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

noordinary

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@haidut Just seen an ad for a product called Elysium Basic (checked their website and it's: nicotinamide ribosome + pterostilbene), that ad's main promise was to increase NAD+
Wow, that is going mainstream!
note: not affiliated with the company, not going to buy it, just thought it's worth mentioning
 
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haidut

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@haidut Just seen an ad for a product called Elysium Basic (checked their website and it's: nicotinamide ribosome + pterostilbene), that ad's main promise was to increase NAD+
Wow, that is going mainstream!
note: not affiliated with the company, not going to buy it, just thought it's worth mentioning

Yeah, unfortunately they are still pursuing the same old and discredited theory that activating sirtuins is the key to reverse aging and disease. Pterostilbene is just a more bioavailable form of resveratrol and Peat wrote a whole article on the resveratrol scam. I posted about it a few times too. If you search the forum for resveratrol you will find the threads. The infamous drug Vioxx, which killed quite a few people is also a stilbene and most/all stilbenes (including resveratrol) are estrogenic.
Aside from the nicotinamide riboside being crazy expensive for no good reason, a much better supplement to raise NAD/NADH ratio and achieve a host of other benefits would be a combination of plan niacinamide with methylene blue.
 

Dhair

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Yeah, unfortunately they are still pursuing the same old and discredited theory that activating sirtuins is the key to reverse aging and disease. Pterostilbene is just a more bioavailable form of resveratrol and Peat wrote a whole article on the resveratrol scam. I posted about it a few times too. If you search the forum for resveratrol you will find the threads. The infamous drug Vioxx, which killed quite a few people is also a stilbene and most/all stilbenes (including resveratrol) are estrogenic.
Aside from the nicotinamide riboside being crazy expensive for no good reason, a much better supplement to raise NAD/NADH ratio and achieve a host of other benefits would be a combination of plan niacinamide with methylene blue.
Have you seen the posts on Hackstasis where PFS sufferers are using your 11-keto-dht and resveratrol together? Gbolduev has created it as one of his protocols. He says resveratrol will increase estrogen signalling, which will make DHT "more sensitive." I didn't see how this could be possible, but I do know that there are people saying that his has been very beneficial for them, and they feel better almost immediately. Apparently resveratrol can cross the blood brain barrier quite easily.
Can you think of any reason why this might be curing some people? I was just wondering if you might be able to offer some kind of explanation.
 
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haidut

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Have you seen the posts on Hackstasis where PFS sufferers are using your 11-keto-dht and resveratrol together? Gbolduev has created it as one of his protocols. He says resveratrol will increase estrogen signalling, which will make DHT "more sensitive." I didn't see how this could be possible, but I do know that there are people saying that his has been very beneficial for them, and they feel better almost immediately. Apparently resveratrol can cross the blood brain barrier quite easily.
Can you think on any reason why this might be curing some people? I was just wondering if you might be able to offer some kind of explanation.

Resveratrol does increase estrogen signalling, that's for sure. But I thought all those people on hackstasis were cured with the RU486 protocol? Why are they doing an androgen + estrogen now?
 

Dhair

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Resveratrol does increase estrogen signalling, that's for sure. But I thought all those people on hackstasis were cured with the RU486 protocol? Why are they doing an androgen + estrogen now?
Here's the latest, from gbold:

I gave tons of ways to fix it,. minerals route, high dose progesterone, RU route. Thorne extra with resveratrol route,

clomid protocol.

People wrote the feedbacks so far:

Manganese zinc work for some people. stopped hairloss and increased libido with erections and everything

Resveratrol worked for some people increased libido even without taking DHT

Ella Ru increased baselines.

Pine pollen increased baseline

Copper magnesium potassium. works for some people.

Fasting , chelation. works for some people.

These protocol were all outlined and some people are trying them out. But others like Belikewater asking about progesterone, when progesterone was already outlined many times as a cure for some cases. And constantly talking about 5 alpha 1 with zero ability to increase it. Since it can only be increased as a feedback loop.

CD nuts protocol if you rotate estrogenic herbs you will be cured. but might as well just take resveratrol and be done with it.


RU486 looks to be insanely expensive and I think that's the main reason why people were wanting you to come out with an RU486 product. I actually would support this, because I understand why it might be helpful. It looks like it has to be cycled for some reason like everything else. Some of these things seem to be contradictory. If estrogenic herbs and resveratrol are meant to make DHT more sensitive and cure PFS, then why would progesterone work in ANY case?
 
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haidut

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Here's the latest, from gbold:

I gave tons of ways to fix it,. minerals route, high dose progesterone, RU route. Thorne extra with resveratrol route,

clomid protocol.

People wrote the feedbacks so far:

Manganese zinc work for some people. stopped hairloss and increased libido with erections and everything

Resveratrol worked for some people increased libido even without taking DHT

Ella Ru increased baselines.

Pine pollen increased baseline

Copper magnesium potassium. works for some people.

Fasting , chelation. works for some people.

These protocol were all outlined and some people are trying them out. But others like Belikewater asking about progesterone, when progesterone was already outlined many times as a cure for some cases. And constantly talking about 5 alpha 1 with zero ability to increase it. Since it can only be increased as a feedback loop.

CD nuts protocol if you rotate estrogenic herbs you will be cured. but might as well just take resveratrol and be done with it.


RU486 looks to be insanely expensive and I think that's the main reason why people were wanting you to come out with an RU486 product. I actually would support this, because I understand why it might be helpful. It looks like it has to be cycled for some reason like everything else. Some of these things seem to be contradictory. If estrogenic herbs and resveratrol are meant to make DHT more sensitive and cure PFS, then why would progesterone work in ANY case?

I don't like RU486 as it has toxicities and studies showing it has estrogenic effects as well. Also, it is a very niche product and not much in line with Peat's work, which I try to stay within. Btw, the pine pollen mentioned above has androsterone as its main active ingredient. So, again, why not just take a higher dose androsterone or 11-keto DHT, progesterone, or a combination of progesterone and one of these androgens? Seems to be safer than taking an estrogenic chemical. Anyways, I don't want this to turn with a proxy argument between the two forums. Also, it is not on topic with this thread so maybe we can discuss it elsewhere but I don't really have an interest in RU486 or ulipristal.
 

Dhair

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I don't like RU486 as it has toxicities and studies showing it has estrogenic effects as well. Also, it is a very niche product and not much in line with Peat's work, which I try to stay within. Btw, the pine pollen mentioned above has androsterone as its main active ingredient. So, again, why not just take a higher dose androsterone or 11-keto DHT, progesterone, or a combination of progesterone and one of these androgens? Seems to be safer than taking an estrogenic chemical. Anyways, I don't want this to turn with a proxy argument between the two forums. Also, it is not on topic with this thread so maybe we can discuss it elsewhere but I don't really have an interest in RU486 or ulipristal.
Agreed, I don't want to hijack the thread. I might just PM you. Thanks for responding.
 

johnwester130

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How would you inhibit FAS? What would you do simultaneously (ie in terms of oxidative metabolism). I assume the answer will be MB, thyroid, Niacinamide, Thiamine, Riboflavin . . . ?

yep, Riboflavin is the most important

"Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by high energy light, it can spread the damage to other components of the mitochondria, including the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when riboflavin's actions are disturbed.

Vitamin K is also extremely light sensitive, and it interacts closely with coenzyme Q in regulating mitochondrial metabolism. For example, mitochondrial Complex-I, NADH-ubiquinone reductase, is probably the most easily damaged part of the mitochondrion, and it is protected by vitamin K
. "

"Furthermore, because of its structural similarity to coenzyme Q10, it is likely that MK-7 is a Q10 mimetic with respect to the mitochondria and supports mitochondrial adenosine triphosphate (ATP) production in the respiratory chain."

" Riboflavin
, coenzyme Q10,
vitamin K,
niacinamide,
thiamine, and
selenium
are the nutrients that most directly relate to mitochondrial energy production.
"
 
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Wagner83

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I don't like RU486 as it has toxicities and studies showing it has estrogenic effects as well. Also, it is a very niche product and not much in line with Peat's work, which I try to stay within. Btw, the pine pollen mentioned above has androsterone as its main active ingredient. So, again, why not just take a higher dose androsterone or 11-keto DHT, progesterone, or a combination of progesterone and one of these androgens? Seems to be safer than taking an estrogenic chemical. Anyways, I don't want this to turn with a proxy argument between the two forums. Also, it is not on topic with this thread so maybe we can discuss it elsewhere but I don't really have an interest in RU486 or ulipristal.
For the record gbol had said a long time ago dht + estrogens fixed libido issues for PFS guys (I'd expect it to massively increase libido for all though), but he had also said it was a pointless route as as soon as you stop taking them benefits go away.
 
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haidut

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For the record gbol had said a long time ago dht + estrogens fixed libido issues for PFS guys (I'd expect it to massively increase libido for all though), but he had also said it was a pointless route as as soon as you stop taking them benefits go away.

If DHT + estrogens solve the issues then plain T should work just as well as it feeds both DHT and E pathways, and is also an androgen agonist. Also, whether you take the steroid combo or the RU486 there seems to be the need for continuous on/off regimen. With the androgens the benefits are claimed to stop after you stop taking the steroids and for RU486 you have to periodically take it to keep re-sensitizing the receptors because after a course of RU486 you are supposed to stop it and then all of your hormones would surge, which will make you feel better but after a while will downregulate the receptors due to those same elevations. So, one way or another, cycling seems to be needed :): I know, I know, bodybuilders will just roll their eyes and say "I told you cycle and PCT is the way to go" :):
Maybe something like vitamin D would be better as it also re-sensitizes steroid receptors so lower androgen doses are needed, prevents androgen deactivation (glucuronidation) and it also acts as antagonist on GR (which is what RU486 does).
Calcirol - Liquid Supplement With Vitamin D3
I wonder how many PFS people have severe vitamin D deficiency...
 
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GAF

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yep, Riboflavin is the most important

"Riboflavin, vitamin B2, is an essential component of the mitochondrial respiratory enzymes, and it is very easily destroyed by light (blue light and especially ultraviolet). When it is excited by high energy light, it can spread the damage to other components of the mitochondria, including the cytochromes and the polyunsaturated fatty acids. The other B vitamins are affected when riboflavin's actions are disturbed.

Vitamin K is also extremely light sensitive, and it interacts closely with coenzyme Q in regulating mitochondrial metabolism. For example, mitochondrial Complex-I, NADH-ubiquinone reductase, is probably the most easily damaged part of the mitochondrion, and it is protected by vitamin K
. "

Riboflavin and light is a very interesting topic. One of Riboflavin's roles is to stimulate glutathione production. Riboflavin and UV A light are used in a number of medical applications such as "corneal crosslinking" which strengthens collagen and is also used in the cleaning of pathogens from blood. I have a theory that Riboflavin and light are designed to interact with one another in various destructive and constructive ways and then glutathione comes along to clean up the mess. I have not found a source where this topic is really explained or examined at all, but I think the mystery of Vitamin B2 and light is nowhere close to being understood.

If anyone has any secret sources, I would be interested in any links or suggestions.
 

Wagner83

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If DHT + estrogens solve the issues then plain T should work just as well as it feeds both DHT and E pathways, and is also an androgen agonist. Also, whether you take the steroid combo or the RU486 there seems to be the need for continuous on/off regimen. With the androgens the benefits are claimed to stop after you stop taking the steroids and for RU486 you have to periodically take it to keep re-sensitizing the receptors because after a course of RU486 you are supposed to stop it and then all of your hormones would surge, which will make you feel better but after a while will downregulate the receptors due to those same elevations. So, one way or another, cycling seems to be needed :): I know, I know, bodybuilders will just roll their eyes and say "I told you cycle and PCT is the way to go" :):
Maybe something like vitamin D would be better as it also re-sensitizes steroid receptors so lower androgen doses are needed, prevents androgen deactivation (glucuronidation) and it also acts as antagonist on GR (which is what RU486 does).
Calcirol - Liquid Supplement With Vitamin D3
I wonder how many PFS people have severe vitamin D deficiency...
Interesting. Ther are expectations for the continuous need for ru cycles, you can see in a couple of the pfs logs that "ella" seems to have improved the condition a couple of members so far (high dose oral androsterone too). I don't think the ideas you mentioned (antagonist to GR, resensitize androgens receptors) are inclusive of all the ideas gbol had in mind, from what I remember one of his main ideas was that dht is supposed to oppose estrogens but in PFS (some of them only?) progesterone opposes estrogens. Like you said it's difficult to start a discussion about someone's ideas while he's on an other forum, I just talk from remote memories and he can't answer, I thought it could be a source of curiosity for your own research (if it makes any sense that is). Tribulus/protodioscin are also said to help with androgens receptors, I have to say I have not noticed much from it though.
 
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LeeLemonoil

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Riboflavin and light is a very interesting topic. One of Riboflavin's roles is to stimulate glutathione production. Riboflavin and UV A light are used in a number of medical applications such as "corneal crosslinking" which strengthens collagen and is also used in the cleaning of pathogens from blood. I have a theory that Riboflavin and light are designed to interact with one another in various destructive and constructive ways and then glutathione comes along to clean up the mess. I have not found a source where this topic is really explained or examined at all, but I think the mystery of Vitamin B2 and light is nowhere close to being understood.

If anyone has any secret sources, I would be interested in any links or suggestions.


That's my line of thought as well, ever since I've read about corneal crosslinking. I also theorize that there might be a hormetic response to when light degradation of B2 is harmful and when it is beneficial to tissue.

I've also wondered if the prevalence of corneal diseases such as astigmatism and Keratoconus has to do with blue light exposure from TVs an Monitors in the recent decades. @Ella is the Keratoconus-expert on here

Not to hijack this thread though, Thanks for all contributors, an essential read this thread, great info.
 

LeeLemonoil

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Interesting Article @Amazoniac, thanks for posting. Regarding K1 and MK-4, are thes two citations not contradictory? @Travis

"Phylloquinone, usually considered distinct from the menaquinones, is merely MK‐4 with a more heavily saturated lipophilic tail. "

"The degree of lipophilicity in the tails most likely dictates mobility of the quinones in the membrane, with the partially saturated isoprenyl tail of MK allowing for greater freedom of movement compared to the mostly unsaturated chain of K1. Additionally, longer chain MKs are likely stiffer and more viscous in the membrane due to the greater surface areas available for van der Waals interactions. For these reasons, the preferential incorporation of one MK over another into a redox‐active enzyme is most likely due to availability within the membrane as well as the ability of the enzyme to accommodate different length side chains. In microsomal fractions, MK2 and MK3 were shown to have much higher activities than K1"
 

Amazoniac

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Interesting Article @Amazoniac, thanks for posting. Regarding K1 and MK-4, are thes two citations not contradictory? @Travis

"Phylloquinone, usually considered distinct from the menaquinones, is merely MK‐4 with a more heavily saturated lipophilic tail. "

"The degree of lipophilicity in the tails most likely dictates mobility of the quinones in the membrane, with the partially saturated isoprenyl tail of MK allowing for greater freedom of movement compared to the mostly unsaturated chain of K1. Additionally, longer chain MKs are likely stiffer and more viscous in the membrane due to the greater surface areas available for van der Waals interactions. For these reasons, the preferential incorporation of one MK over another into a redox‐active enzyme is most likely due to availability within the membrane as well as the ability of the enzyme to accommodate different length side chains. In microsomal fractions, MK2 and MK3 were shown to have much higher activities than K1"
Good catch. I think he meant unsaturated.
 

Travis

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Interesting Article @Amazoniac, thanks for posting. Regarding K1 and MK-4, are thes two citations not contradictory? @Travis
"Phylloquinone, usually considered distinct from the menaquinones, is merely MK‐4 with a more heavily saturated lipophilic tail. "

"The degree of lipophilicity in the tails most likely dictates mobility of the quinones in the membrane, with the partially saturated isoprenyl tail of MK allowing for greater freedom of movement compared to the mostly unsaturated chain of K1. Additionally, longer chain MKs are likely stiffer and more viscous in the membrane due to the greater surface areas available for van der Waals interactions. For these reasons, the preferential incorporation of one MK over another into a redox‐active enzyme is most likely due to availability within the membrane as well as the ability of the enzyme to accommodate different length side chains. In microsomal fractions, MK2 and MK3 were shown to have much higher activities than K1"
Where did this second quote come from? Phylloquinone is certainly abbreviated K₁, and I've seen no exception for this. And since you cannot change the degree of saturation without changing the name of the compound, the phrase in bold represents a false clause (and it lacks a proper subscript). The phylloquinone tail is certainly mostly saturated; the MK‐series are unsaturated since they derive from the same isoprene groups used to make cholesterol, coenzyme Q, and heme (and isoprene can be derived from leucine, a little‐known fact). The phylloquinone tail is removed first, and the isoprene groups are added second.

The cellular distribution is interesting. What isn't mentioned above is the slightly higher water solubility of unsaturated vs unsaturated lipids. They also have a greater movement (less moment of intertia, and volume), and are constantly wiggling despite the fact that line depictions are always drawn static—a freeze‐frame model of reality with little attention given to ionic radii, bond length, or partial charge (among other things). Here is an animation of normal inversions ammonia, to give an idea of how molecules change form from one moment to the next. Infrared spectroscopy data can give one an idea of how a molecule stretches, wiggles, and twists (as in long molecules like DNA polymer).
 
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Amazoniac

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Vitamin A and Carotenoids as Antioxidants in a Physiological Contex
Summary:
Under selected conditions, vitamin A and Carotenoids can both accept and donate electrons, and carotenoids can also quench singlet oxygen. Thus both sets of compounds can theoretically participate in a biological antioxidant network. Under physiological conditions, vitamin A esters are transported and stored in a lipid matrix that contains other antioxidants, and retinol and its active metabolites are largely bound in clefts of specific retinoid-binding proteins. Thus, vitamin A seems to be protected in vivo by other antioxidants and proteins rather than protecting other molecules. Carotenoids are largely distributed in lipoproteins, membranes, and the lipid phases of intracellular structures, usually together with vitamin E. Carotenoids can interact with other antioxidants in vitro, but whether they play similar significant roles in vivo is not clear. Nonetheless, some genetic conditions and precancerous lesions respond to carotenoids, and the dietary intake of carotenoids has been associated with a reduced risk of several chronic diseases. Carotenoids seem to act per se in such systems rather than by their conversion into vitamin A.
@Travis ("Retinol [], which contains 5 conjugated double bonds"..)
 

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