Elevated Energy Production in Chronic Fatigue Syndrome Patients

[alex3619]

Maybe this is a local effect, while the global situation is that of hypometabolism.

Yes, but you also have to take into account temporal effects. Its not only a spacial average, its a time average as well. Production and use might vary by time of day, depending on circadian or other timed factors. One of the reasons I did my biochem degree was because I got lost trying to figure out tissue and circadian factors in these things. I still get lost of course, this is complex stuff.

For example, you could have some chemical produced at a particular level, or it could be produced at a low level except for a major spike, etc. Something like that happens with some hormones.

 

[Valentijn]

Very interesting. Hyper-glycolysis might explain my constant sugar craving. Not sure if other people get that too?

Sometimes, but just when I moderately over-exert.

Of course these are white blood cells that are being used not muscles, so maybe they are working harder fighting infections or something? (Free-wheeling with ideas now). I wonder what a comparison of muscle mitochondria would look like?

I think one theory regarding Naviaux's findings was that some functions (energy to function) were getting down-regulated because the focus was on ramping up the immune system instead.

 

[alex3619]

Is glucose uptake a different process from glycolysis? I may be misunderstanding the processes.

Glycolysis is how the cell uses glucose to create energy, and feeds into the mitochondrial energy production. Glucose uptake is about the cell's ability to absorb glucose from the bloodstream, at least that is how I recall it.

 

[trishrhymes]

I wonder whether the monocytes are producing more energy in ME patients is because these are the cells involved in immune reactions. Maybe these cells need more energy but their mito can't respond sufficiently so they use more glycolysis to produce the energy.

Maybe I don't know what I'm talking about.

Clearly something is different in the energy production system. Looks like there's a way to go before we know what.

Scientifically absolutely fascinating. As a patient, endlessly frustrating.

 

[Keela Too]

Sounds reasonable @trishrhymes

 

[Cheesus]

Could it be that we have excess ATP because we are unable to utilise it properly, so the body produces more to try and compensate?

 

[J.G]

Thinking about it some more, this paper by @ChrisArmstrong and colleagues comes to mind, stating he and colleagues believe glycolysis might be inhibited and (some form of) amino acid catabolism may be taking up the slack as a source of ATP production. But the Lawson paper finds elevated ATP from non-mitochondrial sources, likely glycolysis. I'm not sure if this circle can be squared, or if either theory has got to give.

 

[Keela Too]

Would amino acid catabolism be a non-mitochondrial source of ATP? .

Hmmmm - I'm trying to remember, but I "think" amino acids still feed into either the lower part of Glycolysis or the Kreb's Cycle and from there into the Electron Transport Chain... would need to check.

Okay found this quote when I did a search (site is slow to load, but below is the quote beneathe the link when I did the search.... it's what I thought.)
https://www.khanacademy.org/science...tween-cellular-respiration-and-other-pathways

"Amino acids, lipids, and other carbohydrates can be converted to various intermediates of glycolysis and the citric acid cycle, allowing them to slip into the cellular respiration pathway through a multitude of side doors"

 

[Simon]

My memory was that she did find a glycolysis problem. Have I remembered wrong?

Well, glycolysis can go to lactate or go to pyruvate and wasn't producing the pyruvate needed. The block was at the end of glycolysis, but glycolysis itself was producing ATP

 

[alex3619]

Could it be that we have excess ATP because we are unable to utilise it properly, so the body produces more to try and compensate?

Yes, I think it could.

PS A further possibility is we are not producing much ATP but have geared up for it, but simply cannot use it much and so it accumulates.

 

[Gijs]

Yes, I think 4 times so far, 2 USA, 1 Japan, and 1 Norway. ATP and general metabolites are not the same. Also using ATP to do things will require other things being present, including metabolites. If we are forcing ATP production to try to do things, then it seems the problem may not be mitochondrial, and something is blocking us using ATP rather than making it. That might even be autoantibodies.

Please keep in mind that this finding is new and we need more research.

These studies didn't find the same metabolic problems. Their findings are totally different!

 

[alex3619]

These studies didn't find the same metabolic problems. Their findings are totally different!

There are still lots of questions, and lots of research needed. We definitely don't have the answers yet. What we have are intriguing questions.

I actually expect to see differences. Something like this I would expect to be a spectrum issue. I want to see all this research published though so we can look at the details. So far we have very few details for most of it.

 

[Gijs]

There are still lots of questions, and lots of research needed. We definitely don't have the answers yet. What we have are intriguing questions.

I actually expect to see differences. Something like this I would expect to be a spectrum issue. I want to see all this research published though so we can look at the details. So far we have very few details for most of it.

I agree. Very intriguing guestions. If there is a guestion, there is an answer. We still can't find it. The more i read about this disease the more absurd it becomes. It is against all scientific paradigms.

 

[anciendaze]

All these vital metabolic cycles involve feedback. Any defect which is not lethal in a rather short term will necessarily involve feedback attempting to correct it. One indication of increased glycolysis has turned up, but that is a small part of the cycle. I've been asked about low levels of pyruvic acid before, and they are also part of that cycle.

Other research indicates we enter anaerobic metabolism at unusually low levels of exertion, and this gets worse during PEM. Anaerobic glycolysis appears to be part of the problem. Even a simplified diagram of the cycle shows that this important metabolic pathway is far from simple.

And, just reporting for myself, I do have a constant craving for sweets that I have to control. I assume this indicates a shortage of energy, but attempting to get doctors to follow this up in any useful way has been futile. The last time I took a glucose tolerance test it took me three days to recover, which sounds like PEM.

 

[A.B.]

And, just reporting for myself, I do have a constant craving for sweets that I have to control. I assume this indicates a shortage of energy, but attempting to get doctors to follow this up in any useful way has been futile. The last time I took a glucose tolerance test it took me three days to recover, which sounds like PEM.

I have to eat every 3-4 hours. It seems that the transition into a fasting state is problematic. I can also feel the after effects of episodes of significant hypoglycemia for about two days.

 

[Barry53]

@Keela Too yes muscle version of study definitely worth knowing.

Is all that energy going to the immune system? Baffling.

I cannot pretend to understand the medical knowledge you all have, but I have been pondering something similar from a simple physics point of view.

My wife eats normally, so energy is going into her system at a normal rate. But she can only walk very slowly, and needs lots of breaks/rests no matter what she does, so energy is usefully consumed much more slowly than normal. But energy in has to equal energy out, so there is lots of energy going somewhere else, wasted. Basic rule of physics. So where does all that wasted energy go? I'm guessing (hoping) it is not just my wife this conundrum applies to.

Some excess energy gets dumped when she overheats (a symptom I gather is common for many with ME/CFS), but I doubt that accounts for all of it by any means. Does some of it just go "down the pan" (trying to be delicate here!), simply not absorbed by the body at all? Or does it get dissipated some other way?

Energy cannot simply disappear, and the only evidence I see of excess energy dissipating is my wife overheating. I would be really interested to know where the rest of it goes.

 

[RogerBlack]

Energy cannot simply disappear, and the only evidence I see of excess energy dissipating is my wife overheating. I would be really interested to know where the rest of it goes.

Overheating - not wearing as many clothes as you otherwise might and feeling OK - can eat up quite a lot of energy.
It would be interesting to know resting metabolic rate of CFS patients and controls.

 

[RogerBlack]

This is needed to determine the tissue distribution. Indeed if it were not unethical and very dangerous, I would want to know about nerve mitochondria as well.

Doesn't the tongue have renewable nerves that could be sampled?
Also, deep skin biopsies.
Perhaps not enough.
I know I'd sacrifice a toe

 

[Barry53]

I do have a constant craving for sweets

My wife and I have discussed this, and we conclude (just our own belief I emphasise) it is the body's/brain's evolved survival response to the body being low on useful energy. For a normal healthy person it is a quick-fix mechanism that we have.The trouble is of course, if you have ME/CFS it doesn't work, because most of that quick-fix energy does not do anything useful at all.

 

[Cheesus]

Doesn't the tongue have renewable nerves that could be sampled?

I think there are regenerative nerves in the sinuses/nose, as I read somewhere they were using them experimentally to treat paralysis in animals.