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jb116

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Sugar and adequate thiamine should help a lot regarding the pyruvate to CO2 route.
 

GAF

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Thx jb116.
Yesterday I ran out of energy at 430pm and had to nap. I usually take a B1 mono daily but did not yesterday. I will take one now. Took my 20dropshot 30min ago.
 

Jsaute21

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@haidut - so glad you came out with this. Have been hounding you for a long time about it as i am sure others have. You're #2 on the GOAT rankings to PEAT. Climbing quickly though. In all seriousness, its surprising a ketoacid aids glycolysis no? Or am i being a simpleton thinking this way?
 
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haidut

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@haidut - so glad you came out with this. Have been hounding you for a long time about it as i am sure others have. You're #2 on the GOAT rankings to PEAT. Climbing quickly though. In all seriousness, its surprising a ketoacid aids glycolysis no? Or am i being a simpleton thinking this way?

PDH is not part of glycolysis. It is the first enzyme that is part of OXPHOS and is inside the mitochondria. But yeah, I was surprised too that pyruvate stimulates its own oxidation.
 
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haidut

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@haidut, What is the BEST thing we can do, to ensure the Pyruvate goes to CO2. Most likely is to make sure we have enough sugar on hand, right?

The purpose of pyruvate in this product is not to boost CO2. It is to activate PDH so that the sugar you eat is properly metabolized. But as far as ensuring most pyruvate going towards CO2 - thiamine, niacinamide, magnesium and keeping fatty acids low are the main things that ensure high CO2 synthesis.
 
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haidut

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Day 3 20 drop shot in OJ. Had a strong alert productive day - made lots of $ today. Forgot to smudge 4 drops on GF this morning.

I won't keep boring everyone but plan is to keep up the 20 drop shots daily until 4/15 at least. If it quits working and I start pooping out I will report in. Otherwise assume the stuff is still helping my naturally sputtering engine run a lot better.

Great, thanks for the feedback. Keep us posted.
 
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chimdp

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@haidut

I'm still a little confused by the GSSG:GSH ratio thing and your responses to @Mufasa and @Dave Clark ...

I think I get the explanation on the redox status needing to shift form reduction to oxidation in many people, but I would think there would be a difference in improving the ratio while keeping some GSH and improving the ratio by dropping GSH to nearly zero. Take the quote below for example,

Well, it is explained in the thread. GSH is VERY high in cancer and many other chronic degenerative conditions. I did not say it should be brought down to zero, not sure where you saw that suggestion. I pointed out the bringing GSH down to zero as an example of how these two chemicals can shift the balance strongly towards oxidation. Most people have their redox status shifted towards reduction and by lowering GSH, NADH, lactate, etc their status shifts towards oxidation, which increases metabolism.

You say it should not be brought down to zero, but in your original product post below you say (bold and italics),

As a result, the more familiar NAD/NADH and GSSG/GSH ratios also rise. The former needs no introduction, but the latter is extremely important in cancer. Cancer cells accumulate massive amounts of GSH and they use it to protect themselves from the ROS generated by chemotherapy. In fact, the high GSH levels is considered the primary factor in "chemotherapy resistance" and Big Pharma has spend a lot of money on trying to identify chemicals that can deplete GSH. Well, as one of the studies in the references section below shows, administering high dose acetoacetate for just one day dropped GSH levels to zero, while a more moderate dose (available in our product) also dropped GSH levels down to zero after 3-4 days of administration. As it turns out, pyruvate is also capable of such effects GSH-depleting effects.

Are you not saying that if we were to take the dose listed on the bottle for 3-4 days, it would drop our GSH levels to zero? And I also get where that would be helpful in cancer patients, but still not sure why zero would be desirable in normal or somewhat normal individuals? If you are saying that taking the dose on the bottle will lead to zero GSH in 3-4 days, could one infer that a non-cancer patient may want to take the product every other day to avoid a complete zeroing of GSH?

Do you have a reference for that?
Very often the exact opposite is claimed.

Not saying that I disagree, but I would like to read more evidence.

Lastly and sorry for the long post..., I was curious if there were any references for this in non-cancer patients as Mufasa had requested? From Wikipedia quoted below, they say that an increased ratio of GSSG:GSH is a sign of oxidative stress, not to mention the bullet point list below that names several of the key functions of GSH which make it seem like it would be detrimental to drop GSH too low (except maybe in the case of cancer patients undergoing treatment). Especially concerning is the last bullet point that that says low levels of GSH cause systematic breakage of the cell and excessively low levels cause rapid cell death? It seems there are a lot of positives to this product based on all the studies on EP and EA, but I just want to make sure I'm not doing anything detrimental when it comes to the GSSG:GSH ratio. Any explanation for those like myself who don't have the scientific background you do would be greatly appreciated.


"In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress.[24]

Glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein S-glutathionylation, a redox-regulated post-translational thiol modification.

Glutathione has multiple functions:

  • It maintains levels of reduced glutaredoxin and glutathione peroxidase.[25]
  • It is one of the major endogenous antioxidants produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.[26][27][28]
  • Regulation of the nitric oxide cycle is critical for life, but can be problematic if unregulated.[29] Glutathione enhances the function of citrulline as part of the nitric oxide cycle.
  • It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system, and the lungs.[citation needed]
  • It has a vital function in iron metabolism. Yeast cells depleted of GSH or containing toxic levels of GSH show an intense iron starvation-like response and impairment of the activity of extramitochondrial ISC enzymes thus inhibiting oxidative endoplasmic reticulum folding, followed by death.[30]
  • It has roles in progression of the cell cycle, including cell death.[5] GSH levels regulate redox changes to nuclear proteins necessary for the initiation of cell differentiation. Differences in GSH levels also determine the expressed mode of cell death, being either apoptosis or cell necrosis. Manageably low levels result in the systematic breakage of the cell whereas excessively low levels result in rapid cell death.[31]"
 
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haidut

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@haidut

I'm still a little confused by the GSSG:GSH ratio thing and your responses to @Mufasa and @Dave Clark ...

I think I get the explanation on the redox status needing to shift form reduction to oxidation in many people, but I would think there would be a difference in improving the ratio while keeping some GSH and improving the ratio by dropping GSH to nearly zero. Take the quote below for example,



You say it should not be brought down to zero, but in your original product post below you say (bold and italics),



Are you not saying that if we were to take the dose listed on the bottle for 3-4 days, it would drop our GSH levels to zero? And I also get where that would be helpful in cancer patients, but still not sure why zero would be desirable in normal or somewhat normal individuals? If you are saying that taking the dose on the bottle will lead to zero GSH in 3-4 days, could one infer that a non-cancer patient may want to take the product every other day to avoid a complete zeroing of GSH?



Lastly and sorry for the long post..., I was curious if there were any references for this in non-cancer patients as Mufasa had requested? From Wikipedia quoted below, they say that an increased ratio of GSSG:GSH is a sign of oxidative stress, not to mention the bullet point list below that names several of the key functions of GSH which make it seem like it would be detrimental to drop GSH too low (except maybe in the case of cancer patients undergoing treatment). Especially concerning is the last bullet point that that says low levels of GSH cause systematic breakage of the cell and excessively low levels cause rapid cell death? It seems there are a lot of positives to this product based on all the studies on EP and EA, but I just want to make sure I'm not doing anything detrimental when it comes to the GSSG:GSH ratio. Any explanation for those like myself who don't have the scientific background you do would be greatly appreciated.


"In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than 10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress.[24]

Glutathione participates in thiol protection and redox regulation of cellular thiol proteins under oxidative stress by protein S-glutathionylation, a redox-regulated post-translational thiol modification.

Glutathione has multiple functions:

  • It maintains levels of reduced glutaredoxin and glutathione peroxidase.[25]
  • It is one of the major endogenous antioxidants produced by the cells, participating directly in the neutralization of free radicals and reactive oxygen compounds, as well as maintaining exogenous antioxidants such as vitamins C and E in their reduced (active) forms.[26][27][28]
  • Regulation of the nitric oxide cycle is critical for life, but can be problematic if unregulated.[29] Glutathione enhances the function of citrulline as part of the nitric oxide cycle.
  • It is used in metabolic and biochemical reactions such as DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Thus, every system in the body can be affected by the state of the glutathione system, especially the immune system, the nervous system, the gastrointestinal system, and the lungs.[citation needed]
  • It has a vital function in iron metabolism. Yeast cells depleted of GSH or containing toxic levels of GSH show an intense iron starvation-like response and impairment of the activity of extramitochondrial ISC enzymes thus inhibiting oxidative endoplasmic reticulum folding, followed by death.[30]
  • It has roles in progression of the cell cycle, including cell death.[5] GSH levels regulate redox changes to nuclear proteins necessary for the initiation of cell differentiation. Differences in GSH levels also determine the expressed mode of cell death, being either apoptosis or cell necrosis. Manageably low levels result in the systematic breakage of the cell whereas excessively low levels result in rapid cell death.[31]"

The reason I bolded the point about dropping GSH to zero is to highlight how potent an effect it could have. Very few chemicals out there are known to be able to achieve that, so it is definitely something noteworthy about acetoacetate that deserves highlighting. Again, it does not mean this is an outcome people should strive for. How is this not clear??
In some people lowering GSH as much as possible is desirable. Again, nowhere did I say the goal is to drop it zero. Most chronic diseases are conditions of excessive reductive stress, not oxidative stress. Hence, lowering GSH and thus raising the GSSG/GSH ratio may help in many cases. If you search Peat's website for GSH you will find quite a bit of other information that should answer your questions.
 

chimdp

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The reason I bolded the point about dropping GSH to zero is to highlight how potent an effect it could have. Very few chemicals out there are known to be able to achieve that, so it is definitely something noteworthy about acetoacetate that deserves highlighting. Again, it does not mean this is an outcome people should strive for. How is this not clear??
In some people lowering GSH as much as possible is desirable. Again, nowhere did I say the goal is to drop it zero. Most chronic diseases are conditions of excessive reductive stress, not oxidative stress. Hence, lowering GSH and thus raising the GSSG/GSH ratio may help in many cases. If you search Peat's website for GSH you will find quite a bit of other information that should answer your questions.

Thanks for the reply Haidut! I'll check out the Peat website articles.

I'm guessing it's a highly variable answer, but thought I'd ask anyways... Do you have an approximation of how quickly GSH levels tend to increase after the use of a product like Pyrucet has ceased?
 
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haidut

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Thanks for the reply Haidut! I'll check out the Peat website articles.

I'm guessing it's a highly variable answer, but thought I'd ask anyways... Do you have an approximation of how quickly GSH levels tend to increase after the use of a product like Pyrucet has ceased?

Unless the person is somehow HYPER metabolic, GSH levels probably recover within days as the GSSG gets quickly reduced back to GSH in the absence of continuing exposure to an oxidizing agent.
 

truegrit

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Has anyone had better success with oral versus topical?


Oral definitely increases my appetite more noticeably (which I'm not sure is a proxy for overall potency). Otherwise I'm still trying to define better. I'm taking it largely for athletic performance, so I may not be the typical use case here. I do suspect oral is more potent overall but tough to make that a hard-and-fast rule at this point.
 
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Jsaute21

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Oral definitely increases my appetite more noticeably (which I'm not sure is proxy for overall potency). Otherwise I'm still trying to define better. I'm taking it largely for athletic performance, so I may not be the typical use case here. I do suspect oral is more potent overall but tough to make that a hard-and-fast rule at this point.

Same boat here.
 

jaakkima

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Do we know what the half life of the EP would be? Also, for targeting bowel inflammation/endotoxin and the clotting response should orally or topically be equally ok or different?
 
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SB4

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Does anyone know how long it takes to reach peak serum after ingestion? Also what search terms to use when trying to find this information. I have tried "bioavalibility" and "peak serum" but couldn't find what I was looking for.
 
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haidut

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Do we know what the half life of the EP would be? Also, for targeting bowel inflammation/endotoxin and the clotting response should orally or topically be equally ok or different?

Half life is unlikely to be very long as both the EP and EA can be metabolized into their respective constituents and those then get quickly oxidized. I would say 3-4 hours for half life. However, the effects from activating PDH and suppressing FAO can last much longer depending on the person. A study with calcium pyruvate found it half life to be about 5 hours.
The bioavailability of calcium in the form of pyruvate, carbonate, citrate–malate in healthy postmenopausal women
 
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