@Learner1
https://mmbr.asm.org/content/80/2/429
My pet theory is that it is supplying acetyl CoA in the presence of carbs where LCT would not. Therefore if there is some kind of problem getting glucose to acetylCoA (PDH?) this helps skirt the issue a little.
THIS IS A GREAT POST and I want to add to it that CHOLANGITIS is clogged bile ducts !! and it can results in antibodies to the E2 complex of the PDC . I have been researching this for some time -- because I had oxalate toxicity and severe gall bladder issues in 2013. I feel much better now but need to be very vigilant to make sure I avoid foods which inhibit bile production and I need to eat soluble fiber to bind the thick sludgy bile and force it to be excreted.https://sci-hub.tw/10.1016/j.mehy.2019.109260
Apparently this has been discussed before but I missed it last time, so have just caught up. It's a paper from some Norwegian researches that found supplying oxalates in the form of some type of spinach drink, dramatically improved symptoms in some patients. This paper is laying out what they think the mechanism is.
I think these images help to explain what is going on:
As far as I understand it, they are proposing that something is stopping DHLA (dihydrolipoic acid)[Reduced lipoyllysine] from recycling back into LA (lipoic acid)[Oxidized lipoyllysine]. This causes a backup in the PDC (Pyruvate Dehydrogenase Complex) and Pyruvate does not get transformed into Acetyl-CoA, leaving an energy deficit.
Now is the bit that gets confusing. They say that 2 pyruvate need to enter into the mitochondria and react with PDC for the enzyme to work. This is because one of the pyruvate needs to enter the E1 complex and the other needs to get transformed into lactate, and in the process recycle the NADH+H+ that is generated at the last step of the PDC in the E3 complex.
So in healthy people there apparently is a 1:1 ratio of Pyruvate and Lactate (in the mitochondria?). However, and I am not sure if this is correct, what happens in CFS is the 2 pyruvate enter the mito, one is converted to lactate, and the other stays as pyruvate when it should be converted to Acetyl-CoA. This is because DHLA is not recycling into LA backing up the whole system.
Then I assume the relative lack of Acetyl-CoA causes the mito to ask for more pyruvate or perhaps the left over pyruvate gets turned into Lactate via LDH. This causes a spike in Lactate whenever the cell is mildly stressed or needs to use more energy. I would have though this increased Lactate would be due to pyruvate backlog turning into Lactate in the cytosol in order to replace the missing energy from Acetyl-CoA.
Now they intend to get around this problem using oxalates. As far as I am aware oxalate reverses the conversion of Pyruvate to lactate and of Pyruvate to Oxaloacetate. Since Pyruvate has 3 choices, convert to Lactate, Oxaloacetate, or Acetyl-CoA, perhaps by "inhibiting" the other 2 we can force more Acetyl-CoA. It appears they are advocating doing this in conjuction with providing LA and possibly Riboflaving / Thiamine to try to overcome the DHLA block.
What I have been able to piece together from another thread is that 2 people tried high oxalates (through spinach I believe) and felt better for a short while then worse. However, according to the researches, there where a handful of people they tested this drink on who achieved remission as long as they kept drinking the drink.
I am particularly interested in this as I have significantly improved my carb tolerance (though it is still not great) by taking MCT oil with carbs. I speculate that the mechanism is via providing cells (/the liver) with so much Acetyl-CoA from the MCTs that pyruvate will ignore PDH and instead go through PC into Oxaloacetate. These researches seem to be presenting a similar mechanism for oxalates.
The serologic hallmark of PBC (Primary biliary cholangitis)
directed against the 
E2 subunit of the pyruvate dehydrogenase multi-enzyme complex located in the inner membrane of mitochondria. " Maxillary molars were missing bilaterally, and she was wearing an ill-fitted denture
. Her MIO was 16 mm; this interfered with her daily activities, including chewing, talking, yawing,
In our presented case, using immunohistochemistry, we also detected the presence of IL-17-positive cells in the liver with PBC (Fig. 2). Additionally, using RT-PCR, we observed that IL-17 m-RNA levels
IL-17-producing CD4 (+) helper T (Th17) cells that have been identified as one of the major pathogenic Th cell populations is the basis of the development of many autoimmune diseases, and IL-23 is known to enhance and stabilize them. [11]. https://sci-hub.tw/10.1016/j.mehy.2019.109260
Apparently this has been discussed before but I missed it last time, so have just caught up. It's a paper from some Norwegian researches that found supplying oxalates in the form of some type of spinach drink, dramatically improved symptoms in some patients. This paper is laying out what they think the mechanism is.
I think these images help to explain what is going on:
As far as I understand it, they are proposing that something is stopping DHLA (dihydrolipoic acid)[Reduced lipoyllysine] from recycling back into LA (lipoic acid)[Oxidized lipoyllysine]. This causes a backup in the PDC (Pyruvate Dehydrogenase Complex) and Pyruvate does not get transformed into Acetyl-CoA, leaving an energy deficit.
Now is the bit that gets confusing. They say that 2 pyruvate need to enter into the mitochondria and react with PDC for the enzyme to work. This is because one of the pyruvate needs to enter the E1 complex and the other needs to get transformed into lactate, and in the process recycle the NADH+H+ that is generated at the last step of the PDC in the E3 complex.
So in healthy people there apparently is a 1:1 ratio of Pyruvate and Lactate (in the mitochondria?). However, and I am not sure if this is correct, what happens in CFS is the 2 pyruvate enter the mito, one is converted to lactate, and the other stays as pyruvate when it should be converted to Acetyl-CoA. This is because DHLA is not recycling into LA backing up the whole system.
Then I assume the relative lack of Acetyl-CoA causes the mito to ask for more pyruvate or perhaps the left over pyruvate gets turned into Lactate via LDH. This causes a spike in Lactate whenever the cell is mildly stressed or needs to use more energy. I would have though this increased Lactate would be due to pyruvate backlog turning into Lactate in the cytosol in order to replace the missing energy from Acetyl-CoA.
Now they intend to get around this problem using oxalates. As far as I am aware oxalate reverses the conversion of Pyruvate to lactate and of Pyruvate to Oxaloacetate. Since Pyruvate has 3 choices, convert to Lactate, Oxaloacetate, or Acetyl-CoA, perhaps by "inhibiting" the other 2 we can force more Acetyl-CoA. It appears they are advocating doing this in conjuction with providing LA and possibly Riboflaving / Thiamine to try to overcome the DHLA block.
What I have been able to piece together from another thread is that 2 people tried high oxalates (through spinach I believe) and felt better for a short while then worse. However, according to the researches, there where a handful of people they tested this drink on who achieved remission as long as they kept drinking the drink.
I am particularly interested in this as I have significantly improved my carb tolerance (though it is still not great) by taking MCT oil with carbs. I speculate that the mechanism is via providing cells (/the liver) with so much Acetyl-CoA from the MCTs that pyruvate will ignore PDH and instead go through PC into Oxaloacetate. These researches seem to be presenting a similar mechanism for oxalates.
here is the section of the article on thisTHIS IS A GREAT POST and I want to add to it that CHOLANGITIS is clogged bile ducts !! and it can results in antibodies to the E2 complex of the PDC . I have been researching this for some time -- because I had oxalate toxicity and severe gall bladder issues in 2013. I feel much better now but need to be very vigilant to make sure I avoid foods which inhibit bile production and I need to eat soluble fiber to bind the thick sludgy bile and force it to be excreted.
I think this is made much worse by high oxalate diet -- because oxalates inhibit bile production ! CLEVELAND CLINIC Dr Aaron Miller gave a presentation to the TLO oxalate group on this in Nov 2023. You can find this on my timeline in facebook Search for youtube and Cleveland Clinic and oxalates under my profile. I dont know if I can post a link here .
but I want you to see this about the E2 unit and cholangitis: "
in 95%–98% of the patients is the presence of M2 anti-mitochondrial autoantibodies (AMAs)
"The present case involved a 54-year-old woman who had severe pain on the left side of the TMJ and had a limited mouth interincisal opening (MIO) for the past 6 months.
On clinical examination, we did not observe any facial swelling or asymmetry, and there was no tenderness of the masticatory muscles on palpation.
Result
Biochemical and immunological examination results showed high γ-GTP, ALP, AMA, anti-mitochondrial-M2 (AMA2) antibody, and IgM levels in the peripheral blood sample. AMA2, a specific antibody for PBC, and high IgM levels were detected only in the synovia from the affected side of the TMJ (Table 1).
Discussion
The discovery of the cytokine identity of the IL-17 family and the discovery that IL-23 mediates the proliferation of IL-17 producing T cells led to the discovery of a new subset of Th cells called Th17 cells. Like Th1 and Th2 cells, Th17 cells require…”
https://www.sciencedirect.com/science/article/abs/pii/S2212555818303399
and i DEFINITELY DONT THINK SPINACH WILL IMPROVE THIS ISSUE. lol High oxalate diet will inhibit bile production . this is directly from DR Araron Miller from Cleveland Clinic. this is a 3 min section of the longer youtube video : https://www.facebook.com/share/v/19yWqr7XHg/THIS IS A GREAT POST and I want to add to it that CHOLANGITIS is clogged bile ducts !! and it can results in antibodies to the E2 complex of the PDC . I have been researching this for some time -- because I had oxalate toxicity and severe gall bladder issues in 2013. I feel much better now but need to be very vigilant to make sure I avoid foods which inhibit bile production and I need to eat soluble fiber to bind the thick sludgy bile and force it to be excreted.
I think this is made much worse by high oxalate diet -- because oxalates inhibit bile production ! CLEVELAND CLINIC Dr Aaron Miller gave a presentation to the TLO oxalate group on this in Nov 2023. You can find this on my timeline in facebook Search for youtube and Cleveland Clinic and oxalates under my profile. I dont know if I can post a link here .
but I want you to see this about the E2 unit and cholangitis: "
in 95%–98% of the patients is the presence of M2 anti-mitochondrial autoantibodies (AMAs)
"The present case involved a 54-year-old woman who had severe pain on the left side of the TMJ and had a limited mouth interincisal opening (MIO) for the past 6 months.
On clinical examination, we did not observe any facial swelling or asymmetry, and there was no tenderness of the masticatory muscles on palpation.
Result
Biochemical and immunological examination results showed high γ-GTP, ALP, AMA, anti-mitochondrial-M2 (AMA2) antibody, and IgM levels in the peripheral blood sample. AMA2, a specific antibody for PBC, and high IgM levels were detected only in the synovia from the affected side of the TMJ (Table 1).
Discussion
The discovery of the cytokine identity of the IL-17 family and the discovery that IL-23 mediates the proliferation of IL-17 producing T cells led to the discovery of a new subset of Th cells called Th17 cells. Like Th1 and Th2 cells, Th17 cells require…”
https://www.sciencedirect.com/science/article/abs/pii/S2212555818303399
