NAD/NADH Ratio - The One Metabolic Cause To Rule Them All

[aguilaroja]

...
And this makes me want to rant about the Breslow Mechanism.
....false paradigms can have inertia;
...Authoritarianism plays an important role; especially when considering things that cannot even be seen directly – like molecules. Explanations printed in the shiniest books are usually considered to be the truth.

A. J. Knell's PhD 1970 dissertation† provides a 144-page β-slap of the Breslow mechanism of how exactly this enzyme works – how thiamine removes carbon dioxide from pyruvate.
...And he goes into great detail on all of his points.

The Breslow Mechanism in rarely drawn with the entire thiamine molecule. This is done partly to save space and time; but also, the rest of the thiamine molecule actually gets in the way if you try to do this. Knell mentioned in point (a) that it was impossible to build models – It's hard to even draw...

And you would think that Breslow intermediate #3 would be practically irreversible
...So this intermediate might not have ever been made, anywhere. Not even inside the enzyme.

....Another nice thing about this is that you have an S-linked acetyl group, which how they are usually shuttled around in the body by coenzyme A.

Thanks for this discussion. The thread is going in many directions....
As thiamine's significance has been discussed in many posts, this is a big point, in addition to the lesson about insidious dogma.

This account is delightfully expressed.

 

[aguilaroja]

Maybe "The one metabolic cause to rule them all" but feel free to name it something simpler if you want....

LOL

Maybe a direwolf banner emblazened with "Lactate is Coming" :^)

 

[haidut]

You believe that infections are treatable by forcing an oxidative state, right? Since everything is interdependent, whether you're depleted by an infection or malnutrition, by boosting metabolism with those substances, if you're not able to restore flow in enough time, it will only serve to deplete you even more. As this happens, and you keep insisting on supplying nutrients, there will be an excess of them because they can't be used, which goes against the idea of keeping things moving and leaving nothing attractive behind. Maybe I'm wrong.

gbolduev believes that there's no such thing as maladaptation and you believe that people should get out of a suppressed state as soon as possible, even if that means using crutches, and it doesn't matter much if it was a proper response or not. Correct?

What's the reason why you think that higher doses of niacinamide are usually needed to restore activity?

Btw, since you asked if the metabolic congestion from infection can be relieved by supplements alone. It seems St. Gyorgyi believed it could - by quinones.
https://raypeatforum.com/community/quotes/117/

I would still consider antibiotics first though and only use the quinones if the antibiotics fail.

 

[haidut]

LOL

Maybe a direwolf banner emblazened with "Lactate is Coming" :^)

Lol, or "the all-seeing eye of lactate".

 

[haidut]

gbolduev believes that there's no such thing as maladaptation

If you don't believe in that then you don't believe in evolution both in the mainstream and Lamarckian sense. Adaptation is the fundamental ability of all things living. It requires energy and when the demands for adaptation exceed the supply of energy you get into the general adaptation syndrome (GAS) Selye spend his life researching and publishing about. Being stuck in GAS is by definition maladaptation.

 

[haidut]

Epic post(s) haidut! Do you have a daily target for how many magnesium mg's? Thank you.

I think anywhere from 200m to 400mg would be a good intake but the problem is that it is only retained if there is enough ATP, which makes it a bit of catch 22. In order to have ATP you need magnesium but in order to retain the magnesium you need ATP. Thyroid helps retain magnesium, as well as possibly methylene blue. Magnesium complexes with succinic or malic acid seem to enter the mitochondria more easily.

 

[Hans]

Would eating pure fructose increase just citric acid? And eating just glucose increase both citric acid and succinic acid? So would eating fruit like and apple with a 2:1 ratio of fructose:glucose increase citric acid more than succinic acid?

 

[haidut]

Would eating pure fructose increase just citric acid? And eating just glucose increase both citric acid and succinic acid? So would eating fruit like and apple with a 2:1 ratio of fructose:glucose increase citric acid more than succinic acid?

Why would eating pure fructose increase citric acid more than glucose or even sucrose? Fructose has some very important benefits including activation of the enzyme PDH, as well as increasing glycogen storage more than any other sugar.

 

[Makrosky]

I think anywhere from 200m to 400mg would be a good intake but the problem is that it is only retained if there is enough ATP, which makes it a bit of catch 22. In order to have ATP you need magnesium but in order to retain the magnesium you need ATP. Thyroid helps retain magnesium, as well as possibly methylene blue. Magnesium complexes with succinic or malic acid seem to enter the mitochondria more easily.

I remember last summer I was using topical magnessium chloride, then after applying it to my torso I would put on top of it some drops of stressnon in DMSO. I think the DMSO helped the magnessium to be more bioavaliable. Could it be?

 

[Hans]

Correct me if I'm wrong, but I was under the impression that fructose doesn't go through the whole TCA cycle, just the citrate step and then out again? So not affecting succinate levels?

 

[haidut]

Correct me if I'm wrong, but I was under the impression that fructose doesn't go through the whole TCA cycle, just the citrate step and then out again? So not affecting succinate levels?

You may be thinking of fructose avoiding the full glycolysis cycle not the Krebs cycle. Once it gets converted to pyruvate it enter Krebs just like glucose does. But unlike glucose, fructose actually stimulates PDH.
Glucose and sucrose for diabetes.
"...One of the points at which fatty acids suppress the use of glucose is at the point at which it is converted into fructose, in the process of glycolysis. When fructose is available, it can by-pass this barrier to the use of glucose, and continue to provide pyruvic acid for continuing oxidative metabolism, and if the mitochondria themselves aren't providing sufficient energy, it can leave the cell as lactate, allowing continuing glycolytic energy production. In the brain, this can sustain life in an emergency."

 

[haidut]

I remember last summer I was using topical magnessium chloride, then after applying it to my torso I would put on top of it some drops of stressnon in DMSO. I think the DMSO helped the magnessium to be more bioavaliable. Could it be?

Yes, quite possibly. A few other people on the forum reported better absorption of MgCl when used topically with DMSO.

 

[Wagner83]

haidut, in the OP you talk about MB and given other posts of yours I've seen, it sounds like one of your favourites. Do you have any idea why Ray has spoken about it but rarely recommends it over dhea/preg/progesterone/thyroid/low dose niacinamide etc..? I've not seen him recommend it that much.

 

[haidut]

haidut, in the OP you talk about MB and given other posts of yours I've seen, it sounds like one of your favourites. Do you have any idea why Ray has spoken about it but rarely recommends it over dhea/preg/progesterone/thyroid/low dose niacinamide etc..? I've not seen him recommend it that much.

He has talked about it in a few newsletter, has KMUD interviews about it, and recommends it to people over email. It seems he most often recommends it either for mood disorders or cancer. Not sure why he is more reserved about it but could be its potential to inhibit MAO-A and interact with tyramine in foods.

 

[Makrosky]

Yeah I've read him mentioning MB in at least a couple of newsletters in the last year.

 

[opiath]

@haidut
You keep promoting thiamine, niacinamide and biotin as safe metabolism "solvers".
My experience with them has been everything but positive.
Even though I have high lactate and low breathing drive these vitamins always make me feel worse after a short-lived positive effect.
I have a history of eating tons of PUFA in the form of peanut butter (150kg over the span of 5 years, which equals 12kg of PUFA).
As we all know by know PUFAs powerfully inhibit cytochrome c oxidase and massively reduce oxygen consumption.
So my question to you is, if cytochrome is inhibited why do you consider forcing the krebs cycle with thiamine,NAD and biotin to be a good thing?
Don't you think the body is making an adaptation by downregulating pyruvate enzymes on purpose in order to prevent NADH generation. Since NADH cannot be oxidized without a functional cytochrome c oxidase.

 

[Tarmander]

The science in undeniable. I can see in the charts and chemical formulae; the logic.

But what do you do with this stack? B vitamins and MB. We have been experimenting with these for years now. They can help for sure...they can also cause insomnia, anxiety, disruption, etc. I have taken all of these substances, and the issue is not the logic, but the practicality.

I take this stack, I get insomnia, do I push through? Dial back the dose? Increase the dose? I feel good, do I increase the dose? I feel nothing, what is happening? I started this stack and am more hungry and am gaining weight, is that temporary? On and on.

 

[haidut]

@haidut
You keep promoting thiamine, niacinamide and biotin as safe metabolism "solvers".
My experience with them has been everything but positive.
Even though I have high lactate and low breathing drive these vitamins always make me feel worse after a short-lived positive effect.
I have a history of eating tons of PUFA in the form of peanut butter (150kg over the span of 5 years, which equals 12kg of PUFA).
As we all know by know PUFAs powerfully inhibit cytochrome c oxidase and massively reduce oxygen consumption.
So my question to you is, if cytochrome is inhibited why do you consider forcing the krebs cycle with thiamine,NAD and biotin to be a good thing?
Don't you think the body is making an adaptation by downregulating pyruvate enzymes on purpose in order to prevent NADH generation. Since NADH cannot be oxidized without a functional cytochrome c oxidase.

Those are not the only things I recommend. I wrote a few sentences on MB as well. So, the optimal approach will depend on the issue. If glycolysis is not excessive and Krebs is working fine but the problem is in ETC then saturated fat and MB would probably be better to handle the issue. Maybe I should have stratified them into groups - i.e which nutrient targets which step of the metabolism. But I thought it was clear from my writing that biotin, niacinamide and thiamine do not participate in ETC, only in glycolysis (all 3) and Krebs cycle (niacinamide as NAD).

 

[haidut]

The science in undeniable. I can see in the charts and chemical formulae; the logic.

But what do you do with this stack? B vitamins and MB. We have been experimenting with these for years now. They can help for sure...they can also cause insomnia, anxiety, disruption, etc. I have taken all of these substances, and the issue is not the logic, but the practicality.

I take this stack, I get insomnia, do I push through? Dial back the dose? Increase the dose? I feel good, do I increase the dose? I feel nothing, what is happening? I started this stack and am more hungry and am gaining weight, is that temporary? On and on.

There could also be an issue with endotoxin, for which reducing bacterial load or absorption of endotoxin in the bloodstream is the only thing that will help. The vitamins and MB may not help consistently if every time you eat you get hit with an endotoxin load. Short of killing off every bug in your gut periodically with antibiotics, I think the carrot salad and charcoal are the other things to be considered on a regular basis. And of course, checking for a chronic bacterial infection somewhere which can derail many pro-metabolic "cocktails".

 

[opiath]

Those are not the only things I recommend. I wrote a few sentences on MB as well. So, the optimal approach will depend on the issue. If glycolysis is not excessive and Krebs is working fine but the problem is in ETC then saturated fat and MB would probably be better to handle the issue. Maybe I should have stratified them into groups - i.e which nutrient targets which step of the metabolism. But I thought it was clear from my writing that biotin, niacinamide and thiamine do not participate in ETC, only in glycolysis (all 3) and Krebs cycle (niacinamide as NAD).

It is not that I have misunderstood your writing.
I just don't think most people with metabolism problems have deficiencies in the glycolysis/krebs cycle area.
It feels like ETC is the problem for most because of past PUFA intake and b vitamins can make this worse.
I could be wrong. Just laying my thoughts and my personal experience.
Saturated fat improves oxidative phosphorylation for sure. This has been the most helpful thing for me whenever I can digest enough of it.
Do you know if MB can be obtained in Bulgaria?