Poll: Are most ME symptoms in beginning driven by drastic impairment of glucose metabolism?

[Judee]

that the viral infection caused an aberrant immune response that then, through some signalling, caused the downregulation or impairment of glucose as fuel for cellular respiration?

Yes, that too. The virus causes a sort of short-circuit in all of our systems--cns, endocrine, autonomic, etc.

And depending on the degree of the resulting continually compounding damage, things like antivirals will either work or they won't. I think that's why doctors like Montoya say the longer we have this the harder it is to treat with the antivirals.

@leokitten, I hope this is more helpful to you than my original post.

 

[leokitten]

FWIW ..I thought you were making assumptions by taking this poll on glucose metabolism

People make polls to ask what other people think on PR, based on plenty of real scientific and anecdotal evidence, not based on any assumptions.

 

[leokitten]

Actually, I think they are still driving our symptoms to some extent.

For instance, this article talks about the stealthiness of EBV and its ability to hide in our B cells and camouflage itself.

The author states that, "...the virus has a card up its sleeve. Unlike most infections, it isn’t conquered by the immune response. Instead it waves a white flag and retreats into hiding, lurking inside B cells – a type of white blood cell in the immune system." (That 'B cells' link is not mine but from the article and takes you to Wikipedia for an explanation of B cells. It may not work from here but I wanted to put that out just in case someone is curious why it is blue.)

https://scienceblog.cancerresearchu...rus-and-the-immune-system-are-cures-in-sight/

And if I am understanding the videos and documentation by Dr Montoya UC Berkeley, he believes this too. He uses the term virus-reactivation a lot.

I'm thinking that a lot of viruses have a camouflage system and that seems to be confirmed by this PR thread.

What about this theory, which is completely plausible and not at all a stretch:

The reason PWME possibly have problems from chronic reactivation of ubiquitous viruses that exist in almost every adult, is because of impaired cellular respiration and function affecting all cells including, and most importantly, NK and other immune cells that are supposed to keep these viruses suppressed like they do in healthy people.

So by getting metabolic problems in order then the immune system will start suppressing viral reactivation again. Herpes and other viruses that live dormant are always looking for signals of immune weaknesses in order to reactivate.

 

[ebethc]

People make polls to ask what other people think on PR, based on plenty of real scientific and anecdotal evidence, not based on any assumptions.

can you please post the scientific study that says glucose metabolism causes cfs?

 

[Hip]

I found the work of some German researchers on coxsackievirus B myocarditis very interesting. They found that CVB infection induces an autoantibody which targets and impedes mitochondrial function, which they think is the cause of the energy deficit in the heart muscle in myocarditis. I posted some info about their research in this post.

 

[leokitten]

can you please post the scientific study that says glucose metabolism causes cfs?

No where in this thread did I ask about the root cause(s) of ME. In fact, I explicitly wrote to specify that I’m asking if people think glucose metabolic dysfunction could be a main downstream cause and driver of symptoms. I wrote that because I knew people would just misunderstand the poll.

Some of the scientific evidence that cellular metabolic dysfunction, in particular involving glucose metabolism, is a major player in ME/CFS:

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.

Metabolic features of chronic fatigue syndrome.

Metabolism in chronic fatigue syndrome.

 

[ebethc]

No where in this thread did I ask about the root cause(s) of ME. In fact, I explicitly wrote to specify that I’m asking if people think glucose metabolic dysfunction could be a main downstream cause and driver of symptoms. I wrote that because I knew people would just misunderstand the poll.

Some of the scientific evidence that cellular metabolic dysfunction, in particular involving glucose metabolism, is a major player in ME/CFS:

Cellular bioenergetics is impaired in patients with chronic fatigue syndrome.

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome.

Index markers of chronic fatigue syndrome with dysfunction of TCA and urea cycles.

Metabolic features of chronic fatigue syndrome.

Metabolism in chronic fatigue syndrome.

none of those mention glucose, so there's no scientific proof after all...

I guess I don't know what your point is... I agree that glucose is impacted in CFS, but neither one of us has proof... Dr Maureen Hanson is testing some metabolic measures like lipid metabolism, and maybe she's testing glucose metabolism, but I haven't seen any published results..

 

[alex3619]

none of those mention glucose, so there's no scientific proof after all...

I guess I don't know what your point is... I agree that glucose is impacted in CFS, but neither one of us has proof... Dr Maureen Hanson is testing some metabolic measures like lipid metabolism, and maybe she's testing glucose metabolism, but I haven't seen any published results..

Not so. There is a lot of work on glycolysis. Glycolysis is the energy pathway for glucose. Proof is something else though. Science is not about proof as much as people like to think, but best evidence and explanation. One good new study could change everything. Furthermore we have sepsis as the metabolic twin for ME. In sepsis there most definitely is a glucose problem, very similar to what we see in ME. Again this is cutting edge research, and it might be overturned or only be for a subgroup, but right now this is what we know.

What I am curious about is the data showing that the expressed gene changes found in ME match those in African Sleeping Sickness.

I understood this thread to be about symptoms downstream of changes in glucose metabolism. This would include evidence of altered aerobic metabolism, altered glycolysis, elevated lactate, and blocks at pyrovate dehydrogenase, amongst other findings.

The whole point of this shift, in sepsis at least, is to stop the body using glucose, and lowering the oxygen need, so the immune system can focus on glycolytic use of glucose to fight for survival, without much mitochondrial energy production. This can produce energy much faster than with mitochondria, but its very demanding on glucose supply.

 

[ebethc]

Not so. There is a lot of work on glycolysis. Glycolysis is the energy pathway for glucose. Proof is something else though. Science is not about proof as much as people like to think, but best evidence and explanation. One good new study could change everything. Furthermore we have sepsis as the metabolic twin for ME. In sepsis there most definitely is a glucose problem, very similar to what we see in ME. Again this is cutting edge research, and it might be overturned or only be for a subgroup, but right now this is what we know.

What I am curious about is the data showing that the expressed gene changes found in ME match those in African Sleeping Sickness.

I understood this thread to be about symptoms downstream of changes in glucose metabolism. This would include evidence of altered aerobic metabolism, altered glycolysis, elevated lactate, and blocks at pyrovate dehydrogenase, amongst other findings.

The whole point of this shift, in sepsis at least, is to stop the body using glucose, and lowering the oxygen need, so the immune system can focus on glycolytic use of glucose to fight for survival, without much mitochondrial energy production. This can produce energy much faster than with mitochondria, but its very demanding on glucose supply.

I believe you... I agree w you... read the thread..

 

[bertiedog]

So glucose metabolism is shut down generally, and ramped up in the immune system.

One of the first symptoms that caused me massive issues at the beginning of my illness in the 80s was an abnormal response to glucose, although I didn't know it then, I just got horrendous hypoglycaemic attacks. I have lost count of the many times it caused me to practically fall off the chair I was sitting on because I was so dizzy. In the end the only way I could stabilise my blood sugar and stop it from dropping so low and so very quickly was low dose Prednisolone and no sugar and more fat.

It's hugely improved with a higher fat, good protein and lower carb diet but the way my body handles glucose is still abnormal even on Pred but I no longer see numbers that are less than 4.7 and therefore I feel a lot better for that and most days can exercise to quite a good level even doing 13000 steps the other day when on a Spa break which involved lots of rest. I should stress that is not normal for me, usually when at home it's more like 8500.

I still get PEM and am suffering with this today having got lost in the woods yesterday! There is no energy in my legs and my body is tiring very quickly and I realise that this is what so many with ME have daily. Again I relate to this because I am exactly the same when I have a virus or infection and these can be very frequent at times.

I am convinced there is something very "off" with the way our bodies handle glucose but I also believe that there has to be something more than this to cause all the symptoms we experience.

Pam

 

[alex3619]

One of the first symptoms that caused me massive issues at the beginning of my illness in the 80s was an abnormal response to glucose, although I didn't know it then, I just got horrendous hypoglycaemic attacks.

I was considered diabetic due to high blood sugar, but back when I was regularly testing I got what seemed like hypoglycemic attacks. So I checked my blood sugar - well below the minimum for the normal reference range, and glucose or other carbs reversed it fairly fast. Supposedly this cannot happen in type 2 diabetes, and this was the first sign that I might have something else. To this day the picture is not clear. It now seems that it might indeed happen in sepsis and ME. We need more science, more data, and better hypotheses.

 

[Wishful]

So all of your ME symptoms are only brought about from mental exertion? You could do any amount of exercise and nothing happens related to ME?

Not exactly. Most of my symptoms exist at a baseline level regardless of activity--physical and mental--and diet, sleep, etc. Physical activity that I am accustomed to, such as walking or biking, I can (and have) done for hours without triggering PEM of otherwise affecting my ME symptoms. Even a few minutes of activity that I am not accustomed to, such as washing windows or climbing a ladder (strains muscles past the limits normal for walking/biking) can trigger PEM 24 hrs later, although I now block this by taking cumin. Cumin doesn't block the PEM-like response to mental activities such as driving or socializing, so it's not exactly the same as the physically-induced PEM. T-cell activation from other causes, such as viral infections, produce the same sort of symptoms as physically-induced PEM (which makes me believe that IFN-g is involved).

Since the thread is about glucose metabolism, I'll say that I believe that my glucose metabolism is working fine, and that metabolizing glucose doesn't affect my ME symptoms.

 

[Wishful]

Some of the scientific evidence that cellular metabolic dysfunction, in particular involving glucose metabolism, is a major player in ME/CFS:

"Is a major player" is not the same as "being a core factor". It could just as well be a common secondary effect of ME/CFS. The research papers you listed likely don't cover all ME/CFS subgroups. They likely are studying one or more of the larger subgroups, so their findings of metabolic dysfunction are common to those subgroups. They might not have had a patient from the subgroup without metabolic dysfunction. Thus their understanding of ME/CFS is incomplete.

We'll just have to wait for the researchers to understand all the pathways involved. They might find a specific reaction that leads to glucose metabolism dysfunction, but find that the cause of that lies elsewhere, perhaps in the immune system.

 

[leokitten]

We'll just have to wait for the researchers to understand all the pathways involved. They might find a specific reaction that leads to glucose metabolism dysfunction, but find that the cause of that lies elsewhere, perhaps in the immune system.

I totally agree with this. As mentioned above, this poll is not about upstream causes, just to ask the question whatever upstream chain of events causes glucose metabolic dysfunction and that this upheaval of cellular energy generation is actually driving most symptoms.

My ME started with a strong viral-like illness and 2 week fever with large and hard lymph nodes on neck and groin. My EBV/CMV/HHV-6 titers were off the charts when doctors finally thought they should look at those a few months later. The thing is I'm not so sure now, 5 1/2 years later, these viruses are still causing the downstream effects and keeping me in a disease state. I took Valcyte + Famvir for years. Also Immunovir for probably a year or so along with those. I still take Famvir every day. These drugs have done nothing and for most people who had suspected herpes viral triggered ME these drugs don't improve the disease. I agree with you and I think, if anything, the immune system is stuck after the initial trigger and there is a direct interplay with cellular metabolic dysfunction in a big subgroup.

 

[Wishful]

Yes, the immune system being stuck in an abnormal state is my favorite hypothesis. I think it's specifically the microglial cells, and that the kynurenine balance is involved, which in turn is strongly affected by mitochondrial metabolism (specifically superoxide/peroxynitrite production). I have no problem imagining that glucose metabolism would also be affected as a secondary effect.