Ron Davis: Preliminary data shows problems with energy metabolism

[JES]

Yep, unless we know mitochondria is the causative factor driving this disease there is little more point in treating them than in any other CFS/ME treatment. The same logic can be used for motivating e.g. the antiviral approach because enteroviruses have been found in CFS/ME patients at high percentage. All this tells us so far is obeservations but without tying them to a theory. Actually even the antiviral approach seems to have produced better results than the the mitochondrial supplements, based on comments from users on this board.

 

[Ben H]

Yep, unless we know mitochondria is the causative factor driving this disease there is little more point in treating them than in any other CFS/ME treatment. The same logic can be used for motivating e.g. the antiviral approach because enteroviruses have been found in CFS/ME patients at high percentage. All this tells us so far is obeservations but without tying them to a theory. Actually even the antiviral approach seems to have produced better results than the the mitochondrial supplements, based on comments from users on this board.

Mitochondria have been implicated, and Ron Davis and the OMF have also found this to very much be the case:

http://www.openmedicinefoundation.org/expanded-mecfs-metabolomics-study/


It's not as simple as giving someone some d ribose, or coq10 (insert any mitochondrial supplement here) if an underlying mechanism, potentially CDR, is abnormally regulating the innate function of the mitochondria.

It would be like throwing fuel at a faulty engine. It's not going to help anything. It isn't that simple. Therefore just because you don't respond to a mitochondrial supplement(s), does not mean you don't have mitochondrial issues.

As Davis says, almost every aspect of M.E can be explained by the mitochondria not functioning properly.

You can't have a theory, without making a huge amount of observations. The OMF are going about this in the correct manner.


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[Ben H]

On targeting problems with supplements and other things: suppose you needed ten things to get the mitochondria working again. ABCDEFGHIJ. Now suppose you take a supplement that fixes A, but the others are not fixed. What happens? Probably not much. Suppose you did your investigation and found supplements for ABCDEF but they did not work. Why not? Maybe G through J were not even known. Maybe some supplements do not work too well, or at the wrong doses, or you have secondary problems that stop them from working.

The point of finding exact mechanisms is you know what to test for. Guesswork is minimized, though never entirely absent. So you can, with the aid of tests, start fixing the whole alphabet.

Here is an issue that many of us have found though - sometimes we find stuff that helps a lot, then it stops working. I think ME and commonly CFS are probably maintained by some feedback mechanism. Until that is gone then dropping in supplements will just kick the feedback to stop them from working. Once we understand the mechanisms then we can figure out ways to circumvent them.

Good points Alex. Have you got round to reading this yet?

http://www.sciencedirect.com/science/article/pii/S1567724913002390


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[Justin30]

I'm concerned about absorption issues. My daughter is unable to gain weight. She just looks wasted. I suppose some items can be introduced IV, because the gut is not working right.

Other severely ill have had to do this.

 

[JamBob]

I am curious to know if anyone knows if metabolomics can measure what happens dynamically in the body at different time points to provide a comparison? Or is it a static model of a single state?

I am convinced that my condition will never be understood until some dynamic tests are developed that measure me at point 1 (resting state) and point 2 (after some kind of challenge - exertion/stress and in a severe state of PEM). If you measure me in a resting state, I might look relatively normal.

I know that the VO2 max test does this but I think there is a lot more wrong than my aerobic capacity after exertion or stress.

 

[ScottTriGuy]

Good points Alex. Have you got round to reading this yet?

http://www.sciencedirect.com/science/article/pii/S1567724913002390


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@Ben Howell I have a question I hope you, and others, may be able to answer as I am chemistry-comprehension-impaired (in all senses).

The intro to the above abstract states:

"The CDR is maintained by extracellular nucleotide (purinergic) signaling."

I take 4 antiretrovirals for HIV, 2 of these are nucleoside analogues, abacavir and lamivudine. (Note I underlined the 's')

Could these nucleosides medications impact nucleotide signaling in my body?

 

[Ben H]

I am curious to know if anyone knows if metabolomics can measure what happens dynamically in the body at different time points to provide a comparison? Or is it a static model of a single state?

I am convinced that my condition will never be understood until some dynamic tests are developed that measure me at point 1 (resting state) and point 2 (after some kind of challenge - exertion/stress and in a severe state of PEM). If you measure me in a resting state, I might look relatively normal.

I know that the VO2 max test does this but I think there is a lot more wrong than my aerobic capacity after exertion or stress.

Good question. We need someone with more knowledge on the subject.

However, from what I have researched and seen, Metabolomics is a metabolic snapshot, of hundreds of metabolites from many different metabolic pathways. Those metabolites seem to register high,low, normal, with some common findings between patients so far. But many seem to be out of whack. Some of Whitneys were out by 20SD, which is insane.

So I *believe* it is static in that sense, however with a good analysis it would be able to explain why on exertion you may have severe PEM, from the metabolites that are involved, if that's the case.

But, I may be wrong.



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[Ben H]

@Ben Howell I have a question I hope you, and others, may be able to answer as I am chemistry-comprehension-impaired (in all senses).

The intro to the above abstract states:

"The CDR is maintained by extracellular nucleotide (purinergic) signaling."

I take 4 antiretrovirals for HIV, 2 of these are nucleoside analogues, abacavir and lamivudine. (Note I underlined the 's')

Could these nucleosides medications impact nucleotide signaling in my body?

Hey @ScottTriGuy

I'm not sure. I'm no expert at all, just have a base in biochem. I don't know about the antiretrovirals. The study referenced used Suramin on a similar model in mice, which resolved issues. But that is Mice, not humans. The therapy seems to be based off antipurigenics like Suramin.

Nucleosides and Nucleotides are different, ofcourse, so I doubt it, as a guess. I think it requires a specific targeted antipurigenic. It's all cutting edge, though some of the drugs may not be.


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[Mel9]

So has Whitney. But now we have data on what to target.

I guess you have already tested for microbial pathogens? I have Borrelia and am starting to be cured using antibiotics.

What has really surprised me is that the herx Reactions on bacterial cell death feel EXACTLY like the PEM I used to experience after exercise. (And others here have reorted the same thing)

The only difference is that the herx occurs 4 hours after I take the antibiotics, whereas PEM occrred from 24 to 36 hours after exercise (in the days when I could actually exercise).

So could PEM be a form of herx reaction?

Could Whitney be suffering from non-stop herx reactions?

Would such non-stop reactions damage the functioning of his mitochondria?

I'm sure you have already done this, but Next Generation Sequencing could be done, using bacterial primers, on Whitney's blood?

 

[alex3619]

Good points Alex. Have you got round to reading this yet?

http://www.sciencedirect.com/science/article/pii/S1567724913002390


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I read this some time ago. Its a very broad hypothesis, and unproven in any disease state from what I can tell. That does not mean its wrong though. I would like to see more research, including in ME.

 

[alex3619]

Could Whitney be suffering from non-stop herx reactions?

One of the hypotheses about these things is that PEM might occur during increased bacterial product translocation, and note I said product not bacteria. This could include LPS.

 

[alex3619]

I was put on antipuragenics back in about 1984 or -5 or so. They did not help. Yet that was the specific drug I was on then, due to a misdiagnosis of gout ... when today I would probably be diagnosed with fibro.

 

[Ben H]

I read this some time ago. Its a very broad hypothesis, and unproven in any disease state from what I can tell. That does not mean its wrong though. I would like to see more research, including in ME.

It seems to have been suggested now on OMF website that it is implicated in M.E.

http://www.openmedicinefoundation.org/expanded-mecfs-metabolomics-study/


"Dr. Naviaux completed an initial study of 90 participants (both healthy controls and patients) that showed abnormal metabolites in patients. The abnormalities indicate the mitochondria is in hypometabolism due to a chronic cell danger responsestate in ME/CFS patients."

We haven't seen the research yet, but the statement seems very telling.

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[Mij]

I don't see any damage to the mitochondia 'only' dysfunction just like all the other problems they have found in ME/CFS. Dysfunctions... I think you can find dysfunction in the mitochondira if you have the flu too. It doesn't say anything at this point.

I tend to agree with this. From what I've read is that it takes A LOT of hard hits to damage the mito DNA.

 

[Ben H]

I tend to agree with this. From what I've read is that it takes A LOT of hard hits to damage the mito DNA.

I'm not sure where Gijs got the 'damage' to the mitochondria from, no one was suggesting that.

It's been suggested repeatedly that it looks like the mitochondria are not regulated properly, and that infact the mitochondria are not damaged or faulty inherently.



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[alex3619]

We haven't seen the research yet

.. and I eagerly await it. Its far from proven though, but it is definitely interesting.

 

[alex3619]

It's been suggested repeatedly that it looks like the mitochondria are not regulated properly, and that infact the mitochondria are not damaged or faulty inherently.

Except for the studies showing ragged red fibers, from the 90s I think, which are a sign of mitochondrial damage. However that was far from conclusive. Damage does not have to be overtly visible though. This story is far from played out, and I suspect we might wind up with a new mitochondrial test before its done.

 

[aimossy]

Would be interesting to see what happens to metabolomics results and microbiome after exercise as well. There are so many measure points in different aspects that could happen in that scenario.

 

[aimossy]

Hey @Sasha where is that post of yours. I think you win quote of the year when you said Ron Davis is the Mick Jagger of ME/CFS research right now. You had me on the floor with that. I hope someone tells Ron Davis and it gives him a chuckle.

Best line! It's so true.

 

[Ben H]

.. and I eagerly await it. Its far from proven though, but it is definitely interesting.

Me too. However I can't see Davis and team stating the quote I gave from OMF if they were not certain, through evidence and research. Its a big claim.

Except for the studies showing ragged red fibers, from the 90s I think, which are a sign of mitochondrial damage. However that was far from conclusive. Damage does not have to be overtly visible though. This story is far from played out, and I suspect we might wind up with a new mitochondrial test before its done.

Yes I know the studies you're referring to, and you're right ofcourse damage does not have to be visible. I was specifically talking about the OMF. I think Davis is saying that this is not like mitochondrial myopathy in terms of damage. Everything Davis and the OMF have found thus far point to regulation.

But yes, until the research is out, it's impossible to know exactly.

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