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Suggested Pathology of Systemic Exertion Intolerance Disease: Impairment of E2/E3 Subunit of PDH

SlamDancin

Senior Member
Messages
513
@sb4 Did you get a chance to read through the paper on SAH and secondary PDH suppression?

I’d like to see if there is a connection between Vagal activity and PDH, because Mestinon and other Vagus activating methods I learned through selfhacked, are seemingly very helpful.

Almost like with improved Vagal function you can actually do a form of GET, which for me is more stretching, foam roller, PT type exercise, and I’m able to actually get stronger and add muscle without triggering PEM. Slowly my baseline parasympathetic/sympathetic balance seems to be imoroving. Food for thought. There is a hepatic branch, a cardiac branch and a brain branch to the Vagus nerve and so it seemingly is involved in all possible major centers of metabolism and autonomic function.

Tagging some people who might be interested;
@Mary @pattismith @mariovitali @ScottTriGuy @gregh286
 

ScottTriGuy

Stop the harm. Start the research and treatment.
Messages
1,402
Location
Toronto, Canada
...to see if there is a connection between Vagal activity and PDH,...

Interesting.

I know that some of my 'nausea' (for lack of better words) feels like a nerve being strummed - very intense and qualitatively different from stomach 'nausea'.

Kind of related, I've been keeping my eye on this research that stimulates cranial nerves...

an investigational medical device, which involves sequenced noninvasive stimulation applied to the tongue. It is generally hypothesized in the existing literature that the tongue stimulation engages the trigeminal (CN-V) and facial (CN-VII) cranial nerves, which converge on and co-modulate visual, vestibular, nociceptive and visceral sensory signals via the brainstem and cerebellum, producing a neuromodulatory effect [3, 4, 5]. Recent evidence suggests that the trigeminal nerve is involved in networks of activity which affect sensorimotor and cognitive functions, and that modulation may relieve symptoms of particular brain pathologies

https://heliusmedical.com/index.php/our-research/peer-reviewed-publications
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
@SlamDancin Just read the abstract. As for vagus nerve, I am sure it helps some people however I have done many things to try and help it as I have many sympathetic dominant symptoms. The only time I really was able to relax through acupuncture it felt great however my POTS went through the roof. I suspect my sympathetic dominance is a compensatory mechanism.
 

junkcrap50

Senior Member
Messages
1,324
Maybe relevant:

Popeye was right: Spinach chemical should be banned for athletes, German scientists say
https://www.euronews.com/2019/06/25...-be-banned-for-athletes-german-scientists-say
It might seem unlikely that humans could get super-human strength from spinach, like cartoon character Popeye the Sailor, but its creator Elzie Crisler Segar may have been been on to something.

Scientists at the Freie Universität Berlin's Institute of Pharmacy have recommended that ecdysterone, a hormone found in spinach, be included in the list of prohibited substances for athletes.

During a 10-week study, led by the university's Institute of Pharmacy, participants were split into four groups.

One was a control group, another received a placebo, while the third and fourth respectively received two and eight capsules containing 100 mg of ecdysterone from spinach extract every day.

"Significantly higher increases in muscle mass were observed in those participants that were dosed with ecdysterone," the study said in published notes.

"Even more relevant with respect to sports performance, significantly more pronounced increases in one-repetition bench press performance were observed," it added.

Maria Parr, one of the study's scientists, told ARD and ARTE that their "hypothesis was that we would see an increase in performance, but we didn't expect it to be that big."

"We recommended to WADA (the World Anti-Doping Agency) in our report that the substance be added to the doping list. We think that if it increases performance, then that unfair advantage should be eliminated," she added.
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
Just been reading into vitamin C and found out that when ascorbic acid is oxidized it turns into dehydroascorbic acid, this is susceptible to breaking down by H2O and indeed many plants try to prevent this by various means including lowering pH in places with vit C and H2O present.

Once it is broken down by water it is further broken down into various molecules including oxalate. Long short but could this be responsible for some of the CFS improvement in people taking Vit C? Could be a number of other things though.

I have been taking K citrate in decent doses over the last couple of weeks and haven't noticed any kidney pain or anything like that so perhaps I can trial high dose spinach at some point and skirt the kidney stones issue.
 

bread.

Senior Member
Messages
499
Interesting.

I know that some of my 'nausea' (for lack of better words) feels like a nerve being strummed - very intense and qualitatively different from stomach 'nausea'.

Kind of related, I've been keeping my eye on this research that stimulates cranial nerves...

an investigational medical device, which involves sequenced noninvasive stimulation applied to the tongue. It is generally hypothesized in the existing literature that the tongue stimulation engages the trigeminal (CN-V) and facial (CN-VII) cranial nerves, which converge on and co-modulate visual, vestibular, nociceptive and visceral sensory signals via the brainstem and cerebellum, producing a neuromodulatory effect [3, 4, 5]. Recent evidence suggests that the trigeminal nerve is involved in networks of activity which affect sensorimotor and cognitive functions, and that modulation may relieve symptoms of particular brain pathologies

https://heliusmedical.com/index.php/our-research/peer-reviewed-publications


do you have EDS, or EDS like symptoms?
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I'd followed this thread at the beginning but had lost track for awhile. I found it again by searching for "oxalate."

I recently did another Genova Diagnostics NutrEval, something I've been doing every 9 months. The results were a bit dismaying, but the analysis seems to point to oxalate overload.

Though I eat adequate amounts and supplement robustly, I was depleted in magnesium, B6, folate, B2, B12, A, E, ALA, and glutathione. Lipid peroxides, 8OH-dG, and heavy metals have all increased, when the trend on the previous 3 tests had been improving.

I've been on a lower carb, plant-based Paleo diet for 6 years, eating plenty of spinach, kale, beets, nuts and raspberries, all high oxalate. In 5/18, I had high oxalic acid show up on an OAT test. In 3/19 high oxalates showed up on a urine test. A recent stool test showed very low oxalobacter, low lactobacillus, and low bifidobacteria, all of which help to metabolize oxalates, and which were killed off by azithromycin and doxycycline for chlamydia pneumoniae.

My current symptoms seem to point to this oxalate problem as well, with kidney pain, intermittent sulfur smell, and itchy eyes. No kidney stones yet, fortunately. My energy has plateaued. And a recent DEXA showed early osteoporosis and all bone markers have shown I'm losing bone, even though I'm tall and lift weights and walk as I can.

Other values - malate has been very high and pyruvate and lactate are both LOW, after exercise. And I'm dumping taurine - the value was so high in the scale, there wasn't a number.


My conclusion is that oxalates are NOT a good thing. They can damage mitochondria, damage thyroid, damage kidneys, liver, etc. Spinach is the single highest oxalate food - I haven't at all focused on eating it, but its in almost every mixed salad green product out there.

I'm still figuring out what to do next, but changing diet (not very pleasant) is on the list, lowering vitamin C supplementation, and taking calcium or potassium citrate and digestive enzymes ahead of every meal.

I am interested in the ALA involvement - I tend to be depleted in it even though I take it.

Also am interested in if my high malate goes to high ocaloacetate which then goes to more oxalate and acetate, and how malate coukd be lowered - other Krebs intermediates are normal.

I'm open to any thoughts here...
 

nandixon

Senior Member
Messages
1,092
I am interested in the ALA involvement - I tend to be depleted in it even though I take it.
@Learner1

Glad you brought this up. The authors of the study, as well as Genova, have a very common and widespread misunderstanding about the nature of alpha-lipoic acid. (In fact, Genova has been essentially providing the same wrong information about ALA for going on at least 20 years now as Metametrix before that company merged into Genova.)

Mammals, including humans, have no ability to incorporate exogenous ALA into any of the handful of enzymes in the body that actually require ALA.

Humans are missing a "salvage pathway" that allows some other organisms (like bacteria) to be able to utilize free ALA for the enzymes that actually require it.

All of the necessary ALA in humans has to be built up in a stepwise fashion (from octanoic aka caprylic acid, for example) on the enzyme that uses the ALA as that enzyme is being made in the cells. This is called de novo synthesis.

Whenever free ALA is taken (orally or otherwise) it is always being used in a pharmaceutical way, i.e., as a drug. All of the dozens or hundreds of actions that have been reported for free ALA with respect to humans are not naturally required actions (although the authors of those studies would like for things to appear otherwise).

Humans normally never have more than just trace amounts of free ALA floating around and this is just due to degradation of the enzymes that contain it. There is no requirement for free ALA because it has no naturally required biological purpose in humans. Again, it is always made de novo on the enzymes where required.

Like any drug, supplemented ALA has potential benefits together with potential negative side effects. But one of those benefits is most definitely not increasing the incorporation of ALA into the pyruvate dehydrogenase complex as the authors of the study of this thread are mistakenly thinking. That is impossible.

It's unfortunate that ALA has always been referred to as a "cofactor" because that implies something that is easily replaceable and removable. It also implies that it is something necessary to be supplied, which is not true.

The difference between ALA in its enzymes and another cofactor like riboflavin in the MTHFR enzyme (for example) is like the difference between holding a ball in your hand in the latter case versus your hand being attached to your arm in the former case. Your hand is not very easily removed or replaced.

Here is one of the latest (very technical) updates on this situation from 2016, but it's been known for over 20 years by virtue of labeling studies that humans cannot utilize free ALA for its actual required purposes in the human body. (Having ALA around for antioxidant purposes, for example, is not a required purpose. That is a drug purpose.):

Assembly of Lipoic Acid on Its Cognate Enzymes: an Extraordinary and Essential Biosynthetic Pathway
The above-described studies clearly demonstrate that mammals lack the ability to attach exogenous lipoic acid to the essential enzymes that require the lipoyl cofactor for activity.
https://mmbr.asm.org/content/80/2/429
 

nandixon

Senior Member
Messages
1,092
@sb4, I'm not sure how well taking extra caprylic acid can drive the formation of ALA (it might not be very rate limiting). It may be your just getting one of the effects of using medium chain triglycerides in general, although I think caprylic acid has some other specific effects as well. I tried taking it myself a long time ago and I think I generally felt a little better using it too.
 

sb4

Senior Member
Messages
1,654
Location
United Kingdom
@sb4, I'm not sure how well taking extra caprylic acid can drive the formation of ALA (it might not be very rate limiting). It may be your just getting one of the effects of using medium chain triglycerides in general, although I think caprylic acid has some other specific effects as well. I tried taking it myself a long time ago and I think I generally felt a little better using it too.
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.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
@nandixon Thank you for providing this insight. I'm afraid the article you attached is a but too dense for me. My previous knowledge of ALA has been from Lester Packer, the UC Berkeley scientist who worked with the antioxidant network concept, where antioxidants work together, not individually. This paper is by him on ALA - is it wrong?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022059/

I take C8 oil as well - not sure if it helps or not.

But my main reason for posting was to share that oxalates, which are in many healthy foods, can be counterproductive.
 

nandixon

Senior Member
Messages
1,092
@Learner, No, that paper is not wrong, but all of the effects of alpha-lipoic acid he is talking about never actually occur in humans (at least not to any appreciable extent) unless ALA is actually supplemented.

He sort of says that at the end of the paper, although in a sort of obfuscated way. I've noticed over the years that several of the ALA researchers do that, I suspect to try to make it appear that they are working on perfectly natural biological processes rather than what is more akin to a drug effect (possibly for funding purposes). Here's what he says at the end:

R-α-Lipoic acid, a cofactor for four enzyme complexes exclusively located in mitochondria, is essential for energy production and the regulation of carbohydrate and protein metabolism. Lipoic acid is synthesized in vivo and it is almost entirely covalently bound to the E2 component of three α-ketodehydrogenase complexes and the glycine cleavage system. Hence, it would be expected that only trace amounts are available from dietary sources. However, when lipoic acid is supplemented in the diet, it is readily absorbed and present in all cell compartments and extracellular fluids where it acts as a redox modulator and antioxidant par excellence.