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Ron Davis: Preliminary data shows problems with energy metabolism

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
He should have omitted "ancient."
Well, I feel ancient a lot of the time. ;)

"Ancient" refers to the evolutionary development. The brain stem is evolved from simpler brain stems in just about every vertebrate going back as far as we can trace. Its the most basic part of the brain. Its also where we keep finding problems in ME and CFS .... either directly in MRI scans, for example, or indirectly in circadian disruption. Sleep, for example, was recently identified to have its circadian pattern regulated not just by the SCN in the hypothalamus, but also another region in the brain stem, a second circadian center.

My possible trigger was measles encephalitis. I wonder if they are thinking along the lines that some cells may be damaged in the brain stem and that this causes improper signalling.

CFS and ME spontaneous remissions can be very sudden ... minutes to an hour; they can also last only hours. So from disabled to normal to disabled within a day. That sounds like a dynamic problem to me, possibly in regulation. Once the dynamics are understood, at least for a subset, I expect we will be able to target therapies against specific issues.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
The deconditioning card is massively overplayed and food for the psychs. I do not think that deconditioning will be responsible for much, if any of the abnormalities that are found via metabolomics.

Other complications? Possibly.



B
From my observations, and just my opinion, I think deconditioning is major for severely disabled ME patients in bed for many years, mostly due to bone remodelling. For the rest its a minor secondary phenomenon. Its something I worry about. We need better answers, but thankfully we are seeing signs we are getting those answers.
 

Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
From my observations, and just my opinion, I think deconditioning is major for severely disabled ME patients in bed for many years, mostly due to bone remodelling. For the rest its a minor secondary phenomenon. Its something I worry about. We need better answers, but thankfully we are seeing signs we are getting those answers.

Valid point about bone remodelling (I have trained many deconditioned people in my career, some extremely decondioned for various and similar reasons) and in my experience, it was not a huge issue, over time.

My response was in relation to what will be found on metabolomics. I don't think deconditioning will play much (any) part here. I wasn't talking about the physical or structural side of things, fwiw.


B
 
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Messages
2,087
@Rose49 studying the severe me/cfs people is very positive because it makes it easier to detect biomarkers and because that group has never been studied before. A negative is that there are more potential confounds. A bedbound person is going to suffer from more complications (eg. deconditioning)than the milder cfs/me people.
With having only a healthy control group how does the study separate biomarkers of CFS and the complications caused by CFS?

I was also wondering about additional complications or factors in the most severely ill. ( although not deconditioning as such ). I guess they are hoping the results point them in the right direction and that they will try to verify them in other ( more moderate ) patients in phase 2. But that's a guess.
 

Simon

Senior Member
Messages
3,789
Location
Monmouth, UK
With having only a healthy control group how does the study separate biomarkers of CFS and the complications caused by CFS?
Interesting point

The deconditioning card is massively overplayed and food for the psychs. I do not think that deconditioning will be responsible for much, if any of the abnormalities that are found via metabolomics.

Other complications? Possibly.
In general, the deconditioning card has indeed been outrageously overplayed, I agree. There's a study somewhere from Peter White showing that outpatients at a CBT clinic are no more deconditioned than sedentary healthy controls, not to mention the evidence from bed rest studies with healthy sedentary controls (originally done as an earth-bound proxy for weightlessness in space, also done now, I think, to look at problems from health) [really wish I''d got my act together and written a blog on this].

I think it could be an issue for more severely deconditioned patients like those in this study (remember, most mecfs specialists won't see patients like this, who are too ill to attend a clinic, so their deconditioning model is for outpatients, and it doesn't hold up).

Whether it would be expected to affect energy metabolism, I don't know. I also have no idea how you'd find appropriate controls - bed rest studies usually involved participants exercising lying down. I'm pretty sure the NASA etc studies did find changes in the immune system. I think it's an issue worth discussing.

Added: I wonder if there's any data on people confined to bed by other illnesses/disability, or even intensive care patients (who I think are studied) - or even those in comas?
 
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Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
Interesting point

In general, the deconditioning card has indeed been outrageously overplayed, I agree. There's a study somewhere from Peter White showing that outpatients at a CBT clinic are no more deconditioned than healthy controls, not to mention the evidence from bed rest studies with healthy sedentary controls (originally done as an earth-bound proxy for weightlessness in space, also done now, I think, to look at problems from health) [really wish I''d got my act together and written a blog on this].

I think it could be an issue for more severely deconditioned patients like those in this study (remember, most mecfs specialists won't see patients like this, who are too ill to attend a clinic, so their deconditioning model is for outpatients, and it doesn't hold up).

Whether it would be expected to affect energy metabolism, I don't know. I also have no idea how you'd find appropriate controls - bed rest studies usually involved participants exercising lying down. I'm pretty sure the NASA etc studies did find changes in the immune system. I think it's an issue worth discussing.

Added: I wonder if there's any data on people confined to bed by other illnesses/disability, or even intensive care patients (who I think are studied) - or even those in comas?

Hey @Simon

Some really good points. Those were indeed the studies I was thinking of, along with the vo2 max ones.

Deconditioning is absolutely going to be a factor for anyone who has been in bed, whether through choice (like the paid NASA participants) or the chronically ill. I've had to train people who have been bed bound and some with bone abnormalities, and there are limitations, at first, but all improved over time in objective measures of strength. Maybe that's why I'm less worried about it on the physical side of things, having had a perspective so to speak (and I am also housebound and sometimes bedbound so it has crossed my mind).

I can't see it affecting metabolomics though, and certainly nothing compared to the fundamental issues with energy metabolism to the extremes that have been suggested. I'd love to hear Rons's view on this! Maybe I'm wrong.

Though one thing to remember is that it would be hard to use metabolomics findings for a biomarker, which seems to be the way things are panning, if deconditioning was confounding the issues significantly.



B
 
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cmt12

Senior Member
Messages
166
This is another important aspect that needs to be part of the story. There is one command for a danger response, which would mean an activated HPA and high cortisol. Then, there is a later response which seems to be attempting to suppress the original mechanism.

I propose that the fluctuations of symptoms are more the result of the effectiveness of this secondary response rather than any impact on the original danger signal, which would instead result in a binary effect of symptom-less to fully symptomatic (on-off switch). In other words, over-exertion does not cause damage to any part of the danger mechanism structure, but interferes (via increased stress) with the secondary response's attempt to suppress symptoms, which causes symptoms to present more fully for a short time until stress alleviates and the secondary response can refocus its entire efforts back on the suppression of the original danger response.

The other option is that there is only one mechanism and the reason why it is contradicting itself (danger response, HPA suppression) is because it is broken. However, I don't see an explanation for fluctuating symptoms with this view.
 
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duncan

Senior Member
Messages
2,240
"Ancient" refers to the evolutionary development. The brain stem is evolved from simpler brain stems in just about every vertebrate going back as far as we can trace. Its the most basic part of the brain. Its also where we keep finding problems in ME and CFS .... either directly in MRI scans, for example, or indirectly in circadian disruption. Sleep, for example, was recently identified to have its circadian pattern regulated not just by the SCN in the hypothalamus, but also another region in the brain stem, a second circadian center.


Nods. I just thought a) there is little need to qualify in that way , and b) it carries a Robert E. Howard vibe somehow. It may be trying too hard in the wrong way. But I am quibbling over inconsequential crap. I happen to enjoy where they are going with this.

My possible trigger was measles encephalitis. I wonder if they are thinking along the lines that some cells may be damaged in the brain stem and that this causes improper signalling.

Similarly, I am fairly certain my trigger was Lyme encephalomyelitis. I have some evidence of global damage. If they can narrow down the real source, e.g., the brain stem, super.

CFS and ME spontaneous remissions can be very sudden ... minutes to an hour; they can also last only hours. So from disabled to normal to disabled within a day. That sounds like a dynamic problem to me, possibly in regulation. Once the dynamics are understood, at least for a subset, I expect we will be able to target therapies against specific issues.

.The relapsing remitting nature can be explained a couple ways (none of them necessarily right,lol). What's harder to easily explain is how sudden it can be. Yes, you are so right. Perhaps for us the precipitating factor - and the peculiar screeching suddeness of relapses - is related to PEM. Not saying that all PEM triggers relapse, of course - rather, that the abruptness and intensity may somehow loop back into a PEM episode.

ETA - I'm not so sure about that thought of mine that maybe PEM precipitates relapse. I can turn for the worse without any overt PEM episode, and I never really know how long it will last, or how deep I will sink.

This isn't easy, on any level.
 
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Janet Dafoe

Board Member
Messages
867
Hey @Simon

Some really good points. Those were indeed the studies I was thinking of, along with the vo2 max ones.

Deconditioning is absolutely going to be a factor for anyone who has been in bed, whether through choice (like the paid NASA participants) or the chronically ill. I've had to train people who have been bed bound and some with bone abnormalities, and there are limitations, at first, but all improved over time in objective measures of strength. Maybe that's why I'm less worried about it on the physical side of things, having had a perspective so to speak (and I am also housebound and sometimes bedbound so it has crossed my mind).

I can't see it affecting metabolomics though, and certainly nothing compared to the fundamental issues with energy metabolism to the extremes that have been suggested. I'd love to hear Rons's view on this! Maybe I'm wrong.

Though one thing to remember is that it would be hard to use metabolomics findings for a biomarker, which seems to be the way things are panning, if deconditioning was confounding the issues significantly.



B
In Ron (et al)'s trauma study some of the patients were bed bound (some for over a year) burn victims. Preliminary anaslyis looks like their metabolite levels are quite different from both bed bound and non-bedbound ME/CFS patients. Needs to be looked at further.
 

Janet Dafoe

Board Member
Messages
867
Valid point about bone remodelling (I have trained many deconditioned people in my career, some extremely decondioned for various and similar reasons) and in my experience, it was not a huge issue, over time.

My response was in relation to what will be found on metabolomics. I don't think deconditioning will play much (any) part here. I wasn't talking about the physical or structural side of things, fwiw.


B
@Ben Howell Your new career when you're better! Super scientifically savvy personal trainer for reconditioning ME/CFS patients! You're so knowledgable of both the science and the body.
 

Ben H

OMF Volunteer Correspondent
Messages
1,131
Location
U.K.
In Ron (et al)'s trauma study some of the patients were bed bound (some for over a year) burn victims. Preliminary anaslyis looks like their metabolite levels are quite different from both bed bound and non-bedbound ME/CFS patients. Needs to be looked at further.

Hey Janet,

Thanks for responding!

That's fascinating. I'm presuming they are quite different to healthy controls then...

I'd forgot Ron had done that study. That could be a really fascinating cross reference.


B
 

Janet Dafoe

Board Member
Messages
867
Nods. I just thought a) there is little need to qualify in that way , and b) it carries a Robert E. Howard vibe somehow. It may be trying too hard in the wrong way. But I am quibbling over inconsequential crap. I happen to enjoy where they are going with this.



Similarly, I am fairly certain my trigger was Lyme encephalomyelitis. I have some evidence of global damage. If they can narrow down the real source, e.g., the brain stem, super.



.The relapsing remitting nature can be explained a couple ways (none of them necessarily right,lol). What's harder to easily explain is how sudden it can be. Yes, you are so right. Perhaps for us the precipitating factor - and the peculiar screeching suddeness of relapses - is related to PEM. Not saying that all PEM triggers relapse, of course - rather, that the abruptness and intensity may somehow loop back into a PEM episode.

ETA - I'm not so sure about that PEM precipitating a relapse. I can turn for the worse without any overt PEM episode, and I never really know how long it will last, or how deep I will sink.
Hey Janet,

Thanks for responding!

That's fascinating. I'm presuming they are quite different to healthy controls then...

I'd forgot Ron had done that study. That could be a really fascinating cross reference.


B
Yes the metabolites of the burn victims are also different from healthy people.
 

Janet Dafoe

Board Member
Messages
867
I can sometimes feel the relapse starting with a wave of fatigue washing over me. This seems rather difficult to explain as anything but an immune reaction or the brain shifting gears. Probably the immune system flaring up.
It could also be explained by the energy generating system of the body shutting down. All those other systems require energy. Immune. Brain. Gut. etc.
 

duncan

Senior Member
Messages
2,240
I can sometimes feel the relapse starting with a wave of fatigue washing over me. This seems rather difficult to explain as anything but an immune reaction or the brain shifting gears. Probably the immune system flaring up.

My worst relapses almost always come with an odd sensation of poison. I have other symptoms that signal a relapse, but when I have that poison feelings in my hands and feet and face, I know it will be a long and bad ride.
 

Groggy Doggy

Guest
Messages
1,130
@alex3619

I can't agree more about improper signalling. It's puzzling for me to understand the spontaneous remissions throughout the day. I wish there was a way to get a hold of sophisticated monitoring devices, because I want to know what's happening before/during/after a spontaneous remission.

I cycle from feeling extremely weak, in pain, tired, foggy brain, slurred speech, jerky motor movement, can't walk a straight line....to then feeling good, clear headed, energetic, smooth movements, ease of conversation, reduced pain, and good balance.

I wish I knew the triggers. it's almost feels like my electrical systems shorts out, but I don't understand why the cycles happen as fast as they do...almost like someone is flipping a switch.

The one constant I consistently noticed is the related to the temperature of the air. If the temperature drops to about 60 degrees, I start to feel better! Then as it gets to low 50's, I feel even better. One night I stood outside in the winter, it was about 36 degrees, and I felt like the energizer bunny.

The other constant is short lived, but if am very tired and then I slowly consume a tall glass of water/salt/lemon juice, then wait a few minutes, I have a small burst of energy for up to one hour.

So for me, my cell signaling issues seem related to adjustments in temperature/heat and sodium kinesis.

GD
 

Groggy Doggy

Guest
Messages
1,130
@duncan

Yes, that's a great description and exactly how I feel too; when I start to down cycle (feels like I am being poisoned). And me too, I can tell by observing my hands, if they start to swell, then I know it's going to be a longer than normal crash.

GD
 

Sushi

Moderation Resource Albuquerque
Messages
19,935
Location
Albuquerque
The one constant I consistently noticed is the related to the temperature of the air. If the temperature drops to about 60 degrees, I start to feel better!
I am watching the temperature factor right now as I am in an area that is experiencing a severe heat wave (100 F +). I try to stay inside in an air-conditioned space but yesterday I went out for only 5 minutes to get the mail etc. I felt much more ill for the rest of the day--it was immediate, headache and all.

I also have a cooling vest that I freeze and use when I have to go out. I wear an HR monitor and tried to walk (without the vest) about 50 yards right before dusk when the temperature had dropped a lot but was still uncomfortable. I noted a raised HR. I backtracked, put on the vest and tried again. My HR was 10 points lower.
 

Groggy Doggy

Guest
Messages
1,130
@Rose49

I think it's good to study bedbound patients, in hopes of getting more consistent feedback data. But the majority of us are non-bedbound patients, and assuming we share spontanious remissions throughout the day, then our metabolite levels would need to be taken throughout the day (and aligned with patient feedback as to how they perceived their energy level to be when the metabolite levels were taken). I think this may be one of the reasons that ME is so difficult to study (dynamic changes in the body). It is also a reason that ME is hard to grasp/understand, and gain public support. I generally only leave my home when I am feeling better, and thus the only time public/others observe me. But for people l know well, that observe me at home, it almost scares them to see me in a down cycle. They can't comprehend how I can look deathly ill. I almost need to carry videos with me at the next ME protest. (this is how I look at my worst, and at my best, and in any given day, I cycle back and forth between them)

I can't thank you and Ron enough for tackling this challenging research and supporting our community.

GD