Organic Acid Test (OAT) results – do we ALL show the Warburg effect?

ljimbo423

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Adding my results of Lactate/Pyruvate. I have a high Pyruvate, and low ratio.
I'm not sure if I understand correctly, can anyone advise me how to read this result?
I read your results the same way you do. High pyruvate, normal lactate and a low lactate to pyruvate ratio.

I think they calculate the lactate to pyruvate ratio by dividing your lactate level by your pyruvate level. Which equals 6.64, as it says. 9.5 (lactate) divided by 1.43 (pyruvate) = 6.64
 

ljimbo423

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Do you know what this result - High pyruvate, normal lactate and a low lactate to pyruvate ratio may point to?
I'm really not sure. This might be one possibility.

There have been one or 2 studies that have shown the Pyruvate Dehydrogenase (PDH) Enzyme is impaired in ME/CFS. That could cause an elevated level of Pyruvate.

Because PDH is needed to process Pyruvate, so that it can fuel the Krebs cycle also known as the Tricarboxylic acid cycle. If PDH isn't functioning right, Pyruvate can build up, because it's not be used. High Pyruvate and normal Lactate levels would also cause the Lactate to Pyruvate ratio to be low.

Vitamin B-1 is a co-factor that is needed for PDH to function normally. Alpha Lipoic Acid helps to block Pyruvate Kinase. Pyruvate Kinase can impair the functioning of PDH. So one or both of these supplements might help you.

I take both and they help me quite a lot.
 
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Here is a new paper on the Warburg Effect (AKA aerobic glycolysis)

Increased demand for NAD+ relative to ATP drives aerobic glycolysis (Luengo et al., 2021)
https://www.cell.com/molecular-cell/fulltext/S1097-2765(20)30904-7
Excerpt:
Thanks for posting the link. I loved this paper. Nice disocvery. So one possiblity is one could try supplmenting NAD+ and see what happens. If one is not going thru krebs cycle but getting anerobic glyoclosis (fermentation) instead becasue of a mitochondiral resperiation problem (as some say happens in CFS) then boositing NAD+ levels should do absolutely nothing to energy levels etc. If on the other hand, this is happening (i.e. les Krebs, more fermentation) because the demand for NAD+ is greater than teh demand for ATP (as per the author of this recent paper), then by giving the body all the NAD+ it wants, that should restore normal Krebs. I myself won't be trying this experiment though i can see others wanting to do this. For me, I keep thinking i may have a cancer growing, so if i give it NAD+ i'm just giving it even more fuel that it wants...
 

Pyrrhus

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So one possiblity is one could try supplmenting NAD+ and see what happens. If one is not going thru krebs cycle but getting anerobic glyoclosis (fermentation) instead becasue of a mitochondiral resperiation problem (as some say happens in CFS) then boositing NAD+ levels should do absolutely nothing to energy levels etc. If on the other hand, this is happening (i.e. les Krebs, more fermentation) because the demand for NAD+ is greater than teh demand for ATP (as per the author of this recent paper), then by giving the body all the NAD+ it wants, that should restore normal Krebs.
I like your thinking, very methodical!
 
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Do we have any healthy control OAT's to really compare to? Do we know what the average healthy persons oat actually looks like? I did try to google this recently but came up pretty much non existent on examples, apart from really dodgy examples that semed to be made up.

@Pearshaped I pretty much asked this question back on page 1 of the thread :p Going to paste @WantedAlive 's response to me below for you :)

godlovesatrier said:
So what does this all mean? What can we take to correct the issue?
Well, ain't that the million dollar question! As I describe in this thread introduction, ME research has good evidence to suggest glycolytic impairment.

I'm proposing enzyme PKM2 is implicated here, it always is in warburg effect, why would it be different in ME/CFS? If it was as simple as suppressing PKM2, in theory bypassing glycolysis, and fueling OXPHOS with a Keto diet should work. It does for some and did for me.

Transitioning into ketosis over 3 days I went from moderate ME to near remission. It was truly transformational, and felt exactly like I'd unloaded 80kg off my back.

HOWEVER, two days later, I went for a storming 300m walk across a car park with a slight incline, and by 250m it all started to fall apart. The next day I was back down to moderate-severe and I've never recovered since, on any diet.

Today I'm still semi-Keto, wheelchair-bound grade-2 severe, I can't walk 5m. So what did I 'break' on that walk? Looking at Fisher's research on impaired complex V and Prusty's fragmentation when mitochondria are subjected to stress tests, maybe that's what happened. It was a sudden and catastrophic failure of energy production, of keto fueled mitochondria and not of glycolysis.

Maybe therefore, over-expressed PKM2 which is thought to be pro-fusion, is actually a consequence of stress induced mitochondrial fragmentation, and what's "in the plasma" of ME patients might be driving that.

Exosomes have been suggested as one possibility, which could be packages say from mitochondrial fragmentation, and I have sighted recent Alzheimer's research using exosomes on mitochondria which induce not dissimilar results to Fishers ME/CFS findings. All still wild speculation of course. Simple answer, we need more quality research!
 

WantedAlive

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what does all this mean in short?
what can we do?
Or what could we take?
@Pearshaped In short, if these OAT results of PwME are representing Warburg glycolysis, which I believe it does, it likely means that our immune system is chronically activated, possibly autoimmune or persistent pathogen. Pro-inflammatory macrophages and T-cells rely heavily on Warburg glycolysis to provide intermediates for proliferation and export of lactate to alkalise the cell thought to aid division, although we are still learning about why this metabolic shift is favoured. An activated immune system is intended to be short lived to clear the pathogen, a chronically activated immune system is very damaging to the host.

What can we do? In theory, we can dampen this pro-inflammatory effect from a furnace to a fire by restricting this Warburg glycolysis. Glycolysis relies on glucose, so we can starve it with the ketogenic diet, limiting both carbohydrate and protein as sources of glucose. There are some pharmacologic approaches, as tested in AI diseases such as multiple sclerosis. There is good discussion on this in this study, quite a good read. Possibly an inhibitor of LDHA, limiting the conversion of pyruvate to lactate, might help in ME/CFS. Not many of these options are available yet though.

However, there's no cure here, just a suppressant. The keto diet helped me enourmously, but briefly, so ME/CFS seems to have a way of overcoming this interfering with glycolysis. How this happens would be extremely useful to know.
 
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Do you think it adapts because it runs out of fat stores to burn? This was one PR members experience with keto. He said it stopped working after 12 months and believed that was the reason. @WantedAlive

In my case my body acts oddly. When crashing it seems to require carbs to function and get back to a baseline. I used to be able to feed it protein in a crash and it would lift out. But that was with stimulants. Without those it doesn't seem to work. Anyway I have found carb restriction is very useful. I would say I'm always at 135g a day. Currently trying to restrict to 80 but finding it difficult.
 

Jwarrior77

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This was mine. Can anyone more knowledgeable explain metabolically what could be going on? I believe the OAT test explained that this could be clostridium and candida creating too much oxalate along with interrupting my neurotransmitter conversion. Any insight would be appreciated.
 

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Methyl90

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@sb4 You're correct. The principle of the Warburg effect being that glycolysis continues to consume glucose but the last step converting to pyruvate is reduced allowing backup of intermediates to pass through the PPP for nucleotide synthesis, cell proliferation, and NADPH. Note also in Armstrong & McGregor’s paper that blood glucose is increased in PwME suggesting glucose excretion in urine is probably also increased.

Ron Davis tested ethyl-pyruvate successfully in his nanometer, but he cautioned not to try this.
Did you warn not to try it due to reduced glutathione depletion? I have it and after two days I think she ran out of little glutathione I had but I must say that the first day she gave a big hand.
 

Learner1

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This was mine. Can anyone more knowledgeable explain metabolically what could be going on? I believe the OAT test explained that this could be clostridium and candida creating too much oxalate along with interrupting my neurotransmitter conversion. Any insight would be appreciated.
You have an oxalate problem. It may be genetic, but going on a low oxalate diet, taking a form of citrate before each meal and ensuring you have adequate P5P would be helpful. Join the Trying Low Oxalates FB group and the spreadsheet subgroup for help.

High oxalates create oxidative stress, impair mitochondrial function and encourage candida. Dealing with them would be an important first step, then retest after 6-8 months to see where you are.
 

wastwater

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Could it be a genetic defect as I suspect PITX2 effect on PDP2 (pyruvate dehydrogenase) for myself
I’ve not had OAT testing but presume things will be out of range
 

Learner1

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Could it be a genetic defect as I suspect PITX2 effect on PDP2 (pyruvate dehydrogenase) for myself
I’ve not had OAT testing but presume things will be out of range
Likely not. Cancer has been pretty thoroughly analyzed for genetic defects And there isn't one common one in this area. I've had mine thoroughly analyzed and nothing like that came up, though I am aware of some others.