Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS

Hip

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Has anyone tried sodium dichloroacetate?
I took my first sodium dichloroacetate 200 mg oral dose yesterday. It seemed to make me sleepy for a few hours (increased fatigue is apparently one of the side effects of DCA), rather than boosting energy.

Then today I noticed I felt a bit depressed (another side effect of DCA). But I did not feel depressed yesterday while taking DCA, so this depression could just be a coincidence (since I get depression which comes and goes).

I am not going to take any DCA today, but may try again tomorrow, perhaps with 300 mg.


DCA has unusual half life characteristics: when you first take it, the half life is less than 1 hour, but DCA possesses some unknown mechanism by which it inhibits its own metabolism and elimination, so with continued use, the half life goes up to several hours (ref: here).
 

Hip

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What about a smaller dosage? Why are you deciding to go up?
Because I am aiming for a DCA dosage of 300 mg taken three times a day, which is the sort of dosage used in cancer treatment (for 80 kg person, around 800 mg a day is used for preventative anti-cancer maintenance, and around 1,600 mg a day for intense cancer treatment — see this post).

But you are right, it might also be worth trying lower doses as well.
 
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Bdeep86

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Because I am aiming for a DCA dosage of 300 mg taken three times a day, which is the sort of dosage used in cancer treatment (for 80 kg person, around 800 mg a day is used for anti-cancer maintenance, and around 1,600 mg a day for intense cancer treatment — see this post).

But you are right, it might also be worth trying lower doses as well.
Thats what I would try. Any idea of the dosage that the one woman was using that had tried it on here some time back. I think i saw you had quoted her before.
 

junkcrap50

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Because I am aiming for a DCA dosage of 300 mg taken three times a day, which is the sort of dosage used in cancer treatment (for 80 kg person, around 800 mg a day is used for preventative anti-cancer maintenance, and around 1,600 mg a day for intense cancer treatment — see this post).

But you are right, it might also be worth trying lower doses as well.
I'll have to re-find it tomorrow, but I did come across a paper that gave some DCA dose recommendations for patients with PHD gene deficiency for maintenance and continuous PDK inhibition. You may not need to take cancer level doses.
 
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I'll have to re-find it tomorrow, but I did come across a paper that gave some DCA dose recommendations for patients with PHD gene deficiency for maintenance and continuous PDK inhibition. You may not need to take cancer level doses.
I'm interested in this too.
 

Hip

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Thats what I would try. Any idea of the dosage that the one woman was using that had tried it on here some time back. I think i saw you had quoted her before.
It did not say.


Just found this rat study, in which 5 mg of intravenous DCA per kg body weight was used to reduce lactate accumulation in rat endurance exercising. Since oral DCA has near 100% bioavailability (ref: 1), the intravenous DCA dose would be the same as the oral dose.

That equates to an oral human dose of 0.8 mg of DCA per kg body weight (to get human mg/kg from rat mg/kg, you need to divide by 6.2).

So for an 80 kg person, the human dose would be 64 mg of DCA.

So I could certainly try a dose around that 64 mg mark, and see what happens.
 

Marco

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I don't know if you have already observed in some previous post that a metabolic alteration similar to the one depicted by Fluge and colleagues in ME/CFS, has been described in mice infected with influenza A virus, during the first 7 days of infection (Yamane K et al. 2014). In that study they found a decrease in PDH activity, a depletion of ATP in tissues, and an increase in PDK4 expression.

As antibodies are not produced during the first week after an infection, this PDH disfunction is due to other factors than autoantibodies.
I'd noticed the same thing with respect to sepsis as discussed here :

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS

Somewhat downstream but HMGB1 released as a result of impaired PDH activity acts as a proximal primer and activator of microglia in 'stress' http://www.jneurosci.org/content/35/1/316 and normal aging http://www.jneurosci.org/content/36/30/7946

Microglia may have already been primed at the stage ME/CFS patients associate with a 'triggering' infection. Or some immune defect means the initial infection established microglial priming which responds disproportionately to various 'stressors'.

ETA

I should have explained what I think may be the implications of this downstream signalling.

I doubt that this metabolic defect in itself can explain all the symptoms. In the same way that you can have a torn disc but with appropriate medication experience little or at lease less pain - downstream signalling is important in how you experience the problem. We could otherwise just just run out of energy and otherwise feel OK.

Secondly this later immune signalling via HMGB1 provides a possible clear link between this metabolic defect and neuroinflammation/activated microglia (assuming both findings are replicated).

Thirdly, in the event that the metabolic defect can't just be fixed, it may be possible to minimise the symptoms experienced by blocking immune signals such as HMGB1 and attenuating the subsequent immune cascade.
 
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Sidereal

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@Sidereal Your comments on the above?
We already know from the Australian metabolomics study by Armstrong et al. that ME/CFS metabolism resembles sepsis and starvation. Montoya's cytokine profile was also consistent with SIRS, although these data are unpublished as far as I know. In that sense, PDH downregulation is not at all surprising and is exactly what you'd expect; the shocking thing is only that it's taken researchers 30+ years to start looking at metabolic dysfunction in a disease characterised by an inability to produce sufficient energy to meet daily requirements.

The question is what is driving this. The Norwegians seem to think it's an antibody. A much more plausible explanation is a chronic but extremely mild and slow moving form of sepsis. Not in the classic sense of an overwhelming infection with one particular pathogen landing you in the ICU (there is absolutely no evidence of ME/CFS being caused by an infection in the classic sense of the word) but rather constant mild immune/microglial aggravation due to severe gut dysbiosis and permeability to LPS as shown in Hanson's recent studies and Armstrong's data.
 

halcyon

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the shocking thing is only that it's taken researchers 30+ years to start looking at metabolic dysfunction in a disease characterised by an inability to produce sufficient energy to meet daily requirements.
Ramsay looked at this back in the late 70s. They found ME patients had low pyruvate levels. I'm not sure how well that jives with these findings, but it was pretty clear by the 80s that he considered the muscle weakness part of the disease at least a metabolic dysfunction.
 

Sidereal

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Ramsay looked at this back in the late 70s. They found ME patients had low pyruvate levels. I'm not sure how well that jives with these findings, but it was pretty clear by the 80s that he considered the muscle weakness part of the disease at least a metabolic dysfunction.
Do you have a reference for the low pyruvate study by any chance?