Pyruvate Dehydrogenase Deficiencies and Cures?

[Learner1]

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

Enada. NADH 10mg is sublingual. It helps me a lot. I take it when I need extra energy, like before exercise or when I need to function late in the day. I don't overuse it, though, a) because its expensive, and b) because I'm leery about pushing my mitochondria too hard when they're compromised.

A chemist I know doesn't think NADH Shpykd work because it can't get digested. Butvtge sublingual gets it right into the bloodstream And I feel the effects within 15 min. He is a fan of Niagen/Niacel, which I've tried in high doses, and it does nothing for me. A friend who tried them side by side with me found Niagen helps her and NADH does not.

We concluded our pathways are needing different things.

And, while I find Ray Peat interesting, I take him with a grain of salt.

 

[frozenborderline]

Enada. NADH 10mg is sublingual. It helps me a lot. I take it when I need extra energy, like before exercise or when I need to function late in the day. I don't overuse it, though, a) because its expensive, and b) because I'm leery about pushing my mitochondria too hard when they're compromised.

A chemist I know doesn't think NADH Shpykd work because it can't get digested. Butvtge sublingual gets it right into the bloodstream And I feel the effects within 15 min. He is a fan of Niagen/Niacel, which I've tried in high doses, and it does nothing for me. A friend who tried them side by side with me found Niagen helps her and NADH does not.

We concluded our pathways are needing different things.

And, while I find Ray Peat interesting, I take him with a grain of salt.

I take some of ray peat's recommendations with a grain of salt, but he is on a higher tier than your average fad diet guru or alternative health person, imo. I mean he did substantial research on estrogen, and he seems well versed in bioenergetics (he recommended szent-gyorgi's book on submolecular biology to me).
I think ray is probably wrong about some things and tries to be deliberately contrarian sometimes, but I will always take his takes seriously, but also with a grain of salt, as a lot of them are speculation, albeit speculation with citations, ya know?

 

[Learner1]

Agreed!

 

[frozenborderline]

he does generally respond to my emails, so I've (politely) challenged his idea of cfs being reductive stress with some studies... waiting to hear his take on those

 

[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

http://raypeat.com/articles/aging/aspirin-brain-cancer.shtml

 

[ljimbo423]

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

There is one thing that I've been learning in the last few years of dealing with CFS. That is, what might help one person can make the next feel absolutely awful and vise-versa.

So it really is about 99% trial and error. Having said that, I still look for things that have helped people. Then research them and decide if it's something I want to spend the money on to see if it helps me.

It can be really frustrating at times not knowing what will help and what won't but that's the nature of CFS. I find that NADH gives me too much energy, to the point of excess anxiety and insomnia even at very low doses.

What's really weird is several years ago I had no problem taking 5-10mg a day. I guess my body chemistry has changed and therefore the different reaction to NADH. I have not tried niagen yet.

Some thing you might want to do is buy the smallest quantity of something you want to try. That way if it don't work, you haven't spent $30 on something that's useless.

Jim

 

[frozenborderline]

There is one thing that I've been learning in the last few years of dealing with CFS. That is, what might help one person can make the next feel absolutely awful and vise-versa.

So it really is about 99% trial and error. Having said that, I still look for things that have helped people. Then research them and decide if it's something I want to spend the money on to see if it helps me.

It can be really frustrating at times not knowing what will help and what won't but that's the nature of CFS. I find that NADH gives me too much energy, to the point of excess anxiety and insomnia even at very low doses.

What's really weird is several years ago I had no problem taking 5-10mg a day. I guess my body chemistry has changed and therefore the different reaction to NADH. I have not tried niagen yet.

Some thing you might want to do is buy the smallest quantity of something you want to try. That way if it don't work, you haven't spent $30 on something that's useless.

Jim

that's interesting and i wonder why that is. I thought we were getting closer to a unifying cfs theory... I guess it depends partially on diagnostic criteria?

 

[ljimbo423]

that's interesting and i wonder why that is. I thought we were getting closer to a unifying cfs theory... I guess it depends partially on diagnostic criteria?

I think there are many variables in each person, even though we have the same illness and therefore the same core issues. Different genetics, and different epigenetics etc, alter the functioning of different pathways and metabolic processes.

I think those are some of the main reasons why we often respond very differently to supps. Epigenentics, which can turn genes on and off can have a big impact on how metabolic pathways function.

Epigenetics are changed by diet, exposure to toxins, stress levels, nutrient intake, infections (past and present), etc. So we have the ability to alter our epigenetics in favor of health through a healthy diet, lowering stress, supps, less toxin intake or exposure etc.

Jim

 

[Basilico]

Has anyone here tried keto or phenylbutyrate therapy with any success?

While I know that there are some people with CFS who do improve somewhat with either a keto or a low-carb diet, it did nothing for me or my husband.

However, we both tried an experiment that involved taking Ketone salts directly (to bypass any potential roadblocks with the ketone pathway). He responded to it in an interesting way, but I was a non-responder. For some reason, it seems like maybe men respond better to ketone supplementation and/or a keto diet in general, but this is based only on anecdotal evidence. He chronicled the whole thing here: http://forums.phoenixrising.me/inde...-tolerance-and-reduced-pem.52639/#post-897919

 

[frozenborderline]

Enada. NADH 10mg is sublingual. It helps me a lot. I take it when I need extra energy, like before exercise or when I need to function late in the day. I don't overuse it, though, a) because its expensive, and b) because I'm leery about pushing my mitochondria too hard when they're compromised.

A chemist I know doesn't think NADH Shpykd work because it can't get digested. Butvtge sublingual gets it right into the bloodstream And I feel the effects within 15 min. He is a fan of Niagen/Niacel, which I've tried in high doses, and it does nothing for me. A friend who tried them side by side with me found Niagen helps her and NADH does not.

We concluded our pathways are needing different things.

And, while I find Ray Peat interesting, I take him with a grain of salt.

I am going to need things like this for when I go back to school :/ have you ever used kratom? even though I am prescribed stims, I can't take them ever since I got CFS/lyme, I have a newfound sensitivity. so kratom has helped at some points

 

[frozenborderline]

Enada. NADH 10mg is sublingual. It helps me a lot. I take it when I need extra energy, like before exercise or when I need to function late in the day. I don't overuse it, though, a) because its expensive, and b) because I'm leery about pushing my mitochondria too hard when they're compromised.

A chemist I know doesn't think NADH Shpykd work because it can't get digested. Butvtge sublingual gets it right into the bloodstream And I feel the effects within 15 min. He is a fan of Niagen/Niacel, which I've tried in high doses, and it does nothing for me. A friend who tried them side by side with me found Niagen helps her and NADH does not.

We concluded our pathways are needing different things.

And, while I find Ray Peat interesting, I take him with a grain of salt.

do you really think NADH would cause stress? in this case i guess it would be reductive stress not oxidative, if it DID cause stress, but I just am guessing/hoping that something that FEEDS the kreb's cycle wouldn't be as possibly stressful as an actual stimulant

 

[Learner1]

I mean pushing the mitochondria to run faster when they may not be in the best shape may be counterproductive.

The production of ATP throws off superoxide radicals, and if you don't make enough superoxide dismutase to defang them and peroxynitrites are created you can accrue damage to mitochondrial membranes and DNA.

 

[frozenborderline]

I mean pushing the mitochondria to run faster when they may not be in the best shape may be counterproductive.

The production of ATP throws off superoxide radicals, and if you don't make enough superoxide dismutase to defang them and peroxynitrites are created you can accrue damage to mitochondrial membranes and DNA.

I thought that the mitochondria aren't thought to be actually damaged in cfs according to ron davis... thought that there was just a problem in pyruvate oxidation. do you really think burnout is a serious risk with NADH?

 

[frozenborderline]

I mean pushing the mitochondria to run faster when they may not be in the best shape may be counterproductive.

The production of ATP throws off superoxide radicals, and if you don't make enough superoxide dismutase to defang them and peroxynitrites are created you can accrue damage to mitochondrial membranes and DNA.

I thought that the mitochondria aren't thought to be actually damaged in cfs according to ron davis... thought that there was just a problem in pyruvate oxidation. do you really think burnout is a serious risk with NADH?

 

[Learner1]

Many of us have damaged mitochondria. Damaged mitochondria are linked to many diseases of aging. They are damaged as described in the papers I attached.

In my case, I'm lousy at BH4 recycling, lousy at SOD production, great at peroxynitrite production, have a lousy Kennedy pathway and am lousy at glutathione production. Oh, and I had stage 3 cancer - cancer mitochondria are abnormal, and I've been on ciprofloxacin, paclitaxel, and carboplatin, all known to damage mitochondria.

So, while some people may simply have a PDH problem, many of us have a plethora issues.

 

[frozenborderline]

[QUOTE="debored13, post: 931089, member: 31864So then I looked at what is a treatment for pyruvate dehydrogenase complex deficiency, and also symptoms of that disease. That disease seems more severe in some ways than CFS, but I wonder if that is simply because it comes on earlier... or is a more complete deficiency in pyruvate dehydrogenase than CFS is. One of the main problems seems to be the buildup of lactic acid, which people with CFS also have.
One of the treatments is a ketogenic diet.

@debored13

Are you saying one of the treatments of pyruvate dehydrogenase complex deficiency is a ketogenic diet?
Or is it a buildup of lactic acid which is treated by a keotgenic diet?[/QUOTE]
well, PDH complex deficiency leads to a buildup of lactic acid, I believe. either way, one of the treatments is a keto diet. that's not like the first line treatment but it apparently works for some...

 

[frozenborderline]

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.

I have to state again how much this gives me hope. i feel like i'm heading for being bedbound and I hope that with the right supplements I could make improvement. at this point I've accepted having an illness but I don't think i've accepted getting steadily worse.
Will be trying all these supplements--my pregnenolone just came today

 

[Learner1]

Glad you have hope! Its the only mindset to have!

It just makes a lot of sense to me that my body wasn't always this way, and if I got here somehow, there's got to be a way out.

Its pretty complex, so having good data and knowing what problems you need to solve and prioritizing solving them in the most effective, least risky way will get us there faster. Oh, and hoping the scientists come up with some lovely shortcut...

 

[frozenborderline]

There's a little bit of a catch 22 where having CFS isn't always conducive to sifting through data and learning science. But I try to do so whenever I have the energy to spare ...
I showed some of this stuff to a biochem friend. She doesn't quite know what to make of it but might help me synthesize grey market stuff like triheptanoin!

 

[rodgergrummidge]

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


See here the list of drugs with mitochondrial toxicity

I @pattismith I also came across the mito tox table (you pasted above) while trawling the internet for mito-toxins. But I dont trust the list because they dont provide references/sources or any reasons for the proposed mechanisms. In some cases they incorrectly interpret a drug as being toxic when in fact, depending on the context, can be therapeutic (eg metformin). Do you know where to find a properly referenced list of mitochondrial toxins? I cant seem to find one...

Rodger