when a medication provides some extra energy, the disease then responds by targeting that extra energy, and down-regulating it back to the very low energy baseline that is the normal state of ME/CFS.

In other words, when there are any departures from this restricted, low energy state of ME/CFS, the disease seems to sense this and dynamically respond, by applying the brakes to any high energy expenditure. That's what it seems like, anyway.

 

[Sidereal]

Which is why there will never be an effective drug treatment aimed at symptom management for ME/CFS. The disease literally knows when you've messed with it and it just pulls another metabolic lever to drag you back down to the sick homeostasis it wants to be in.

 

[Sidereal]

The answer? Low grade chronic sepsis from some form of intracellular infection (Lyme the no:1 culprit), which may translocate to other organ sites such as the brain = neurological disease, aka there is your Myalgic Encephalopathy demonstrated.

I think there is no need to posit unlikely factors such as an ongoing Lyme or other bacterial infection in everyone with this diagnosis. Many people who have never been near a tick have ME or CFS. Chronic translocation of LPS and products like ammonia and hydrogen sulphide (H2S) via a leaky gut full of pathogenic bacteria can account for the symptoms (including myalgia and encephalopathy) and the observed metabolic derangements. H2S in particular has been studied in animal models of induction of hibernation-like states.