Naviaux et. al.: Metabolic features of chronic fatigue syndrome

[Christian Godbout]

I apologize if the following has already been addressed a dozen times thusfar…

I have a question about the relationship between PEM and hypometabolism.

The "dauer" state to me evokes a static state with little fluctuations, whereas my experience of this illness is roller coaster like - from my baseline (very poor to begin with), then down into PEM, and back up to my baseline, and so on.

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

I am asking because PEM doesn't feel like a shut-down, but more like a sudden activation. Not a quantitative change but a qualitative one - I don't just feel "more" exhaustion than hours earlier, but rather as though a process of a different nature had kicked in (it lasts 3 days, happens almost every week …I never learn…), a process in which my metabolism, far from going quiet, seems to be "roaring" inside (heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out)

Rather than some intensified dauer state, could these shifts between baseline and PEM consist of a to and fro between dauer and cdr? Could the marked fluctuations in ME/CFS reflect swings between hypo and hyper states?

Thank you … (thank you @Rose49 , thank you Ron Davis, my best wishes to your son, my thoughts with your daughter as well, thank you Linda Tannenbaum, thank you Dr Naviaux et al. of course, thank you @Ben Howell , and while I'm at it, thank you to all the wonderful interlocutors here on PR!)

 

[Gingergrrl]

@Ben Howell My question is the opposite of the last poster and am curious what Dr. Davis would say re: someone who does not get PEM and every day/week is literally the same with no fluctuations?

I've tracked this with intricate detail and have not had what people on PR describe as a PEM episode yet I am very ill and my level of muscle weakness especially breathing weakness with my lungs and diaphragm is the same every day. If I try to stand/walk, the consequences of breathlessness and chest pain are instant vs. delayed and the same every time.

But in wheelchair, I have no limits. Tonight am going to a "Back to School Night" at my daughters new high school and I can spend hours talking to 7-8 different teachers and no cognitive issues or delayed reactions or PEM and then can go out the next night(s) if needed. But standing up from wheelchair to get dressed, I am completely out of breath within seconds.

Am curious if this fits with any known pattern of ME/CFS that Dr. Davis has seen in his severely ill patients or if this really is a different process? My other biggest problem was mast cell allergic reactions but they are much better since IVIG (but for now am assuming it is a temporary remission and they will be back).

Am curious if Dr. Davis has found people with various autoantibodies or paraneoplastic antibodies (without cancer) and if he considers them to have a different illness or would this still be a subgroup of ME/CFS?

Treatments like IVIG and RTX are recommended for me, and they are also recommended for certain subgroups in ME/CFS, but I am not sure if that means we have the same illness vs. just being recommended the same treatments?

I hope this question makes sense and I explained it well. I get many PM's from people with proven or suspected autoantibodies who are not sure where they fit in, and some are afraid to post publicly about it, so am asking on behalf of all of us! Thank you so much in advance!

 

[JaimeS]

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

My impression is that you rev the needs of the body by demanding more without the mechanism in place to provide more. You go into a state of shock via energy deficit.

Of course microbiome research would call it septic shock. I'm still trying to mesh these two theories, because I think both have too much evidence for one to be 'right' and one to be 'wrong'. My personal experience is more sepsis-like: I seize and develop a fever if I push too hard.

But seizures are also present in severe mitochondrial dysfunction, so actually that does still fit with a hypometabolic picture.

-J

 

[Sidereal]

My temperature drops even further during the state of PEM. I think this reflects the metabolism getting into a crisis due to dangerously low ATP.

My personal experience is more sepsis-like: I seize and develop a fever if I push too hard.

Me too. Back when I was less sick I would get the fever and seizure-like blackouts from exertion but as I crashed further and further into Dauer my temp now drops when I push too hard. Sepsis of course can present with either high or low temp. The ones with low temps have worse outcomes, probably because they metabolism is crashed due to the infection and they can't fight it off.

 

[JaimeS]

My temperature drops even further during the state of PEM. I think this reflects the metabolism getting into a crisis due to dangerously low ATP.

Me too. Back when I was less sick I would get the fever and seizure-like blackouts from exertion but as I crashed further and further into Dauer my temp now drops when I push too hard. Sepsis of course can present with either high or low temp. The ones with low temps have worse outcomes, probably because they metabolism is crashed due to the infection and they can't fight it off.

More and more interesting, so I hope this is considered related enough to the article to be considered 'on topic'.

Weirdly, the creepiest 'cytokine storm' moment I've ever had was when I started feeling 'off', checked my temperature -- it was dropping -- and moved quickly to bed. Despite the lower-than-usual temperature, it was like I could feel something scary coming. By the time I made it to bed I was shaking, feeling like I was freezing. I got scared and checked my temp again -- normal?! But five minutes later it had climbed to 100 F.

I went from around 97 F to around 103 F -- for our Celsius friends, that's 36 to 39.5 degrees -- in 15 minutes.

Since then I've observed that my temperature always drops right before I'm about to get a fever with this illness. I've never had anything that dramatic happen again, but when I start to feel crappy, my temperature is low, and a short time later it's a mild fever.

-J

 

[valentinelynx]

when I start to feel crappy, my temperature is low, and a short time later it's a mild fever.

Hmm. I haven't noticed the low, but on occasions when I get a fever out of the blue, it comes on pretty fast: from normal to shivering and 103.5 in about an hour? Why these fevers happen I don't know - they really seem out of the blue, but typically occur in the wee hours of the morning (I'm usually awake then).

 

[Groggy Doggy]

I apologize if the following has already been addressed a dozen times thusfar…

I have a question about the relationship between PEM and hypometabolism.

The "dauer" state to me evokes a static state with little fluctuations, whereas my experience of this illness is roller coaster like - from my baseline (very poor to begin with), then down into PEM, and back up to my baseline, and so on.

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

I am asking because PEM doesn't feel like a shut-down, but more like a sudden activation. Not a quantitative change but a qualitative one - I don't just feel "more" exhaustion than hours earlier, but rather as though a process of a different nature had kicked in (it lasts 3 days, happens almost every week …I never learn…), a process in which my metabolism, far from going quiet, seems to be "roaring" inside (heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out)

Rather than some intensified dauer state, could these shifts between baseline and PEM consist of a to and fro between dauer and cdr? Could the marked fluctuations in ME/CFS reflect swings between hypo and hyper states?

I am at the 3 year mark, and suffer from intermittent states. I ping pong back and forth from a mild hypo state to a hypo state depending on different environmental factors (outside temperature, and seasonal influences). I also experience minutes (up to one hour) of feeling almost completely normal. So because of my ongoing daily fluctuations, (mild hypo, hypo, normal) my symptoms do not align with Naviaux's theories/models.

 

[Kati]

I am at the 3 year mark, and suffer from intermittent states. I ping pong back and forth from a mild hypo state to a hypo state depending on different environmental factors (outside temperature, and seasonal influences). I also experience minutes (up to one hour) of feeling almost completely normal. So because of my ongoing daily fluctuations, (mild hypo, hypo, normal) my symptoms do not align with Naviaux's theories/models.

I don't think you can be certain until you get the metabolomic testing. You could be surprised of the findings.

 

[halcyon]

How much are they charging?

The authors on this paper from Gordon weren't even open to patients when I inquired. I'm scared to know how much they charge. Their second string doctors in the office ranged anywhere from $400 to $700+ per visit if I recall correctly.

 

[geraldt52]

The authors on this paper from Gordon weren't even open to patients when I inquired. I'm scared to know how much they charge. Their second string doctors in the office ranged anywhere from $400 to $700+ per visit if I recall correctly.

I'm not a patient of Gordon Medical, but I did inquire once. I believe the figures you quote were for the initial visit, with follow up visits much less. They also accepted no forms of insurance, at least at that time.

 

[cmt12]

I apologize if the following has already been addressed a dozen times thusfar…

I have a question about the relationship between PEM and hypometabolism.

The "dauer" state to me evokes a static state with little fluctuations, whereas my experience of this illness is roller coaster like - from my baseline (very poor to begin with), then down into PEM, and back up to my baseline, and so on.

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

I am asking because PEM doesn't feel like a shut-down, but more like a sudden activation. Not a quantitative change but a qualitative one - I don't just feel "more" exhaustion than hours earlier, but rather as though a process of a different nature had kicked in (it lasts 3 days, happens almost every week …I never learn…), a process in which my metabolism, far from going quiet, seems to be "roaring" inside (heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out)

Rather than some intensified dauer state, could these shifts between baseline and PEM consist of a to and fro between dauer and cdr? Could the marked fluctuations in ME/CFS reflect swings between hypo and hyper states?

Thank you … (thank you @Rose49 , thank you Ron Davis, my best wishes to your son, my thoughts with your daughter as well, thank you Linda Tannenbaum, thank you Dr Naviaux et al. of course, thank you @Ben Howell , and while I'm at it, thank you to all the wonderful interlocutors here on PR!)

Your assessment that there is more going on is correct. My view is that there are at least two different categories of fatigue. There is the static, flu-like fatigue and then the PEM fatigue that is infrequent but crushing.
*Different types of fatigue in that they are derived from a different source rather than simply different levels of severity of the same category of fatigue (aka there is more to the puzzle than a stuck dauer state).

 

[picante]

I've been trying to understand "dauer" and Googled it but still not sure exactly what it means. What would be the best translation or most similar word in English?

I haven't got through this thread by any means, but this word has been vexing me, too. It's German. If I want a better (more transparent) word, I guess I would start with the German-English dictionary on linguee:
Dauer Substantiv, feminin
duration n (meistens verwendet)
Die Dauer der Tests wird zwei Wochen nicht überschreiten. The duration of the tests will not exceed two weeks.
period n
term n
seltener: [less often]:
life
length
length of time
standing
permanence
durability
time span
endurance
continuity
perpetuity
lifespan
shelf life
continuance

Of all these equivalents, my favorite by far is "shelf life". We've got a very looooong shelf life in this metabolic state of ours.

 

[Forbin]

Although it seems to translate to something like either "persistence" or "endurance," I get the feeling that "dauer" in this context is more akin to "hunkering down." This seems to be what the C. elegans larvae are, doing - i.e. forestalling maturation until conditions are more favorable.

To hunker down is also to be prepared to stay in a particular place or situation for as long as necessary, esp. for protection or to achieve something.

We hunkered down in the cellar while the storm raged outside.

http://dictionary.cambridge.org/us/dictionary/english/hunker-down

 

[picante]

Well, without having read the previous messages, I just wanted to share my analysis on the paper that I have made in Spanish:

Wonderful! Translators are essential in getting the word out.

 

[KME]

I apologize if the following has already been addressed a dozen times thusfar…

I have a question about the relationship between PEM and hypometabolism.

The "dauer" state to me evokes a static state with little fluctuations, whereas my experience of this illness is roller coaster like - from my baseline (very poor to begin with), then down into PEM, and back up to my baseline, and so on.

Would a crash in the context of Dr Naviaux's ideas simply be a process where I suddenly "hypometabolize" myself even more??

I am asking because PEM doesn't feel like a shut-down, but more like a sudden activation. Not a quantitative change but a qualitative one - I don't just feel "more" exhaustion than hours earlier, but rather as though a process of a different nature had kicked in (it lasts 3 days, happens almost every week …I never learn…), a process in which my metabolism, far from going quiet, seems to be "roaring" inside (heart pounding, ears ringing, increased insomnia, and above all, fever-like cerebral malaise that knocks me out)

Rather than some intensified dauer state, could these shifts between baseline and PEM consist of a to and fro between dauer and cdr? Could the marked fluctuations in ME/CFS reflect swings between hypo and hyper states?

Thank you … (thank you @Rose49 , thank you Ron Davis, my best wishes to your son, my thoughts with your daughter as well, thank you Linda Tannenbaum, thank you Dr Naviaux et al. of course, thank you @Ben Howell , and while I'm at it, thank you to all the wonderful interlocutors here on PR!)

I think this is a great question relating to this study, as any model of ME/CFS has to be able to explain PEM. I suspect Naviaux et al and Davis would be able to offer a nice theory if asked (maybe @Ben Howell ?) that would tie in well with their findings.

I suspect it would be something along the lines of patients being in a hypometabolic state, with purposely limited ATP production, trying to do some non-hibernating/non-dauer activities, i.e. those that only people in normal metabolic states can do comfortably/safely/without PEM. At a certain point instead of having limited ATP, you have none, 'cos you squandered it all on activities that were beyond you, so you have a sudden crash (or a more gradual one if you got down to very very little ATP instead of none). With complete rest you then gradually build up enough ATP again to get back to the limited levels you need to "just" be in dauer, so you're more comfortable, i.e. you still have ME/CFS but you don't have active PEM.

Kind of like you're on a low income but then you buy a designer outfit, totally out of your price range, so you then can't afford food that month. On your low income you can usually afford food, but once you blow your budget, you cannot afford food (aka have PEM). Or you don't buy a designer outfit but you just buy lots of little things that add up to more than your low income can accommodate that month. Myhill's explanations might be helpful if this makes no sense.

 

[adreno]

at a certain point instead of having limited ATP, you have none, 'cos you squandered it all on activities that were beyond you, so you have a sudden crash

I think this makes sense. A crash is likely a ATP deficient state, or expressed another way, a ATP debt is owed.

 

[Mij]

I'm beginning to feel that prolonged ATP depletion is irreversible damage to the mito membrane and the cell dies. We can only protect the new mitos (that may not be as efficient) to prevent worsening.

 

[Janet Dafoe]

I'm beginning to feel that prolonged ATP depletion is irreversible damage to the mito membrane and the cell dies. We can only protect the new mitos (that may not be as efficient) to prevent worsening.

I'm wondering what you base this on? Any data? Why do you think this?

 

[Mij]

Hi @Rose49 my M.E doctor and integrative functional doctor was telling me this years ago. After being ill for over 25yrs and overdoing (including aerobic exercise ) over and over again my PEM has gotten a lot worse and has stayed there. I have never gone back to baseline to where I was more functional. I avoid overdoing so I haven't had PEM in over a year, but if I go over just a little I'm down.

My doctor explained to me that constant mtdna damage cause cells to die.

There are a lot papers on this subject:

http://www.humpath.com/spip.php?article8790

 

[Seven7]

I wonder how my remissions on other viruses (colds, and Zica) fit with all this. I used to get remissions with my periods but now I only get significant better (would not call remission).

Also, I have been trying to repair my anaerobic thresh hold for 5 years ( is 115BPM) but no matter what I do is like whatever aerobic capacity I lost, is gone for ever. I can recover up to certain point then I hit a wall (about 70 to 80%).