Pyruvate Dehydrogenase Deficiencies and Cures?

[Learner1]

I have no attachment to vegetarianism. at the urging of my nutritionist, i'm introducing meat... i was already a sort of pescetarian but didn't eat fish enough to be used to it. My problem is I don't know if i'm ready to do keto until i get better at digesting meat/protein. I know I'm low in a specific digestive enzyme from testing (i forget which) which bears out how I have a hard time digesting heavy food and a lot of upset stomach. So I guess I want to work on my digestion before I just go straight to doing keto.

A phased approach makes sense. Digestive enzymes with every meal are quite helpful.

 

[junkcrap50]

very interesting! phenylbutyrate is worth a try, it is also a treatment for ammonia detox.

The first treatment to try for PDH impairment is Thiamine, co-factor of PDH:

this study is about babies under 2 years diagnosed with PDH deficiency:

[Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment
Seventeen patients received thiamine treatment: eight did not respond, four showed sustained response and the others responded temporarily/questionably. Sustained response was noted at thiamine doses >400 mg/day. ........ However, this distinction is equivocal and treatment with thiamine (>400 mg/day) should be commenced on all patients suspected of having PDHC deficiency.]

As you notice, the dose of thiamine is very high,if you compare it to the small weight of a baby.

Some ME patients here seems to respond well to high Thiamine dose.

I do myself benefit from high Benfothiamine doses, but sometimes have thiamine injections when it is not enought, and also supplement with B12 injections (hydroxo B12).

Keto diet has been tryed for PDH deficiency with some successes and some ME patients are doing well on it, (although pancreatitis can be a side effect in some cases)

If you have poor enzymes, maybe a enzyme supplementation could help?

I too was going to suggest high dose thiamine as a possible treatmetn for PDH deficiency. Here are some links:

https://www.healthrising.org/blog/2...gia-mecfs-found-early-reports-spark-interest/
http://www.prohealth.com/library/showarticle.cfm?libid=18113
http://www.prohealth.com/library/showarticle.cfm?libid=18187
http://www.hormonesmatter.com/thiamine-fibromyalgia-chronic-fatigue/
http://forums.phoenixrising.me/inde...ent-story-focus-on-thiamine-deficiency.24059/
http://www.prohealth.com/library/showarticle.cfm?libid=18976

 

[frozenborderline]

I may ask about getting prescribed the shots. I'm jumping the gun though. Even though I'm excited about the narrowing down of possible etiology of CFS, I haven't even had enough of a full diagnostic workup to be sure I have it. I have had these symptoms since I got Lyme. Is lyme even a recognized trigger of CFS? I know CFS tends to have viral triggers... Anyway what I should be looking at is biomarkers and diagnostics, so I can know whether I should be treating what I have as a) chronic lyme infection b) "Post treatment lyme disease syndrome", or c) CFS/ME. have there been threads about diagnostic biomarkers/metabolic testing/cytokine testing here?

 

[frozenborderline]

C

I haven't had a full recovery as there are other factors beyond lack of pyruvate making me ill, but keto definitely reduced my symptoms:

• what was the % calories composed by carbs in the keto diet?

About 10%

• how long before the keto diet gave significant improvements

Within 2 weeks

• what CFS symptoms did the keto diet improve?

Brain fog, cognitive dysfunction, fatigue

• were blood/urine ketones measured to confirm ketosis?

They were measured multiple times on lab tests as well as using keto strips from Wal-Mart

• How much improvement in CFS symptoms was obtained?

Enough to keep me on the diet for several months

• any other comments?

I did it using C8 oil and endogenous ketones. I've switched to low carb Paleo and don't obsess about ketosis and have maintained what I gained.

But, like I said, this isn't the one magic bullet, I also have infectious and immune issues that are contributing greatly to my illness, do I need to use multiple strategies and not just this diet.

c8 oil, hmm. I am curious about C7 oil (triheptanoin)

 

[Chocolove]

It's very important to note that all the thiamine in the world won't work if you don't have enough magnesium onboard and approximately 70% of Americans are estimated to have a dietary deficiency of magnesium.
This is because the enzymes that utilize thiamine also require the co-factor of magnesium. A check of enzyme data bases reveals that many of your body's enzymes require magnesium. Thus many people may be suffering from a variety of nutrient deficiencies - ultimately caused by a magnesium deficiency. Just as consumption does not equal absorption, consumption of some vitamins may be fruitless without cofactors like magnesium.

You may be interested in these PubMed articles although research largely focuses on abnormalities in juveniles:
https://www.ncbi.nlm.nih.gov/pubmed/?term=thiamine+responsive+pyruvate+dehydrogenase+deficiency

And this thread:
http://forums.phoenixrising.me/inde...genase-function-depends-on-thiamine-b1.48757/

 

[Chocolove]

Thiamine and magnesium deficiencies: Keys to disease - ResearchGate
https://www.researchgate.net/.../270163334_Thiamine_and_magnesium_deficiencies_K...
Oct 9, 2017 - On Dec 15, 2014 D Lonsdale published: Thiamine and magnesium ... shown experimentally to produce reversible damage to mitochondria and ...

 

[frozenborderline]

I take some fairly bioavailable magnesium supplements

 

[Learner1]

c8 oil, hmm. I am curious about C7 oil (triheptanoin)

Here is info on C8 oil:

https://ketosource.co.uk/caprylic-acid-c8/

Looks like you can wait a couple of years to find out how this trial comes out:

https://clinicaltrials.gov/ct2/show/NCT02021526

More in the attached...

 

[frozenborderline]

I'm going to try and acquire c7 oil even tho it's not fda approved, but I haven't found many vendors of it. gonna try contacting the glut1 foundation.

 

[frozenborderline]

"

I think CFS is likely to involve “reductive stress,” producing lactate because pyruvate isn’t being oxidized fast enough, and in that case I think the reducing supplements, NADH and ubiquinol, could make it worse. Ubiquinone and niacinamide seem more appropriate, since they are the oxidizing forms. Drinking alcohol shifts cells to the reducing side, and a B vitamin deficiency can have similar effects. Vitamin D, thyroid, aspirin, and pregnenolone help to maintain mitochondrial oxidation.

Show original message"
--Ray Peat

 

[Learner1]

Interesting. I did find this to be aware of:

Another important issue is that triheptanoin is contraindicated in patients with inborn errors of fatty acid oxidation, such as medium-chain acyl-CoA dehydrogenase deficiency - MCAD, short-chain acyl-CoA dehydrogenase deficiency - SCAD, short-chain-3 hydroxyacyl-CoA dehydrogenase deficiency –SCHAD and HMG CoA (3-hydroxy-3-methyl-glutaryl-CoA) synthase deficiency. Therefore, patients will need to be carefully screened for these disorders, taking into account medical histories, blood acyl-carnitine profiles and urine organic acid analyses.

 

[frozenborderline]

Interesting. I did find this to be aware of:

ok... yeah it is generally considered really safe but if CFS involves those fatty acid metabolism problems then things could get nasty... maybe i'll ask my doctor about screening for this..

 

[frozenborderline]

good looks

 

[frozenborderline]

what i don't get is, NADH being shown to help w/ fatigue in a recent study, suggesting that reduction is helpful and some ppl hypothesize cfs to be caused by oxidative stress, but I was talking to a respected physiologist and he said he thinks that CFS is caused by reductive stress... in which pyruvate, instead of being oxidized, is reduced into lactic acid. he said that NADH/ubiquinol would be bad and that you want the oxidizing versions--ubiquinone and niacinamide

 

[Learner1]

NADH has a positive effect on my energy within 15 minutes of taking it.

Niacinamide has good properties, but too much can impact methylation which is not good for some of us. And nicotinamide riboside does nothing for me, though it dramatically helps others.

And my doctor, who is extremely knowledgeable has me on ubiquinol.

I suspect its not a black and white thing...

 

[frozenborderline]

All good thoughts.

While we're all looking for the magic pill, the incinvenent truth is that our bodies have complex biochemistry and a small handful of interventions isn't likely to fix us.

Until the scientists come up with something better, many of us have concluded that if PDH isn't working, then we're best off feeding with fats and protein, and not depending on carbs.

For each step in the Krebs cycle, there are cofactors that help get to the next step, along with things that inhibit each step. These can be manipulated.

But there's more to it than that. Mitochondria need methylation working properly. They need lipids for membrane health, and they need carnitine, CoQ10, B3, etc.

You really need to look at all the nutrients the body requires, amino acids, lipids, B vitamins, antioxidants, minerals, phytochemicals, etc. And to ensure you're getting enough of all of them.

You might also look into Robert Naviaux's Cell Danger Response paper where he lays out a number of biochemical pathways and maps them from bad to good - when cells sense danger, their chemistry changes, and becoming healthy is a matter of moving from the threatened state to the healthy state. You can manipulate them and ideally, you'll begin to improve.

There's a lot to all of this, and no one has all the answers yet...but we all keep asking and thinking and trying...

have you personally made any improvement with any of this? if so, what do you recommend?

at this point i've been getting worse and worse and want to go back to school so i'm trying to do damage control--between now and then rest a lot and then methodically (i.e. methodical the way shooting a gun in the dark at a supposed intruder is methodical) try each and every thing that could affect the kreb's cycle. i really should be off my "device" and getting ready for sleep but one more thought I had is the low dose naltrexone thing. while it doesn't have a direct effect on cellular respiration, it works differently in low doses and is not just an opioid antagonist. may do some anti-inflammatory/immune modulating stuff via glial cells.

 

[frozenborderline]

I'll make a new thread on this when I get a chance, but: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/

 

[pattismith]

"

I think CFS is likely to involve “reductive stress,” producing lactate because pyruvate isn’t being oxidized fast enough, and in that case I think the reducing supplements, NADH and ubiquinol, could make it worse. Ubiquinone and niacinamide seem more appropriate, since they are the oxidizing forms. Drinking alcohol shifts cells to the reducing side, and a B vitamin deficiency can have similar effects. Vitamin D, thyroid, aspirin, and pregnenolone help to maintain mitochondrial oxidation.

Show original message"
--Ray Peat

I don't know where you find this statment, but it seems all wrong to me.

Ubiquinol is the form prescribed by mito spécialists, for two reasons :

-ubiquinol is better absorbed in the gut than ubiquinone
-ubiquinone is supposed to be quickly reduced after absorption, but the enzymatic complex involved can be deficient with aging or with some pathologies.

For NADH, you will find several studies stating that Nicotinamide Riboside (NAD+ precursor) is actually an effective form, but not every patient do well with it.

And for Aspirin (acetyl salicylic acid), it is toxic to mitochondria!

"Aspirin has been shown to have three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the intermembrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons.[10] In short, aspirin buffers and transports the protons, acting as a competitor to ATP synthase"


See here the list of drugs with mitochondrial toxicity

 

[Learner1]

have you personally made any improvement with any of this? if so, what do you recommend?

at this point i've been getting worse and worse and want to go back to school so i'm trying to do damage control--between now and then rest a lot and then methodically (i.e. methodical the way shooting a gun in the dark at a supposed intruder is methodical) try each and every thing that could affect the kreb's cycle. i really should be off my "device" and getting ready for sleep but one more thought I had is the low dose naltrexone thing. while it doesn't have a direct effect on cellular respiration, it works differently in low doses and is not just an opioid antagonist. may do some anti-inflammatory/immune modulating stuff via glial cells.

Yes, I've made a great deal of improvement in working all of this. I was sleeping 16 hours a day and brain fogged and unable to think or do much with PEM and POTS, but now I sleep 8 to 9 hours a day, am clear headed most of the time, PEM is more rare, POTS is improving.

I've attacked this on multiple fronts. First, replenishing nutrients I was deficient in. My body uses huge quantities of B vitamins, antioxidants, lipids and amino acids. And working on my gut - I had no lactobacillus or bifidobacteria.

Then, working on my hormones and normalizing my sleep. I take thyroid, hydrocortisone, pregnenolone, progesterone, DHEA, and testosterone. And a sleep cocktail of aminos, magnesium, B6, etc.

Then, attacking infections, first holistically, and then after figuring out my immune system was broken, with LDN, antivirals, antibiotics, high doses of vitamin C, and oxygen therapies. I also get IV immunoglobulins to help and to work on the autoimmune antibodies causing POTS caused by the infections and am considering 10 Pass oxygen and Rituximab.

And I'm on a low carb, Paleo diet and exercise carefully, lifting weights and walking, to promote mitochondrial biogenesis.

It's a lot, but it's all helping. I found the attached model of treating CFS and found it helpful in explaining my abnormal lab results and the approach my doctors are using to help me - I have problems in every box in the chart.

Good luck in figuring out where you need to go in seeking a solution. This is a multi headed beast.

 

[frozenborderline]

I don't know where you find this statment, but it seems all wrong to me.

Ubiquinol is the form prescribed by mito spécialists, for two reasons :

-ubiquinol is better absorbed in the gut than ubiquinone
-ubiquinone is supposed to be quickly reduced after absorption, but the enzymatic complex involved can be deficient with aging or with some pathologies.

For NADH, you will find several studies stating that Nicotinamide Riboside (NAD+ precursor) is actually an effective form, but not every patient do well with it.

And for Aspirin (acetyl salicylic acid), it is toxic to mitochondria!

"Aspirin has been shown to have three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the intermembrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons.[10] In short, aspirin buffers and transports the protons, acting as a competitor to ATP synthase"


See here the list of drugs with mitochondrial toxicity

This was speculation from Ray Peat. He is a respected physiologist and in no way a quack. That doesn't mean he can't be wrong though.

As for ubiquinol being better than ubiquinone, isn't it partially dependent on whether you want more oxidation or more reduction?? I need to understand redox reactions better though. I was making progress on understanding this but the last few days have been sleep deprived, which, with CFS, fucks me up way more than a "normal" person.

As for aspirin, I'll have to do more research on it. i've always thought it was good for you. I'll dig up an explanation.

Either way, i'll probably try NADH, or niagen, which is expensive, but I'm down to try anything at this point.