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

[Methyl90]

Hello everyone, I was wondering if inhibiting the 4 pyruvate kinase complexes could facilitate PDH? Has anyone tried calcium pyruvate or ethyl pyruvate? ALA also appears to inhibit all 4 complexes.

 

[Methyl90]

I forgot ... don't try to push too hard with the B1 to upregulate the PDH because you will have an increase in NADH which in turn will increase the PDK.

Rather, Niacinamide is very effective in inhibiting circulating fatty acids as well as increasing NAD + ... it helps to use glucose but you don't have to eat a high-fat diet otherwise you will worsen insulin resistance ... (which is not what you want).

For those fearful of its effects in methylation, use low dosages of 25-50mg 1-2 times a day.

 

[Methyl90]

Melatonin Increase PDH activity and inibhit PDK:

http://www.melatonin-research.net/index.php/MR/article/view/44

I have a PDH deficiency present from birth and I have experienced melatonin ... in MY personal case it works because by activating the enzyme it seems to me that night is day.

I can't take it before bed but I want to test it (although it is not recommended for its effects on sleep) during the day.

 

[Methyl90]

Some PDK inhibitory molecules ... as you can read pyruvate and ALA R are mentioned.

I tested 500mg of Calcium Pyruvate but notice anithing.

I believe that among the 4 PDKs the most difficult to keep under control is number 4.

 

[wastwater]

Ammonia

 

[WantedAlive]

Has anyone tried calcium pyruvate or ethyl pyruvate?

I've tried both. Like you, calcium pyruvate was mostly unnoticeable. The Ethyl Pyruvate was an emulsion made by a lab friend. I sipped about 5ml only, and had a horrible reaction to it, but I think it was the acacia gum or vinegar ingredients (I've reacted to gum before). So not a valid test of EP, which I was pretty cautious about anyway.

Do you have the original research document link those attachments belong to? That looks interesting.

 

[Methyl90]

@WantedAlive I understand, you probably react badly to many supplements like me. Regarding the original link, honestly no, I can try to investigate because I have no idea where I found it from.

If I find it, I'll put it here or write to you privately.

Have you tried out ALA R? High Doses of Thiamine HCL?

 

[WantedAlive]

Have you tried out ALA R? High Doses of Thiamine HCL?

I have RALA every day, have done for 4 years now. Its one of the more effective supplements. I used to use high doses of thiamine and/or benfotiamine but didn't really help any. There isn't much I haven't tried, even tried 3 FMT's!

 

[Levant]

Here's my results but from what I think is before my ME/CFS onset:

 

[Levant]

You say you had this done 1 month before ME onset, yet your onset wasn't viral (sudden) but perhaps more gradual? So I'm guessing you weren't feeling well to have the OATS test done? So its possible you did have ME at the time you did the test or you were developing ME.

It's certainly possible, though I think I'm differentiating between chronic fatigue, and full-blown me/cfs. When the results were taken, I felt a bit fatigued and perpetually hung-over, but definitely no PEM, or any other of the cardinal symptoms of ME.
Up until 1 month after that OAT test I was working 9-hr shifts along with daily high-intensity exercise, consistently less than 5 hrs sleep a night and a bucketful of stress - but no PEM and the exercise felt energising. When the cfs hit, it was noticeable that something more serious was wrong

 

[Levant]

Which is why I wondered if mitochondrial dysfunction is something that predisposes to me/cfs, or arises from it, or both

 

[Levant]

I have RALA every day, have done for 4 years now. Its one of the more effective supplements. I used to use high doses of thiamine and/or benfotiamine but didn't really help any. There isn't much I haven't tried, even tried 3 FMT's!

Btw, did the FMTs help in any way?

 

[Learner1]

@Levant What have you done to address your oxalate problem, which can drive a lot of other problems? It can cause oxidative stress, sap your mineral co-factorsV vitamins, and antioxidants?

Dealing with the oxalates with a low oxalate diet and supplements like garcinia cambogia (for the hydroxycitrate) or calcium, magnesium, or potassium citrate and B6 is the best treatment, while replenishing minerals and antioxidants is helpful.

The lowoxalate.info website and Trying Low Oxalates FB group are both helpful resources - the latter has the most accurate list of oxalate foods.

 

[Levant]

@Levant What have you done to address your oxalate problem, which can drive a lot of other problems? It can cause oxidative stress, sap your mineral co-factorsV vitamins, and antioxidants?

Dealing with the oxalates with a low oxalate diet and supplements like garcinia cambogia (for the hydroxycitrate) or calcium, magnesium, or potassium citrate and B6 is the best treatment, while replenishing minerals and antioxidants is helpful.

The lowoxalate.info website and Trying Low Oxalates FB group are both helpful resources - the latter has the most accurate list of oxalate foods.

Thanks! That's great info! The naturopath I was being treated by suggested that the elevated oxalates were due to fungal dysbiosis and mould sensitivity, so I've been on diet and supplements for that but without noticeable improvement.
I'll try tackling the oxalate issue directly like you suggest.

 

[Badpack]

So if we expect the Warburg effect without having cancer, wouldnt it be worth a try to act on it ? Trying to reduce the PKM 2 ? I found this study very interesting.

https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32756

Its about Benserazide reducing PKM2. It should be really safe to try because it shouldnt do much if you dont need it.

 

[Pyrrhus]

Fascinating new article on infections and the Warburg Effect from the minds at the PolyBio Research Initiative:

Pathogens Hijack Host Cell Metabolism: Intracellular Infection as a Driver of the Warburg Effect in Cancer and Other Chronic Inflammatory Conditions
https://ij.hapres.com/htmls/IJ_1341_Detail.html

The Warburg effect refers to a metabolic state in which cells preferentially use aerobic glycolysis rather than oxidative phosphorylation to generate ATP and macromolecules.

A number of chronic inflammatory conditions are characterized by host cells that adopt a sustained, pathological Warburg-like metabolism. In cancer, previously healthy cells shift into a Warburg state centered on rapid energy production and increased cell proliferation that drives tumor formation. Macrophage in atherosclerotic plaque and in sarcoidosis granuloma can also harbor a Warburg-like phenotype that promotes an inflammatory milieu.

The question of why host cells in patients with cancer and other chronic inflammatory conditions adapt a pathological Warburg-like metabolism is a matter of debate. This review/hypothesis piece explores how intracellular infection can contribute to this Warburg metabolism or related pathological metabolic states. We detail molecular mechanisms by which viral, bacterial, and protozoan intracellular pathogens can induce, or contribute to, a Warburg-like metabolism in infected host cells in order to meet their own replication and nutritional needs.

We also discuss how host defense towards infection may impact cellular metabolic changes. We then provide examples of how many of these same intracellular pathogens have been identified in tumors, atherosclerotic lesions, granuloma, and other tissues containing cells with a Warburg or altered metabolism. Last, we examine further trends associated with infection and host cell metabolism, including how pathogen-driven hijacking of host cell lipid metabolism can support viral, bacterial, and parasite survival and replication.

(spacing added for readability)

EDIT: new thread here:
https://forums.phoenixrising.me/thr...-other-chronic-inflammatory-conditions.86656/

 

[Levant]

Fascinating stuff, first I'm hearing of this Warburg effect theory. I guess it relates to the use of dichloroacetic acid as a potential treatment for me/cfs right?

Why do some ME/CFS patients benefit from treatment with sodium dichloroacetate, but others do not?
Author links open overlay panelFrankComhaire
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https://doi.org/10.1016/j.mehy.2018.08.014Get rights and content

Abstract
Myalgic Encephalopathy/Chronic Fatigue Syndrome (ME/CFS) is an enigmatic disease the pathogenesis of which remains elusive. Pragmatic proof-of-principle of the hypothetical mechanisms causing the clinical symptoms has been delivered, but it is hard to explain why some patients do respond favourably to treatment with sodium dichloroacetate (DCA), which enhances the activity of the mitochondrial enzyme pyruvate dehydrogenase, but other patients experience no benefit from this substance.
In a prospective trial including 35 ME/CFS patients, logistic regression analysis with stepwise elimination has identified 6 pre-treatment characteristics allowing for the differentiation between responders (n = 13) and non-reponders (n = 22) with high accuracy (P < 0.0001; area under the ROC-curve = 0.92). A formula was derived generating the probability of belonging to the group of responders. This finding may assist in selecting ME/CFS patients suitable for treatment with DCA, but requires further studies as to the predictive capacity of the derived formula.

 

[Badpack]

Well its from Van Elzakker and he clearly has Cfs in mind while writing about this. Could be in the same vein as Prusty is looking.

Yeah it kinda relates to dichloroacetate. Dichloroacetate is about activating more PDH1 while i think about deactivating PDH2.

 

[Levant]

True, should act in a similar way. Could be interesting to try both drugs at once.

 

[sb4]

Yeah it kinda relates to dichloroacetate. Dichloroacetate is about activating more PDH1 while i think about deactivating PDH2.

What do you mean by deactivating PDH2?