The Stanford Paradox: Elevated Energy Production Found in Chronic Fatigue Syndrome (ME/CFS)

[AndyPR]

Article on a study which was discussed on the forums here - http://forums.phoenixrising.me/inde...n-in-chronic-fatigue-syndrome-patients.47443/

Producing energy is a big problem in Chronic Fatigue Syndrome (ME/CFS). In fact it’s probably the problem in ME/CFS, which is why the findings of mitochondrial dysfunction and lowered ATP production have made sense. When the metabolomics studies suggested that chronic fatigue syndrome (ME/CFS) was a hypometabolic state, the field seemed set: energy production (ATP) was low and the mitochondrial activity probably was too. Fatiguing disease and low ATP production: it seemed to make so much sense.


Last year the Xinnan Wang lab produced a breakthrough in understanding Parkinson’s disease

Then came the study with the eye-catching title: “Elevated Energy Production in Chronic Fatigue Syndrome Patients.” It suggested that far from being low, cellular energy production was actually abnormally high in ME/CFS patients. Even for a field that’s had more than its share of inconsistent findings, that was a real lu-lu.

The results, though, could not be ignored. They didn’t come from a small research group but from the Xinnan Wang Lab at Stanford. Last year the lab – which is devoted entirely to studying the mitochondria – made headlines with its potentially seminal finding in Parkinson’s disease. It uncovered a defect that prevented Parkinson’s patients from removing their mitochondria as their mitochondria start to wear out. That defect left those mitochondria pumping toxins into the brain. Because the defect was present in different types of Parkinson’s patients, it suggested that a “mitochondriopathy” might lie at the core of the disease.

Plus the patient samples in the Wang ME/CFS study came from some of our best ME/CFS experts. Plus it was funded by an ME/CFS group – the Chronic Fatigue Initiative – that hires only the best researchers. There was no looking past this result.

https://www.healthrising.org/blog/2...duction-found-chronic-fatigue-syndrome-mecfs/

 

[Aroa]

At the end of this article Cort said :

"...Naviaux’s follow up to his striking ME/CFS metabolomics study should be done this year (and published next).."

Does it mean that they may now prioritize Ron´s studies ?

 

[JaimeS]

If this is the study I think it is, they grew the mitochondria in an amino acid-rich medium; that is, they removed it from the environment of CFS plasma and popped it into an environment that was rich with resources the mitochondria needed: to wit, amino acids, which have been shown to be favored by cellular respiration in ME/CFS patients (proteins and fats over carbohydrates).

What this implies to me is that the mitochondria may have made fundamental shifts in order to do their jobs in the environment of ME/CFS patient plasma. It does not (necessarily) follow that this greater energy output occurs within the body of the patient at all, where fewer resources may be available.

J

 

[Alvin2]

I can't say i fully understand this (and my information comprehension is at maybe 50% right now) but it may be that they are reading a compensatory mechanism lower the main source raised by a compensatory source, and end up with less total but more then expected from an alternate source.
Assuming OMF knows about this study i suspect they will figure it out

For that Parkinsons study they don't explain in much detail, and they seem to not be interested in alpha synuclein which has been shown to be very involved in Parkinsons.

 

[lilpink]

I'd be curious to know what that means for someone who can no longer eat vegetables and has to survive mainly on carbs and some animal protein.


Edit: I appreciate what we eat and cell milieu isn't the same per se.

 

[Daisymay]

If this is the study I think it is, they grew the mitochondria in an amino acid-rich medium; that is, they removed it from the environment of CFS plasma and popped it into an environment that was rich with resources the mitochondria needed: to wit, amino acids, which have been shown to be favored by cellular respiration in ME/CFS patients (proteins and fats over carbohydrates).

What this implies to me is that the mitochondria may have made fundamental shifts in order to do their jobs in the environment of ME/CFS patient plasma. It does not (necessarily) follow that this greater energy output occurs within the body of the patient at all, where fewer resources may be available.

J

Thanks for the explanation Jamie. Is there any consensus as to whether PWME should be increasing their protein/AA intake or is it too soon to say as it may not be as simple as that?

 

[JaimeS]

Too soon to say it's as simple as that, I think, @Daisymay -- I definitely feel best when I eat more protein and healthy fats, and fewer carbs. I can even say pretty confidently that too many carbs / sugar make my symptoms much worse, and there was a time I could not tolerate them at all. This doesn't seem directly connected to pathogenic bloom, either.

But this is an individual response!

 

[Effi]

I definitely feel best when I eat more protein and healthy fats, and fewer carbs. I can even say pretty confidently that too many carbs / sugar make my symptoms much worse, and there was a time I could not tolerate them at all.

I'm exactly the same: more protein, more veg, less carbs. Sugar/carbs make my symptoms much worse. But one thing I have found out is that AFTER I have overdone things mentally (concentrated too long/too much), a fast-absorption sugar (like pure dextrose tablets) make me feel a bit better. I have experimented a bit with this, i.e. tried to take the dextrose BEFORE concentrating to see if that would lengthen my concentration span, but it doesn't do anything, and might even make me feel a bit worse. I am curious as to what the mechanism would be behind this... (Sorry if this is off topic.)

 

[JaimeS]

Same @Effi. Once in a great while, I need sugar desperately. Not sure what's behind it.

 

[Forbin]

What this implies to me is that the mitochondria may have made fundamental shifts in order to do their jobs in the environment of ME/CFS patient plasma. It does not (necessarily) follow that this greater energy output occurs within the body of the patient at all, where fewer resources may be available.

Yeah - It's probably a weak analogy, but, as I was reading Cort's article, the metaphor that came to mind for cells in serum was of a car in which both the gas and and brake were being applied at the same time. The engine is revving high (as the cells try to compensate for "starvation"), but it is going nowhere. Take the cells out of the serum and you remove the brake - and the car runs off way too fast.

 

[JaimeS]

I like it, @Forbin

 

[Daisymay]

Too soon to say it's as simple as that, I think, @Daisymay -- I definitely feel best when I eat more protein and healthy fats, and fewer carbs. I can even say pretty confidently that too many carbs / sugar make my symptoms much worse, and there was a time I could not tolerate them at all. This doesn't seem directly connected to pathogenic bloom, either.

But this is an individual response!

I'm the same. I too feel better eating more protein, well meat actually which wasn't that easy for a vegetarian of some years but I do feel I really need it.

 

[BruceInOz]

What this implies to me is that the mitochondria may have made fundamental shifts in order to do their jobs in the environment of ME/CFS patient plasma. It does not (necessarily) follow that this greater energy output occurs within the body of the patient at all, where fewer resources may be available.

The part of the study that found increased cristae in the mitochondria does seem to saying that "the mitochondria may have made fundamental shifts in order to do their jobs in the environment of ME/CFS patient plasma". I.e., something in the serum prevents the utilisation or production of ATP so the mitochondria get the signal they need to increase production so increase the cristae density. Then when out of the serum they produce more ATP.

Will be very interesting if Wang gets to compare in and out of the serum as she said she would like to.

 

[Murph]

Some good news from the piece here:
--

> When I asked, though, which diseases from a mitochondrial standpoint ME/CFS is most similar to, Dr. Wang mentioned cancer. Since we know that the PBMCs Dr. Wang was studying do not come from cancer patients, it appears that we and the medical world are probably in for some surprises: something different is causing these cells to act the way they are.


"Cancer patients have increased glycolysis rates and disruption of their mitochondrial metabolism – it is called Warburg theory. It believes that mitochondria do not function well to produce enough ATP in patients’ cells and as a compensation to meet the high ATP demand glycolysis is upregulated," Wang said.
--

The overlap with cancer is a real piece of good fortune. This means we have a giant workforce of people with potentially relevant expertise who could flood into the field if it got funding and/or if a single major study showed a way their metabolism research might hold the key to ME/CFS.

Even absent such a funding influx, progress in cancer research and drug development (one of the best funded diseases in the world) is likely to yield clues and maybe even approved treatments that can be repurposed.

 

[rosie26]

Yeah - It's probably a weak analogy, but, as I was reading Cort's article, the metaphor that came to mind for cells in serum was of a car in which both the gas and and brake were being applied at the same time. The engine is revving high (as the cells try to compensate for "starvation"), but it is going nowhere. Take the cells out of the serum and you remove the brake - and the car runs off way too fast.

That's exactly how it was for me at my severe onset. The first 2-3 years I was stuck in this position. I hope I never experience the this full-blown level again. Unbearable stuff..

 

[wastwater]

Just putting down a marker to follow this thread

 

[AndyPR]

Just putting down a marker to follow this thread

There is always the "Watch Thread" button that will do the same thing. It's just above the original post in each thread and above the first post on every subsequent page in a thread.

 

[lilpink]

I can even say pretty confidently that too many carbs / sugar make my symptoms much worse, and there was a time I could not tolerate them at all

It is very individual. I'm the opposite as regards carbs and always have been.

 

[Gijs]

Why paradox? We have at least 2 types of ME patiënts: 1. overactive ANS, 2. underactive ANS.

 

[anni66]

Sarah Myhill identified 2 distinct groups - this related to how energy was produced- one group was problems with pyruvate ( glycolysis) . It was in her last joint paper.